Testing for HER2 in patients with colorectal cancer (CRC) should become a new standard of care, say experts discussing new results from a phase 2 trial showing benefit with trastuzumab deruxtecan (T-DXd, marketed as Enhertu, AstraZeneca/Daiichi Sankyo).

This drug is approved in the United States for use in the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have already received two or more prior anti–HER2-based regimens in the metastatic setting.

Results come from a phase 2 study, dubbed DESTINY-CRC01, in patients with previously treated HER2+ advanced CRC.

The results show that, in patients with the highest degree of HER2 positivity, T-DXd was associated with an objective response rate of over 45% and a median progression-free survival (PFS) of almost 7 months.

They “demonstrate, in our opinion, the potential of T-DXd as a treatment option” for patients with advanced HER2-positive colorectal cancer that is refractory to standard therapies, said lead investigator Salvatore Siena, MD, from Niguarda Cancer Center, in Milan, Italy.

He presented the results at the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because of the coronavirus pandemic.

At the same time, results from another study, this time in gastric cancer patients, were published online in the New England Journal of Medicine.
 

Interstitial lung disease as adverse event

The safety profile of T-DXd seen in the colorectal trial “is consistent with what has been previously reported,” said Siena, adding that most of the adverse events were low grade. But he noted there was also a serious adverse effect – interstitial lung disease (ILD). This occurred in 6% of patients, two of whom died. This is “an important risk and requires careful monitoring and proper intervention,” he emphasized.

The ILD adverse effect in this study is “a concern…and something to consider,” commented discussant for the study Michael S. Lee, MD, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill. But he added that these are the “the best data so far for subsequent anti-HER2 therapy in colorectal cancer”.

Also, the dose of drug used in this trial was higher than that approved for breast cancer, and the incidence of ILD “begs the question of whether we should be using a lower dose in this patient population,” said Autumn J. McRee, MD, also from Lineberger, in a highlights session at the meeting.

“The question here really is whether an HER2-specific approach is superior to what we would offer to these patients in the standard of care setting,” McRee said.

She noted that the patients in DESTINY-CRC01 were “heavily pretreated…and if you think about what our options are in the refractory setting, we do have two approved treatments: regorafenib [Stivarga, Bayer] and TAS-102 [Lonsurf, Taiho Oncology].”

The current data suggest, however, that T-DXd is associated with a trend toward higher response rates and improved survival outcomes, as well as lower monthly costs.

“Without a doubt, this trial is clinically relevant,” she said, adding that it’s “important not to miss these patients.”

“They are rare…but I would argue that testing for HER2 amplification in colorectal cancer should be considered standard of care,” she said.

She added that, based on the current evidence, the trial “may be” practice changing, although it is “still to be determined how to sequence HER2 targeted therapies.”
 

Study details

The trial was conducted in 78 patients with previously treated unresectable and/or metastatic CRC that was HER2 expressing, RAS/BRAF wild type, and patients had to have received at least two prior regimens, including prior anti-HER2 treatment. Patients with current or suspected ILD were excluded.

Patients were divided into three cohorts based on the degree of HER2 positivity:

• HER2+ with immunohistochemistry (IHC) scoring 3+ or IHC2+/in-situ-hybridization (ISH)+ (cohort A, n = 53)
• HER2 IHC2+/ISH– (cohort B, n = 7)
• HER2 IHC1+ (cohort C, n = 18)

All patients received T-DXd at 6.4 mg/kg intravenously every 3 weeks until progression or intolerable toxicity.

Across the three cohorts, the median age was 58.5 years, and nearly half (47.4%) of patients were female. The vast majority (98.7%) of patents had ECOG performance status 0 or 1, and the primary tumor site was the left colon or rectum in 89.7%.

Siena noted that “the median number of prior lines of standard therapies was four, ranging from two to 11.” All patients had previously received irinotecan and oxaliplatin, and 20.5% had received an anti-HER2 drug.

At the data cutoff on August 9, 2019, 38.5% of patients remained on treatment. The reason for discontinuation was progressive disease in 41%, and clinical progression in 9%.

Siena reported that the overall response rate, as confirmed by independent central review, was 45.3% in cohort A, with all but one of the 24 responders having a partial response. No responses were recorded in cohorts B and C.

Stable disease was seen in 37.7% of cohort A patients, giving a disease control rate of 83%. The median duration of response was not reached.

Median PFS was 6.9 months in cohort A, and the medial overall survival was not reached.

In terms of safety, 50.9% of patients in cohort A and 48.7% patients overall experienced drug-related treatment emergent adverse events, with 22.6% and 17.9%, respectively, having serious drug-related events.

The most common treatment-emergent adverse events were nausea, anemia, reduced neutrophil count, fatigue, and decreased appetite.

There were two deaths related to the study drug, as determined by investigator assessment: one from pneumonitis and one as a result of ILD, with both occurring in cohort A.

Looking specifically at ILD, Siena said there were five events – two grade 2, one grade 3, and two grade 5 – at a median time to reported onset of 80 days. All patients received corticosteroids, as per the study protocol, and two recovered.

Study discussant Lee commented that biomarker testing, such as for HER2, “is part of our standard of care for colorectal cancer,” although studies such as the current one are providing new data to “better refine” treatment approaches.

Lee said that, overall, T-DXd had a response rate and PFS survival “that looked similar to prior data from previous single arm phase 2 studies,” with response rates generally ranging from 30% to 50%, “and this compares favorably with other standard of care options” for chemotherapy-refractory patients.

Nevertheless, there are several ongoing questions related to the treatment of HER2 amplified metastatic CRC patients, some of which are being addressed in the ongoing SWOG S1613 study.

Lee said that, for now, he would recommend that patients with HER2 amplification enroll in a clinical trial, if possible. “However, if that’s not feasible, there are a range of options to consider,” including trastuzumab plus lapatinib (Tykerb, Novartis), or trastuzumab plus pembrolizumab (Keytruda, Merck).

However, “none of these options are FDA approved so there will be issues potentially with financial toxicity and other regulatory issues,” he said.

The study was funded by Daiichi Sankyo Co, Ltd.

Siena reports stock and other ownership interests with Guardant Health and Myriad Genetics; a consulting or advisory role with Amgen, Bayer, Bristol-Myers Squibb, CheckmAb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Roche/Genentech, Seattle Genetics; research funding from MSD Oncology (Inst); patents, royalties, and other intellectual property from Amgen; and travel, accommodations, expenses from Amgen, Bayer, and Roche. Other coauthors report potential conflicts of interest. The full list can be found with the original article.

Lee reports: Research Funding – Amgen (Inst); Bristol-Myers Squibb (Inst); EMD Serono (Inst); Exelixis (Inst); Genentech/Roche (Inst); Pfizer (Inst); Travel, Accommodations, Expenses – Genentech/Roche.

McRee reports honoraria from Cor2Ed and Onc Live; research funding from AstraZeneca (Inst), BioMed Valley Discoveries (Inst), Boston Biomedical (Inst), Inovio Pharmaceuticals (Inst), Merck (Inst), Novartis (Inst), Rgenix (Inst), and Takeda (Inst); and travel, accommodations, expenses from Cor2Ed.

This article first appeared on Medscape.com.

Testing for HER2 in patients with colorectal cancer (CRC) should become a new standard of care, say experts discussing new results from a phase 2 trial showing benefit with trastuzumab deruxtecan (T-DXd, marketed as Enhertu, AstraZeneca/Daiichi Sankyo).

This drug is approved in the United States for use in the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have already received two or more prior anti–HER2-based regimens in the metastatic setting.

Results come from a phase 2 study, dubbed DESTINY-CRC01, in patients with previously treated HER2+ advanced CRC.

The results show that, in patients with the highest degree of HER2 positivity, T-DXd was associated with an objective response rate of over 45% and a median progression-free survival (PFS) of almost 7 months.

They “demonstrate, in our opinion, the potential of T-DXd as a treatment option” for patients with advanced HER2-positive colorectal cancer that is refractory to standard therapies, said lead investigator Salvatore Siena, MD, from Niguarda Cancer Center, in Milan, Italy.

He presented the results at the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because of the coronavirus pandemic.

At the same time, results from another study, this time in gastric cancer patients, were published online in the New England Journal of Medicine.
 

Interstitial lung disease as adverse event

The safety profile of T-DXd seen in the colorectal trial “is consistent with what has been previously reported,” said Siena, adding that most of the adverse events were low grade. But he noted there was also a serious adverse effect – interstitial lung disease (ILD). This occurred in 6% of patients, two of whom died. This is “an important risk and requires careful monitoring and proper intervention,” he emphasized.

The ILD adverse effect in this study is “a concern…and something to consider,” commented discussant for the study Michael S. Lee, MD, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill. But he added that these are the “the best data so far for subsequent anti-HER2 therapy in colorectal cancer”.

Also, the dose of drug used in this trial was higher than that approved for breast cancer, and the incidence of ILD “begs the question of whether we should be using a lower dose in this patient population,” said Autumn J. McRee, MD, also from Lineberger, in a highlights session at the meeting.

“The question here really is whether an HER2-specific approach is superior to what we would offer to these patients in the standard of care setting,” McRee said.

She noted that the patients in DESTINY-CRC01 were “heavily pretreated…and if you think about what our options are in the refractory setting, we do have two approved treatments: regorafenib [Stivarga, Bayer] and TAS-102 [Lonsurf, Taiho Oncology].”

The current data suggest, however, that T-DXd is associated with a trend toward higher response rates and improved survival outcomes, as well as lower monthly costs.

“Without a doubt, this trial is clinically relevant,” she said, adding that it’s “important not to miss these patients.”

“They are rare…but I would argue that testing for HER2 amplification in colorectal cancer should be considered standard of care,” she said.

She added that, based on the current evidence, the trial “may be” practice changing, although it is “still to be determined how to sequence HER2 targeted therapies.”
 

Study details

The trial was conducted in 78 patients with previously treated unresectable and/or metastatic CRC that was HER2 expressing, RAS/BRAF wild type, and patients had to have received at least two prior regimens, including prior anti-HER2 treatment. Patients with current or suspected ILD were excluded.

Patients were divided into three cohorts based on the degree of HER2 positivity:

• HER2+ with immunohistochemistry (IHC) scoring 3+ or IHC2+/in-situ-hybridization (ISH)+ (cohort A, n = 53)
• HER2 IHC2+/ISH– (cohort B, n = 7)
• HER2 IHC1+ (cohort C, n = 18)

All patients received T-DXd at 6.4 mg/kg intravenously every 3 weeks until progression or intolerable toxicity.

Across the three cohorts, the median age was 58.5 years, and nearly half (47.4%) of patients were female. The vast majority (98.7%) of patents had ECOG performance status 0 or 1, and the primary tumor site was the left colon or rectum in 89.7%.

Siena noted that “the median number of prior lines of standard therapies was four, ranging from two to 11.” All patients had previously received irinotecan and oxaliplatin, and 20.5% had received an anti-HER2 drug.

At the data cutoff on August 9, 2019, 38.5% of patients remained on treatment. The reason for discontinuation was progressive disease in 41%, and clinical progression in 9%.

Siena reported that the overall response rate, as confirmed by independent central review, was 45.3% in cohort A, with all but one of the 24 responders having a partial response. No responses were recorded in cohorts B and C.

Stable disease was seen in 37.7% of cohort A patients, giving a disease control rate of 83%. The median duration of response was not reached.

Median PFS was 6.9 months in cohort A, and the medial overall survival was not reached.

In terms of safety, 50.9% of patients in cohort A and 48.7% patients overall experienced drug-related treatment emergent adverse events, with 22.6% and 17.9%, respectively, having serious drug-related events.

The most common treatment-emergent adverse events were nausea, anemia, reduced neutrophil count, fatigue, and decreased appetite.

There were two deaths related to the study drug, as determined by investigator assessment: one from pneumonitis and one as a result of ILD, with both occurring in cohort A.

Looking specifically at ILD, Siena said there were five events – two grade 2, one grade 3, and two grade 5 – at a median time to reported onset of 80 days. All patients received corticosteroids, as per the study protocol, and two recovered.

Study discussant Lee commented that biomarker testing, such as for HER2, “is part of our standard of care for colorectal cancer,” although studies such as the current one are providing new data to “better refine” treatment approaches.

Lee said that, overall, T-DXd had a response rate and PFS survival “that looked similar to prior data from previous single arm phase 2 studies,” with response rates generally ranging from 30% to 50%, “and this compares favorably with other standard of care options” for chemotherapy-refractory patients.

Nevertheless, there are several ongoing questions related to the treatment of HER2 amplified metastatic CRC patients, some of which are being addressed in the ongoing SWOG S1613 study.

Lee said that, for now, he would recommend that patients with HER2 amplification enroll in a clinical trial, if possible. “However, if that’s not feasible, there are a range of options to consider,” including trastuzumab plus lapatinib (Tykerb, Novartis), or trastuzumab plus pembrolizumab (Keytruda, Merck).

However, “none of these options are FDA approved so there will be issues potentially with financial toxicity and other regulatory issues,” he said.

The study was funded by Daiichi Sankyo Co, Ltd.

Siena reports stock and other ownership interests with Guardant Health and Myriad Genetics; a consulting or advisory role with Amgen, Bayer, Bristol-Myers Squibb, CheckmAb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Roche/Genentech, Seattle Genetics; research funding from MSD Oncology (Inst); patents, royalties, and other intellectual property from Amgen; and travel, accommodations, expenses from Amgen, Bayer, and Roche. Other coauthors report potential conflicts of interest. The full list can be found with the original article.

Lee reports: Research Funding – Amgen (Inst); Bristol-Myers Squibb (Inst); EMD Serono (Inst); Exelixis (Inst); Genentech/Roche (Inst); Pfizer (Inst); Travel, Accommodations, Expenses – Genentech/Roche.

McRee reports honoraria from Cor2Ed and Onc Live; research funding from AstraZeneca (Inst), BioMed Valley Discoveries (Inst), Boston Biomedical (Inst), Inovio Pharmaceuticals (Inst), Merck (Inst), Novartis (Inst), Rgenix (Inst), and Takeda (Inst); and travel, accommodations, expenses from Cor2Ed.

This article first appeared on Medscape.com.

Testing for HER2 in patients with colorectal cancer (CRC) should become a new standard of care, say experts discussing new results from a phase 2 trial showing benefit with trastuzumab deruxtecan (T-DXd, marketed as Enhertu, AstraZeneca/Daiichi Sankyo).

This drug is approved in the United States for use in the treatment of unresectable or metastatic HER2-positive breast cancer in patients who have already received two or more prior anti–HER2-based regimens in the metastatic setting.

Results come from a phase 2 study, dubbed DESTINY-CRC01, in patients with previously treated HER2+ advanced CRC.

The results show that, in patients with the highest degree of HER2 positivity, T-DXd was associated with an objective response rate of over 45% and a median progression-free survival (PFS) of almost 7 months.

They “demonstrate, in our opinion, the potential of T-DXd as a treatment option” for patients with advanced HER2-positive colorectal cancer that is refractory to standard therapies, said lead investigator Salvatore Siena, MD, from Niguarda Cancer Center, in Milan, Italy.

He presented the results at the 2020 annual meeting of the American Society of Clinical Oncology, held virtually because of the coronavirus pandemic.

At the same time, results from another study, this time in gastric cancer patients, were published online in the New England Journal of Medicine.
 

Interstitial lung disease as adverse event

The safety profile of T-DXd seen in the colorectal trial “is consistent with what has been previously reported,” said Siena, adding that most of the adverse events were low grade. But he noted there was also a serious adverse effect – interstitial lung disease (ILD). This occurred in 6% of patients, two of whom died. This is “an important risk and requires careful monitoring and proper intervention,” he emphasized.

The ILD adverse effect in this study is “a concern…and something to consider,” commented discussant for the study Michael S. Lee, MD, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill. But he added that these are the “the best data so far for subsequent anti-HER2 therapy in colorectal cancer”.

Also, the dose of drug used in this trial was higher than that approved for breast cancer, and the incidence of ILD “begs the question of whether we should be using a lower dose in this patient population,” said Autumn J. McRee, MD, also from Lineberger, in a highlights session at the meeting.

“The question here really is whether an HER2-specific approach is superior to what we would offer to these patients in the standard of care setting,” McRee said.

She noted that the patients in DESTINY-CRC01 were “heavily pretreated…and if you think about what our options are in the refractory setting, we do have two approved treatments: regorafenib [Stivarga, Bayer] and TAS-102 [Lonsurf, Taiho Oncology].”

The current data suggest, however, that T-DXd is associated with a trend toward higher response rates and improved survival outcomes, as well as lower monthly costs.

“Without a doubt, this trial is clinically relevant,” she said, adding that it’s “important not to miss these patients.”

“They are rare…but I would argue that testing for HER2 amplification in colorectal cancer should be considered standard of care,” she said.

She added that, based on the current evidence, the trial “may be” practice changing, although it is “still to be determined how to sequence HER2 targeted therapies.”
 

Study details

The trial was conducted in 78 patients with previously treated unresectable and/or metastatic CRC that was HER2 expressing, RAS/BRAF wild type, and patients had to have received at least two prior regimens, including prior anti-HER2 treatment. Patients with current or suspected ILD were excluded.

Patients were divided into three cohorts based on the degree of HER2 positivity:

• HER2+ with immunohistochemistry (IHC) scoring 3+ or IHC2+/in-situ-hybridization (ISH)+ (cohort A, n = 53)
• HER2 IHC2+/ISH– (cohort B, n = 7)
• HER2 IHC1+ (cohort C, n = 18)

All patients received T-DXd at 6.4 mg/kg intravenously every 3 weeks until progression or intolerable toxicity.

Across the three cohorts, the median age was 58.5 years, and nearly half (47.4%) of patients were female. The vast majority (98.7%) of patents had ECOG performance status 0 or 1, and the primary tumor site was the left colon or rectum in 89.7%.

Siena noted that “the median number of prior lines of standard therapies was four, ranging from two to 11.” All patients had previously received irinotecan and oxaliplatin, and 20.5% had received an anti-HER2 drug.

At the data cutoff on August 9, 2019, 38.5% of patients remained on treatment. The reason for discontinuation was progressive disease in 41%, and clinical progression in 9%.

Siena reported that the overall response rate, as confirmed by independent central review, was 45.3% in cohort A, with all but one of the 24 responders having a partial response. No responses were recorded in cohorts B and C.

Stable disease was seen in 37.7% of cohort A patients, giving a disease control rate of 83%. The median duration of response was not reached.

Median PFS was 6.9 months in cohort A, and the medial overall survival was not reached.

In terms of safety, 50.9% of patients in cohort A and 48.7% patients overall experienced drug-related treatment emergent adverse events, with 22.6% and 17.9%, respectively, having serious drug-related events.

The most common treatment-emergent adverse events were nausea, anemia, reduced neutrophil count, fatigue, and decreased appetite.

There were two deaths related to the study drug, as determined by investigator assessment: one from pneumonitis and one as a result of ILD, with both occurring in cohort A.

Looking specifically at ILD, Siena said there were five events – two grade 2, one grade 3, and two grade 5 – at a median time to reported onset of 80 days. All patients received corticosteroids, as per the study protocol, and two recovered.

Study discussant Lee commented that biomarker testing, such as for HER2, “is part of our standard of care for colorectal cancer,” although studies such as the current one are providing new data to “better refine” treatment approaches.

Lee said that, overall, T-DXd had a response rate and PFS survival “that looked similar to prior data from previous single arm phase 2 studies,” with response rates generally ranging from 30% to 50%, “and this compares favorably with other standard of care options” for chemotherapy-refractory patients.

Nevertheless, there are several ongoing questions related to the treatment of HER2 amplified metastatic CRC patients, some of which are being addressed in the ongoing SWOG S1613 study.

