Despite standard blood monitoring and routine imaging, patients with colorectal cancer (CRC) tend to have multiple, incurable metastases when relapse occurs.

A new study indicates that postsurgical circulating tumor DNA (ctDNA) testing may improve our ability to predict relapse in patients with stage I-III CRC.

ctDNA testing outperformed carcinoembryonic antigen (CEA) testing in predicting relapse-free survival, and ctDNA was detected about 8 months prior to relapse detection via CT.

Tenna V. Henriksen, of Aarhus University in Denmark, presented these results at the 2021 Gastrointestinal Cancers Symposium (abstract 11).

The multi-institutional study included 260 patients with CRC – 4 with stage I disease, 90 with stage II, and 166 with stage III disease.

Patients were monitored with plasma ctDNA testing within 2 months of primary surgery. Some patients were monitored with follow-up ctDNA sampling every 3 months for an additional 3 years.

Individual tumors and matched germline DNA were interrogated with whole-exome sequencing, and somatic single nucleotide variants were identified. Personalized multiplex PCR assays were developed to track tumor-specific single nucleotide variants via the Signatera® ctDNA assay.

The researchers retrospectively assessed ctDNA’s performance in:

• Stratifying the postoperative risk of relapse.
• Quantifying the benefit of adjuvant chemotherapy in patients who had or did not have ctDNA in plasma.
• Efficiently detecting relapse, in comparison with standard surveillance tests.

Surveillance CT scans were performed at 12 and 36 months but not at the frequency recommended in NCCN guidelines.

In all, 165 patients received adjuvant chemotherapy. The decision to give chemotherapy was made on a clinical basis by treating physicians who were blinded to the results of ctDNA testing.
 

Results

Of the 260 patients analyzed, 48 relapsed. The median follow-up was 28.4 months overall and 29.9 months in the nonrelapse cases.

The researchers assessed postoperative ctDNA status prior to adjuvant chemotherapy in 218 patients and after adjuvant chemotherapy in 108 patients.

In the prechemotherapy group, 20 patients were ctDNA positive, and 80% of them relapsed. In contrast, 13% of the 198 ctDNA-negative patients relapsed. The hazard ratio (HR) for relapse-free survival was 11 (95% confidence interval, 5.9-21; P < .0001).

After adjuvant chemotherapy, 12.5% of the ctDNA-negative patients relapsed, compared with 83.3% of the ctDNA-positive patients. The HR for relapse-free survival was 12 (95% CI, 4.9-27; P < .0001).

Results from longitudinal ctDNA testing in 202 patients suggested that serial sampling is more useful than sampling at a single point in time. The recurrence rate was 3.4% among patients who remained persistently ctDNA negative, compared with 89.3% in patients who were ctDNA positive. The HR for relapse-free survival was 51 (95% CI, 20-125; P < .0001).

In a subgroup of 29 patients with clinical recurrence detected by CT imaging, ctDNA detection occurred a median of 8.1 months earlier than radiologic relapse.

Among the 197 patients who had serial CEA and ctDNA measurements, longitudinal CEA testing correlated with relapse-free survival (HR, 4.9; 95% CI, 3.2-15, P < .0001) but not nearly as well as ctDNA testing (HR, 95.7; 95% CI, 28-322, P < .0001) in a univariable analysis.

In a multivariable analysis, the HR for relapse-free survival was 1.8 (95% CI, 0.77-4.0; P = .184) for longitudinal CEA and 80.55 (95% CI, 23.1-281; P < .0001) for longitudinal ctDNA.

“[W]hen we pit them against each other in a multivariable analysis, we can see that all the predictive power is in the ctDNA samples,” Ms. Henriksen said. “This indicates that ctDNA is a stronger biomarker compared to CEA, at least with relapse-free survival.”

Availability is not actionability

Study discussant Michael J. Overman, MD, of MD Anderson Cancer Center in Houston, acknowledged that this research substantiates the ability of postoperative ctDNA detection to risk stratify patients with stage III CRC, the predominant stage of participants in the study.

The current results reinforce the researchers’ previously published work (JAMA Oncol. 2019;5[8]:1124-31) and affirm similar findings by other groups (JAMA Oncol. 2019;5[12]:1710-17 and JAMA Oncol. 2019;5[8]:1118-23).

However, Dr. Overman cautioned that “availability is not the same as actionability.”

He also said the “tumor-informed mutation” approach utilized in the Signatera assay differs from the simpler “panel-based” approach, which is also undergoing clinical testing and offers the additional opportunity to test potentially actionable epigenetic targets such as DNA methylation.

Furthermore, the practicality of integrating the tumor-informed mutation approach into the time constraints required in clinical practice was not evaluated in the current analysis.

Dr. Overman pointed out that 16 of the 20 ctDNA-positive patients who received adjuvant chemotherapy sustained a recurrence, so the chemotherapy benefit was lower than expected.

Finally, although ctDNA outperformed CEA in detecting relapse, the greatest impact of ctDNA is its potential to inform the clinician’s decision to escalate and deescalate treatment with impact on survival – a potential that remains unfulfilled.

Next steps

Ms. Henriksen closed her presentation with the perspective that, for serial ctDNA monitoring to be implemented in clinical settings, testing in randomized clinical trials will be needed.

In Denmark, the IMPROVE-IT study is enrolling patients with stage I or low-risk stage II CRC. In this trial, ctDNA-positive patients will receive adjuvant chemotherapy, and ctDNA-negative patients will have longitudinal ctDNA testing but no adjuvant chemotherapy.

A second study, IMPROVE-IT2, will assess the value of ctDNA to direct intensified radiologic surveillance to improve the application of potentially curative treatment for patients with stage II (high-risk) or stage III CRC. Patients with negative ctDNA tests will be followed with longitudinal ctDNA testing only.

In his talk, Dr. Overman highlighted several prospective studies assessing the value of ctDNA testing.

One of these is the ongoing COBRA study (NRG-GI-005), which uses a ctDNA assay (Guardant Lunar-1) for patients with stage IIA CRC for whom standard adjuvant chemotherapy is not indicated.

The patients in COBRA are randomized to active surveillance or assay-directed therapy. Patients assigned to assay-directed therapy have samples analyzed for ctDNA, which would guide the decision about adjuvant chemotherapy. If the postoperative sample is ctDNA positive and the patient accepts adjuvant chemotherapy, the patient could receive one of two standard adjuvant chemotherapy regimens. If ctDNA negative, the patient would be followed with active surveillance alone.

Dr. Overman also highlighted the planned CIRCULATE US trial (NRG-GI008). The aim of this trial is to test intensified adjuvant treatment for stage III CRC patients with positive ctDNA tests. It will employ the Signatera assay.

Ideally, these ongoing trials will provide the evidence base needed for clinicians to optimize adjuvant therapy and surveillance using ctDNA technology.

The current study was sponsored by the Danish Council for Independent Research, The Novo Nordisk Foundation, The Danish Cancer Society, and Natera Inc. Ms. Henriksen disclosed no conflicts of interest. Dr. Overman disclosed relationships with Array BioPharma, Bristol-Myers Squibb, Gritstone Oncology, Janssen, MedImmune, Merck, Novartis, Pfizer, Promega, Roche/Genentech, and Spectrum Pharmaceuticals.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
 

Despite standard blood monitoring and routine imaging, patients with colorectal cancer (CRC) tend to have multiple, incurable metastases when relapse occurs.

A new study indicates that postsurgical circulating tumor DNA (ctDNA) testing may improve our ability to predict relapse in patients with stage I-III CRC.

ctDNA testing outperformed carcinoembryonic antigen (CEA) testing in predicting relapse-free survival, and ctDNA was detected about 8 months prior to relapse detection via CT.

Tenna V. Henriksen, of Aarhus University in Denmark, presented these results at the 2021 Gastrointestinal Cancers Symposium (abstract 11).

The multi-institutional study included 260 patients with CRC – 4 with stage I disease, 90 with stage II, and 166 with stage III disease.

Patients were monitored with plasma ctDNA testing within 2 months of primary surgery. Some patients were monitored with follow-up ctDNA sampling every 3 months for an additional 3 years.

Individual tumors and matched germline DNA were interrogated with whole-exome sequencing, and somatic single nucleotide variants were identified. Personalized multiplex PCR assays were developed to track tumor-specific single nucleotide variants via the Signatera® ctDNA assay.