Lee said that, for now, he would recommend that patients with HER2 amplification enroll in a clinical trial, if possible. “However, if that’s not feasible, there are a range of options to consider,” including trastuzumab plus lapatinib (Tykerb, Novartis), or trastuzumab plus pembrolizumab (Keytruda, Merck).

However, “none of these options are FDA approved so there will be issues potentially with financial toxicity and other regulatory issues,” he said.

The study was funded by Daiichi Sankyo Co, Ltd.

Siena reports stock and other ownership interests with Guardant Health and Myriad Genetics; a consulting or advisory role with Amgen, Bayer, Bristol-Myers Squibb, CheckmAb, Clovis Oncology, Daiichi Sankyo, Incyte, Merck, Novartis, Roche/Genentech, Seattle Genetics; research funding from MSD Oncology (Inst); patents, royalties, and other intellectual property from Amgen; and travel, accommodations, expenses from Amgen, Bayer, and Roche. Other coauthors report potential conflicts of interest. The full list can be found with the original article.

Lee reports: Research Funding – Amgen (Inst); Bristol-Myers Squibb (Inst); EMD Serono (Inst); Exelixis (Inst); Genentech/Roche (Inst); Pfizer (Inst); Travel, Accommodations, Expenses – Genentech/Roche.

McRee reports honoraria from Cor2Ed and Onc Live; research funding from AstraZeneca (Inst), BioMed Valley Discoveries (Inst), Boston Biomedical (Inst), Inovio Pharmaceuticals (Inst), Merck (Inst), Novartis (Inst), Rgenix (Inst), and Takeda (Inst); and travel, accommodations, expenses from Cor2Ed.

This article first appeared on Medscape.com.

Patients with Merkel cell carcinoma and chronic immunosuppression may fare better or worse on immunotherapy based on the reason for immunosuppression, according to recent research at the annual meeting of the Society for Investigative Dermatology, held virtually.

About 10% of patients with Merkel cell carcinoma (MCC) are immunosuppressed at diagnosis, and these patients tend to have a more aggressive disease course and worse disease-specific survival compared with immunocompetent patients, Lauren Zawacki, a research assistant in the Nghiem Lab at the University of Washington, Seattle, said in her presentation. Although patients are receiving immune checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 as treatments, the efficacy and side effects on immunosuppressed patients have not been well studied because many of these patients are not eligible for clinical trials.

Ms. Zawacki and colleagues analyzed data from a prospective Seattle registry of 1,442 patients with MCC, identifying 179 patients with MCC who had chronic immunosuppression due to chronic lymphocytic leukemia (CLL), solid organ transplants, autoimmune disorders, other hematological malignancies, and HIV and AIDS. Non-Hodgkin lymphoma comprised 7 of 8 patients in the group with other hematological malignancies, and Crohn’s disease made up 5 of 6 patients in the autoimmune disorder group. Of the 179 patients with MCC and immunosuppression, 31 patients were treated with either anti-PD-1 or anti-PD-L1 therapy.

There was an objective response rate of 52%, with 14 patients having a complete response, 2 patients having a partial response, and 15 patients experiencing disease progression. Of the patients with disease progression, 11 died of MCC. The response rate in immunocompromised patients is similar to results seen by her group in immunocompetent patients (Nghiem P et al. N Engl J Med 2016; 374:2542-52), said Ms. Zawacki. “While the overall objective response rate is comparable between immunocompetent and immunosuppressed patients, the response rates vary greatly between the different types of immunosuppression,” she said.

When grouping response rates by immunosuppression type, they found 2 of 11 patients with CLL (18%) and 2 of 6 patients with autoimmune disease (33%) had an objective response, while 2 of 3 patients with HIV/AIDS (66%) and 7 of 7 patients with other hematologic malignancies (100%) had an objective response.

“While the numbers of the cohort are small, there still seems to be a considerable difference in the response rate between the different types of immune suppression, which is critical when we’re treating patients who typically have a more aggressive disease course,” said Ms. Zawacki.

In particular, the finding of no patients with MCC and CLL achieving a complete response interested Ms. Zawacki and her colleagues, since about one-fourth of patients in the Seattle registry have this combination of disease. “Not only did none of the CLL patients have a complete response, but 7 out of the 11 patients with CLL died from MCC,” she explained. When examining further, the researchers found 45% of patients in this group discontinued because of side effects of immunotherapy and had a median time to recurrence of 1.5 months. “This finding suggests that CLL in particular plays a large role in impairing the function of the immune system, leading to not only a more aggressive disease course, but a poorer response to immunotherapy,” she said.

“There is a significant need for improved interventions for patients with CLL and autoimmune disorders,” she added. “Research for immunosuppressed patients is critical given the associated aggressive disease course and their lack of inclusion in clinical trials.”

Ms. Zawacki acknowledged the small number of patients in the study as a limitation, and patients who received follow-up at outside facilities may have received slightly different care, which could impact adverse event reporting or reasons for study discontinuation.

“A multi-institutional study would be beneficial to expand the number of patients in that cohort and to help confirm the trend observed in this study. In addition, future studies should assess the role of combination systemic therapy, such as neutron radiation and immunotherapy together in order to see if the objective response can be approved among immunosuppressed patients,” she said.

This study was supported by funding from the MCC Patient Gift Fund, the National Cancer Institute, and a grant from NIH. Ms. Zawacki reports no relevant conflicts of interest.

SOURCE: Zawacki L. SID 2020, Abstract 497.

Patients with Merkel cell carcinoma and chronic immunosuppression may fare better or worse on immunotherapy based on the reason for immunosuppression, according to recent research at the annual meeting of the Society for Investigative Dermatology, held virtually.

About 10% of patients with Merkel cell carcinoma (MCC) are immunosuppressed at diagnosis, and these patients tend to have a more aggressive disease course and worse disease-specific survival compared with immunocompetent patients, Lauren Zawacki, a research assistant in the Nghiem Lab at the University of Washington, Seattle, said in her presentation. Although patients are receiving immune checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 as treatments, the efficacy and side effects on immunosuppressed patients have not been well studied because many of these patients are not eligible for clinical trials.

Ms. Zawacki and colleagues analyzed data from a prospective Seattle registry of 1,442 patients with MCC, identifying 179 patients with MCC who had chronic immunosuppression due to chronic lymphocytic leukemia (CLL), solid organ transplants, autoimmune disorders, other hematological malignancies, and HIV and AIDS. Non-Hodgkin lymphoma comprised 7 of 8 patients in the group with other hematological malignancies, and Crohn’s disease made up 5 of 6 patients in the autoimmune disorder group. Of the 179 patients with MCC and immunosuppression, 31 patients were treated with either anti-PD-1 or anti-PD-L1 therapy.

There was an objective response rate of 52%, with 14 patients having a complete response, 2 patients having a partial response, and 15 patients experiencing disease progression. Of the patients with disease progression, 11 died of MCC. The response rate in immunocompromised patients is similar to results seen by her group in immunocompetent patients (Nghiem P et al. N Engl J Med 2016; 374:2542-52), said Ms. Zawacki. “While the overall objective response rate is comparable between immunocompetent and immunosuppressed patients, the response rates vary greatly between the different types of immunosuppression,” she said.

When grouping response rates by immunosuppression type, they found 2 of 11 patients with CLL (18%) and 2 of 6 patients with autoimmune disease (33%) had an objective response, while 2 of 3 patients with HIV/AIDS (66%) and 7 of 7 patients with other hematologic malignancies (100%) had an objective response.

“While the numbers of the cohort are small, there still seems to be a considerable difference in the response rate between the different types of immune suppression, which is critical when we’re treating patients who typically have a more aggressive disease course,” said Ms. Zawacki.

In particular, the finding of no patients with MCC and CLL achieving a complete response interested Ms. Zawacki and her colleagues, since about one-fourth of patients in the Seattle registry have this combination of disease. “Not only did none of the CLL patients have a complete response, but 7 out of the 11 patients with CLL died from MCC,” she explained. When examining further, the researchers found 45% of patients in this group discontinued because of side effects of immunotherapy and had a median time to recurrence of 1.5 months. “This finding suggests that CLL in particular plays a large role in impairing the function of the immune system, leading to not only a more aggressive disease course, but a poorer response to immunotherapy,” she said.

“There is a significant need for improved interventions for patients with CLL and autoimmune disorders,” she added. “Research for immunosuppressed patients is critical given the associated aggressive disease course and their lack of inclusion in clinical trials.”

Ms. Zawacki acknowledged the small number of patients in the study as a limitation, and patients who received follow-up at outside facilities may have received slightly different care, which could impact adverse event reporting or reasons for study discontinuation.

“A multi-institutional study would be beneficial to expand the number of patients in that cohort and to help confirm the trend observed in this study. In addition, future studies should assess the role of combination systemic therapy, such as neutron radiation and immunotherapy together in order to see if the objective response can be approved among immunosuppressed patients,” she said.

This study was supported by funding from the MCC Patient Gift Fund, the National Cancer Institute, and a grant from NIH. Ms. Zawacki reports no relevant conflicts of interest.

SOURCE: Zawacki L. SID 2020, Abstract 497.

Patients with Merkel cell carcinoma and chronic immunosuppression may fare better or worse on immunotherapy based on the reason for immunosuppression, according to recent research at the annual meeting of the Society for Investigative Dermatology, held virtually.

About 10% of patients with Merkel cell carcinoma (MCC) are immunosuppressed at diagnosis, and these patients tend to have a more aggressive disease course and worse disease-specific survival compared with immunocompetent patients, Lauren Zawacki, a research assistant in the Nghiem Lab at the University of Washington, Seattle, said in her presentation. Although patients are receiving immune checkpoint inhibitors such as anti-PD-1 and anti-PD-L1 as treatments, the efficacy and side effects on immunosuppressed patients have not been well studied because many of these patients are not eligible for clinical trials.

Ms. Zawacki and colleagues analyzed data from a prospective Seattle registry of 1,442 patients with MCC, identifying 179 patients with MCC who had chronic immunosuppression due to chronic lymphocytic leukemia (CLL), solid organ transplants, autoimmune disorders, other hematological malignancies, and HIV and AIDS. Non-Hodgkin lymphoma comprised 7 of 8 patients in the group with other hematological malignancies, and Crohn’s disease made up 5 of 6 patients in the autoimmune disorder group. Of the 179 patients with MCC and immunosuppression, 31 patients were treated with either anti-PD-1 or anti-PD-L1 therapy.

There was an objective response rate of 52%, with 14 patients having a complete response, 2 patients having a partial response, and 15 patients experiencing disease progression. Of the patients with disease progression, 11 died of MCC. The response rate in immunocompromised patients is similar to results seen by her group in immunocompetent patients (Nghiem P et al. N Engl J Med 2016; 374:2542-52), said Ms. Zawacki. “While the overall objective response rate is comparable between immunocompetent and immunosuppressed patients, the response rates vary greatly between the different types of immunosuppression,” she said.

When grouping response rates by immunosuppression type, they found 2 of 11 patients with CLL (18%) and 2 of 6 patients with autoimmune disease (33%) had an objective response, while 2 of 3 patients with HIV/AIDS (66%) and 7 of 7 patients with other hematologic malignancies (100%) had an objective response.

“While the numbers of the cohort are small, there still seems to be a considerable difference in the response rate between the different types of immune suppression, which is critical when we’re treating patients who typically have a more aggressive disease course,” said Ms. Zawacki.

In particular, the finding of no patients with MCC and CLL achieving a complete response interested Ms. Zawacki and her colleagues, since about one-fourth of patients in the Seattle registry have this combination of disease. “Not only did none of the CLL patients have a complete response, but 7 out of the 11 patients with CLL died from MCC,” she explained. When examining further, the researchers found 45% of patients in this group discontinued because of side effects of immunotherapy and had a median time to recurrence of 1.5 months. “This finding suggests that CLL in particular plays a large role in impairing the function of the immune system, leading to not only a more aggressive disease course, but a poorer response to immunotherapy,” she said.

“There is a significant need for improved interventions for patients with CLL and autoimmune disorders,” she added. “Research for immunosuppressed patients is critical given the associated aggressive disease course and their lack of inclusion in clinical trials.”

Ms. Zawacki acknowledged the small number of patients in the study as a limitation, and patients who received follow-up at outside facilities may have received slightly different care, which could impact adverse event reporting or reasons for study discontinuation.

“A multi-institutional study would be beneficial to expand the number of patients in that cohort and to help confirm the trend observed in this study. In addition, future studies should assess the role of combination systemic therapy, such as neutron radiation and immunotherapy together in order to see if the objective response can be approved among immunosuppressed patients,” she said.

This study was supported by funding from the MCC Patient Gift Fund, the National Cancer Institute, and a grant from NIH. Ms. Zawacki reports no relevant conflicts of interest.

SOURCE: Zawacki L. SID 2020, Abstract 497.

This is the second of a two-part article on the role of racism and bias in the U.S. maternal mortality crisis and part of an ongoing Ob.Gyn. News feature series on the crisis. Part one of the story explored existing data, societal factors, and patient experiences related to structural racism, overt racism, and implicit bias as factors contributing to racial disparities in maternal outcomes. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders.



The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality.

Maternal health advocates are bracing for the impact, but in the spotlight that the pandemic is training on the inequities and the health system changes taking shape in its wake, some also see hope for a shift in at least one important driver of the racial health disparities: access to care.

Non-Hispanic black women are at least three times more likely than Hispanic women and non-Hispanic white women to experience pregnancy-related death, and indigenous women are more than twice as likely, according to the latest data from the Centers for Disease Control and Prevention’s National Center for Health Statistics. The added strain COVID-19 is putting on the system stands to further limit the access to care that many pregnant women of color experience and to exacerbate racial disparities, panelists agreed during a recent National Maternal Health Patient Centered Outcomes Research Network webinar entitled “The Impact of COVID-19 on Black, Brown, and Native Pregnant People.”

“The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said panelist Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative (NBEC), a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health.
 

Hope for solutions from the ashes of a pandemic

The weaknesses in the system that Dr. Crear-Perry spoke of are in many ways a product of structural racism as described in a conceptual report in The Lancet, titled “America: Equity and Equality in Health,” which dug into the entrenched and tangled historical roots of racist sociological and political factors that formed a foundation for health inequity over time.

Today, people of color remain more likely to be excluded from access to health insurance and adequate health care. The authors defined structural racism as “the totality of ways in which societies foster racial discrimination through mutually reinforcing systems of housing, education, employment, earnings, benefits, credit, media, health care, and criminal justice.” Today, largely as a result of these “reinforcing systems,” people of color remain more likely to be excluded from access to health insurance and adequate health care. At the same time, and for the same reasons, they are more likely to work in the service industry, be essential workers, and use mass transit, each of which increases the risk of exposure to COVID-19, Dr. Crear-Perry explained.

“It’s important for us to know that, for maternal mortality, it’s the same thing that happens,” she said. That means the focus on COVID-19–related disparities helps magnify and elevate the conversation regarding similar disparities in maternal outcomes.

It also means that some of the care delivery solutions embraced and facilitated amid the pandemic, such as extension of Medicaid coverage for up to a year after giving birth and broader use and insurance coverage of telemedicine, could finally gain traction; those are solutions long-sought by advocates like Dr. Crear-Perry and others as a means for alleviating racial disparities in maternal outcomes and addressing the maternal mortality crisis.

Therein lies the hope, she explained in an interview. “Some of the policies that we know would have been helpful prior to COVID-19 now are being seen as really important.”
 

Solution: Extending coverage

During a May 7 virtual Congressional hearing on “America’s Two Public Health Crises: The Impact of COVID-19 on Racial Inequities and Maternal Mortality in the U.S.,” cosponsored by the American College of Obstetricians and Gynecologists, the March of Dimes, and the NBEC, Dr. Crear-Perry further explained the importance of extended coverage and care access.

Asked what Congress could do immediately to “ensure that the pandemic does not compound the nation’s maternal mortality crisis, including unacceptable rates among black women,” she didn’t hesitate.

“Well, it would be amazing if we could get Medicaid extended for 12 months post delivery,” she said. “As you can imagine right now, we have moms who are birthing in hospitals where they have to worry about, 2 months later, not having coverage for themselves.”

If that mom is exposed to COVID-19 and has no insurance coverage and a newborn at home, the likelihood that she will call a provider if she develops symptoms is low, Dr. Crear-Perry said. “This is a great opportunity for us to really rethink some of those policies that we know are barriers, that we have created for people to be able to thrive after they have a baby and during child birth.”

Current policies are centered around an arbitrary cutoff of about 6 weeks for postpartum care, but the CDC reports that a third of all postpartum deaths occur between 1 week and 12 months after birth.

“We need our policies to reflect the current knowledge and the science,” she said. “Just like babies have automatic insurance coverage for a year later, mothers should have the same.”

Medicaid finances nearly half of all births in the United States, according to a 2019 Kaiser Family Foundation brief, which explained that federal law requires Medicaid coverage for only 60 days post partum for women who are eligible. Decisions regarding coverage after 60 days are determined by individual states; those that expanded Medicaid under the Affordable Care Act typically allow extended coverage – but only with reapplication at 60 days.

Many women in nonexpansion states become uninsured after pregnancy-related coverage ends, as do some in expansion states for whom reapplying is a hurdle too high to clear with a newborn baby to care for at home, Dr. Crear-Perry said.

Addressing these coverage gaps is key to improving access, and it is a core component of the Black Maternal Health Momnibus Act of 2020, a nine-bill package introduced in March by Rep. Lauren Underwood (D-Ill.), Rep. Alma Adams (D-N.C.), Sen. Kamala Harris (D-Calif.), and members of the Black Maternal Health Caucus to “fill gaps in existing legislation to comprehensively address every dimension of the Black maternal health crisis in America.”

One bill in the package addresses extended coverage with a goal to “promote innovative payment models to incentivize high-quality maternity care and continuity of health insurance coverage from pregnancy through labor and delivery and up to 1 year post partum.” Another focuses on promoting alternative ways to access care, such as through telemedicine.

Solution: Expanding care access

“There is a need for the democratization of care,” Dr. Crear-Perry said. “There is a need for people to have more ways to get care. This idea that the only way you can get prenatal care is you have to come to me at my office, has been a burden for working people for a long, long time.”

The COVID-19 pandemic necessitates increased use of telemedicine, but building blocks to allow patients to use it effectively must be put in place, she said. That means expanding broadband access, providing patients with blood pressure cuffs and other tools for use remotely, and expanding reimbursement to include not just video, but also phone calls.

Heart Safe Motherhood, a University of Pennsylvania text-based intervention developed to address postpartum hypertension – a leading cause of maternal morbidity and mortality, and at the start of the program, the leading cause of 7-day readmissions among obstetric patients, demonstrated the value of such approaches to care.

The program involves remote blood pressure monitoring using a digital monitor provided to at-risk patients at discharge. Text-based monitoring reminders encourage patients to check their blood pressure twice daily for the first 7 days.

“In our randomized, controlled trial, we saw our ability to meet ACOG guidelines on postpartum blood monitoring leap from 0% to 82%, compared to in-person office visits and 7-day readmissions from hypertension drop from 3% to 0%,” an update at the program website states.

ACOG

Rebekah Gee, MD, an ob.gyn. and director of the Louisiana State University Health System in New Orleans, also noted the importance of finding ways to deliver care “that are outside the traditional norm.

“Telemedicine, home visiting ... I think there are a wide variety of ways,” she said, noting that these kind of approaches not only help circumvent roadblocks to care, such as lack of transportation, but also can feel more personal and approachable for some women.
 

Solution: Measuring, investing, diversifying, respecting

The aims of other bills in the Momnibus Act also mirror several solutions proposed by maternal health advocates interviewed for this article. Among them are:

• Development of improved data collection processes and quality measures to better understand the factors that contribute to the crisis overall and among special populations, and to inform solutions for addressing them.
• Investments in social determinants of health that influence maternal health outcomes, like housing, transportation, and nutrition.
• Commitment to the growth and diversification of the perinatal workforce to ensure that every mom receives maternity care and support from people she can trust to provide quality care and treat her with respect.

The latter is one that Dr. Gee, Dr. Crear-Perry, and others particularly emphasized.

“We need patient advocates like doulas, midwives and others who are better listeners and better able to advocate for patients,” Dr. Gee said. This would better allow for women’s desires in the childbirth experience to be addressed appropriately, she said, adding that this is something that “frankly, a lot of doctors do not have the time to do.”

That’s why the efforts to address maternal mortality have to focus on the health care system, not just on doctors’ behavior with respect to bias, she said.

Dr. Gee also said there is a need for culturally appropriate literacy and numeracy communications “that respect how people seek and understand information.” This varies by population, which is why it’s important to provide the same approach to care “no matter what the patient looks like,” while also understanding that different patients communicate in different ways.

A 2019 study published in Social Science & Medicine underscored how communication differences can affect outcomes; using a national sample of women who gave birth in U.S. hospitals, the authors found that those who had declined care for themselves or their infant during their childbirth hospitalization were more likely to report receiving poor treatment based on race or ethnicity. They concluded that, in the context of childbirth care, women – particularly black women – pay a penalty for what is perceived as uncooperative behavior.

This is another area where doulas and other patient advocates can help, Dr. Gee said.

Doulas have long been an integral part of the birthing process for many women, particularly women of color, and evidence suggests the supportive care they provide helps to improve outcomes. In fact, several states – including Oregon, Minnesota, and New York, among others – have expanded or have proposed expanding Medicaid coverage to include doula services for pregnant beneficiaries, a move cheered by doula associations and other maternal health advocates.

In many ways, it’s about “respectful maternity care,” which is something Dr. Crear-Perry has been working to promote through the NBEC in partnership with ACOG and the Robert Wood Johnson Foundation. It’s also something the World Health Organization has promoted by establishing global standards for such care.

“We’re hoping to socialize that as a norm in United States ... to really see what it would look like to value what birthing people want and to see them as partners in their birth,” she said.

However, the 2019 Giving Voice to Mothers study demonstrating consistently higher rates of mistreatment during obstetrical care for women of color than for comparable white women shows that the United States is falling short of those standards. The national study of 2,700 women examined how race, ethnicity, and place of birth interact with the experience of receiving maternity care in the United States, and showed that 1 in 6 experienced one or more types of mistreatment – with consistently higher rates among women of color, even after adjusting for interactions between race and other maternal characteristics, Saraswathi Veda, MD, of the Birth Place Lab and professor of midwifery at the University of British Columbia, Vancouver, and colleagues reported in Reproductive Health.
 

Solution: Listening, learning, reflecting, partnering

Timoria McQueen Saba, birth trauma survivor and maternal health advocate, has described experiencing instances of mistreatment throughout her obstetric care, and like Dr. Crear-Perry, she said trust and collaboration in care is imperative for improving outcomes.

“I think the most important thing you can do is really consider a patient a partner in the care you give them,” she said during a panel discussion at the 2019 ACOG annual meeting. “You’re not experts in their lived experience ... center a patient’s voice or the voice of a patient’s family. Incorporate that into your learning.”

During a virtual workshop held May 19-20 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Judette Louis, MD, chair of the department of obstetrics and gynecology at the University of South Florida, Tampa, and president of the Society of Maternal-Fetal Medicine, provided practical guidance for addressing racism and implicit bias in practice and in research to reduce disparities in outcomes.

In an interview, she summarized her key points, reiterating solutions proposed by Dr. Gee and Dr. Crear-Perry and addressed in the Momnibus Act, and also offering a few others:

First, put aside the notion that disparities are genetically driven. For a variety of reasons, that just doesn’t make sense. For one thing, not all blacks are African American.

“My family is from the Caribbean,” she said. “Is it really conceivable that we’re all so similar?”

Look also at the disparities among Native Americans, she said. “How can you take 500 distinct tribes that live across a wide geographic area and lump them into one group and assume that they are similar?”

The problem is racism, not race. “When you keep saying ‘it’s about race, it’s about race, it’s about race’ – that sends a message to the person who is of that race that there is something inherently broken about [them],” she said.

Recognize that the roots of the problem run deep. Learn about and support efforts to address the underlying structural factors that contribute to the problem, Dr. Louis emphasized, and recognize your own bias. “We all have it. The key is to recognize [biases] and mitigate them when taking care of patients.”

That’s easier said than done, at least judging by one survey of maternal-fetal medicine specialists in which 84% of respondents agreed that disparities impact practice, but only 29% agreed their own personal biases affect how they care for patients, she noted.

Tools are available to help individuals identify implicit bias, and training programs for health care providers can help, as well, she said. Implicit bias tests and training programs that help to identify and address bias and racism on individual and organizational levels are increasingly available through academic centers, health systems, and advocacy organizations.

Hope for solutions: Progress and promise

Like Dr. Crear-Perry, Dr. Louis sees hope for reducing disparities and improving maternal outcomes.

In another survey of SMFM members to identify the practice issues most important to them, racial disparities ranked in the top three.

“It says a lot that our [maternal-fetal medicine specialists] really see this as a problem and they want it fixed,” she said. “And I think it says that a lot of people need to work on this, not just us.”

Indeed, many are engaged in that work. Veronica Gillispie, MD, medical director of the Louisiana Perinatal Quality Collaborative and Pregnancy-Associated Mortality Review, has been instrumental in recent initiatives to improve maternal outcomes in Louisiana, and she too said she feels optimistic.

“I am hopeful and I do see signs of hope,” she said in an interview.

Teams that she works with and trains seem invested, institutions are increasingly implementing faculty training on racism and bias, and Oschner Health, where Dr. Gillispie practices as an ob.gyn., appointed its first chief diversity officer in February.

Medical students she works with are attuned to the issues of racism, bias, and disparities, and they show a desire to enact change, she said. “They already get it, and they are working to make it better.”

Dr. Crear-Perry also predicts practice-changing results from studies looking at the delivery of obstetrical care and the role of supportive care, and she pointed out another aspect of the COVID-19 crisis that provides an important lesson for health care providers who care for birthing people: the scarcity of personal protective equipment amid the pandemic.

“My friends who are ob.gyns., who are now not getting access to the things they need to stay safe to practice medicine and who are feeling very marginalized at this moment, feeling not valued – that’s how birthing people [of color] feel,” she said. “I’m hoping that builds a sense of empathy.

”I’m hoping at the end of this crisis, that those ob.gyns. will think of patients as allies in fighting for more access to health for everybody and for more resources to do their work,” Dr. Crear-Perry said. “We’re all in this together.”

[email protected]

This is the second of a two-part article on the role of racism and bias in the U.S. maternal mortality crisis and part of an ongoing Ob.Gyn. News feature series on the crisis. Part one of the story explored existing data, societal factors, and patient experiences related to structural racism, overt racism, and implicit bias as factors contributing to racial disparities in maternal outcomes. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders.



The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality.

Maternal health advocates are bracing for the impact, but in the spotlight that the pandemic is training on the inequities and the health system changes taking shape in its wake, some also see hope for a shift in at least one important driver of the racial health disparities: access to care.

Non-Hispanic black women are at least three times more likely than Hispanic women and non-Hispanic white women to experience pregnancy-related death, and indigenous women are more than twice as likely, according to the latest data from the Centers for Disease Control and Prevention’s National Center for Health Statistics. The added strain COVID-19 is putting on the system stands to further limit the access to care that many pregnant women of color experience and to exacerbate racial disparities, panelists agreed during a recent National Maternal Health Patient Centered Outcomes Research Network webinar entitled “The Impact of COVID-19 on Black, Brown, and Native Pregnant People.”

“The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said panelist Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative (NBEC), a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health.
 

Hope for solutions from the ashes of a pandemic

The weaknesses in the system that Dr. Crear-Perry spoke of are in many ways a product of structural racism as described in a conceptual report in The Lancet, titled “America: Equity and Equality in Health,” which dug into the entrenched and tangled historical roots of racist sociological and political factors that formed a foundation for health inequity over time.

Today, people of color remain more likely to be excluded from access to health insurance and adequate health care. The authors defined structural racism as “the totality of ways in which societies foster racial discrimination through mutually reinforcing systems of housing, education, employment, earnings, benefits, credit, media, health care, and criminal justice.” Today, largely as a result of these “reinforcing systems,” people of color remain more likely to be excluded from access to health insurance and adequate health care. At the same time, and for the same reasons, they are more likely to work in the service industry, be essential workers, and use mass transit, each of which increases the risk of exposure to COVID-19, Dr. Crear-Perry explained.

“It’s important for us to know that, for maternal mortality, it’s the same thing that happens,” she said. That means the focus on COVID-19–related disparities helps magnify and elevate the conversation regarding similar disparities in maternal outcomes.

It also means that some of the care delivery solutions embraced and facilitated amid the pandemic, such as extension of Medicaid coverage for up to a year after giving birth and broader use and insurance coverage of telemedicine, could finally gain traction; those are solutions long-sought by advocates like Dr. Crear-Perry and others as a means for alleviating racial disparities in maternal outcomes and addressing the maternal mortality crisis.

Therein lies the hope, she explained in an interview. “Some of the policies that we know would have been helpful prior to COVID-19 now are being seen as really important.”
 

Solution: Extending coverage

During a May 7 virtual Congressional hearing on “America’s Two Public Health Crises: The Impact of COVID-19 on Racial Inequities and Maternal Mortality in the U.S.,” cosponsored by the American College of Obstetricians and Gynecologists, the March of Dimes, and the NBEC, Dr. Crear-Perry further explained the importance of extended coverage and care access.

Asked what Congress could do immediately to “ensure that the pandemic does not compound the nation’s maternal mortality crisis, including unacceptable rates among black women,” she didn’t hesitate.

“Well, it would be amazing if we could get Medicaid extended for 12 months post delivery,” she said. “As you can imagine right now, we have moms who are birthing in hospitals where they have to worry about, 2 months later, not having coverage for themselves.”

If that mom is exposed to COVID-19 and has no insurance coverage and a newborn at home, the likelihood that she will call a provider if she develops symptoms is low, Dr. Crear-Perry said. “This is a great opportunity for us to really rethink some of those policies that we know are barriers, that we have created for people to be able to thrive after they have a baby and during child birth.”

Current policies are centered around an arbitrary cutoff of about 6 weeks for postpartum care, but the CDC reports that a third of all postpartum deaths occur between 1 week and 12 months after birth.

“We need our policies to reflect the current knowledge and the science,” she said. “Just like babies have automatic insurance coverage for a year later, mothers should have the same.”

Medicaid finances nearly half of all births in the United States, according to a 2019 Kaiser Family Foundation brief, which explained that federal law requires Medicaid coverage for only 60 days post partum for women who are eligible. Decisions regarding coverage after 60 days are determined by individual states; those that expanded Medicaid under the Affordable Care Act typically allow extended coverage – but only with reapplication at 60 days.

Many women in nonexpansion states become uninsured after pregnancy-related coverage ends, as do some in expansion states for whom reapplying is a hurdle too high to clear with a newborn baby to care for at home, Dr. Crear-Perry said.

Addressing these coverage gaps is key to improving access, and it is a core component of the Black Maternal Health Momnibus Act of 2020, a nine-bill package introduced in March by Rep. Lauren Underwood (D-Ill.), Rep. Alma Adams (D-N.C.), Sen. Kamala Harris (D-Calif.), and members of the Black Maternal Health Caucus to “fill gaps in existing legislation to comprehensively address every dimension of the Black maternal health crisis in America.”

One bill in the package addresses extended coverage with a goal to “promote innovative payment models to incentivize high-quality maternity care and continuity of health insurance coverage from pregnancy through labor and delivery and up to 1 year post partum.” Another focuses on promoting alternative ways to access care, such as through telemedicine.

Solution: Expanding care access

“There is a need for the democratization of care,” Dr. Crear-Perry said. “There is a need for people to have more ways to get care. This idea that the only way you can get prenatal care is you have to come to me at my office, has been a burden for working people for a long, long time.”

The COVID-19 pandemic necessitates increased use of telemedicine, but building blocks to allow patients to use it effectively must be put in place, she said. That means expanding broadband access, providing patients with blood pressure cuffs and other tools for use remotely, and expanding reimbursement to include not just video, but also phone calls.

Heart Safe Motherhood, a University of Pennsylvania text-based intervention developed to address postpartum hypertension – a leading cause of maternal morbidity and mortality, and at the start of the program, the leading cause of 7-day readmissions among obstetric patients, demonstrated the value of such approaches to care.

The program involves remote blood pressure monitoring using a digital monitor provided to at-risk patients at discharge. Text-based monitoring reminders encourage patients to check their blood pressure twice daily for the first 7 days.

“In our randomized, controlled trial, we saw our ability to meet ACOG guidelines on postpartum blood monitoring leap from 0% to 82%, compared to in-person office visits and 7-day readmissions from hypertension drop from 3% to 0%,” an update at the program website states.

ACOG

Rebekah Gee, MD, an ob.gyn. and director of the Louisiana State University Health System in New Orleans, also noted the importance of finding ways to deliver care “that are outside the traditional norm.

“Telemedicine, home visiting ... I think there are a wide variety of ways,” she said, noting that these kind of approaches not only help circumvent roadblocks to care, such as lack of transportation, but also can feel more personal and approachable for some women.
 

Solution: Measuring, investing, diversifying, respecting

The aims of other bills in the Momnibus Act also mirror several solutions proposed by maternal health advocates interviewed for this article. Among them are:

• Development of improved data collection processes and quality measures to better understand the factors that contribute to the crisis overall and among special populations, and to inform solutions for addressing them.
• Investments in social determinants of health that influence maternal health outcomes, like housing, transportation, and nutrition.
• Commitment to the growth and diversification of the perinatal workforce to ensure that every mom receives maternity care and support from people she can trust to provide quality care and treat her with respect.

The latter is one that Dr. Gee, Dr. Crear-Perry, and others particularly emphasized.

“We need patient advocates like doulas, midwives and others who are better listeners and better able to advocate for patients,” Dr. Gee said. This would better allow for women’s desires in the childbirth experience to be addressed appropriately, she said, adding that this is something that “frankly, a lot of doctors do not have the time to do.”

That’s why the efforts to address maternal mortality have to focus on the health care system, not just on doctors’ behavior with respect to bias, she said.

Dr. Gee also said there is a need for culturally appropriate literacy and numeracy communications “that respect how people seek and understand information.” This varies by population, which is why it’s important to provide the same approach to care “no matter what the patient looks like,” while also understanding that different patients communicate in different ways.

A 2019 study published in Social Science & Medicine underscored how communication differences can affect outcomes; using a national sample of women who gave birth in U.S. hospitals, the authors found that those who had declined care for themselves or their infant during their childbirth hospitalization were more likely to report receiving poor treatment based on race or ethnicity. They concluded that, in the context of childbirth care, women – particularly black women – pay a penalty for what is perceived as uncooperative behavior.

This is another area where doulas and other patient advocates can help, Dr. Gee said.

Doulas have long been an integral part of the birthing process for many women, particularly women of color, and evidence suggests the supportive care they provide helps to improve outcomes. In fact, several states – including Oregon, Minnesota, and New York, among others – have expanded or have proposed expanding Medicaid coverage to include doula services for pregnant beneficiaries, a move cheered by doula associations and other maternal health advocates.

In many ways, it’s about “respectful maternity care,” which is something Dr. Crear-Perry has been working to promote through the NBEC in partnership with ACOG and the Robert Wood Johnson Foundation. It’s also something the World Health Organization has promoted by establishing global standards for such care.

“We’re hoping to socialize that as a norm in United States ... to really see what it would look like to value what birthing people want and to see them as partners in their birth,” she said.

However, the 2019 Giving Voice to Mothers study demonstrating consistently higher rates of mistreatment during obstetrical care for women of color than for comparable white women shows that the United States is falling short of those standards. The national study of 2,700 women examined how race, ethnicity, and place of birth interact with the experience of receiving maternity care in the United States, and showed that 1 in 6 experienced one or more types of mistreatment – with consistently higher rates among women of color, even after adjusting for interactions between race and other maternal characteristics, Saraswathi Veda, MD, of the Birth Place Lab and professor of midwifery at the University of British Columbia, Vancouver, and colleagues reported in Reproductive Health.
 

Solution: Listening, learning, reflecting, partnering

Timoria McQueen Saba, birth trauma survivor and maternal health advocate, has described experiencing instances of mistreatment throughout her obstetric care, and like Dr. Crear-Perry, she said trust and collaboration in care is imperative for improving outcomes.

“I think the most important thing you can do is really consider a patient a partner in the care you give them,” she said during a panel discussion at the 2019 ACOG annual meeting. “You’re not experts in their lived experience ... center a patient’s voice or the voice of a patient’s family. Incorporate that into your learning.”

During a virtual workshop held May 19-20 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Judette Louis, MD, chair of the department of obstetrics and gynecology at the University of South Florida, Tampa, and president of the Society of Maternal-Fetal Medicine, provided practical guidance for addressing racism and implicit bias in practice and in research to reduce disparities in outcomes.

In an interview, she summarized her key points, reiterating solutions proposed by Dr. Gee and Dr. Crear-Perry and addressed in the Momnibus Act, and also offering a few others:

First, put aside the notion that disparities are genetically driven. For a variety of reasons, that just doesn’t make sense. For one thing, not all blacks are African American.

“My family is from the Caribbean,” she said. “Is it really conceivable that we’re all so similar?”

Look also at the disparities among Native Americans, she said. “How can you take 500 distinct tribes that live across a wide geographic area and lump them into one group and assume that they are similar?”

The problem is racism, not race. “When you keep saying ‘it’s about race, it’s about race, it’s about race’ – that sends a message to the person who is of that race that there is something inherently broken about [them],” she said.

Recognize that the roots of the problem run deep. Learn about and support efforts to address the underlying structural factors that contribute to the problem, Dr. Louis emphasized, and recognize your own bias. “We all have it. The key is to recognize [biases] and mitigate them when taking care of patients.”

That’s easier said than done, at least judging by one survey of maternal-fetal medicine specialists in which 84% of respondents agreed that disparities impact practice, but only 29% agreed their own personal biases affect how they care for patients, she noted.

Tools are available to help individuals identify implicit bias, and training programs for health care providers can help, as well, she said. Implicit bias tests and training programs that help to identify and address bias and racism on individual and organizational levels are increasingly available through academic centers, health systems, and advocacy organizations.

Hope for solutions: Progress and promise

Like Dr. Crear-Perry, Dr. Louis sees hope for reducing disparities and improving maternal outcomes.

In another survey of SMFM members to identify the practice issues most important to them, racial disparities ranked in the top three.

“It says a lot that our [maternal-fetal medicine specialists] really see this as a problem and they want it fixed,” she said. “And I think it says that a lot of people need to work on this, not just us.”

Indeed, many are engaged in that work. Veronica Gillispie, MD, medical director of the Louisiana Perinatal Quality Collaborative and Pregnancy-Associated Mortality Review, has been instrumental in recent initiatives to improve maternal outcomes in Louisiana, and she too said she feels optimistic.

“I am hopeful and I do see signs of hope,” she said in an interview.

Teams that she works with and trains seem invested, institutions are increasingly implementing faculty training on racism and bias, and Oschner Health, where Dr. Gillispie practices as an ob.gyn., appointed its first chief diversity officer in February.

Medical students she works with are attuned to the issues of racism, bias, and disparities, and they show a desire to enact change, she said. “They already get it, and they are working to make it better.”

Dr. Crear-Perry also predicts practice-changing results from studies looking at the delivery of obstetrical care and the role of supportive care, and she pointed out another aspect of the COVID-19 crisis that provides an important lesson for health care providers who care for birthing people: the scarcity of personal protective equipment amid the pandemic.