The researchers retrospectively assessed ctDNA’s performance in:

• Stratifying the postoperative risk of relapse.
• Quantifying the benefit of adjuvant chemotherapy in patients who had or did not have ctDNA in plasma.
• Efficiently detecting relapse, in comparison with standard surveillance tests.

Surveillance CT scans were performed at 12 and 36 months but not at the frequency recommended in NCCN guidelines.

In all, 165 patients received adjuvant chemotherapy. The decision to give chemotherapy was made on a clinical basis by treating physicians who were blinded to the results of ctDNA testing.
 

Results

Of the 260 patients analyzed, 48 relapsed. The median follow-up was 28.4 months overall and 29.9 months in the nonrelapse cases.

The researchers assessed postoperative ctDNA status prior to adjuvant chemotherapy in 218 patients and after adjuvant chemotherapy in 108 patients.

In the prechemotherapy group, 20 patients were ctDNA positive, and 80% of them relapsed. In contrast, 13% of the 198 ctDNA-negative patients relapsed. The hazard ratio (HR) for relapse-free survival was 11 (95% confidence interval, 5.9-21; P < .0001).

After adjuvant chemotherapy, 12.5% of the ctDNA-negative patients relapsed, compared with 83.3% of the ctDNA-positive patients. The HR for relapse-free survival was 12 (95% CI, 4.9-27; P < .0001).

Results from longitudinal ctDNA testing in 202 patients suggested that serial sampling is more useful than sampling at a single point in time. The recurrence rate was 3.4% among patients who remained persistently ctDNA negative, compared with 89.3% in patients who were ctDNA positive. The HR for relapse-free survival was 51 (95% CI, 20-125; P < .0001).

In a subgroup of 29 patients with clinical recurrence detected by CT imaging, ctDNA detection occurred a median of 8.1 months earlier than radiologic relapse.

Among the 197 patients who had serial CEA and ctDNA measurements, longitudinal CEA testing correlated with relapse-free survival (HR, 4.9; 95% CI, 3.2-15, P < .0001) but not nearly as well as ctDNA testing (HR, 95.7; 95% CI, 28-322, P < .0001) in a univariable analysis.

In a multivariable analysis, the HR for relapse-free survival was 1.8 (95% CI, 0.77-4.0; P = .184) for longitudinal CEA and 80.55 (95% CI, 23.1-281; P < .0001) for longitudinal ctDNA.

“[W]hen we pit them against each other in a multivariable analysis, we can see that all the predictive power is in the ctDNA samples,” Ms. Henriksen said. “This indicates that ctDNA is a stronger biomarker compared to CEA, at least with relapse-free survival.”

Availability is not actionability

Study discussant Michael J. Overman, MD, of MD Anderson Cancer Center in Houston, acknowledged that this research substantiates the ability of postoperative ctDNA detection to risk stratify patients with stage III CRC, the predominant stage of participants in the study.

The current results reinforce the researchers’ previously published work (JAMA Oncol. 2019;5[8]:1124-31) and affirm similar findings by other groups (JAMA Oncol. 2019;5[12]:1710-17 and JAMA Oncol. 2019;5[8]:1118-23).

However, Dr. Overman cautioned that “availability is not the same as actionability.”

He also said the “tumor-informed mutation” approach utilized in the Signatera assay differs from the simpler “panel-based” approach, which is also undergoing clinical testing and offers the additional opportunity to test potentially actionable epigenetic targets such as DNA methylation.

Furthermore, the practicality of integrating the tumor-informed mutation approach into the time constraints required in clinical practice was not evaluated in the current analysis.

Dr. Overman pointed out that 16 of the 20 ctDNA-positive patients who received adjuvant chemotherapy sustained a recurrence, so the chemotherapy benefit was lower than expected.

Finally, although ctDNA outperformed CEA in detecting relapse, the greatest impact of ctDNA is its potential to inform the clinician’s decision to escalate and deescalate treatment with impact on survival – a potential that remains unfulfilled.

Next steps

Ms. Henriksen closed her presentation with the perspective that, for serial ctDNA monitoring to be implemented in clinical settings, testing in randomized clinical trials will be needed.

In Denmark, the IMPROVE-IT study is enrolling patients with stage I or low-risk stage II CRC. In this trial, ctDNA-positive patients will receive adjuvant chemotherapy, and ctDNA-negative patients will have longitudinal ctDNA testing but no adjuvant chemotherapy.

A second study, IMPROVE-IT2, will assess the value of ctDNA to direct intensified radiologic surveillance to improve the application of potentially curative treatment for patients with stage II (high-risk) or stage III CRC. Patients with negative ctDNA tests will be followed with longitudinal ctDNA testing only.

In his talk, Dr. Overman highlighted several prospective studies assessing the value of ctDNA testing.

One of these is the ongoing COBRA study (NRG-GI-005), which uses a ctDNA assay (Guardant Lunar-1) for patients with stage IIA CRC for whom standard adjuvant chemotherapy is not indicated.

The patients in COBRA are randomized to active surveillance or assay-directed therapy. Patients assigned to assay-directed therapy have samples analyzed for ctDNA, which would guide the decision about adjuvant chemotherapy. If the postoperative sample is ctDNA positive and the patient accepts adjuvant chemotherapy, the patient could receive one of two standard adjuvant chemotherapy regimens. If ctDNA negative, the patient would be followed with active surveillance alone.

Dr. Overman also highlighted the planned CIRCULATE US trial (NRG-GI008). The aim of this trial is to test intensified adjuvant treatment for stage III CRC patients with positive ctDNA tests. It will employ the Signatera assay.

Ideally, these ongoing trials will provide the evidence base needed for clinicians to optimize adjuvant therapy and surveillance using ctDNA technology.

The current study was sponsored by the Danish Council for Independent Research, The Novo Nordisk Foundation, The Danish Cancer Society, and Natera Inc. Ms. Henriksen disclosed no conflicts of interest. Dr. Overman disclosed relationships with Array BioPharma, Bristol-Myers Squibb, Gritstone Oncology, Janssen, MedImmune, Merck, Novartis, Pfizer, Promega, Roche/Genentech, and Spectrum Pharmaceuticals.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
 

Despite standard blood monitoring and routine imaging, patients with colorectal cancer (CRC) tend to have multiple, incurable metastases when relapse occurs.

A new study indicates that postsurgical circulating tumor DNA (ctDNA) testing may improve our ability to predict relapse in patients with stage I-III CRC.

ctDNA testing outperformed carcinoembryonic antigen (CEA) testing in predicting relapse-free survival, and ctDNA was detected about 8 months prior to relapse detection via CT.

Tenna V. Henriksen, of Aarhus University in Denmark, presented these results at the 2021 Gastrointestinal Cancers Symposium (abstract 11).

The multi-institutional study included 260 patients with CRC – 4 with stage I disease, 90 with stage II, and 166 with stage III disease.

Patients were monitored with plasma ctDNA testing within 2 months of primary surgery. Some patients were monitored with follow-up ctDNA sampling every 3 months for an additional 3 years.

Individual tumors and matched germline DNA were interrogated with whole-exome sequencing, and somatic single nucleotide variants were identified. Personalized multiplex PCR assays were developed to track tumor-specific single nucleotide variants via the Signatera® ctDNA assay.

The researchers retrospectively assessed ctDNA’s performance in:

• Stratifying the postoperative risk of relapse.
• Quantifying the benefit of adjuvant chemotherapy in patients who had or did not have ctDNA in plasma.
• Efficiently detecting relapse, in comparison with standard surveillance tests.

Surveillance CT scans were performed at 12 and 36 months but not at the frequency recommended in NCCN guidelines.

In all, 165 patients received adjuvant chemotherapy. The decision to give chemotherapy was made on a clinical basis by treating physicians who were blinded to the results of ctDNA testing.
 

Results

Of the 260 patients analyzed, 48 relapsed. The median follow-up was 28.4 months overall and 29.9 months in the nonrelapse cases.

The researchers assessed postoperative ctDNA status prior to adjuvant chemotherapy in 218 patients and after adjuvant chemotherapy in 108 patients.

In the prechemotherapy group, 20 patients were ctDNA positive, and 80% of them relapsed. In contrast, 13% of the 198 ctDNA-negative patients relapsed. The hazard ratio (HR) for relapse-free survival was 11 (95% confidence interval, 5.9-21; P < .0001).