“My friends who are ob.gyns., who are now not getting access to the things they need to stay safe to practice medicine and who are feeling very marginalized at this moment, feeling not valued – that’s how birthing people [of color] feel,” she said. “I’m hoping that builds a sense of empathy.

”I’m hoping at the end of this crisis, that those ob.gyns. will think of patients as allies in fighting for more access to health for everybody and for more resources to do their work,” Dr. Crear-Perry said. “We’re all in this together.”

[email protected]

This is the second of a two-part article on the role of racism and bias in the U.S. maternal mortality crisis and part of an ongoing Ob.Gyn. News feature series on the crisis. Part one of the story explored existing data, societal factors, and patient experiences related to structural racism, overt racism, and implicit bias as factors contributing to racial disparities in maternal outcomes. Here we explore potential solutions for addressing the inequities as proposed by thought leaders and key stakeholders.



The emerging racial disparities in COVID-19 incidence and outcomes in the United States are on a collision course with long-standing racial disparities in U.S. maternal care and mortality.

Maternal health advocates are bracing for the impact, but in the spotlight that the pandemic is training on the inequities and the health system changes taking shape in its wake, some also see hope for a shift in at least one important driver of the racial health disparities: access to care.

Non-Hispanic black women are at least three times more likely than Hispanic women and non-Hispanic white women to experience pregnancy-related death, and indigenous women are more than twice as likely, according to the latest data from the Centers for Disease Control and Prevention’s National Center for Health Statistics. The added strain COVID-19 is putting on the system stands to further limit the access to care that many pregnant women of color experience and to exacerbate racial disparities, panelists agreed during a recent National Maternal Health Patient Centered Outcomes Research Network webinar entitled “The Impact of COVID-19 on Black, Brown, and Native Pregnant People.”

“The saying is that ‘the virus doesn’t discriminate,’ but it understands our biases, right? So, the virus takes advantage of the weaknesses in our system,” said panelist Joia A. Crear-Perry, MD, an ob.gyn. and founder and president of the National Birth Equity Collaborative (NBEC), a New Orleans–based research, training, and advocacy organization working to optimize black maternal and infant health.
 

Hope for solutions from the ashes of a pandemic

The weaknesses in the system that Dr. Crear-Perry spoke of are in many ways a product of structural racism as described in a conceptual report in The Lancet, titled “America: Equity and Equality in Health,” which dug into the entrenched and tangled historical roots of racist sociological and political factors that formed a foundation for health inequity over time.

Today, people of color remain more likely to be excluded from access to health insurance and adequate health care. The authors defined structural racism as “the totality of ways in which societies foster racial discrimination through mutually reinforcing systems of housing, education, employment, earnings, benefits, credit, media, health care, and criminal justice.” Today, largely as a result of these “reinforcing systems,” people of color remain more likely to be excluded from access to health insurance and adequate health care. At the same time, and for the same reasons, they are more likely to work in the service industry, be essential workers, and use mass transit, each of which increases the risk of exposure to COVID-19, Dr. Crear-Perry explained.

“It’s important for us to know that, for maternal mortality, it’s the same thing that happens,” she said. That means the focus on COVID-19–related disparities helps magnify and elevate the conversation regarding similar disparities in maternal outcomes.

It also means that some of the care delivery solutions embraced and facilitated amid the pandemic, such as extension of Medicaid coverage for up to a year after giving birth and broader use and insurance coverage of telemedicine, could finally gain traction; those are solutions long-sought by advocates like Dr. Crear-Perry and others as a means for alleviating racial disparities in maternal outcomes and addressing the maternal mortality crisis.

Therein lies the hope, she explained in an interview. “Some of the policies that we know would have been helpful prior to COVID-19 now are being seen as really important.”
 

Solution: Extending coverage

During a May 7 virtual Congressional hearing on “America’s Two Public Health Crises: The Impact of COVID-19 on Racial Inequities and Maternal Mortality in the U.S.,” cosponsored by the American College of Obstetricians and Gynecologists, the March of Dimes, and the NBEC, Dr. Crear-Perry further explained the importance of extended coverage and care access.

Asked what Congress could do immediately to “ensure that the pandemic does not compound the nation’s maternal mortality crisis, including unacceptable rates among black women,” she didn’t hesitate.

“Well, it would be amazing if we could get Medicaid extended for 12 months post delivery,” she said. “As you can imagine right now, we have moms who are birthing in hospitals where they have to worry about, 2 months later, not having coverage for themselves.”

If that mom is exposed to COVID-19 and has no insurance coverage and a newborn at home, the likelihood that she will call a provider if she develops symptoms is low, Dr. Crear-Perry said. “This is a great opportunity for us to really rethink some of those policies that we know are barriers, that we have created for people to be able to thrive after they have a baby and during child birth.”

Current policies are centered around an arbitrary cutoff of about 6 weeks for postpartum care, but the CDC reports that a third of all postpartum deaths occur between 1 week and 12 months after birth.

“We need our policies to reflect the current knowledge and the science,” she said. “Just like babies have automatic insurance coverage for a year later, mothers should have the same.”

Medicaid finances nearly half of all births in the United States, according to a 2019 Kaiser Family Foundation brief, which explained that federal law requires Medicaid coverage for only 60 days post partum for women who are eligible. Decisions regarding coverage after 60 days are determined by individual states; those that expanded Medicaid under the Affordable Care Act typically allow extended coverage – but only with reapplication at 60 days.

Many women in nonexpansion states become uninsured after pregnancy-related coverage ends, as do some in expansion states for whom reapplying is a hurdle too high to clear with a newborn baby to care for at home, Dr. Crear-Perry said.

Addressing these coverage gaps is key to improving access, and it is a core component of the Black Maternal Health Momnibus Act of 2020, a nine-bill package introduced in March by Rep. Lauren Underwood (D-Ill.), Rep. Alma Adams (D-N.C.), Sen. Kamala Harris (D-Calif.), and members of the Black Maternal Health Caucus to “fill gaps in existing legislation to comprehensively address every dimension of the Black maternal health crisis in America.”

One bill in the package addresses extended coverage with a goal to “promote innovative payment models to incentivize high-quality maternity care and continuity of health insurance coverage from pregnancy through labor and delivery and up to 1 year post partum.” Another focuses on promoting alternative ways to access care, such as through telemedicine.

Solution: Expanding care access

“There is a need for the democratization of care,” Dr. Crear-Perry said. “There is a need for people to have more ways to get care. This idea that the only way you can get prenatal care is you have to come to me at my office, has been a burden for working people for a long, long time.”

The COVID-19 pandemic necessitates increased use of telemedicine, but building blocks to allow patients to use it effectively must be put in place, she said. That means expanding broadband access, providing patients with blood pressure cuffs and other tools for use remotely, and expanding reimbursement to include not just video, but also phone calls.

Heart Safe Motherhood, a University of Pennsylvania text-based intervention developed to address postpartum hypertension – a leading cause of maternal morbidity and mortality, and at the start of the program, the leading cause of 7-day readmissions among obstetric patients, demonstrated the value of such approaches to care.

The program involves remote blood pressure monitoring using a digital monitor provided to at-risk patients at discharge. Text-based monitoring reminders encourage patients to check their blood pressure twice daily for the first 7 days.

“In our randomized, controlled trial, we saw our ability to meet ACOG guidelines on postpartum blood monitoring leap from 0% to 82%, compared to in-person office visits and 7-day readmissions from hypertension drop from 3% to 0%,” an update at the program website states.

ACOG

Rebekah Gee, MD, an ob.gyn. and director of the Louisiana State University Health System in New Orleans, also noted the importance of finding ways to deliver care “that are outside the traditional norm.

“Telemedicine, home visiting ... I think there are a wide variety of ways,” she said, noting that these kind of approaches not only help circumvent roadblocks to care, such as lack of transportation, but also can feel more personal and approachable for some women.
 

Solution: Measuring, investing, diversifying, respecting

The aims of other bills in the Momnibus Act also mirror several solutions proposed by maternal health advocates interviewed for this article. Among them are:

• Development of improved data collection processes and quality measures to better understand the factors that contribute to the crisis overall and among special populations, and to inform solutions for addressing them.
• Investments in social determinants of health that influence maternal health outcomes, like housing, transportation, and nutrition.
• Commitment to the growth and diversification of the perinatal workforce to ensure that every mom receives maternity care and support from people she can trust to provide quality care and treat her with respect.

The latter is one that Dr. Gee, Dr. Crear-Perry, and others particularly emphasized.

“We need patient advocates like doulas, midwives and others who are better listeners and better able to advocate for patients,” Dr. Gee said. This would better allow for women’s desires in the childbirth experience to be addressed appropriately, she said, adding that this is something that “frankly, a lot of doctors do not have the time to do.”

That’s why the efforts to address maternal mortality have to focus on the health care system, not just on doctors’ behavior with respect to bias, she said.

Dr. Gee also said there is a need for culturally appropriate literacy and numeracy communications “that respect how people seek and understand information.” This varies by population, which is why it’s important to provide the same approach to care “no matter what the patient looks like,” while also understanding that different patients communicate in different ways.

A 2019 study published in Social Science & Medicine underscored how communication differences can affect outcomes; using a national sample of women who gave birth in U.S. hospitals, the authors found that those who had declined care for themselves or their infant during their childbirth hospitalization were more likely to report receiving poor treatment based on race or ethnicity. They concluded that, in the context of childbirth care, women – particularly black women – pay a penalty for what is perceived as uncooperative behavior.

This is another area where doulas and other patient advocates can help, Dr. Gee said.

Doulas have long been an integral part of the birthing process for many women, particularly women of color, and evidence suggests the supportive care they provide helps to improve outcomes. In fact, several states – including Oregon, Minnesota, and New York, among others – have expanded or have proposed expanding Medicaid coverage to include doula services for pregnant beneficiaries, a move cheered by doula associations and other maternal health advocates.

In many ways, it’s about “respectful maternity care,” which is something Dr. Crear-Perry has been working to promote through the NBEC in partnership with ACOG and the Robert Wood Johnson Foundation. It’s also something the World Health Organization has promoted by establishing global standards for such care.

“We’re hoping to socialize that as a norm in United States ... to really see what it would look like to value what birthing people want and to see them as partners in their birth,” she said.

However, the 2019 Giving Voice to Mothers study demonstrating consistently higher rates of mistreatment during obstetrical care for women of color than for comparable white women shows that the United States is falling short of those standards. The national study of 2,700 women examined how race, ethnicity, and place of birth interact with the experience of receiving maternity care in the United States, and showed that 1 in 6 experienced one or more types of mistreatment – with consistently higher rates among women of color, even after adjusting for interactions between race and other maternal characteristics, Saraswathi Veda, MD, of the Birth Place Lab and professor of midwifery at the University of British Columbia, Vancouver, and colleagues reported in Reproductive Health.
 

Solution: Listening, learning, reflecting, partnering

Timoria McQueen Saba, birth trauma survivor and maternal health advocate, has described experiencing instances of mistreatment throughout her obstetric care, and like Dr. Crear-Perry, she said trust and collaboration in care is imperative for improving outcomes.

“I think the most important thing you can do is really consider a patient a partner in the care you give them,” she said during a panel discussion at the 2019 ACOG annual meeting. “You’re not experts in their lived experience ... center a patient’s voice or the voice of a patient’s family. Incorporate that into your learning.”

During a virtual workshop held May 19-20 by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Judette Louis, MD, chair of the department of obstetrics and gynecology at the University of South Florida, Tampa, and president of the Society of Maternal-Fetal Medicine, provided practical guidance for addressing racism and implicit bias in practice and in research to reduce disparities in outcomes.

In an interview, she summarized her key points, reiterating solutions proposed by Dr. Gee and Dr. Crear-Perry and addressed in the Momnibus Act, and also offering a few others:

First, put aside the notion that disparities are genetically driven. For a variety of reasons, that just doesn’t make sense. For one thing, not all blacks are African American.

“My family is from the Caribbean,” she said. “Is it really conceivable that we’re all so similar?”

Look also at the disparities among Native Americans, she said. “How can you take 500 distinct tribes that live across a wide geographic area and lump them into one group and assume that they are similar?”

The problem is racism, not race. “When you keep saying ‘it’s about race, it’s about race, it’s about race’ – that sends a message to the person who is of that race that there is something inherently broken about [them],” she said.

Recognize that the roots of the problem run deep. Learn about and support efforts to address the underlying structural factors that contribute to the problem, Dr. Louis emphasized, and recognize your own bias. “We all have it. The key is to recognize [biases] and mitigate them when taking care of patients.”

That’s easier said than done, at least judging by one survey of maternal-fetal medicine specialists in which 84% of respondents agreed that disparities impact practice, but only 29% agreed their own personal biases affect how they care for patients, she noted.

Tools are available to help individuals identify implicit bias, and training programs for health care providers can help, as well, she said. Implicit bias tests and training programs that help to identify and address bias and racism on individual and organizational levels are increasingly available through academic centers, health systems, and advocacy organizations.

Hope for solutions: Progress and promise

Like Dr. Crear-Perry, Dr. Louis sees hope for reducing disparities and improving maternal outcomes.

In another survey of SMFM members to identify the practice issues most important to them, racial disparities ranked in the top three.

“It says a lot that our [maternal-fetal medicine specialists] really see this as a problem and they want it fixed,” she said. “And I think it says that a lot of people need to work on this, not just us.”

Indeed, many are engaged in that work. Veronica Gillispie, MD, medical director of the Louisiana Perinatal Quality Collaborative and Pregnancy-Associated Mortality Review, has been instrumental in recent initiatives to improve maternal outcomes in Louisiana, and she too said she feels optimistic.

“I am hopeful and I do see signs of hope,” she said in an interview.

Teams that she works with and trains seem invested, institutions are increasingly implementing faculty training on racism and bias, and Oschner Health, where Dr. Gillispie practices as an ob.gyn., appointed its first chief diversity officer in February.

Medical students she works with are attuned to the issues of racism, bias, and disparities, and they show a desire to enact change, she said. “They already get it, and they are working to make it better.”

Dr. Crear-Perry also predicts practice-changing results from studies looking at the delivery of obstetrical care and the role of supportive care, and she pointed out another aspect of the COVID-19 crisis that provides an important lesson for health care providers who care for birthing people: the scarcity of personal protective equipment amid the pandemic.

“My friends who are ob.gyns., who are now not getting access to the things they need to stay safe to practice medicine and who are feeling very marginalized at this moment, feeling not valued – that’s how birthing people [of color] feel,” she said. “I’m hoping that builds a sense of empathy.

”I’m hoping at the end of this crisis, that those ob.gyns. will think of patients as allies in fighting for more access to health for everybody and for more resources to do their work,” Dr. Crear-Perry said. “We’re all in this together.”

[email protected]

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

Erythema associated with chronic graft-versus-host disease (GVHD) after allogenic stem cell transplantation is likely to resolve regardless of when it appears, while sclerosis that develops more than 3 months after a chronic GVHD diagnosis is less likely to resolve, according to research presented during a plenary session at the annual meeting of the Society for Investigative Dermatology, held virtually.

In addition, greater improvement in erythema, as measured by body surface area (BSA) in the study was significantly associated with higher patient survival, Laura X. Baker, BS, a medical student at Vanderbilt University, and coinvestigators at Vanderbilt Dermatology Translational Research Clinic in Nashville, Tenn., said in her presentation.

This new significant association between erythema response and survival could inform future studies,” she said. “Our findings highlight the importance of thorough skin exams in chronic GVHD patients.”

Ms. Baker and colleagues performed a prospective, observational study of 242 patients with chronic GVHD and cutaneous manifestations, enrolled in the Chronic GVHD Consortium across nine centers between 2007 and 2012.

Patients had either erythema or sclerosis at the time of enrollment, which was considered incident if erythema or sclerosis appeared less than 3 months after diagnosis of chronic GVHD, or prevalent if erythema or sclerosis appeared 3 months or later after a chronic GVHD diagnosis. All patients were enrolled in the Chronic GVHD Consortium within 3 years of a transplant and were receiving systemic immunosuppressive therapy.

Transplant clinicians examined patients every 6 months, assessing clinical parameters such as skin involvement. Ms. Baker and colleagues used the 2005 National Institutes of Health (NIH) criteria to assess a complete response, a partial response, or no cutaneous response using measurements made by the transplant clinicians. The NIH criteria recommend calculating the change in BSA at the first follow-up visit to determine these changes (Pavletic S et al. Biol Blood Marrow Transplant. 2006 Mar;12[3]:252-66). Researchers also developed a Cox regression model to evaluate overall survival and non-relapse mortality.

Among those with erythema, 133 patients had incident cases and 52 had prevalent cases of cutaneous chronic GVHD. At first follow-up after a finding of cutaneous involvement, the mean BSA was 4.5%, but the median BSA was zero, “meaning that more than half of the patients had complete disappearance of any erythema by the first follow-up,” Ms. Baker said. By the second follow-up visit, 74% of patients with erythema had complete responses, 9% achieved a partial response, and 18% had no response. A similar complete response rate was seen among patients with prevalent cases.

Among patients with sclerosis, there were 43 incident and 47 prevalent cases. Among patients with incident sclerosis, 68% achieved a clear response, 2% a partial response, and 30% no response. But only 28% of those with prevalent sclerosis had a complete response, 4% had a partial response, and 68% had no response.

Most erythema showed a complete response by the first follow-up, and it was not dependent on time from cGVHD diagnosis, Ms. Baker said. However, while most sclerosis within 3 months of cGVHD diagnosis showed a response, sclerosis present beyond the initial 3 months did not generally respond by the first follow-up.

“These findings could inform clinical care and expectations in addition to guiding the selection of outcome measures and endpoint definitions in clinical trials,” she added.

The researchers also looked at overall survival and nonrelapse mortality among patients with incident and prevalent erythema. After adjustment for age and BSA at enrollment, patients with incident cases of erythema with a complete response had significantly better odds of overall survival compared with patients who had no clinical response (hazard ratio, 0.50; 95% confidence interval; 0.25-1.00; P = .05).

Overall survival was greater in patients with prevalent cases of erythema (HR, 0.29; 95% CI, 0.09-0.87; P = .03). Nonrelapse mortality was also significantly lower among prevalent cases with complete or partial clinical response for erythema (HR, 0.19; 95% CI, 0.06-0.64; P = .01).

In a subgroup analysis, 113 patients with incident cases of erythema that had other organ cGVHD had significantly greater overall survival than did patients without a clinical response (HR, 0.20; 95% CI, 0.08-0.46; P < .005). Median survival distance after the first follow-up between patients with and without a clinical response was 28.9 months among incident cases, and 33.7 months among prevalent erythema cases.

“We knew that erythema is not a direct cause of mortality,” Ms. Baker said. Our results suggest the association between erythema response and survival is important and could inform future study.”

The researchers noted their study was limited by transplant clinicians measuring BSA rather than dermatologists, patients being treated at top transplant centers, and their GVHD diagnosis being within 3 years of a transplant, which could limit generalizability of the findings.

This study was funded by a career development award from the U.S. Department of Veterans Affairs and grants from the National Institutes of Health/National Cancer Institute.

SOURCE: Baker L. SID 2020, Abstract 434.

Poziotinib, a pan-EGFR inhibitor, shrank tumors in a majority of patients with previously treated non–small cell lung cancer and EGFR exon 20 insertion mutations, but most of these patients did not achieve a response in the ongoing phase 2 ZENITH20 study.

The overall response rate (ORR) in the 115 patients was 14.8%, according to Xiuning Le, MD, PhD, of MD Anderson Cancer Center in Houston, who reported these results at the AACR virtual meeting I.

The ORR fell short of the greater than 17% required to meet the primary endpoint, but 65% of patients experienced tumor shrinkage, Dr. Le noted.