After adjuvant chemotherapy, 12.5% of the ctDNA-negative patients relapsed, compared with 83.3% of the ctDNA-positive patients. The HR for relapse-free survival was 12 (95% CI, 4.9-27; P < .0001).

Results from longitudinal ctDNA testing in 202 patients suggested that serial sampling is more useful than sampling at a single point in time. The recurrence rate was 3.4% among patients who remained persistently ctDNA negative, compared with 89.3% in patients who were ctDNA positive. The HR for relapse-free survival was 51 (95% CI, 20-125; P < .0001).

In a subgroup of 29 patients with clinical recurrence detected by CT imaging, ctDNA detection occurred a median of 8.1 months earlier than radiologic relapse.

Among the 197 patients who had serial CEA and ctDNA measurements, longitudinal CEA testing correlated with relapse-free survival (HR, 4.9; 95% CI, 3.2-15, P < .0001) but not nearly as well as ctDNA testing (HR, 95.7; 95% CI, 28-322, P < .0001) in a univariable analysis.

In a multivariable analysis, the HR for relapse-free survival was 1.8 (95% CI, 0.77-4.0; P = .184) for longitudinal CEA and 80.55 (95% CI, 23.1-281; P < .0001) for longitudinal ctDNA.

“[W]hen we pit them against each other in a multivariable analysis, we can see that all the predictive power is in the ctDNA samples,” Ms. Henriksen said. “This indicates that ctDNA is a stronger biomarker compared to CEA, at least with relapse-free survival.”

Availability is not actionability

Study discussant Michael J. Overman, MD, of MD Anderson Cancer Center in Houston, acknowledged that this research substantiates the ability of postoperative ctDNA detection to risk stratify patients with stage III CRC, the predominant stage of participants in the study.

The current results reinforce the researchers’ previously published work (JAMA Oncol. 2019;5[8]:1124-31) and affirm similar findings by other groups (JAMA Oncol. 2019;5[12]:1710-17 and JAMA Oncol. 2019;5[8]:1118-23).

However, Dr. Overman cautioned that “availability is not the same as actionability.”

He also said the “tumor-informed mutation” approach utilized in the Signatera assay differs from the simpler “panel-based” approach, which is also undergoing clinical testing and offers the additional opportunity to test potentially actionable epigenetic targets such as DNA methylation.

Furthermore, the practicality of integrating the tumor-informed mutation approach into the time constraints required in clinical practice was not evaluated in the current analysis.

Dr. Overman pointed out that 16 of the 20 ctDNA-positive patients who received adjuvant chemotherapy sustained a recurrence, so the chemotherapy benefit was lower than expected.

Finally, although ctDNA outperformed CEA in detecting relapse, the greatest impact of ctDNA is its potential to inform the clinician’s decision to escalate and deescalate treatment with impact on survival – a potential that remains unfulfilled.

Next steps

Ms. Henriksen closed her presentation with the perspective that, for serial ctDNA monitoring to be implemented in clinical settings, testing in randomized clinical trials will be needed.

In Denmark, the IMPROVE-IT study is enrolling patients with stage I or low-risk stage II CRC. In this trial, ctDNA-positive patients will receive adjuvant chemotherapy, and ctDNA-negative patients will have longitudinal ctDNA testing but no adjuvant chemotherapy.

A second study, IMPROVE-IT2, will assess the value of ctDNA to direct intensified radiologic surveillance to improve the application of potentially curative treatment for patients with stage II (high-risk) or stage III CRC. Patients with negative ctDNA tests will be followed with longitudinal ctDNA testing only.

In his talk, Dr. Overman highlighted several prospective studies assessing the value of ctDNA testing.

One of these is the ongoing COBRA study (NRG-GI-005), which uses a ctDNA assay (Guardant Lunar-1) for patients with stage IIA CRC for whom standard adjuvant chemotherapy is not indicated.

The patients in COBRA are randomized to active surveillance or assay-directed therapy. Patients assigned to assay-directed therapy have samples analyzed for ctDNA, which would guide the decision about adjuvant chemotherapy. If the postoperative sample is ctDNA positive and the patient accepts adjuvant chemotherapy, the patient could receive one of two standard adjuvant chemotherapy regimens. If ctDNA negative, the patient would be followed with active surveillance alone.

Dr. Overman also highlighted the planned CIRCULATE US trial (NRG-GI008). The aim of this trial is to test intensified adjuvant treatment for stage III CRC patients with positive ctDNA tests. It will employ the Signatera assay.

Ideally, these ongoing trials will provide the evidence base needed for clinicians to optimize adjuvant therapy and surveillance using ctDNA technology.

The current study was sponsored by the Danish Council for Independent Research, The Novo Nordisk Foundation, The Danish Cancer Society, and Natera Inc. Ms. Henriksen disclosed no conflicts of interest. Dr. Overman disclosed relationships with Array BioPharma, Bristol-Myers Squibb, Gritstone Oncology, Janssen, MedImmune, Merck, Novartis, Pfizer, Promega, Roche/Genentech, and Spectrum Pharmaceuticals.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
 

The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.

Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.

“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”

The study was published online Jan. 20 in Neurology.

“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.

The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.

“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
 

Renewing the immune system

The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.

“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”

Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.

Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.

For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.

Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.

Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.

Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.

However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.

In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.

“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
 

Potent and durable efficacy, with caveats

Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”

The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”

He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”

To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.

The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.

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

The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.

Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.

“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”

The study was published online Jan. 20 in Neurology.

“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.

The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.

“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
 

Renewing the immune system

The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.

“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”

Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.

Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.

For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.

Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.

Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.

Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.

However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.

In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.

“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
 

Potent and durable efficacy, with caveats

Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”

The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”

He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”

To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.

The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.

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

The benefits of autologous hematopoietic stem cell transplant (AHSCT) for patients with multiple sclerosis (MS) persist for more than 10 years in the majority of patents, new data show. The study reports on 210 Italian patients who underwent AHSCT between 2007 and 2019. Among the entire study cohort, 79.5% of patients had not experienced worsening of disability at 5 years, and 65.5% had not experienced it at 10 years.

Patients with relapsing remitting MS had better results, with 85.5% experiencing no worsening of disability at 5 years, and 71.3% at 10 years. Among patients with progressive MS, 71.0% showed no worsening of disability at 5 years, and 57.2% at 10 years.

“This is the longest follow-up of AHSCT in MS patients so far to be reported,” said study author Matilde Inglese, MD, University of Genoa (Italy). “We have shown AHSCT to be highly effective to prevent long-term disability worsening in most treated patients.”

The study was published online Jan. 20 in Neurology.

“We suggest that AHSCT should be considered as a treatment strategy for MS not responding to conventional therapy,” the authors concluded.

The study had no control group, so a direct comparison is not possible. Nevertheless, Dr. Inglese said she believed these results are better than those that would be achieved with disease-modifying drug therapy for similar patients.

“The best patient candidates for this procedure are those with highly active multiple sclerosis who are not responsive to high-efficacy drugs, such as alemtuzumab or ocrelizumab,” Dr. Inglese commented. “Younger patients with an aggressive form of relapsing remitting MS tend to do the best, although patients with progressive forms of MS who still have active lesions on MRI also benefit.”
 

Renewing the immune system

The transplant procedure involves giving high-dose cyclophosphamide to stimulate mobilization of bone marrow stem cells, which are collected from peripheral blood. Patients then undergo intense immunosuppression with a cocktail of drugs to remove the autoreactive T cells, and the stem cells, which are not autoreactive, are reinfused.

“We are effectively renewing the immune system,” Dr. Inglese said. “While it is not correct to call it a cure, as we are not eliminating the etiology of the disease, it is the closest to complete suppression of the disease that we can get.”

Other results from the study show that among patients with relapsing remitting MS, rates of relapse-free survival were 78.1% at 5 years and 63.5% at 10 years.

Better results were achieved for patients who received the BEAM+ATG conditioning regimen for immunosuppression. That regimen includes carmustine, cytosine-arabinoside, etoposide, and melphalan, followed by rabbit antithymocyte globulin. Among patients with relapsing remitting disease who were treated with this protocol, rates of relapse-free survival were 86.4% at 5 years and 77.0% at 10 years.

For patients with relapsing remitting MS, the probability of achieving NEDA-3 status (no evidence of disease activity, including the absence of clinical relapses, disability worsening, and MRI inflammatory activity) was 62.2% at 5 years and 40.5% at 10 years.

Among those patients with relapsing remitting MS who received the BEAM+ATG conditioning protocol, NEDA-3 status was achieved in 67.7% at 5 years and in 54.9% at 10 years.

Three deaths occurred within 100 days following AHSCT (1.4% of the entire study population). One patient developed pulmonary thromboembolism, received fibrinolytic treatment, and died 48 hours later after intracranial hemorrhage. The second patient experienced engraftment failure and died 24 days after transplant because of an opportunistic infection. The third patient died 1 month after transplant from Wernicke-like encephalopathy. All the patients who died received the BEAM+ATG conditioning regimen. No transplant-related deaths occurred in patients who underwent transplant after 2007.

Dr. Inglese noted that the mortality rate associated with AHSCT has been greatly reduced in recent years. “We are seeing a very low mortality rate – about 0.3% – thanks to improvements in the procedure and better patient selection. This seems acceptable, given that we are treating patients with very aggressive disease who have a high risk of becoming significantly disabled relatively early in life,” she commented.

However, it is vitally important that the procedure be conducted in a specialized center with a highly experienced multidisciplinary team, she stressed.

In the Neurology article, the authors concluded: “Although patients with RRMS [relapsing remitting MS] are those who benefit the most from transplant, AHSCT has been also shown to prevent disability worsening in a large proportion of patients with active progressive MS.

“The BEAM+ATG conditioning protocol, although associated with a higher transplant mortality rate, was associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity, allowing complete disease control in a higher proportion of patients,” they wrote.
 

Potent and durable efficacy, with caveats

Commenting on these latest findings, Jeffrey A. Cohen, MD, of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic, said: “AHSCT appears to have potent and durable efficacy in MS but is associated with significant risk and cost.”

The patients who are most likely to benefit are young and have experienced the onset of disease relatively recently. They are still ambulatory with highly active MS and have experienced recent clinical relapses and/or MRI lesion activity, and such activity continues despite disease-modifying therapy, Dr. Cohen noted. He added that “AHSCT is a reasonable option for such patients who have essentially failed the available disease-modifying therapy options.”

He pointed out that the key question is where AHSCT belongs in the overall MS algorithm relative to other high-efficacy therapies. “We need to know whether it should be used more broadly rather than as a last resort.”

To address that question, several randomized trials comparing AHSCT with high-efficacy disease-modifying therapy are in progress, including the National Institutes of Health–sponsored BEAT-MS trial in the United States (for which Dr. Cohen is the lead investigator) and four European trials – NET-MS (for which Dr. Inglese is the lead investigator), STAR-MS, RAM-MS, and COAST-MS.

The current study was partially funded and supported by the Italian Multiple Sclerosis Foundation. Dr. Inglese disclosed no relevant financial relationships.

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

As mutated strains of the coronavirus represent new threats in the pandemic, vaccine makers are racing to respond.

Moderna, whose two-dose vaccine has been authorized for use in the United States since Dec. 18, said on Jan. 25 that it is now investigating whether a third dose of the vaccine will better prevent the spread of a variant first seen in South Africa, while it also tests a new vaccine formula for the same purpose.

“Out of an abundance of caution and leveraging the flexibility of our mRNA platform, we are advancing an emerging variant booster candidate against the variant first identified in the Republic of South Africa into the clinic to determine if it will be more effective … against this and potentially future variants,” Moderna CEO Stéphane Bancel said in a statement. Pfizer and BioNTech, whose vaccine was also authorized in December, announced on Jan. 20 that their COVID-19 vaccine creates antibodies that could protect vaccine recipients from the U.K. variant B.1.1.7.

Moderna on Jan. 25 said laboratory tests have shown its COVID-19 vaccine could protect against the U.K. strain but that it is less effective – while still meeting efficacy benchmarks – against the strain identified in South Africa. Data from the study were submitted to a preprint server on Jan. 25 but have not yet been peer reviewed.

“This is not a problem yet,” Paul Offit, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNBC.

“Prepare for it. Sequence these viruses,” he said. “Get ready just in case a variant emerges, which is resistant.”

There were at least 195 confirmed cases of patients infected with the U.K. variant, which is believed to be as much as 70% more transmissible, in the United States as of Jan. 22, according to the Centers for Disease Control and Prevention. No cases from the South African variant have been confirmed in the United States. To try to prevent the variant from entering the country, President Joe Biden plans to ban travel from South Africa, except for American citizens and permanent residents.

The U.S. has reported more than 25 million total COVID-19 cases, according to data from Johns Hopkins University, marking another major milestone during the pandemic.

That means about 1 in 13 people have contracted the virus, or about 7.6% of the U.S. population.

“Twenty-five million cases is an incredible scale of tragedy,” Caitlin Rivers, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, told The New York Times. She called the pandemic one of the worst public health crises in history.

After the first U.S. case was reported in January 2020, it took more than 9 months to reach 10 million cases in early November. Numbers rose during the holidays, and 10 million more cases were reported by the end of the year.

Following a major surge throughout January 2021, with a peak of more than 300,000 daily cases on some days, the U.S. reached 25 million in about 3 weeks.

Hospitalizations also peaked in early January, with more than 132,000 COVID-19 patients in hospitals across the country, according to the COVID Tracking Project. On Jan. 24, about 111,000 patients were hospitalized, which is the lowest since mid-December.

The U.S. has also reported nearly 420,000 deaths. As recently as the week starting Jan. 17, more than 4,400 deaths were reported in a single day, according to the COVID Tracking Project. Deaths are beginning to drop but still remain above 3,000 daily.

The University of Washington’s Institute for Health Metrics and Evaluation released a new projection Jan. 22 that said new cases would decline steadily in coming weeks. New COVID-19 cases had fallen about 21% in 2 weeks prior to Jan. 25, according to an analysis by The New York Times.

“We’ve been saying since summer that we thought we’d see a peak in January, and I think that, at the national level, we’re around the peak,” Christopher J.L. Murray, MD, director of the institute, told the newspaper.

At the same time, public health officials are concerned that new coronavirus variants could lead to an increase again. Dr. Murray said the variants could “totally change the story.” If the more transmissible strains spread quickly, cases and deaths will surge once more.

“We’re definitely on a downward slope, but I’m worried that the new variants will throw us a curveball in late February or March,” Ms. Rivers told the newspaper.
 

A version of this article first appeared on WebMD.com.

As mutated strains of the coronavirus represent new threats in the pandemic, vaccine makers are racing to respond.

Moderna, whose two-dose vaccine has been authorized for use in the United States since Dec. 18, said on Jan. 25 that it is now investigating whether a third dose of the vaccine will better prevent the spread of a variant first seen in South Africa, while it also tests a new vaccine formula for the same purpose.

“Out of an abundance of caution and leveraging the flexibility of our mRNA platform, we are advancing an emerging variant booster candidate against the variant first identified in the Republic of South Africa into the clinic to determine if it will be more effective … against this and potentially future variants,” Moderna CEO Stéphane Bancel said in a statement. Pfizer and BioNTech, whose vaccine was also authorized in December, announced on Jan. 20 that their COVID-19 vaccine creates antibodies that could protect vaccine recipients from the U.K. variant B.1.1.7.

Moderna on Jan. 25 said laboratory tests have shown its COVID-19 vaccine could protect against the U.K. strain but that it is less effective – while still meeting efficacy benchmarks – against the strain identified in South Africa. Data from the study were submitted to a preprint server on Jan. 25 but have not yet been peer reviewed.

“This is not a problem yet,” Paul Offit, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNBC.

“Prepare for it. Sequence these viruses,” he said. “Get ready just in case a variant emerges, which is resistant.”

There were at least 195 confirmed cases of patients infected with the U.K. variant, which is believed to be as much as 70% more transmissible, in the United States as of Jan. 22, according to the Centers for Disease Control and Prevention. No cases from the South African variant have been confirmed in the United States. To try to prevent the variant from entering the country, President Joe Biden plans to ban travel from South Africa, except for American citizens and permanent residents.

The U.S. has reported more than 25 million total COVID-19 cases, according to data from Johns Hopkins University, marking another major milestone during the pandemic.

That means about 1 in 13 people have contracted the virus, or about 7.6% of the U.S. population.

“Twenty-five million cases is an incredible scale of tragedy,” Caitlin Rivers, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, told The New York Times. She called the pandemic one of the worst public health crises in history.