Overall, 17 patients had a confirmed partial response, 5 had an unconfirmed partial response, and 62 had stable disease, for a disease control rate of 68.7%.

Responses occurred early and were durable, Dr. Le said. The median duration of response was 7.4 months.

Responses were also consistent across subgroups based on the number of prior lines of therapy and prior EGFR tyrosine kinase inhibitor (TKI) therapy.

The median progression-free survival was 4.2 months.
 

Patients, treatment, and safety

The patients, who were enrolled in the first cohort of the ZENITH20 study, had a median age of 61 years. They had received a median of two prior therapies, with most having received both chemotherapy and immunotherapy.

Poziotinib was given at a once-daily dose of 16 mg for 28-day cycles, with follow-up of 24 months. Dose reductions were allowed for adverse events (AEs).

AEs were on target and consistent with EGFR TKI class effects. The most common AEs were rash, diarrhea, stomatitis, and paronychia.

Grade 3 AEs included rash (28%) and diarrhea (25%). No grade 5 treatment-related AEs occurred.

Dose reductions were common, occurring in 68% of patients. The median relative poziotinib dose intensity was 72%, suggesting that response can be maintained at lower dose levels, Dr. Le said.

Drug interruptions were also common, occurring in 88% of patients. Ten percent of patients discontinued treatment permanently, Dr. Le said, noting that this is consistent with findings in prior large trials of second-generation TKIs.
 

Implications

The results of this study are of note because EGFR is a known driver of NSCLC, Dr. Le said. She explained that, while effective treatments exist for more common EGFR mutations, such as the classic sensitizing exon 21 mutation L858R and exon 19 deletion, no approved targeted therapies are available for the approximately 10% of lung cancer patients whose tumors harbor EGFR exon 20 insertions.

“Those EGFR exon 20 insertions are not sensitive to most of the approved EGFR inhibitors,” Dr. Le said. She noted that, in one study, the median progression-free survival following treatment with an approved agent was 14 months in patients with classical mutations, compared with 2 months in those with exon 20 insertions.

The difference is attributable to molecular structural differences. Exon 20 insertions create a smaller and more shallow EGFR protein interaction surface, Dr. Le explained. “So some of the approved inhibitors don’t fit well into the oncogenic molecule,” she said.

Poziotinib has a small size and shape that can fit into the binding pocket of exon 20, and that, along with its mechanism of action, made it a promising candidate for this population, Dr. Le said. She referenced a study of 44 patients at MD Anderson Cancer Center in which poziotinib produced an ORR of 43%.

In the current study, “[p]oziotinib has further demonstrated clinical activity in previously treated lung cancer patients with EGFR exon 20 insertions ... with a toxicity profile similar to that of other second-generation TKIs,” she said.

The findings underscore the promise of EGFR exon 20 insertions as targets for therapeutic intervention, said invited discussant Taofeek Owonikoko, MD, PhD, of Winship Cancer Institute of Emory University in Atlanta.

“Poziotinib showed modest but meaningful efficacy,” he said. “However, its safety remains a challenge. It is expected that ongoing modifications in the dosing schedule will make it a more tolerable agent.”

“Future studies to systematically explore differential sensitivity of various exon 20 insertion mutations by location will be informative, as will [elucidation of] mechanisms of resistance to prioritize combinatorial strategies to further enhance the efficacy of this drug,” Dr. Owonikoko added.
 

Next steps

Analyses of other cohorts in the ZENITH20 trial will be reported at upcoming conferences as the data mature, Dr. Le noted. Cohorts 2-4 include patients with previously treated HER2 exon 20 insertions and treatment-naive patients with EGFR and HER2 exon 20 insertions, respectively.

Additionally, three new cohorts are being added, including one with patients who have EGFR or HER2 exon 20 insertions, one with EGFR patients who failed prior osimertinib treatment, and one with patients who have atypical EGFR or HER2 mutations.

Rather than the once-daily dosing used in cohorts 1-4, twice-daily dosing will be evaluated in these cohorts, Dr. Le said, explaining that the half-life of poziotinib is about 8 hours.

“Recent pharmacological modeling showed that a [twice-daily] regimen would reduce the maximal serum concentration and increase trough, which could lead to optimized drug coverage,” she said. “This may potentially reduce toxicity and improve patient compliance and efficacy.”

ZENITH20 is sponsored by Spectrum Pharmaceuticals Inc. Dr. Le disclosed relationships with Spectrum as well as Eli Lilly, AstraZeneca, EMD Serono, and Boehringer Ingelheim. Dr. Owonikoko disclosed relationships with many companies, not including Spectrum.

[email protected]

SOURCE: Le X et al. AACR 2020, Abstract CT081.

Poziotinib, a pan-EGFR inhibitor, shrank tumors in a majority of patients with previously treated non–small cell lung cancer and EGFR exon 20 insertion mutations, but most of these patients did not achieve a response in the ongoing phase 2 ZENITH20 study.

The overall response rate (ORR) in the 115 patients was 14.8%, according to Xiuning Le, MD, PhD, of MD Anderson Cancer Center in Houston, who reported these results at the AACR virtual meeting I.

The ORR fell short of the greater than 17% required to meet the primary endpoint, but 65% of patients experienced tumor shrinkage, Dr. Le noted.

Overall, 17 patients had a confirmed partial response, 5 had an unconfirmed partial response, and 62 had stable disease, for a disease control rate of 68.7%.

Responses occurred early and were durable, Dr. Le said. The median duration of response was 7.4 months.

Responses were also consistent across subgroups based on the number of prior lines of therapy and prior EGFR tyrosine kinase inhibitor (TKI) therapy.

The median progression-free survival was 4.2 months.
 

Patients, treatment, and safety

The patients, who were enrolled in the first cohort of the ZENITH20 study, had a median age of 61 years. They had received a median of two prior therapies, with most having received both chemotherapy and immunotherapy.

Poziotinib was given at a once-daily dose of 16 mg for 28-day cycles, with follow-up of 24 months. Dose reductions were allowed for adverse events (AEs).

AEs were on target and consistent with EGFR TKI class effects. The most common AEs were rash, diarrhea, stomatitis, and paronychia.

Grade 3 AEs included rash (28%) and diarrhea (25%). No grade 5 treatment-related AEs occurred.

Dose reductions were common, occurring in 68% of patients. The median relative poziotinib dose intensity was 72%, suggesting that response can be maintained at lower dose levels, Dr. Le said.

Drug interruptions were also common, occurring in 88% of patients. Ten percent of patients discontinued treatment permanently, Dr. Le said, noting that this is consistent with findings in prior large trials of second-generation TKIs.
 

Implications

The results of this study are of note because EGFR is a known driver of NSCLC, Dr. Le said. She explained that, while effective treatments exist for more common EGFR mutations, such as the classic sensitizing exon 21 mutation L858R and exon 19 deletion, no approved targeted therapies are available for the approximately 10% of lung cancer patients whose tumors harbor EGFR exon 20 insertions.

“Those EGFR exon 20 insertions are not sensitive to most of the approved EGFR inhibitors,” Dr. Le said. She noted that, in one study, the median progression-free survival following treatment with an approved agent was 14 months in patients with classical mutations, compared with 2 months in those with exon 20 insertions.

The difference is attributable to molecular structural differences. Exon 20 insertions create a smaller and more shallow EGFR protein interaction surface, Dr. Le explained. “So some of the approved inhibitors don’t fit well into the oncogenic molecule,” she said.

Poziotinib has a small size and shape that can fit into the binding pocket of exon 20, and that, along with its mechanism of action, made it a promising candidate for this population, Dr. Le said. She referenced a study of 44 patients at MD Anderson Cancer Center in which poziotinib produced an ORR of 43%.

In the current study, “[p]oziotinib has further demonstrated clinical activity in previously treated lung cancer patients with EGFR exon 20 insertions ... with a toxicity profile similar to that of other second-generation TKIs,” she said.

The findings underscore the promise of EGFR exon 20 insertions as targets for therapeutic intervention, said invited discussant Taofeek Owonikoko, MD, PhD, of Winship Cancer Institute of Emory University in Atlanta.

“Poziotinib showed modest but meaningful efficacy,” he said. “However, its safety remains a challenge. It is expected that ongoing modifications in the dosing schedule will make it a more tolerable agent.”

“Future studies to systematically explore differential sensitivity of various exon 20 insertion mutations by location will be informative, as will [elucidation of] mechanisms of resistance to prioritize combinatorial strategies to further enhance the efficacy of this drug,” Dr. Owonikoko added.
 

Next steps

Analyses of other cohorts in the ZENITH20 trial will be reported at upcoming conferences as the data mature, Dr. Le noted. Cohorts 2-4 include patients with previously treated HER2 exon 20 insertions and treatment-naive patients with EGFR and HER2 exon 20 insertions, respectively.

Additionally, three new cohorts are being added, including one with patients who have EGFR or HER2 exon 20 insertions, one with EGFR patients who failed prior osimertinib treatment, and one with patients who have atypical EGFR or HER2 mutations.

Rather than the once-daily dosing used in cohorts 1-4, twice-daily dosing will be evaluated in these cohorts, Dr. Le said, explaining that the half-life of poziotinib is about 8 hours.

“Recent pharmacological modeling showed that a [twice-daily] regimen would reduce the maximal serum concentration and increase trough, which could lead to optimized drug coverage,” she said. “This may potentially reduce toxicity and improve patient compliance and efficacy.”

ZENITH20 is sponsored by Spectrum Pharmaceuticals Inc. Dr. Le disclosed relationships with Spectrum as well as Eli Lilly, AstraZeneca, EMD Serono, and Boehringer Ingelheim. Dr. Owonikoko disclosed relationships with many companies, not including Spectrum.

[email protected]

SOURCE: Le X et al. AACR 2020, Abstract CT081.

Poziotinib, a pan-EGFR inhibitor, shrank tumors in a majority of patients with previously treated non–small cell lung cancer and EGFR exon 20 insertion mutations, but most of these patients did not achieve a response in the ongoing phase 2 ZENITH20 study.

The overall response rate (ORR) in the 115 patients was 14.8%, according to Xiuning Le, MD, PhD, of MD Anderson Cancer Center in Houston, who reported these results at the AACR virtual meeting I.

The ORR fell short of the greater than 17% required to meet the primary endpoint, but 65% of patients experienced tumor shrinkage, Dr. Le noted.

Overall, 17 patients had a confirmed partial response, 5 had an unconfirmed partial response, and 62 had stable disease, for a disease control rate of 68.7%.

Responses occurred early and were durable, Dr. Le said. The median duration of response was 7.4 months.

Responses were also consistent across subgroups based on the number of prior lines of therapy and prior EGFR tyrosine kinase inhibitor (TKI) therapy.

The median progression-free survival was 4.2 months.
 

Patients, treatment, and safety

The patients, who were enrolled in the first cohort of the ZENITH20 study, had a median age of 61 years. They had received a median of two prior therapies, with most having received both chemotherapy and immunotherapy.

Poziotinib was given at a once-daily dose of 16 mg for 28-day cycles, with follow-up of 24 months. Dose reductions were allowed for adverse events (AEs).

AEs were on target and consistent with EGFR TKI class effects. The most common AEs were rash, diarrhea, stomatitis, and paronychia.

Grade 3 AEs included rash (28%) and diarrhea (25%). No grade 5 treatment-related AEs occurred.

Dose reductions were common, occurring in 68% of patients. The median relative poziotinib dose intensity was 72%, suggesting that response can be maintained at lower dose levels, Dr. Le said.

Drug interruptions were also common, occurring in 88% of patients. Ten percent of patients discontinued treatment permanently, Dr. Le said, noting that this is consistent with findings in prior large trials of second-generation TKIs.
 

Implications

The results of this study are of note because EGFR is a known driver of NSCLC, Dr. Le said. She explained that, while effective treatments exist for more common EGFR mutations, such as the classic sensitizing exon 21 mutation L858R and exon 19 deletion, no approved targeted therapies are available for the approximately 10% of lung cancer patients whose tumors harbor EGFR exon 20 insertions.

“Those EGFR exon 20 insertions are not sensitive to most of the approved EGFR inhibitors,” Dr. Le said. She noted that, in one study, the median progression-free survival following treatment with an approved agent was 14 months in patients with classical mutations, compared with 2 months in those with exon 20 insertions.

The difference is attributable to molecular structural differences. Exon 20 insertions create a smaller and more shallow EGFR protein interaction surface, Dr. Le explained. “So some of the approved inhibitors don’t fit well into the oncogenic molecule,” she said.

Poziotinib has a small size and shape that can fit into the binding pocket of exon 20, and that, along with its mechanism of action, made it a promising candidate for this population, Dr. Le said. She referenced a study of 44 patients at MD Anderson Cancer Center in which poziotinib produced an ORR of 43%.

In the current study, “[p]oziotinib has further demonstrated clinical activity in previously treated lung cancer patients with EGFR exon 20 insertions ... with a toxicity profile similar to that of other second-generation TKIs,” she said.

The findings underscore the promise of EGFR exon 20 insertions as targets for therapeutic intervention, said invited discussant Taofeek Owonikoko, MD, PhD, of Winship Cancer Institute of Emory University in Atlanta.

“Poziotinib showed modest but meaningful efficacy,” he said. “However, its safety remains a challenge. It is expected that ongoing modifications in the dosing schedule will make it a more tolerable agent.”

“Future studies to systematically explore differential sensitivity of various exon 20 insertion mutations by location will be informative, as will [elucidation of] mechanisms of resistance to prioritize combinatorial strategies to further enhance the efficacy of this drug,” Dr. Owonikoko added.
 

Next steps

Analyses of other cohorts in the ZENITH20 trial will be reported at upcoming conferences as the data mature, Dr. Le noted. Cohorts 2-4 include patients with previously treated HER2 exon 20 insertions and treatment-naive patients with EGFR and HER2 exon 20 insertions, respectively.

Additionally, three new cohorts are being added, including one with patients who have EGFR or HER2 exon 20 insertions, one with EGFR patients who failed prior osimertinib treatment, and one with patients who have atypical EGFR or HER2 mutations.

Rather than the once-daily dosing used in cohorts 1-4, twice-daily dosing will be evaluated in these cohorts, Dr. Le said, explaining that the half-life of poziotinib is about 8 hours.

“Recent pharmacological modeling showed that a [twice-daily] regimen would reduce the maximal serum concentration and increase trough, which could lead to optimized drug coverage,” she said. “This may potentially reduce toxicity and improve patient compliance and efficacy.”

ZENITH20 is sponsored by Spectrum Pharmaceuticals Inc. Dr. Le disclosed relationships with Spectrum as well as Eli Lilly, AstraZeneca, EMD Serono, and Boehringer Ingelheim. Dr. Owonikoko disclosed relationships with many companies, not including Spectrum.

[email protected]

SOURCE: Le X et al. AACR 2020, Abstract CT081.

Not only does the use of e-cigarettes not help cigarette smokers who are unmotivated to quit, it has the opposite effect, according to results from a new study.

6okean/iStock/Getty Images Plus

“In our study, people vaping in addition to smoking actually started smoking more,” said study lead investigator Nancy Anoruo, MD, from the University of Massachusetts Medical School in Worcester.

This is “completely contradictory to what the e-cigarette manufacturers are telling us,” she told this news organization.

In their study, Dr. Anoruo and her colleagues looked at whether people were more likely to quit if they smoked e-cigarettes in addition to conventional cigarettes. The research is a substudy of the ongoing Take a Break project, funded by the National Institutes of Health, which is assessing whether a smoking-cessation motivation app helps smokers quit.

In a cohort of 405 smokers who were unmotivated to quit, 248 were defined as dual smokers after responding “yes” to “ever having used” e-cigarettes, and 157 were defined as traditional smokers who only smoked combustible cigarettes. The majority of participants, 82%, were white; 8.8% were black; and 49% were women.

More dual smokers than traditional smokers were younger than 40 years (27% vs. 16%; (P = .02), Dr. Anoruo reported during her virtual presentation at the American Thoracic Society 2020 International Conference.

The dual smokers reported smoking an average of 16 cigarettes a day, compared with 14 a day for the traditional smokers.

All the smokers were encouraged to consider a 3-week period of abstinence from combustible cigarettes. At the end of that period, the researchers compared outcomes reported by participants.
 

Abstinence challenge

Average abstinence intervals were shorter for dual smokers than for traditional smokers (0.93 vs. 1.8 days; P = .01). And dual smokers reported having a harder time quitting completely (6.3% vs. 13.0%; P = .02).

At 6-month follow-up, dual smokers were smoking more cigarettes than traditional smokers (daily average, 12.0 vs. 9.4; P = .04). And the reduction in cigarette use from baseline was smaller for dual smokers than for traditional smokers (21% vs. 33%; P = .04).

“E-cigarettes are not a special magic bullet to get people to quit smoking,” said Dr. Anoruo.

In this study, smoking cessation was defined as abstinence from combustible cigarettes, but that did not mean participants were abstinent from nicotine.

“If, at the end, they stopped smoking traditional cigarettes, we considered that successful smoking cessation,” Dr. Anoruo explained. This definition is in line with the school of thought that e-cigarettes are a harm-reduction tool.

“But we now know that e-cigarettes are not necessarily safe,” she added.

Still, it might be the lesser evil. “You end up taking in less dangerous chemicals, so we consider it quitting if you get off regular cigarettes,” she said.

“We would like to study the psychology of cigarette smokers to find out if they see e-cigarettes as a smoking-cessation aid,” Dr. Anoruo said, and to see if “their belief is driven by the advertising they see about e-cigarette use.”
 

A meager reduction

Similar results were shown last month in a study by Megan Piper, PhD, of University of Wisconsin–Madison and her colleagues, who reported that dual e-cigarette and combustible cigarette use “did not appear to be an effective path to cessation of combustible cigarettes.”

After 1 year, dual smokers smoked three cigarettes less each day than traditional smokers, which is “a meager reduction,” Dr. Piper said in a news release.

“Typically, you can’t have one foot in both camps. Most can’t be vaping and smoking and hope to quit smoking,” she added. “That sustained pattern is not going to help most people quit.”

A version of this article originally appeared on Medscape.com.

Not only does the use of e-cigarettes not help cigarette smokers who are unmotivated to quit, it has the opposite effect, according to results from a new study.

6okean/iStock/Getty Images Plus

“In our study, people vaping in addition to smoking actually started smoking more,” said study lead investigator Nancy Anoruo, MD, from the University of Massachusetts Medical School in Worcester.

This is “completely contradictory to what the e-cigarette manufacturers are telling us,” she told this news organization.

In their study, Dr. Anoruo and her colleagues looked at whether people were more likely to quit if they smoked e-cigarettes in addition to conventional cigarettes. The research is a substudy of the ongoing Take a Break project, funded by the National Institutes of Health, which is assessing whether a smoking-cessation motivation app helps smokers quit.

In a cohort of 405 smokers who were unmotivated to quit, 248 were defined as dual smokers after responding “yes” to “ever having used” e-cigarettes, and 157 were defined as traditional smokers who only smoked combustible cigarettes. The majority of participants, 82%, were white; 8.8% were black; and 49% were women.

More dual smokers than traditional smokers were younger than 40 years (27% vs. 16%; (P = .02), Dr. Anoruo reported during her virtual presentation at the American Thoracic Society 2020 International Conference.

The dual smokers reported smoking an average of 16 cigarettes a day, compared with 14 a day for the traditional smokers.

All the smokers were encouraged to consider a 3-week period of abstinence from combustible cigarettes. At the end of that period, the researchers compared outcomes reported by participants.
 

Abstinence challenge

Average abstinence intervals were shorter for dual smokers than for traditional smokers (0.93 vs. 1.8 days; P = .01). And dual smokers reported having a harder time quitting completely (6.3% vs. 13.0%; P = .02).

At 6-month follow-up, dual smokers were smoking more cigarettes than traditional smokers (daily average, 12.0 vs. 9.4; P = .04). And the reduction in cigarette use from baseline was smaller for dual smokers than for traditional smokers (21% vs. 33%; P = .04).

“E-cigarettes are not a special magic bullet to get people to quit smoking,” said Dr. Anoruo.

In this study, smoking cessation was defined as abstinence from combustible cigarettes, but that did not mean participants were abstinent from nicotine.

“If, at the end, they stopped smoking traditional cigarettes, we considered that successful smoking cessation,” Dr. Anoruo explained. This definition is in line with the school of thought that e-cigarettes are a harm-reduction tool.

“But we now know that e-cigarettes are not necessarily safe,” she added.

Still, it might be the lesser evil. “You end up taking in less dangerous chemicals, so we consider it quitting if you get off regular cigarettes,” she said.

“We would like to study the psychology of cigarette smokers to find out if they see e-cigarettes as a smoking-cessation aid,” Dr. Anoruo said, and to see if “their belief is driven by the advertising they see about e-cigarette use.”
 

A meager reduction

Similar results were shown last month in a study by Megan Piper, PhD, of University of Wisconsin–Madison and her colleagues, who reported that dual e-cigarette and combustible cigarette use “did not appear to be an effective path to cessation of combustible cigarettes.”

After 1 year, dual smokers smoked three cigarettes less each day than traditional smokers, which is “a meager reduction,” Dr. Piper said in a news release.

“Typically, you can’t have one foot in both camps. Most can’t be vaping and smoking and hope to quit smoking,” she added. “That sustained pattern is not going to help most people quit.”

A version of this article originally appeared on Medscape.com.

Not only does the use of e-cigarettes not help cigarette smokers who are unmotivated to quit, it has the opposite effect, according to results from a new study.

6okean/iStock/Getty Images Plus

“In our study, people vaping in addition to smoking actually started smoking more,” said study lead investigator Nancy Anoruo, MD, from the University of Massachusetts Medical School in Worcester.

This is “completely contradictory to what the e-cigarette manufacturers are telling us,” she told this news organization.

In their study, Dr. Anoruo and her colleagues looked at whether people were more likely to quit if they smoked e-cigarettes in addition to conventional cigarettes. The research is a substudy of the ongoing Take a Break project, funded by the National Institutes of Health, which is assessing whether a smoking-cessation motivation app helps smokers quit.

In a cohort of 405 smokers who were unmotivated to quit, 248 were defined as dual smokers after responding “yes” to “ever having used” e-cigarettes, and 157 were defined as traditional smokers who only smoked combustible cigarettes. The majority of participants, 82%, were white; 8.8% were black; and 49% were women.

More dual smokers than traditional smokers were younger than 40 years (27% vs. 16%; (P = .02), Dr. Anoruo reported during her virtual presentation at the American Thoracic Society 2020 International Conference.

The dual smokers reported smoking an average of 16 cigarettes a day, compared with 14 a day for the traditional smokers.

All the smokers were encouraged to consider a 3-week period of abstinence from combustible cigarettes. At the end of that period, the researchers compared outcomes reported by participants.
 

Abstinence challenge

Average abstinence intervals were shorter for dual smokers than for traditional smokers (0.93 vs. 1.8 days; P = .01). And dual smokers reported having a harder time quitting completely (6.3% vs. 13.0%; P = .02).

At 6-month follow-up, dual smokers were smoking more cigarettes than traditional smokers (daily average, 12.0 vs. 9.4; P = .04). And the reduction in cigarette use from baseline was smaller for dual smokers than for traditional smokers (21% vs. 33%; P = .04).

“E-cigarettes are not a special magic bullet to get people to quit smoking,” said Dr. Anoruo.

In this study, smoking cessation was defined as abstinence from combustible cigarettes, but that did not mean participants were abstinent from nicotine.

“If, at the end, they stopped smoking traditional cigarettes, we considered that successful smoking cessation,” Dr. Anoruo explained. This definition is in line with the school of thought that e-cigarettes are a harm-reduction tool.

“But we now know that e-cigarettes are not necessarily safe,” she added.

Still, it might be the lesser evil. “You end up taking in less dangerous chemicals, so we consider it quitting if you get off regular cigarettes,” she said.

“We would like to study the psychology of cigarette smokers to find out if they see e-cigarettes as a smoking-cessation aid,” Dr. Anoruo said, and to see if “their belief is driven by the advertising they see about e-cigarette use.”
 

A meager reduction

Similar results were shown last month in a study by Megan Piper, PhD, of University of Wisconsin–Madison and her colleagues, who reported that dual e-cigarette and combustible cigarette use “did not appear to be an effective path to cessation of combustible cigarettes.”

After 1 year, dual smokers smoked three cigarettes less each day than traditional smokers, which is “a meager reduction,” Dr. Piper said in a news release.

“Typically, you can’t have one foot in both camps. Most can’t be vaping and smoking and hope to quit smoking,” she added. “That sustained pattern is not going to help most people quit.”

A version of this article originally appeared on Medscape.com.

A study that claims to be the first review of all the available evidence of the effectiveness of physical distancing, face masks, and eye protection to prevent spread of COVID-19 and other respiratory diseases has quantified the effectiveness of these protective measures. The study found that greater physical distancing from an exposed person significantly reduces risk of transmission and that N95 masks, particularly for health care workers, are more effective than other face coverings.

The meta-analysis, published online in The Lancet (2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9) also marks the first evaluation of these protective measures in both community and health care settings for COVID-19, the study authors stated.

“The risk for infection is highly dependent on distance to the individual infected and the type of face mask and eye protection worn,” wrote Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ont., and colleagues, reporting on behalf of the COVID-19 Systematic Urgent Review Group Effort, or SURGE.

The study reported that physical distancing of at least 1 meter, or about a yard, “seems to be strongly associated with a large protective effect,” but that distancing of 2 meters or about 6 feet could be more effective.

The study involved a systematic review of 172 observational studies across six continents that evaluated distance measures, face masks, and eye protection to prevent transmission between patients with confirmed or probable COVID-19, other severe acute respiratory syndrome (SARS) disease, and Middle East respiratory syndrome (MERS), and their family members, caregivers and health care workers up to May 3, 2020. The meta-analysis involved pooled estimates from 44 comparative studies with 25,697 participants, including seven studies of COVID-19 with 6,674 participants. None of the studies included in the meta-analysis were randomized clinical trials.

A subanalysis of 29 unadjusted and 9 adjusted studies found that the absolute risk of infection in proximity to an exposed individual was 12.8% at 1 m and 2.6% at 2 m. The risk remained constant even when the six COVID-19 studies in this subanalysis were isolated and regardless of being in a health care or non–health-care setting. Each meter of increased distance resulted in a doubling in the change in relative risk (P = .041).

The study also identified what Dr. Chu and colleagues characterized as a “large reduction” in infection risk with the use of both N95 or similar respirators or face masks, with an adjusted risk of infection of 3.1% with a face covering vs. a 17.4% without. The researchers also found a stronger association in health care settings vs. non–health care settings, with a relative risk of 0.3 vs. 0.56, respectively (P = .049). The protective effect of N95 or similar respirators was greater than other masks, with adjusted odds ratios of 0.04 vs. 0.33 (P = .09).

Eye protection was found to reduce the risk of infection to 5.5% vs. 16% without eye protection.

The study also identified potential barriers to social distancing and use of masks and eye protection: discomfort, resource use “linked with potentially decreased equity,” less clear communication, and a perceived lack of empathy on the part of providers toward patients.

Dr. Chu and colleagues wrote that more “high-quality” research, including randomized trials of the optimal physical distance and evaluation of different mask types in non–health care settings “is urgently needed.” They added, “Policymakers at all levels should, therefore, strive to address equity implications for groups with currently limited access to face masks and eye protection.”

The goal of this study was to “inform WHO guidance documents,” the study noted. “Governments and the public health community can use our results to give clear advice for community settings and healthcare workers on these protective measures to reduce infection risk,” said study co-leader Holger Schünemann, MD, MSc, PhD, of McMaster University.

Prof. Raina MacIntyre, MBBS, PhD, head of the biosecurity research program at the Kirby Institute at the University of New South Wales in Sydney, who authored the comment that accompanied the article, said that this study provides evidence for stronger PPE guidelines.

“The Centers for Disease Control and Prevention initially recommended N95s for health workers treating COVID-19 patients, but later downgraded this to surgical masks and even cloth masks and bandannas when there was a supply shortage,” she said. “This study shows that N95s are superior masks and should prompt a review of guidelines that recommend anything less for health workers.”

Recommending anything less than N95 masks for health workers is like sending troops into battle “unarmed or with bows and arrows against a fully armed enemy,” she said. “We are not talking about a device that costs hundreds or thousands of dollars; a N95 costs less than a dollar to produce. All that is needed to address the supply shortage is political will.”

While the study has some shortcomings – namely that it didn’t provide a breakdown of positive tests among COVID-19 participants – it does provide important insight for physicians, Sachin Gupta, MD, a pulmonary and critical care specialist in San Francisco, said in an interview. “The strength of a meta-analysis is that you’re able to get a composite idea; that’s one up side to this,” he said. “They’re confirming what we knew: that distance matters; that more protective masks reduce risk of infection; and that eye protection has an important role.”

Dr. Chu and colleagues have no relevant financial relationships to disclose. One member of SURGE is participating in a clinical trial comparing medical masks and N95 respirators. The World Health Organization provided partial funding for the study.

SOURCE: Chu DK et al. Lancet. 2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9 .

A study that claims to be the first review of all the available evidence of the effectiveness of physical distancing, face masks, and eye protection to prevent spread of COVID-19 and other respiratory diseases has quantified the effectiveness of these protective measures. The study found that greater physical distancing from an exposed person significantly reduces risk of transmission and that N95 masks, particularly for health care workers, are more effective than other face coverings.

The meta-analysis, published online in The Lancet (2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9) also marks the first evaluation of these protective measures in both community and health care settings for COVID-19, the study authors stated.

“The risk for infection is highly dependent on distance to the individual infected and the type of face mask and eye protection worn,” wrote Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ont., and colleagues, reporting on behalf of the COVID-19 Systematic Urgent Review Group Effort, or SURGE.

The study reported that physical distancing of at least 1 meter, or about a yard, “seems to be strongly associated with a large protective effect,” but that distancing of 2 meters or about 6 feet could be more effective.

The study involved a systematic review of 172 observational studies across six continents that evaluated distance measures, face masks, and eye protection to prevent transmission between patients with confirmed or probable COVID-19, other severe acute respiratory syndrome (SARS) disease, and Middle East respiratory syndrome (MERS), and their family members, caregivers and health care workers up to May 3, 2020. The meta-analysis involved pooled estimates from 44 comparative studies with 25,697 participants, including seven studies of COVID-19 with 6,674 participants. None of the studies included in the meta-analysis were randomized clinical trials.

A subanalysis of 29 unadjusted and 9 adjusted studies found that the absolute risk of infection in proximity to an exposed individual was 12.8% at 1 m and 2.6% at 2 m. The risk remained constant even when the six COVID-19 studies in this subanalysis were isolated and regardless of being in a health care or non–health-care setting. Each meter of increased distance resulted in a doubling in the change in relative risk (P = .041).

The study also identified what Dr. Chu and colleagues characterized as a “large reduction” in infection risk with the use of both N95 or similar respirators or face masks, with an adjusted risk of infection of 3.1% with a face covering vs. a 17.4% without. The researchers also found a stronger association in health care settings vs. non–health care settings, with a relative risk of 0.3 vs. 0.56, respectively (P = .049). The protective effect of N95 or similar respirators was greater than other masks, with adjusted odds ratios of 0.04 vs. 0.33 (P = .09).

Eye protection was found to reduce the risk of infection to 5.5% vs. 16% without eye protection.

The study also identified potential barriers to social distancing and use of masks and eye protection: discomfort, resource use “linked with potentially decreased equity,” less clear communication, and a perceived lack of empathy on the part of providers toward patients.

Dr. Chu and colleagues wrote that more “high-quality” research, including randomized trials of the optimal physical distance and evaluation of different mask types in non–health care settings “is urgently needed.” They added, “Policymakers at all levels should, therefore, strive to address equity implications for groups with currently limited access to face masks and eye protection.”

The goal of this study was to “inform WHO guidance documents,” the study noted. “Governments and the public health community can use our results to give clear advice for community settings and healthcare workers on these protective measures to reduce infection risk,” said study co-leader Holger Schünemann, MD, MSc, PhD, of McMaster University.

Prof. Raina MacIntyre, MBBS, PhD, head of the biosecurity research program at the Kirby Institute at the University of New South Wales in Sydney, who authored the comment that accompanied the article, said that this study provides evidence for stronger PPE guidelines.

“The Centers for Disease Control and Prevention initially recommended N95s for health workers treating COVID-19 patients, but later downgraded this to surgical masks and even cloth masks and bandannas when there was a supply shortage,” she said. “This study shows that N95s are superior masks and should prompt a review of guidelines that recommend anything less for health workers.”

Recommending anything less than N95 masks for health workers is like sending troops into battle “unarmed or with bows and arrows against a fully armed enemy,” she said. “We are not talking about a device that costs hundreds or thousands of dollars; a N95 costs less than a dollar to produce. All that is needed to address the supply shortage is political will.”

While the study has some shortcomings – namely that it didn’t provide a breakdown of positive tests among COVID-19 participants – it does provide important insight for physicians, Sachin Gupta, MD, a pulmonary and critical care specialist in San Francisco, said in an interview. “The strength of a meta-analysis is that you’re able to get a composite idea; that’s one up side to this,” he said. “They’re confirming what we knew: that distance matters; that more protective masks reduce risk of infection; and that eye protection has an important role.”

Dr. Chu and colleagues have no relevant financial relationships to disclose. One member of SURGE is participating in a clinical trial comparing medical masks and N95 respirators. The World Health Organization provided partial funding for the study.

SOURCE: Chu DK et al. Lancet. 2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9 .

A study that claims to be the first review of all the available evidence of the effectiveness of physical distancing, face masks, and eye protection to prevent spread of COVID-19 and other respiratory diseases has quantified the effectiveness of these protective measures. The study found that greater physical distancing from an exposed person significantly reduces risk of transmission and that N95 masks, particularly for health care workers, are more effective than other face coverings.

The meta-analysis, published online in The Lancet (2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9) also marks the first evaluation of these protective measures in both community and health care settings for COVID-19, the study authors stated.

“The risk for infection is highly dependent on distance to the individual infected and the type of face mask and eye protection worn,” wrote Derek K. Chu, MD, PhD, of McMaster University in Hamilton, Ont., and colleagues, reporting on behalf of the COVID-19 Systematic Urgent Review Group Effort, or SURGE.

The study reported that physical distancing of at least 1 meter, or about a yard, “seems to be strongly associated with a large protective effect,” but that distancing of 2 meters or about 6 feet could be more effective.

The study involved a systematic review of 172 observational studies across six continents that evaluated distance measures, face masks, and eye protection to prevent transmission between patients with confirmed or probable COVID-19, other severe acute respiratory syndrome (SARS) disease, and Middle East respiratory syndrome (MERS), and their family members, caregivers and health care workers up to May 3, 2020. The meta-analysis involved pooled estimates from 44 comparative studies with 25,697 participants, including seven studies of COVID-19 with 6,674 participants. None of the studies included in the meta-analysis were randomized clinical trials.

A subanalysis of 29 unadjusted and 9 adjusted studies found that the absolute risk of infection in proximity to an exposed individual was 12.8% at 1 m and 2.6% at 2 m. The risk remained constant even when the six COVID-19 studies in this subanalysis were isolated and regardless of being in a health care or non–health-care setting. Each meter of increased distance resulted in a doubling in the change in relative risk (P = .041).

The study also identified what Dr. Chu and colleagues characterized as a “large reduction” in infection risk with the use of both N95 or similar respirators or face masks, with an adjusted risk of infection of 3.1% with a face covering vs. a 17.4% without. The researchers also found a stronger association in health care settings vs. non–health care settings, with a relative risk of 0.3 vs. 0.56, respectively (P = .049). The protective effect of N95 or similar respirators was greater than other masks, with adjusted odds ratios of 0.04 vs. 0.33 (P = .09).

Eye protection was found to reduce the risk of infection to 5.5% vs. 16% without eye protection.

The study also identified potential barriers to social distancing and use of masks and eye protection: discomfort, resource use “linked with potentially decreased equity,” less clear communication, and a perceived lack of empathy on the part of providers toward patients.

Dr. Chu and colleagues wrote that more “high-quality” research, including randomized trials of the optimal physical distance and evaluation of different mask types in non–health care settings “is urgently needed.” They added, “Policymakers at all levels should, therefore, strive to address equity implications for groups with currently limited access to face masks and eye protection.”

The goal of this study was to “inform WHO guidance documents,” the study noted. “Governments and the public health community can use our results to give clear advice for community settings and healthcare workers on these protective measures to reduce infection risk,” said study co-leader Holger Schünemann, MD, MSc, PhD, of McMaster University.

Prof. Raina MacIntyre, MBBS, PhD, head of the biosecurity research program at the Kirby Institute at the University of New South Wales in Sydney, who authored the comment that accompanied the article, said that this study provides evidence for stronger PPE guidelines.

“The Centers for Disease Control and Prevention initially recommended N95s for health workers treating COVID-19 patients, but later downgraded this to surgical masks and even cloth masks and bandannas when there was a supply shortage,” she said. “This study shows that N95s are superior masks and should prompt a review of guidelines that recommend anything less for health workers.”

Recommending anything less than N95 masks for health workers is like sending troops into battle “unarmed or with bows and arrows against a fully armed enemy,” she said. “We are not talking about a device that costs hundreds or thousands of dollars; a N95 costs less than a dollar to produce. All that is needed to address the supply shortage is political will.”

While the study has some shortcomings – namely that it didn’t provide a breakdown of positive tests among COVID-19 participants – it does provide important insight for physicians, Sachin Gupta, MD, a pulmonary and critical care specialist in San Francisco, said in an interview. “The strength of a meta-analysis is that you’re able to get a composite idea; that’s one up side to this,” he said. “They’re confirming what we knew: that distance matters; that more protective masks reduce risk of infection; and that eye protection has an important role.”

Dr. Chu and colleagues have no relevant financial relationships to disclose. One member of SURGE is participating in a clinical trial comparing medical masks and N95 respirators. The World Health Organization provided partial funding for the study.

SOURCE: Chu DK et al. Lancet. 2020 Jun 2; doi.org/10.1016/ S0140-6736(20)31142-9 .

The Navajo people have dealt with adversity that has tested our strength and resilience since our creation. In Navajo culture, the Holy People or gods challenged us with Naayee (monsters). We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language) is a monster confronting the Navajo today. It has had significant impact on our nation and people.

The Navajo have the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths.¹ The Navajo Nation, which once lagged behind New York, has reported the largest per-capita infection rate in the United States.

These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average numbers of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%.²

Geographical and cultural factors also contribute to the inability to gain a foothold in mitigating the number of cases. The Navajo Nation is the largest tribe in the United States, covering 27,000 square miles over an arid, red rock expanse with canyons and mountains. The population is over 250,000,³ and Navajo have traditionally lived in matrilineal clan units throughout the reservation, the size of West Virginia. The family traditional dwelling, called a “hogan,” often is clustered together. Multiple generations live together in these units. The COVID-19 virus inflicted many Navajo and rapidly spread to the elderly in these close-proximity living quarters.

Most Navajo live away from services and grocery stores and travel back and forth for food and water, which contributes to the virus rapidly being transmitted among the community members. Education aimed at curbing travel and spread of the virus was issued with curfews, commands to stay at home and keep social distance, and protect elders. The Navajo leadership and traditional medicine people, meanwhile, advised the people to follow their cultural values by caring for family and community members and providing a safe environment.
 