After the first U.S. case was reported in January 2020, it took more than 9 months to reach 10 million cases in early November. Numbers rose during the holidays, and 10 million more cases were reported by the end of the year.

Following a major surge throughout January 2021, with a peak of more than 300,000 daily cases on some days, the U.S. reached 25 million in about 3 weeks.

Hospitalizations also peaked in early January, with more than 132,000 COVID-19 patients in hospitals across the country, according to the COVID Tracking Project. On Jan. 24, about 111,000 patients were hospitalized, which is the lowest since mid-December.

The U.S. has also reported nearly 420,000 deaths. As recently as the week starting Jan. 17, more than 4,400 deaths were reported in a single day, according to the COVID Tracking Project. Deaths are beginning to drop but still remain above 3,000 daily.

The University of Washington’s Institute for Health Metrics and Evaluation released a new projection Jan. 22 that said new cases would decline steadily in coming weeks. New COVID-19 cases had fallen about 21% in 2 weeks prior to Jan. 25, according to an analysis by The New York Times.

“We’ve been saying since summer that we thought we’d see a peak in January, and I think that, at the national level, we’re around the peak,” Christopher J.L. Murray, MD, director of the institute, told the newspaper.

At the same time, public health officials are concerned that new coronavirus variants could lead to an increase again. Dr. Murray said the variants could “totally change the story.” If the more transmissible strains spread quickly, cases and deaths will surge once more.

“We’re definitely on a downward slope, but I’m worried that the new variants will throw us a curveball in late February or March,” Ms. Rivers told the newspaper.
 

A version of this article first appeared on WebMD.com.

As mutated strains of the coronavirus represent new threats in the pandemic, vaccine makers are racing to respond.

Moderna, whose two-dose vaccine has been authorized for use in the United States since Dec. 18, said on Jan. 25 that it is now investigating whether a third dose of the vaccine will better prevent the spread of a variant first seen in South Africa, while it also tests a new vaccine formula for the same purpose.

“Out of an abundance of caution and leveraging the flexibility of our mRNA platform, we are advancing an emerging variant booster candidate against the variant first identified in the Republic of South Africa into the clinic to determine if it will be more effective … against this and potentially future variants,” Moderna CEO Stéphane Bancel said in a statement. Pfizer and BioNTech, whose vaccine was also authorized in December, announced on Jan. 20 that their COVID-19 vaccine creates antibodies that could protect vaccine recipients from the U.K. variant B.1.1.7.

Moderna on Jan. 25 said laboratory tests have shown its COVID-19 vaccine could protect against the U.K. strain but that it is less effective – while still meeting efficacy benchmarks – against the strain identified in South Africa. Data from the study were submitted to a preprint server on Jan. 25 but have not yet been peer reviewed.

“This is not a problem yet,” Paul Offit, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNBC.

“Prepare for it. Sequence these viruses,” he said. “Get ready just in case a variant emerges, which is resistant.”

There were at least 195 confirmed cases of patients infected with the U.K. variant, which is believed to be as much as 70% more transmissible, in the United States as of Jan. 22, according to the Centers for Disease Control and Prevention. No cases from the South African variant have been confirmed in the United States. To try to prevent the variant from entering the country, President Joe Biden plans to ban travel from South Africa, except for American citizens and permanent residents.

The U.S. has reported more than 25 million total COVID-19 cases, according to data from Johns Hopkins University, marking another major milestone during the pandemic.

That means about 1 in 13 people have contracted the virus, or about 7.6% of the U.S. population.

“Twenty-five million cases is an incredible scale of tragedy,” Caitlin Rivers, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health, told The New York Times. She called the pandemic one of the worst public health crises in history.

After the first U.S. case was reported in January 2020, it took more than 9 months to reach 10 million cases in early November. Numbers rose during the holidays, and 10 million more cases were reported by the end of the year.

Following a major surge throughout January 2021, with a peak of more than 300,000 daily cases on some days, the U.S. reached 25 million in about 3 weeks.

Hospitalizations also peaked in early January, with more than 132,000 COVID-19 patients in hospitals across the country, according to the COVID Tracking Project. On Jan. 24, about 111,000 patients were hospitalized, which is the lowest since mid-December.

The U.S. has also reported nearly 420,000 deaths. As recently as the week starting Jan. 17, more than 4,400 deaths were reported in a single day, according to the COVID Tracking Project. Deaths are beginning to drop but still remain above 3,000 daily.

The University of Washington’s Institute for Health Metrics and Evaluation released a new projection Jan. 22 that said new cases would decline steadily in coming weeks. New COVID-19 cases had fallen about 21% in 2 weeks prior to Jan. 25, according to an analysis by The New York Times.

“We’ve been saying since summer that we thought we’d see a peak in January, and I think that, at the national level, we’re around the peak,” Christopher J.L. Murray, MD, director of the institute, told the newspaper.

At the same time, public health officials are concerned that new coronavirus variants could lead to an increase again. Dr. Murray said the variants could “totally change the story.” If the more transmissible strains spread quickly, cases and deaths will surge once more.

“We’re definitely on a downward slope, but I’m worried that the new variants will throw us a curveball in late February or March,” Ms. Rivers told the newspaper.
 

A version of this article first appeared on WebMD.com.

It’s been shown that hospitalized cancer patients and those undergoing active treatment are at high risk for severe COVID-19 complications. A new study shows that patients with cancer in remission are at higher risk, too.

For the study, investigators from the University of Pennsylvania, Philadelphia, analyzed 323 patients with SARS-CoV-2 infection in a research database with more than 4,800 patients. About 20% of database patients were Black, but they accounted for almost 65% of the infections, reflecting previous reports of increased risk for COVID among Black people.

A total of 67 of the infected patients had cancer, including 18 patients with active cancer and 49 patients whose cancer was in remission. After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer more than doubled the odds of hospitalization and increased the odds of 30-day mortality nearly sixfold.

Worse outcomes were more strongly associated with active cancer, but patients whose cancer was in remission were also at higher risk than patients who did not have cancer.

It’s not only “patients hospitalized or on treatment ... all oncology patients need to take significant precautions during the pandemic to protect themselves,” senior investigator Kara Maxwell, MD, PhD, hematologist/oncologist and assistant professor at the University of Pennsylvania, said in a press release.

The study was published online on Jan. 21 in JNCI Cancer Spectrum.

The good news is that steps to prevent SARS-CoV-2 infection work, suggests a second report from the University of Pennsylvania. Among 124 cancer patients who underwent outpatient infusions from May to October 2020, not a single one experienced seroconversion over a median of 13 clinical visits. That second study was published on Jan. 16 in medRxiv and is pending peer review.

The zero seroconversion rate likely reflects “the success of transmission mitigation measures within health care facilities,” wrote investigators led by Lova Sun, MD, a hematology/oncology fellow at the University of Pennsylvania.

Like many institutions, the University of Pennsylvania Health System (Penn Medicine) is aggressive in protecting outpatients against the virus, the authors wrote. Among other steps, patients are queried about symptoms and contacts before their office visit, and their temperature is taken when they come in. Masks are worn, check-in is contactless, the number of visitors is limited, and patients who test positive are treated in a separate space.

In addition, patients in the study also reported that they wore masks and practiced social distancing in their daily lives.

Approached for comment, hematologist/oncologist Charles Shapiro, MD, a professor at the Icahn School of Medicine at Mount Sinai and director of translational breast cancer research at Mount Sinai Hospital, both in New York, said he wasn’t surprised that the prevention measures followed at Penn Medicine work. They are very similar to the measures followed at Mount Sinai oncology clinics, and “there’ve been very few COVID cases in our shop,” he added.

The bigger take-home message from both studies is that cancer patients, regardless of their age or if they are in remission, should be prioritized for vaccination against COVID-19, which is the best way to mitigate risk. “I strongly urge my patients to get it” if they can, he said.

The problem in New York is that immunizations are largely limited to people aged 65 years and older. Younger cancer patients are left out, and access has been spotty for all patients. “Vaccine is available one day, then not the next. It’s disheartening,” Dr. Shapiro said in an interview. “Hopefully, with the new administration, this will smooth out,” and the age limit will drop.

The study was supported by the National Institutes of Health, among other organizations. Dr. Lova, Dr. Maxwell, and Dr. Shapiro have disclosed no relevant financial relationships.