Resources are spread out

There are only 13 stores in this expansive reservation,⁴ so tribal members rely on traveling to border towns, such as Farmington and Gallup, N.M., Families usually travel to these towns on weekends to replenish food and supplies. There has been a cluster of cases in Gallup, N.M., so to reduce the numbers, the town shut itself off from outsiders – including the Navajo people coming to buy food, do laundry, and get water and feed for livestock. This has affected and stressed the Navajo further in attempting to access necessities.

Access to health care is already challenging because of lack of transportation and distance. This has made it more difficult to access COVID-19 testing and more challenging to get the results back. The Indian Health Service has been the designated health care system for the Navajo since 1955. The Treaty of Bosque Redondo, signed by the Navajo in 1868, included the provision of health care, as well as education in exchange for tracts of land, that included the Navajo homeland or Dinetah.⁵

The Indian Health Service provides care with hospitals and clinics throughout the reservation. Some of the IHS facilities have been taken over by the Navajo, so there are four Navajo tribally controlled hospitals, along with one private hospital. Coordination of care for a pandemic is, therefore, more challenging to coordinate. This contributes to problems with coordination of the health care, establishing alternate care sites, accessing personal protective equipment, and providing testing sites. The Navajo Nation Council is working hard to equitably distribute the $600 million from the CARES Act.⁶

Dealing with the pandemic is compromised by chronic underfunding from the U.S. government. The treaty obligation of the U.S. government is to provide health care to all federally recognized Native Americans. The IHS, which has been designated to provide that care for a tribal person, gets one-third the Medicare dollars for health care provided for a person in the general population.⁷ Health factors have led to the public health issues of poorly controlled diabetes, obesity, and coronary artery disease, which is related to this underfunding and the high rate of COVID-19 cases. Parts of the reservation are also exposed to high levels of pollution from oil and gas wells from the coal-fueled power plants. Those exposed to these high levels of pollutions have a higher than average number of cases of COVID-19, higher than in areas where the pollution is markedly lower.⁸

The Navajo are having to rely on the strength and resilience of traditional Navajo culture and philosophy to confront this monster, Dikos Nitsaa’igii’ 19. We have relied on Western medicine and its limited resources but now need to empower the strength from our traditional ways of knowing. We have used this knowledge in times of adversity for hundreds of years. The Navajo elders and medicine people have reminded us we have dealt with monsters and know how to endure hardship and be resilient. This helps to ameliorate mental health conditions, but there are still issues that remain challenging.

Those having the virus go through times of shortness of breath, which produces anxiety and panic. The risk of death adds further stress, and for a family-oriented culture, the need to isolate from family adds further stress. For the elderly and young people with more serious disease having to go to the hospital alone without family, often far from home, is so challenging. Connecting family by phone or social media with those stricken is essential to decrease anxiety and isolation. Those infected with the virus can learn breathing exercises, which can help the damage from the virus and decrease emotional activation and triggers. Specific breathing techniques can be taught by medical providers. An effective breathing technique to reduce anxiety is coherent breathing, which is done by inhaling 6 seconds and exhaling for 6 seconds without holding your breath. Behavioral health practitioners are available in the tribal and IHS mental health clinics to refer patients to therapy support to manage anxiety and are available by telemedicine. Many of these programs are offering social media informational sessions for the Navajo community. Navajo people often access traditional healing for protection prayers and ceremonies. Some of the tribal and IHS programs provide traditional counselors to talk to. The Navajo access healing that focuses on restoring balance to the body, mind, and spirit.

Taking action against the virus by social distancing, hand washing, and wearing masks can go a long way in reducing anxiety and fear about getting the virus. Resources to help the Navajo Nation are coming from all over the world, from as far as Ireland,⁹ Doctors Without Borders, ¹⁰ and University of San Francisco.¹¹

Two resources that provide relief on the reservation are the Navajo Relief Fund and United Natives.
 

References

1. Navaho Times. 2020 May 27.

2. Ingalls A et al. BMC Obes. 2019 May 6. doi: 10.1186/s40608-019-0233-9.

3. U.S. Census 2010, as reported by discovernavajo.com.

4. Gould C et al. “Addressing food insecurity on the Navajo reservation through sustainable greenhouses.” 2018 Aug.

5. Native Knowledge 360. Smithsonian Institution. “Bosque Redondo.”

6. Personal communication, Carl Roessel Slater, Navajo Nation Council delegate.

7. IHS Profile Fact Sheet.

8. Wu X et al. medRxiv. 2020 Apr 27.

9. Carroll R. ”Irish support for Native American COVID-19 relief highlights historic bond.” The Guardian. 2020 May 9.

10. Capatides C. “Doctors Without Borders dispatches team to the Navajo Nation” CBS News. 2020 May 11.

11. Weiler N. “UCSF sends second wave of health workers to Navajo Nation.” UCSF.edu. 2020 May 21.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo Nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association. She has no disclosures.

The Navajo people have dealt with adversity that has tested our strength and resilience since our creation. In Navajo culture, the Holy People or gods challenged us with Naayee (monsters). We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language) is a monster confronting the Navajo today. It has had significant impact on our nation and people.

The Navajo have the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths.¹ The Navajo Nation, which once lagged behind New York, has reported the largest per-capita infection rate in the United States.

These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average numbers of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%.²

Geographical and cultural factors also contribute to the inability to gain a foothold in mitigating the number of cases. The Navajo Nation is the largest tribe in the United States, covering 27,000 square miles over an arid, red rock expanse with canyons and mountains. The population is over 250,000,³ and Navajo have traditionally lived in matrilineal clan units throughout the reservation, the size of West Virginia. The family traditional dwelling, called a “hogan,” often is clustered together. Multiple generations live together in these units. The COVID-19 virus inflicted many Navajo and rapidly spread to the elderly in these close-proximity living quarters.

Most Navajo live away from services and grocery stores and travel back and forth for food and water, which contributes to the virus rapidly being transmitted among the community members. Education aimed at curbing travel and spread of the virus was issued with curfews, commands to stay at home and keep social distance, and protect elders. The Navajo leadership and traditional medicine people, meanwhile, advised the people to follow their cultural values by caring for family and community members and providing a safe environment.
 

Resources are spread out

There are only 13 stores in this expansive reservation,⁴ so tribal members rely on traveling to border towns, such as Farmington and Gallup, N.M., Families usually travel to these towns on weekends to replenish food and supplies. There has been a cluster of cases in Gallup, N.M., so to reduce the numbers, the town shut itself off from outsiders – including the Navajo people coming to buy food, do laundry, and get water and feed for livestock. This has affected and stressed the Navajo further in attempting to access necessities.

Access to health care is already challenging because of lack of transportation and distance. This has made it more difficult to access COVID-19 testing and more challenging to get the results back. The Indian Health Service has been the designated health care system for the Navajo since 1955. The Treaty of Bosque Redondo, signed by the Navajo in 1868, included the provision of health care, as well as education in exchange for tracts of land, that included the Navajo homeland or Dinetah.⁵

The Indian Health Service provides care with hospitals and clinics throughout the reservation. Some of the IHS facilities have been taken over by the Navajo, so there are four Navajo tribally controlled hospitals, along with one private hospital. Coordination of care for a pandemic is, therefore, more challenging to coordinate. This contributes to problems with coordination of the health care, establishing alternate care sites, accessing personal protective equipment, and providing testing sites. The Navajo Nation Council is working hard to equitably distribute the $600 million from the CARES Act.⁶

Dealing with the pandemic is compromised by chronic underfunding from the U.S. government. The treaty obligation of the U.S. government is to provide health care to all federally recognized Native Americans. The IHS, which has been designated to provide that care for a tribal person, gets one-third the Medicare dollars for health care provided for a person in the general population.⁷ Health factors have led to the public health issues of poorly controlled diabetes, obesity, and coronary artery disease, which is related to this underfunding and the high rate of COVID-19 cases. Parts of the reservation are also exposed to high levels of pollution from oil and gas wells from the coal-fueled power plants. Those exposed to these high levels of pollutions have a higher than average number of cases of COVID-19, higher than in areas where the pollution is markedly lower.⁸

The Navajo are having to rely on the strength and resilience of traditional Navajo culture and philosophy to confront this monster, Dikos Nitsaa’igii’ 19. We have relied on Western medicine and its limited resources but now need to empower the strength from our traditional ways of knowing. We have used this knowledge in times of adversity for hundreds of years. The Navajo elders and medicine people have reminded us we have dealt with monsters and know how to endure hardship and be resilient. This helps to ameliorate mental health conditions, but there are still issues that remain challenging.

Those having the virus go through times of shortness of breath, which produces anxiety and panic. The risk of death adds further stress, and for a family-oriented culture, the need to isolate from family adds further stress. For the elderly and young people with more serious disease having to go to the hospital alone without family, often far from home, is so challenging. Connecting family by phone or social media with those stricken is essential to decrease anxiety and isolation. Those infected with the virus can learn breathing exercises, which can help the damage from the virus and decrease emotional activation and triggers. Specific breathing techniques can be taught by medical providers. An effective breathing technique to reduce anxiety is coherent breathing, which is done by inhaling 6 seconds and exhaling for 6 seconds without holding your breath. Behavioral health practitioners are available in the tribal and IHS mental health clinics to refer patients to therapy support to manage anxiety and are available by telemedicine. Many of these programs are offering social media informational sessions for the Navajo community. Navajo people often access traditional healing for protection prayers and ceremonies. Some of the tribal and IHS programs provide traditional counselors to talk to. The Navajo access healing that focuses on restoring balance to the body, mind, and spirit.

Taking action against the virus by social distancing, hand washing, and wearing masks can go a long way in reducing anxiety and fear about getting the virus. Resources to help the Navajo Nation are coming from all over the world, from as far as Ireland,⁹ Doctors Without Borders, ¹⁰ and University of San Francisco.¹¹

Two resources that provide relief on the reservation are the Navajo Relief Fund and United Natives.
 

References

1. Navaho Times. 2020 May 27.

2. Ingalls A et al. BMC Obes. 2019 May 6. doi: 10.1186/s40608-019-0233-9.

3. U.S. Census 2010, as reported by discovernavajo.com.

4. Gould C et al. “Addressing food insecurity on the Navajo reservation through sustainable greenhouses.” 2018 Aug.

5. Native Knowledge 360. Smithsonian Institution. “Bosque Redondo.”

6. Personal communication, Carl Roessel Slater, Navajo Nation Council delegate.

7. IHS Profile Fact Sheet.

8. Wu X et al. medRxiv. 2020 Apr 27.

9. Carroll R. ”Irish support for Native American COVID-19 relief highlights historic bond.” The Guardian. 2020 May 9.

10. Capatides C. “Doctors Without Borders dispatches team to the Navajo Nation” CBS News. 2020 May 11.

11. Weiler N. “UCSF sends second wave of health workers to Navajo Nation.” UCSF.edu. 2020 May 21.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo Nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association. She has no disclosures.

The Navajo people have dealt with adversity that has tested our strength and resilience since our creation. In Navajo culture, the Holy People or gods challenged us with Naayee (monsters). We endured and learned from each Naayee, hunger, and death to name a few adversities. The COVID-19 pandemic, or “Big Cough” (Dikos Nitsaa’igii -19 in Navajo language) is a monster confronting the Navajo today. It has had significant impact on our nation and people.

The Navajo have the most cases of the COVID-19 virus of any tribe in the United States, and numbers as of May 31, 2020, are 5,348, with 246 confirmed deaths.¹ The Navajo Nation, which once lagged behind New York, has reported the largest per-capita infection rate in the United States.

These devastating numbers, which might be leveling off, are associated with Navajo people having higher-than-average numbers of diabetes, heart disease, and cancer. This is compounded with 30%-40% of homes having no electricity or running water, and a poverty rate of about 38%.²

Geographical and cultural factors also contribute to the inability to gain a foothold in mitigating the number of cases. The Navajo Nation is the largest tribe in the United States, covering 27,000 square miles over an arid, red rock expanse with canyons and mountains. The population is over 250,000,³ and Navajo have traditionally lived in matrilineal clan units throughout the reservation, the size of West Virginia. The family traditional dwelling, called a “hogan,” often is clustered together. Multiple generations live together in these units. The COVID-19 virus inflicted many Navajo and rapidly spread to the elderly in these close-proximity living quarters.

Most Navajo live away from services and grocery stores and travel back and forth for food and water, which contributes to the virus rapidly being transmitted among the community members. Education aimed at curbing travel and spread of the virus was issued with curfews, commands to stay at home and keep social distance, and protect elders. The Navajo leadership and traditional medicine people, meanwhile, advised the people to follow their cultural values by caring for family and community members and providing a safe environment.
 

Resources are spread out

There are only 13 stores in this expansive reservation,⁴ so tribal members rely on traveling to border towns, such as Farmington and Gallup, N.M., Families usually travel to these towns on weekends to replenish food and supplies. There has been a cluster of cases in Gallup, N.M., so to reduce the numbers, the town shut itself off from outsiders – including the Navajo people coming to buy food, do laundry, and get water and feed for livestock. This has affected and stressed the Navajo further in attempting to access necessities.

Access to health care is already challenging because of lack of transportation and distance. This has made it more difficult to access COVID-19 testing and more challenging to get the results back. The Indian Health Service has been the designated health care system for the Navajo since 1955. The Treaty of Bosque Redondo, signed by the Navajo in 1868, included the provision of health care, as well as education in exchange for tracts of land, that included the Navajo homeland or Dinetah.⁵

The Indian Health Service provides care with hospitals and clinics throughout the reservation. Some of the IHS facilities have been taken over by the Navajo, so there are four Navajo tribally controlled hospitals, along with one private hospital. Coordination of care for a pandemic is, therefore, more challenging to coordinate. This contributes to problems with coordination of the health care, establishing alternate care sites, accessing personal protective equipment, and providing testing sites. The Navajo Nation Council is working hard to equitably distribute the $600 million from the CARES Act.⁶

Dealing with the pandemic is compromised by chronic underfunding from the U.S. government. The treaty obligation of the U.S. government is to provide health care to all federally recognized Native Americans. The IHS, which has been designated to provide that care for a tribal person, gets one-third the Medicare dollars for health care provided for a person in the general population.⁷ Health factors have led to the public health issues of poorly controlled diabetes, obesity, and coronary artery disease, which is related to this underfunding and the high rate of COVID-19 cases. Parts of the reservation are also exposed to high levels of pollution from oil and gas wells from the coal-fueled power plants. Those exposed to these high levels of pollutions have a higher than average number of cases of COVID-19, higher than in areas where the pollution is markedly lower.⁸

The Navajo are having to rely on the strength and resilience of traditional Navajo culture and philosophy to confront this monster, Dikos Nitsaa’igii’ 19. We have relied on Western medicine and its limited resources but now need to empower the strength from our traditional ways of knowing. We have used this knowledge in times of adversity for hundreds of years. The Navajo elders and medicine people have reminded us we have dealt with monsters and know how to endure hardship and be resilient. This helps to ameliorate mental health conditions, but there are still issues that remain challenging.

Those having the virus go through times of shortness of breath, which produces anxiety and panic. The risk of death adds further stress, and for a family-oriented culture, the need to isolate from family adds further stress. For the elderly and young people with more serious disease having to go to the hospital alone without family, often far from home, is so challenging. Connecting family by phone or social media with those stricken is essential to decrease anxiety and isolation. Those infected with the virus can learn breathing exercises, which can help the damage from the virus and decrease emotional activation and triggers. Specific breathing techniques can be taught by medical providers. An effective breathing technique to reduce anxiety is coherent breathing, which is done by inhaling 6 seconds and exhaling for 6 seconds without holding your breath. Behavioral health practitioners are available in the tribal and IHS mental health clinics to refer patients to therapy support to manage anxiety and are available by telemedicine. Many of these programs are offering social media informational sessions for the Navajo community. Navajo people often access traditional healing for protection prayers and ceremonies. Some of the tribal and IHS programs provide traditional counselors to talk to. The Navajo access healing that focuses on restoring balance to the body, mind, and spirit.

Taking action against the virus by social distancing, hand washing, and wearing masks can go a long way in reducing anxiety and fear about getting the virus. Resources to help the Navajo Nation are coming from all over the world, from as far as Ireland,⁹ Doctors Without Borders, ¹⁰ and University of San Francisco.¹¹

Two resources that provide relief on the reservation are the Navajo Relief Fund and United Natives.
 

References

1. Navaho Times. 2020 May 27.

2. Ingalls A et al. BMC Obes. 2019 May 6. doi: 10.1186/s40608-019-0233-9.

3. U.S. Census 2010, as reported by discovernavajo.com.

4. Gould C et al. “Addressing food insecurity on the Navajo reservation through sustainable greenhouses.” 2018 Aug.

5. Native Knowledge 360. Smithsonian Institution. “Bosque Redondo.”

6. Personal communication, Carl Roessel Slater, Navajo Nation Council delegate.

7. IHS Profile Fact Sheet.

8. Wu X et al. medRxiv. 2020 Apr 27.

9. Carroll R. ”Irish support for Native American COVID-19 relief highlights historic bond.” The Guardian. 2020 May 9.

10. Capatides C. “Doctors Without Borders dispatches team to the Navajo Nation” CBS News. 2020 May 11.

11. Weiler N. “UCSF sends second wave of health workers to Navajo Nation.” UCSF.edu. 2020 May 21.
 

Dr. Roessel is a Navajo board-certified psychiatrist practicing in Santa Fe, N.M., working with the local indigenous population. She has special expertise in cultural psychiatry; her childhood was spent growing up in the Navajo Nation with her grandfather, who was a Navajo medicine man. Her psychiatric practice focuses on integrating indigenous knowledge and principles. Dr. Roessel is a distinguished fellow of the American Psychiatric Association. She has no disclosures.

Read Now.

As the United States population becomes increasingly diverse, the population of Americans living with neurological diseases such as multiple sclerosis (MS) will have more varied needs and greater health care inequities that may drive poorer outcomes.

In this supplement to Federal Practitioner, Victor M. Rivera, MD, FAAN, Mitzi Joi Williams, MD, and Patricia Pagnotta, ARNP-C, MSN, CNRN, MSCN discuss MS in minority populations such as African Americans, Hispanic Americans, and the military-veteran population. Topics include population-specific risk factors, disparities in clinical trial participation, and recommendations for improved MS management.

This supplement is sponsored by Biogen.

Read Now.

Read Now.

As the United States population becomes increasingly diverse, the population of Americans living with neurological diseases such as multiple sclerosis (MS) will have more varied needs and greater health care inequities that may drive poorer outcomes.

In this supplement to Federal Practitioner, Victor M. Rivera, MD, FAAN, Mitzi Joi Williams, MD, and Patricia Pagnotta, ARNP-C, MSN, CNRN, MSCN discuss MS in minority populations such as African Americans, Hispanic Americans, and the military-veteran population. Topics include population-specific risk factors, disparities in clinical trial participation, and recommendations for improved MS management.

This supplement is sponsored by Biogen.

Read Now.

Read Now.

As the United States population becomes increasingly diverse, the population of Americans living with neurological diseases such as multiple sclerosis (MS) will have more varied needs and greater health care inequities that may drive poorer outcomes.

In this supplement to Federal Practitioner, Victor M. Rivera, MD, FAAN, Mitzi Joi Williams, MD, and Patricia Pagnotta, ARNP-C, MSN, CNRN, MSCN discuss MS in minority populations such as African Americans, Hispanic Americans, and the military-veteran population. Topics include population-specific risk factors, disparities in clinical trial participation, and recommendations for improved MS management.

This supplement is sponsored by Biogen.

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Almost 80% of epilepsy deaths among adults are potentially avoidable, results of a new study from Scotland suggest. The research shows that such avoidable deaths “remain common and have not declined over time, despite advances in treatment,” Gashirai Mbizvo, MBChB, PhD, clinical research fellow, Muir Maxwell Epilepsy Center, the University of Edinburgh, Scotland, told a press briefing.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which is being conducted as a virtual/online meeting because of the COVID-19 pandemic.