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

It’s been shown that hospitalized cancer patients and those undergoing active treatment are at high risk for severe COVID-19 complications. A new study shows that patients with cancer in remission are at higher risk, too.

For the study, investigators from the University of Pennsylvania, Philadelphia, analyzed 323 patients with SARS-CoV-2 infection in a research database with more than 4,800 patients. About 20% of database patients were Black, but they accounted for almost 65% of the infections, reflecting previous reports of increased risk for COVID among Black people.

A total of 67 of the infected patients had cancer, including 18 patients with active cancer and 49 patients whose cancer was in remission. After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer more than doubled the odds of hospitalization and increased the odds of 30-day mortality nearly sixfold.

Worse outcomes were more strongly associated with active cancer, but patients whose cancer was in remission were also at higher risk than patients who did not have cancer.

It’s not only “patients hospitalized or on treatment ... all oncology patients need to take significant precautions during the pandemic to protect themselves,” senior investigator Kara Maxwell, MD, PhD, hematologist/oncologist and assistant professor at the University of Pennsylvania, said in a press release.

The study was published online on Jan. 21 in JNCI Cancer Spectrum.

The good news is that steps to prevent SARS-CoV-2 infection work, suggests a second report from the University of Pennsylvania. Among 124 cancer patients who underwent outpatient infusions from May to October 2020, not a single one experienced seroconversion over a median of 13 clinical visits. That second study was published on Jan. 16 in medRxiv and is pending peer review.

The zero seroconversion rate likely reflects “the success of transmission mitigation measures within health care facilities,” wrote investigators led by Lova Sun, MD, a hematology/oncology fellow at the University of Pennsylvania.

Like many institutions, the University of Pennsylvania Health System (Penn Medicine) is aggressive in protecting outpatients against the virus, the authors wrote. Among other steps, patients are queried about symptoms and contacts before their office visit, and their temperature is taken when they come in. Masks are worn, check-in is contactless, the number of visitors is limited, and patients who test positive are treated in a separate space.

In addition, patients in the study also reported that they wore masks and practiced social distancing in their daily lives.

Approached for comment, hematologist/oncologist Charles Shapiro, MD, a professor at the Icahn School of Medicine at Mount Sinai and director of translational breast cancer research at Mount Sinai Hospital, both in New York, said he wasn’t surprised that the prevention measures followed at Penn Medicine work. They are very similar to the measures followed at Mount Sinai oncology clinics, and “there’ve been very few COVID cases in our shop,” he added.

The bigger take-home message from both studies is that cancer patients, regardless of their age or if they are in remission, should be prioritized for vaccination against COVID-19, which is the best way to mitigate risk. “I strongly urge my patients to get it” if they can, he said.

The problem in New York is that immunizations are largely limited to people aged 65 years and older. Younger cancer patients are left out, and access has been spotty for all patients. “Vaccine is available one day, then not the next. It’s disheartening,” Dr. Shapiro said in an interview. “Hopefully, with the new administration, this will smooth out,” and the age limit will drop.

The study was supported by the National Institutes of Health, among other organizations. Dr. Lova, Dr. Maxwell, and Dr. Shapiro have disclosed no relevant financial relationships.

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

It’s been shown that hospitalized cancer patients and those undergoing active treatment are at high risk for severe COVID-19 complications. A new study shows that patients with cancer in remission are at higher risk, too.

For the study, investigators from the University of Pennsylvania, Philadelphia, analyzed 323 patients with SARS-CoV-2 infection in a research database with more than 4,800 patients. About 20% of database patients were Black, but they accounted for almost 65% of the infections, reflecting previous reports of increased risk for COVID among Black people.

A total of 67 of the infected patients had cancer, including 18 patients with active cancer and 49 patients whose cancer was in remission. After adjusting for demographics, smoking status, and comorbidities, a diagnosis of cancer more than doubled the odds of hospitalization and increased the odds of 30-day mortality nearly sixfold.

Worse outcomes were more strongly associated with active cancer, but patients whose cancer was in remission were also at higher risk than patients who did not have cancer.

It’s not only “patients hospitalized or on treatment ... all oncology patients need to take significant precautions during the pandemic to protect themselves,” senior investigator Kara Maxwell, MD, PhD, hematologist/oncologist and assistant professor at the University of Pennsylvania, said in a press release.

The study was published online on Jan. 21 in JNCI Cancer Spectrum.

The good news is that steps to prevent SARS-CoV-2 infection work, suggests a second report from the University of Pennsylvania. Among 124 cancer patients who underwent outpatient infusions from May to October 2020, not a single one experienced seroconversion over a median of 13 clinical visits. That second study was published on Jan. 16 in medRxiv and is pending peer review.

The zero seroconversion rate likely reflects “the success of transmission mitigation measures within health care facilities,” wrote investigators led by Lova Sun, MD, a hematology/oncology fellow at the University of Pennsylvania.

Like many institutions, the University of Pennsylvania Health System (Penn Medicine) is aggressive in protecting outpatients against the virus, the authors wrote. Among other steps, patients are queried about symptoms and contacts before their office visit, and their temperature is taken when they come in. Masks are worn, check-in is contactless, the number of visitors is limited, and patients who test positive are treated in a separate space.

In addition, patients in the study also reported that they wore masks and practiced social distancing in their daily lives.

Approached for comment, hematologist/oncologist Charles Shapiro, MD, a professor at the Icahn School of Medicine at Mount Sinai and director of translational breast cancer research at Mount Sinai Hospital, both in New York, said he wasn’t surprised that the prevention measures followed at Penn Medicine work. They are very similar to the measures followed at Mount Sinai oncology clinics, and “there’ve been very few COVID cases in our shop,” he added.

The bigger take-home message from both studies is that cancer patients, regardless of their age or if they are in remission, should be prioritized for vaccination against COVID-19, which is the best way to mitigate risk. “I strongly urge my patients to get it” if they can, he said.

The problem in New York is that immunizations are largely limited to people aged 65 years and older. Younger cancer patients are left out, and access has been spotty for all patients. “Vaccine is available one day, then not the next. It’s disheartening,” Dr. Shapiro said in an interview. “Hopefully, with the new administration, this will smooth out,” and the age limit will drop.

The study was supported by the National Institutes of Health, among other organizations. Dr. Lova, Dr. Maxwell, and Dr. Shapiro have disclosed no relevant financial relationships.

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

A systematic review suggests at least one-third of SARS-CoV-2 infections occur in people who never develop symptoms, providing strong evidence for the prevalence of asymptomatic infections.

The finding that nearly one in three infected people remain symptom free suggests testing should be changed, the investigators noted.

“To reduce transmission from people who are presymptomatic or asymptomatic, we need to shift our testing focus to at-home screening,” lead author Daniel Oran, AM, said in an interview. “Inexpensive rapid antigen tests, provided to millions of people for frequent use, could help us significantly reduce the spread of the virus.”

The systematic review was published online Jan. 22 in Annals of Internal Medicine.

The findings come at a dire time when the official number of COVID-19 cases in the United States exceeds 25 million for the first time. Public health officials have raised concerns about more transmissible, and possibly more deadly, variants of SARS-CoV-2, while a new presidential administration tries to meet the challenge of improving vaccine distribution and acceptance rates.

The results also build on earlier findings from the same research team – Mr. Oran and senior author Eric Topol, MD – that published a review article looking at asymptomatic COVID-19 cases. Even though initial data were more limited, they likewise suggested a broader scope of testing is warranted, pointing out that asymptomatic individuals can transmit SARS-CoV-2 for up to 14 days. Dr. Topol is also editor in chief of Medscape.

In the current systematic review, the highest-quality evidence comes from large studies in England and Spain. The nationally representative evidence included serologic surveys from more than 365,000 people in England and more than 61,000 in Spain. When analyzed separately, about the same proportion of asymptomatic cases emerged: 32.4% in England and 33% in Spain.

“It was really remarkable to find that nationwide antibody testing studies in England and Spain – including hundreds of thousands of people – produced nearly identical results: About one-third of the SARS-CoV-2 infections were completely asymptomatic,” said Mr. Oran, a researcher at Scripps Research Translational Institute in La Jolla, Calif.

The systematic review included 43 studies with PCR testing for active SARS-CoV-2 infection and another 18 with antibody results that indicated present or previous infection. The studies were published up until Nov. 17, 2020.

An appreciation for asymptomatic transmission of SARS-CoV-2 infection has come a long way from initial dismissals about its importance, Dr. Topol noted via Twitter. “When Dr. @camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and disparaged. She was later named a TIME 100 Person of the Year.”
 

Not symptomatic vs. never symptomatic

The term “asymptomatic” could be misleading because some people in this group do progress to develop signs of infection. This “presymptomatic” group of patients is likely a minority, the authors noted. Longitudinal studies indicate that about three-quarters of people who are asymptomatic with SARS-CoV-2 remain so.

Dr. Topol anticipated the one-third asymptomatic finding could draw some feedback about distinguishing asymptomatic from presymptomatic individuals. He tweeted, “Some will argue that there is admixture with presymptomatic cases, but review of all the data supports this estimate as being a conservative one.”

The heterogeneity of the settings, populations and other features of the studies prevented the authors from performing a meta-analysis of the findings.
 

Home is where the test is

Based on their findings, Mr. Oran and Dr. Topol believe “that COVID-19 control strategies must be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.” They suggested frequent use of inexpensive, rapid home tests to identify people who are asymptomatic or presymptomatic, along with programs and housing provided by the government to offer financial assistance and allow this group of people to isolate themselves.

Further research is warranted to determine if and how well vaccines for SARS-CoV-2 prevent asymptomatic infection.

Dr. Topol and Mr. Oran created a short video to highlight the findings from their systematic review.

The study was supported by a grant from the National Institutes of Health.

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

A systematic review suggests at least one-third of SARS-CoV-2 infections occur in people who never develop symptoms, providing strong evidence for the prevalence of asymptomatic infections.

The finding that nearly one in three infected people remain symptom free suggests testing should be changed, the investigators noted.

“To reduce transmission from people who are presymptomatic or asymptomatic, we need to shift our testing focus to at-home screening,” lead author Daniel Oran, AM, said in an interview. “Inexpensive rapid antigen tests, provided to millions of people for frequent use, could help us significantly reduce the spread of the virus.”

The systematic review was published online Jan. 22 in Annals of Internal Medicine.

The findings come at a dire time when the official number of COVID-19 cases in the United States exceeds 25 million for the first time. Public health officials have raised concerns about more transmissible, and possibly more deadly, variants of SARS-CoV-2, while a new presidential administration tries to meet the challenge of improving vaccine distribution and acceptance rates.

The results also build on earlier findings from the same research team – Mr. Oran and senior author Eric Topol, MD – that published a review article looking at asymptomatic COVID-19 cases. Even though initial data were more limited, they likewise suggested a broader scope of testing is warranted, pointing out that asymptomatic individuals can transmit SARS-CoV-2 for up to 14 days. Dr. Topol is also editor in chief of Medscape.

In the current systematic review, the highest-quality evidence comes from large studies in England and Spain. The nationally representative evidence included serologic surveys from more than 365,000 people in England and more than 61,000 in Spain. When analyzed separately, about the same proportion of asymptomatic cases emerged: 32.4% in England and 33% in Spain.

“It was really remarkable to find that nationwide antibody testing studies in England and Spain – including hundreds of thousands of people – produced nearly identical results: About one-third of the SARS-CoV-2 infections were completely asymptomatic,” said Mr. Oran, a researcher at Scripps Research Translational Institute in La Jolla, Calif.

The systematic review included 43 studies with PCR testing for active SARS-CoV-2 infection and another 18 with antibody results that indicated present or previous infection. The studies were published up until Nov. 17, 2020.

An appreciation for asymptomatic transmission of SARS-CoV-2 infection has come a long way from initial dismissals about its importance, Dr. Topol noted via Twitter. “When Dr. @camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and disparaged. She was later named a TIME 100 Person of the Year.”
 

Not symptomatic vs. never symptomatic

The term “asymptomatic” could be misleading because some people in this group do progress to develop signs of infection. This “presymptomatic” group of patients is likely a minority, the authors noted. Longitudinal studies indicate that about three-quarters of people who are asymptomatic with SARS-CoV-2 remain so.

Dr. Topol anticipated the one-third asymptomatic finding could draw some feedback about distinguishing asymptomatic from presymptomatic individuals. He tweeted, “Some will argue that there is admixture with presymptomatic cases, but review of all the data supports this estimate as being a conservative one.”

The heterogeneity of the settings, populations and other features of the studies prevented the authors from performing a meta-analysis of the findings.
 

Home is where the test is

Based on their findings, Mr. Oran and Dr. Topol believe “that COVID-19 control strategies must be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.” They suggested frequent use of inexpensive, rapid home tests to identify people who are asymptomatic or presymptomatic, along with programs and housing provided by the government to offer financial assistance and allow this group of people to isolate themselves.

Further research is warranted to determine if and how well vaccines for SARS-CoV-2 prevent asymptomatic infection.

Dr. Topol and Mr. Oran created a short video to highlight the findings from their systematic review.

The study was supported by a grant from the National Institutes of Health.

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

A systematic review suggests at least one-third of SARS-CoV-2 infections occur in people who never develop symptoms, providing strong evidence for the prevalence of asymptomatic infections.

The finding that nearly one in three infected people remain symptom free suggests testing should be changed, the investigators noted.

“To reduce transmission from people who are presymptomatic or asymptomatic, we need to shift our testing focus to at-home screening,” lead author Daniel Oran, AM, said in an interview. “Inexpensive rapid antigen tests, provided to millions of people for frequent use, could help us significantly reduce the spread of the virus.”

The systematic review was published online Jan. 22 in Annals of Internal Medicine.

The findings come at a dire time when the official number of COVID-19 cases in the United States exceeds 25 million for the first time. Public health officials have raised concerns about more transmissible, and possibly more deadly, variants of SARS-CoV-2, while a new presidential administration tries to meet the challenge of improving vaccine distribution and acceptance rates.

The results also build on earlier findings from the same research team – Mr. Oran and senior author Eric Topol, MD – that published a review article looking at asymptomatic COVID-19 cases. Even though initial data were more limited, they likewise suggested a broader scope of testing is warranted, pointing out that asymptomatic individuals can transmit SARS-CoV-2 for up to 14 days. Dr. Topol is also editor in chief of Medscape.

In the current systematic review, the highest-quality evidence comes from large studies in England and Spain. The nationally representative evidence included serologic surveys from more than 365,000 people in England and more than 61,000 in Spain. When analyzed separately, about the same proportion of asymptomatic cases emerged: 32.4% in England and 33% in Spain.

“It was really remarkable to find that nationwide antibody testing studies in England and Spain – including hundreds of thousands of people – produced nearly identical results: About one-third of the SARS-CoV-2 infections were completely asymptomatic,” said Mr. Oran, a researcher at Scripps Research Translational Institute in La Jolla, Calif.

The systematic review included 43 studies with PCR testing for active SARS-CoV-2 infection and another 18 with antibody results that indicated present or previous infection. The studies were published up until Nov. 17, 2020.

An appreciation for asymptomatic transmission of SARS-CoV-2 infection has come a long way from initial dismissals about its importance, Dr. Topol noted via Twitter. “When Dr. @camilla_rothe reported an asymptomatic transmission a year ago, the @NEJM report was refuted and disparaged. She was later named a TIME 100 Person of the Year.”
 

Not symptomatic vs. never symptomatic

The term “asymptomatic” could be misleading because some people in this group do progress to develop signs of infection. This “presymptomatic” group of patients is likely a minority, the authors noted. Longitudinal studies indicate that about three-quarters of people who are asymptomatic with SARS-CoV-2 remain so.

Dr. Topol anticipated the one-third asymptomatic finding could draw some feedback about distinguishing asymptomatic from presymptomatic individuals. He tweeted, “Some will argue that there is admixture with presymptomatic cases, but review of all the data supports this estimate as being a conservative one.”

The heterogeneity of the settings, populations and other features of the studies prevented the authors from performing a meta-analysis of the findings.
 

Home is where the test is

Based on their findings, Mr. Oran and Dr. Topol believe “that COVID-19 control strategies must be altered, taking into account the prevalence and transmission risk of asymptomatic SARS-CoV-2 infection.” They suggested frequent use of inexpensive, rapid home tests to identify people who are asymptomatic or presymptomatic, along with programs and housing provided by the government to offer financial assistance and allow this group of people to isolate themselves.

Further research is warranted to determine if and how well vaccines for SARS-CoV-2 prevent asymptomatic infection.