As his PhD dissertation, Dr. Mbizvo is investigating the rates, causes, and risk factors for epilepsy-related deaths and the percentage of these that are potentially avoidable.

The National Health Service of Scotland contains various linked administrative data sets. Each resident of Scotland has a unique identifier that facilitates investigations across the health system.

Dr. Mbizvo investigated adults and adolescents aged 16 years and older who died because of epilepsy during 2009-2016. He compared this group to patients of similar age who were living with epilepsy to identify risk factors that might help focus resources. During the study period, 2,149 epilepsy-related deaths occurred. Nearly 60% involved at least one seizure-related hospital admission.
 

Heavy burden

Of the patients who died because of epilepsy, 24% were seen in an outpatient neurologic clinic. “So there’s this heavy burden of admissions not translating to neurology follow-up,” said Dr. Mbizvo.

During the study period, there was no reduction in mortality “despite advances in medical care,” said Dr. Mbizvo.

Younger people with epilepsy were found to be more likely to die. The standardized mortality rate was 6/100,000 (95% confidence interval, 2.3-9.7) among those aged 16-24 years. By contrast, among those aged 45-54 years, the rate was 2/100,000 (95% CI, 1.1-2.1); it was lower in older age groups.

“The overall mortality is not reducing; people are dying young, and neurologists are really not getting involved,” Dr. Mbizvo said.

Among the almost 600 deaths of those aged 16-54 years, 58% were from Scotland’s “most deprived areas,” he noted.

From medical records and antiepileptic drug (AED) use, Dr. Mbizvo looked for risk factors that may have contributed to these epilepsy-related deaths. The most common cause of death in the group aged 16- 54 years was sudden unexpected death in epilepsy (SUDEP), followed by respiratory disorders, such as aspiration pneumonia.

“We think this should be avoidable, in the sense that these are people that could perhaps be targeted early with, for example, antibiotics,” said Dr. Mbizvo.

The next most common cause of death was circulatory disease, largely cardiac arrest.

“The idea is that electroexcitation – an abnormality in the brain – and the heart are related, and maybe that’s translating to a risk of death,” said Dr. Mbizvo.
 

Worrisome group

Mental and behavioral disorders, largely alcohol related, were the next most common cause of death.

“This is a group I worry about,” said Dr. Mbizvo. “I think they’re seen in the acute services and discharged as alcohol-withdrawal seizures. It’s possible that some have epilepsy and are never referred to a neurologist, and this may translate into increased mortality.”

Dr. Mbizvo is analyzing how these results differ from what is seen in the general population of Scotland among those younger than 75 years.

The top cause of death in the general population is neoplasm of the lungs. Aspiration of the lung is near the top for those who died from epilepsy, but the mechanisms leading to lung-related deaths in these populations may differ, said Dr. Mbizvo.

By applying coding methodology from fields unrelated to epilepsy where this approach has been tried, he determined that 78% of epilepsy-related deaths among those younger than 55 years were potentially avoidable.

“As a method, this is still in its infancy and will require validation, but we see this as a start,” Dr. Mbizvo said.

He provided examples from medical records that illustrate avoidable factors that could contribute to death. These included cases in which patients were discharged with the wrong dose of AED and in which patients drowned in a bath after having not been appropriately educated about seizure safety.
 

Can’t plug in

Patients with a first seizure are typically referred quickly to an appropriate service, but Dr. Mbizvo is concerned about those with chronic, stable epilepsy. “These people may at some point decompensate, and there’s no channel to plug them back into neurology services to make it easy for them to access a neurologist,” he said.

Currently, experts tell discharged patients to call if a problem occurs, but the system “is rather ad hoc,” said Dr. Mbizvo.

Because of the COVID-19 crisis, the use of telemedicine is increasing. This is helping to improve the system. “We may be able to build a virtual community for people who are on antiepileptic drugs and who suddenly begin to experience seizures again, to enable them to quickly get help, alongside a defined pathway to an epilepsy specialist,” said Dr. Mbizvo.

He hopes to develop a risk index for epilepsy patients similar to one used in cardiology that assesses risks such as smoking, high cholesterol level, and obesity. Although such a risk score might be similar to the SUDEP risk indices being developed, it will take into account death from any epilepsy-related cause, said Dr. Mbizvo. “Having not yet completed the analysis, I’m not sure which aspects will confer the greatest risk,” he said.

He added that, anecdotally, he has noticed a slight trend toward high mortality among patients with epilepsy who present multiple times at emergency departments in a year.

If this trend is statistically valid, “it could help create a traffic light flagging system on A&Es [accident and emergency departments] in which individuals with epilepsy who, for example, have two or more attendances to A&E in a year become flagged as high risk of death and are plugged into a rapid access epilepsy specialist clinic,” he said.

For their part, neurologists should recognize drug-resistant epilepsy early and refer such patients for assessment for resective surgery. If successful, such surgery reduces the risk for premature mortality, said Dr. Mbizvo.

Patients should not become discouraged by drug resistance, either. Research shows that, with careful reassessment of epilepsy type and drug changes, some patients whose condition is thought to be intractable could experience significant improvement in seizure frequency or seizures could be stopped.

“We need to talk to our patients more about the importance of adherence and encourage them to be honest with us if they don’t like the drugs we’re giving them and, as a result, are not taking them as recommended,” Dr. Mbizvo said.

Physicians also need to screen for mood disorders, especially suicidal ideation. Increasingly, specialists are recognizing mental health as an important area of epilepsy care.

They should also conduct a “safety briefing” perhaps twice a year in which they discuss, for example, SUDEP risk, driving concerns, showering instead of bathing, ensuring that a life guard is present at a swimming pool, and other measures.

Commenting on the study, Josemir W. (Ley) Sander, MD, PhD, professor of neurology and clinical epilepsy at University College London, said he welcomes any effort that highlights the problem of premature death among people with epilepsy and that offers possible ways to mitigate it.

Although the study “shows that premature death among people with epilepsy is a major issue,” many health care providers are not fully aware of the extent of this problem, said Dr. Sander. “For many, epilepsy is just a benign condition in which people have seizures,” he said. A risk score that could identify those at high risk for death and establishing preventive measures “would go a long way to decrease the burden of epilepsy,” he noted.

The study was supported by Epilepsy Research UK and the Juliet Bergqvist Memorial Fund. Dr. Mbizvo and Dr. Sander have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Almost 80% of epilepsy deaths among adults are potentially avoidable, results of a new study from Scotland suggest. The research shows that such avoidable deaths “remain common and have not declined over time, despite advances in treatment,” Gashirai Mbizvo, MBChB, PhD, clinical research fellow, Muir Maxwell Epilepsy Center, the University of Edinburgh, Scotland, told a press briefing.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which is being conducted as a virtual/online meeting because of the COVID-19 pandemic.

As his PhD dissertation, Dr. Mbizvo is investigating the rates, causes, and risk factors for epilepsy-related deaths and the percentage of these that are potentially avoidable.

The National Health Service of Scotland contains various linked administrative data sets. Each resident of Scotland has a unique identifier that facilitates investigations across the health system.

Dr. Mbizvo investigated adults and adolescents aged 16 years and older who died because of epilepsy during 2009-2016. He compared this group to patients of similar age who were living with epilepsy to identify risk factors that might help focus resources. During the study period, 2,149 epilepsy-related deaths occurred. Nearly 60% involved at least one seizure-related hospital admission.
 

Heavy burden

Of the patients who died because of epilepsy, 24% were seen in an outpatient neurologic clinic. “So there’s this heavy burden of admissions not translating to neurology follow-up,” said Dr. Mbizvo.

During the study period, there was no reduction in mortality “despite advances in medical care,” said Dr. Mbizvo.

Younger people with epilepsy were found to be more likely to die. The standardized mortality rate was 6/100,000 (95% confidence interval, 2.3-9.7) among those aged 16-24 years. By contrast, among those aged 45-54 years, the rate was 2/100,000 (95% CI, 1.1-2.1); it was lower in older age groups.

“The overall mortality is not reducing; people are dying young, and neurologists are really not getting involved,” Dr. Mbizvo said.

Among the almost 600 deaths of those aged 16-54 years, 58% were from Scotland’s “most deprived areas,” he noted.

From medical records and antiepileptic drug (AED) use, Dr. Mbizvo looked for risk factors that may have contributed to these epilepsy-related deaths. The most common cause of death in the group aged 16- 54 years was sudden unexpected death in epilepsy (SUDEP), followed by respiratory disorders, such as aspiration pneumonia.

“We think this should be avoidable, in the sense that these are people that could perhaps be targeted early with, for example, antibiotics,” said Dr. Mbizvo.

The next most common cause of death was circulatory disease, largely cardiac arrest.

“The idea is that electroexcitation – an abnormality in the brain – and the heart are related, and maybe that’s translating to a risk of death,” said Dr. Mbizvo.
 

Worrisome group

Mental and behavioral disorders, largely alcohol related, were the next most common cause of death.

“This is a group I worry about,” said Dr. Mbizvo. “I think they’re seen in the acute services and discharged as alcohol-withdrawal seizures. It’s possible that some have epilepsy and are never referred to a neurologist, and this may translate into increased mortality.”

Dr. Mbizvo is analyzing how these results differ from what is seen in the general population of Scotland among those younger than 75 years.

The top cause of death in the general population is neoplasm of the lungs. Aspiration of the lung is near the top for those who died from epilepsy, but the mechanisms leading to lung-related deaths in these populations may differ, said Dr. Mbizvo.

By applying coding methodology from fields unrelated to epilepsy where this approach has been tried, he determined that 78% of epilepsy-related deaths among those younger than 55 years were potentially avoidable.

“As a method, this is still in its infancy and will require validation, but we see this as a start,” Dr. Mbizvo said.

He provided examples from medical records that illustrate avoidable factors that could contribute to death. These included cases in which patients were discharged with the wrong dose of AED and in which patients drowned in a bath after having not been appropriately educated about seizure safety.
 

Can’t plug in

Patients with a first seizure are typically referred quickly to an appropriate service, but Dr. Mbizvo is concerned about those with chronic, stable epilepsy. “These people may at some point decompensate, and there’s no channel to plug them back into neurology services to make it easy for them to access a neurologist,” he said.

Currently, experts tell discharged patients to call if a problem occurs, but the system “is rather ad hoc,” said Dr. Mbizvo.

Because of the COVID-19 crisis, the use of telemedicine is increasing. This is helping to improve the system. “We may be able to build a virtual community for people who are on antiepileptic drugs and who suddenly begin to experience seizures again, to enable them to quickly get help, alongside a defined pathway to an epilepsy specialist,” said Dr. Mbizvo.

He hopes to develop a risk index for epilepsy patients similar to one used in cardiology that assesses risks such as smoking, high cholesterol level, and obesity. Although such a risk score might be similar to the SUDEP risk indices being developed, it will take into account death from any epilepsy-related cause, said Dr. Mbizvo. “Having not yet completed the analysis, I’m not sure which aspects will confer the greatest risk,” he said.

He added that, anecdotally, he has noticed a slight trend toward high mortality among patients with epilepsy who present multiple times at emergency departments in a year.

If this trend is statistically valid, “it could help create a traffic light flagging system on A&Es [accident and emergency departments] in which individuals with epilepsy who, for example, have two or more attendances to A&E in a year become flagged as high risk of death and are plugged into a rapid access epilepsy specialist clinic,” he said.

For their part, neurologists should recognize drug-resistant epilepsy early and refer such patients for assessment for resective surgery. If successful, such surgery reduces the risk for premature mortality, said Dr. Mbizvo.

Patients should not become discouraged by drug resistance, either. Research shows that, with careful reassessment of epilepsy type and drug changes, some patients whose condition is thought to be intractable could experience significant improvement in seizure frequency or seizures could be stopped.

“We need to talk to our patients more about the importance of adherence and encourage them to be honest with us if they don’t like the drugs we’re giving them and, as a result, are not taking them as recommended,” Dr. Mbizvo said.

Physicians also need to screen for mood disorders, especially suicidal ideation. Increasingly, specialists are recognizing mental health as an important area of epilepsy care.

They should also conduct a “safety briefing” perhaps twice a year in which they discuss, for example, SUDEP risk, driving concerns, showering instead of bathing, ensuring that a life guard is present at a swimming pool, and other measures.

Commenting on the study, Josemir W. (Ley) Sander, MD, PhD, professor of neurology and clinical epilepsy at University College London, said he welcomes any effort that highlights the problem of premature death among people with epilepsy and that offers possible ways to mitigate it.

Although the study “shows that premature death among people with epilepsy is a major issue,” many health care providers are not fully aware of the extent of this problem, said Dr. Sander. “For many, epilepsy is just a benign condition in which people have seizures,” he said. A risk score that could identify those at high risk for death and establishing preventive measures “would go a long way to decrease the burden of epilepsy,” he noted.

The study was supported by Epilepsy Research UK and the Juliet Bergqvist Memorial Fund. Dr. Mbizvo and Dr. Sander have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Almost 80% of epilepsy deaths among adults are potentially avoidable, results of a new study from Scotland suggest. The research shows that such avoidable deaths “remain common and have not declined over time, despite advances in treatment,” Gashirai Mbizvo, MBChB, PhD, clinical research fellow, Muir Maxwell Epilepsy Center, the University of Edinburgh, Scotland, told a press briefing.

The findings were presented at the Congress of the European Academy of Neurology (EAN) 2020, which is being conducted as a virtual/online meeting because of the COVID-19 pandemic.

As his PhD dissertation, Dr. Mbizvo is investigating the rates, causes, and risk factors for epilepsy-related deaths and the percentage of these that are potentially avoidable.

The National Health Service of Scotland contains various linked administrative data sets. Each resident of Scotland has a unique identifier that facilitates investigations across the health system.

Dr. Mbizvo investigated adults and adolescents aged 16 years and older who died because of epilepsy during 2009-2016. He compared this group to patients of similar age who were living with epilepsy to identify risk factors that might help focus resources. During the study period, 2,149 epilepsy-related deaths occurred. Nearly 60% involved at least one seizure-related hospital admission.
 

Heavy burden

Of the patients who died because of epilepsy, 24% were seen in an outpatient neurologic clinic. “So there’s this heavy burden of admissions not translating to neurology follow-up,” said Dr. Mbizvo.

During the study period, there was no reduction in mortality “despite advances in medical care,” said Dr. Mbizvo.

Younger people with epilepsy were found to be more likely to die. The standardized mortality rate was 6/100,000 (95% confidence interval, 2.3-9.7) among those aged 16-24 years. By contrast, among those aged 45-54 years, the rate was 2/100,000 (95% CI, 1.1-2.1); it was lower in older age groups.

“The overall mortality is not reducing; people are dying young, and neurologists are really not getting involved,” Dr. Mbizvo said.

Among the almost 600 deaths of those aged 16-54 years, 58% were from Scotland’s “most deprived areas,” he noted.

From medical records and antiepileptic drug (AED) use, Dr. Mbizvo looked for risk factors that may have contributed to these epilepsy-related deaths. The most common cause of death in the group aged 16- 54 years was sudden unexpected death in epilepsy (SUDEP), followed by respiratory disorders, such as aspiration pneumonia.

“We think this should be avoidable, in the sense that these are people that could perhaps be targeted early with, for example, antibiotics,” said Dr. Mbizvo.

The next most common cause of death was circulatory disease, largely cardiac arrest.

“The idea is that electroexcitation – an abnormality in the brain – and the heart are related, and maybe that’s translating to a risk of death,” said Dr. Mbizvo.
 

Worrisome group

Mental and behavioral disorders, largely alcohol related, were the next most common cause of death.

“This is a group I worry about,” said Dr. Mbizvo. “I think they’re seen in the acute services and discharged as alcohol-withdrawal seizures. It’s possible that some have epilepsy and are never referred to a neurologist, and this may translate into increased mortality.”

Dr. Mbizvo is analyzing how these results differ from what is seen in the general population of Scotland among those younger than 75 years.

The top cause of death in the general population is neoplasm of the lungs. Aspiration of the lung is near the top for those who died from epilepsy, but the mechanisms leading to lung-related deaths in these populations may differ, said Dr. Mbizvo.

By applying coding methodology from fields unrelated to epilepsy where this approach has been tried, he determined that 78% of epilepsy-related deaths among those younger than 55 years were potentially avoidable.

“As a method, this is still in its infancy and will require validation, but we see this as a start,” Dr. Mbizvo said.

He provided examples from medical records that illustrate avoidable factors that could contribute to death. These included cases in which patients were discharged with the wrong dose of AED and in which patients drowned in a bath after having not been appropriately educated about seizure safety.
 

Can’t plug in

Patients with a first seizure are typically referred quickly to an appropriate service, but Dr. Mbizvo is concerned about those with chronic, stable epilepsy. “These people may at some point decompensate, and there’s no channel to plug them back into neurology services to make it easy for them to access a neurologist,” he said.

Currently, experts tell discharged patients to call if a problem occurs, but the system “is rather ad hoc,” said Dr. Mbizvo.

Because of the COVID-19 crisis, the use of telemedicine is increasing. This is helping to improve the system. “We may be able to build a virtual community for people who are on antiepileptic drugs and who suddenly begin to experience seizures again, to enable them to quickly get help, alongside a defined pathway to an epilepsy specialist,” said Dr. Mbizvo.

He hopes to develop a risk index for epilepsy patients similar to one used in cardiology that assesses risks such as smoking, high cholesterol level, and obesity. Although such a risk score might be similar to the SUDEP risk indices being developed, it will take into account death from any epilepsy-related cause, said Dr. Mbizvo. “Having not yet completed the analysis, I’m not sure which aspects will confer the greatest risk,” he said.

He added that, anecdotally, he has noticed a slight trend toward high mortality among patients with epilepsy who present multiple times at emergency departments in a year.

If this trend is statistically valid, “it could help create a traffic light flagging system on A&Es [accident and emergency departments] in which individuals with epilepsy who, for example, have two or more attendances to A&E in a year become flagged as high risk of death and are plugged into a rapid access epilepsy specialist clinic,” he said.

For their part, neurologists should recognize drug-resistant epilepsy early and refer such patients for assessment for resective surgery. If successful, such surgery reduces the risk for premature mortality, said Dr. Mbizvo.

Patients should not become discouraged by drug resistance, either. Research shows that, with careful reassessment of epilepsy type and drug changes, some patients whose condition is thought to be intractable could experience significant improvement in seizure frequency or seizures could be stopped.

“We need to talk to our patients more about the importance of adherence and encourage them to be honest with us if they don’t like the drugs we’re giving them and, as a result, are not taking them as recommended,” Dr. Mbizvo said.

Physicians also need to screen for mood disorders, especially suicidal ideation. Increasingly, specialists are recognizing mental health as an important area of epilepsy care.

They should also conduct a “safety briefing” perhaps twice a year in which they discuss, for example, SUDEP risk, driving concerns, showering instead of bathing, ensuring that a life guard is present at a swimming pool, and other measures.

Commenting on the study, Josemir W. (Ley) Sander, MD, PhD, professor of neurology and clinical epilepsy at University College London, said he welcomes any effort that highlights the problem of premature death among people with epilepsy and that offers possible ways to mitigate it.

Although the study “shows that premature death among people with epilepsy is a major issue,” many health care providers are not fully aware of the extent of this problem, said Dr. Sander. “For many, epilepsy is just a benign condition in which people have seizures,” he said. A risk score that could identify those at high risk for death and establishing preventive measures “would go a long way to decrease the burden of epilepsy,” he noted.

The study was supported by Epilepsy Research UK and the Juliet Bergqvist Memorial Fund. Dr. Mbizvo and Dr. Sander have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.