Dr. Topol and Mr. Oran created a short video to highlight the findings from their systematic review.

The study was supported by a grant from the National Institutes of Health.

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

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Palliative care referrals for inpatients with pulmonary arterial hypertension averaged 2%, a retrospective study of more than 30,000 hospital admissions has found.

“Specialty palliative care services (PCS) are present in the vast majority of hospitals with more than 300 beds, and PCS use for patients who are facing serious illness with potentially life-limiting prognoses increasingly is becoming the standard of care,” wrote Vidhu Anand, MD, of the Mayo Clinic, Rochester, Minn., and colleagues. But despite experts recommending PCS in pulmonary arterial hypertension (PAH), data on the use of palliative care referrals for PAH patients are limited, they added.

In a study published in Chest, the researchers used the National (Nationwide) Inpatient Sample to identify 30,495 admissions with a primary diagnosis of PAH between 2001 through 2017. The primary outcome was the use of PCS in these patients.

Overall, inpatient use of PCS was 2.2%, but that figure increased from 0.5% in 2001 to 7.6% in 2017, representing a fivefold increase over the study period, with a significant increase after 2009. The reason for this notable increase remains unclear; however, “it may be related to recognition of palliative care and hospice as a medical subspecialty with board certification in 2008 or identification of palliative care by the National Priorities Partnership as one of six priority areas in 2008,” the researchers said.
 

Incorporating palliative care in a treatment strategy

The perception of PCS as an element of treatment plans for patients with severe lung disease, and not only as end-of-life care, has certainly increased in recent years, Sachin Gupta, MD, FCCP, said in an interview.

Dr. Gupta is a pulmonologist practicing in the San Francisco Bay area, and he did not take part in the study. He recommended early integration of PCS treating patients with PAH. “I have frequently asked PCS to aid early on during inpatient admission with PAH patients for pain management, as well as for aiding in POLST [Physician Orders for Life-Sustaining Treatment] paperwork to be completed. Increased age and comorbidities are certainly risk factors themselves for a longer hospital course and worse outcomes; in addition, in center-based PAH care there are more means available by which to give a patient with right heart failure that ‘one last shot’ – an opportunity for a longer life. I truly think it is a relationship with the patient, built from the outpatient pulmonary hypertension clinic, that allows the treating physician to have a better sense of a patient’s quality of life longitudinally, and to have the candid conversation when things begin to decline.”

Which patients receive PCS?

The study found that socioeconomic factors, and the severity of illness, are the drivers of PCS referrals. In a multivariate analysis, independent predictors of PCS use included white race, private insurance, and higher socioeconomic status. Additional independent predictors of PCS use included increased comorbidities, admission to an urban hospital, admission to a small hospital, presence of heart failure and cardiogenic shock, acute noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation, the researchers noted.

Patients who received PCS consultation were significantly more likely than those not receiving PCS to have DNR status (46.2% vs. 1.8%), longer length of hospital stay (12.9 days vs. 7.2 days), higher hospitalization costs $130,434 vs. $56,499), and higher in-hospital mortality (52.8% vs. 6.4%; P < .001 for all).

Some patients refuse PCS and others are not offered PCS. Dr. Gupta noted that it should be no surprise that not all patients are comfortable with the idea of a PCS referral. “Fear, misunderstanding, and cultural beliefs may be individually or together at the root of resistance to PCS. Their reluctance may be due to a ‘false narrative’ of the purpose of palliative care. The conception of PCS being for end-of-life care may be the result of personal experiences or experience with loved ones. Occasionally, a patient equates PCS with access to narcotics (‘knock me out’), which they may or may not want. I try to reassure patients that there will be no coercion for anything they do not want, and at the end of the day, the medical team is the main driver of their care, not the palliative service.”

Actively drug-abusing PAH patients are a particular challenge, said Dr. Gupta. These patients often refuse palliative care referral both as inpatients and outpatients. “Such patients are an enigma for many PAH-treating physicians as they may survive to discharge, despite a terrible prognosis predicted by their testing.”

In addition, patients in whom organ transplantation is being pursued may not receive timely PCS, he said. “It can be an absolute challenge to bring such patients to the finish line (transplantation), and the timing of PCS referral is often deferred. Arguably, for better or worse, such patients refuse, or more often are not offered, PCS as inpatients while there is still a chance organ transplantation is a viable option for them.”

The use of PCS in less than 10% of PAH admissions is similar to previous studies showing low use of PCS for patients with acute myocardial infarction, heart failure, and COPD, the researchers noted. However, “Given the high morbidity and mortality associated with PAH even after hospitalization, hospital admissions without PCS use represent a missed opportunity,” the investigators wrote.
 

Early warning on the need for PCS

Increasing PCS referrals for PAH patients requires clinicians to be proactive, Dr. Gupta stressed. “Pulmonologists, especially those managing pulmonary hypertension outpatients without the aid of a PAH center, should remain vigilant at all routine visits to calculate a patient’s risk score (i.e. REVEAL 2.0 risk calculator) to stratify their risk of 1-year mortality. Based on this assessment, shared decision making can help guide next steps including early outpatient PCS involvement for those at high risk. I also calculate a patient’s risk score, based on the data I have, when PAH patients are admitted to the hospital. Occasionally, a patient who I initially think is moderate risk turns out to be high risk when I calculate their risk score. In such high-risk patients, PCS consultation should certainly be considered early on.”

The study findings were limited by several factors including the possible coding errors associated with use of discharge diagnosis, lack of data on medication and the cause of PAH, and lack of information on the reasons for PCS referrals, the researchers noted. However, the results “addressed an important knowledge gap highlighting the national use of PCS in PAH,” they said. Further research is needed to address disparities and the integration of PCS into PAH care protocols, they added.

The researchers had no financial conflicts to disclose. The study received no outside funding; one coauthor disclosed support from the National Center for Advancing Translational Sciences Clinical and Translational Science.

Both patients in contact with primary care physicians and patient contact with these physicians in any form – including in office or over the phone – declined over 2-year periods occurring from 2002 to 2017.

The reasons for this less frequent contact and the ramifications for patients and doctors practicing primary care are unclear, according to various experts. But some offered possible explanations for the changes, with patients’ increased participation in high deductible plans and shortages in primary care physicians (PCPs) being among the most often cited.

The findings, which were published online Jan. 11 in Annals of Family Medicine, were derived from researchers using a repeated cross-sectional study of the 2002-2017 Medical Expenditure Panel Survey to characterize trends in primary care use. This survey, which collected information about medical care utilization from individuals and families, included 243,919 participants who were interviewed five times over 2 years. The authors defined primary care physician contact as “in-person visit or contact with a primary care physician (primarily telephone calls) with a reported specialty of family medicine, general internal medicine, geriatrics, general pediatrics, or general practice physician.” According to the paper, “the proportion of individuals with any primary care physician contact was determined for both the population and by age group using logistic regression models,” and negative binomial regression models were used to determine the number of contacts among people with visits during 2-year periods.

The study authors, Michael E. Johansen, MD, MS, and Joshua D. Niforatos, MD, MTS, said their study suggests that previously reported decreases in primary care contact was caused by fewer contacts per patient “as opposed to an absolute decrease in the number of patients in contact with primary care.”

Harold B. Betton, MD, PhD, who practices family medicine in Little Rock, Ark., questioned this claim.

"The paper draws observational conclusions and I fail to see the merit in the observation without knowing what the respondents were asked and not asked," he added. 

Other primary care physicians suggested patients’ participation in alternative pay models and high-deductible plans have played a factor in the declines.

Courtesy of Ada Stewart, MD

“Most of us have gone from fee-for-service, volume-based care to more value-based care,” Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. The data reflect that trend, “whereas we were rewarded more for the number of people we were seeing, now we are trying to get towards more of the value that we provide,” suggested Dr. Stewart, who also practices family medicine with Cooperative Health in Columbia, S.C.

“Given the rise of high-deductible plans and copays, it is not surprising that younger patients, a generally healthier population, might well decrease their visits to a primary care physician. I would suspect that data for patients over 50 might well be different,” William E. Golden, MD, who is medical director at the Arkansas Department of Health & Human Services, noted in an interview.

Eileen Barrett, MD, MPH, also cited greater participation in high-deductible plans as a possible factor that could be leading some patients to forgo visits, as well as increased financial insecurity, rendering it expensive to have the visit and also to take time from work for the visit.

“I would wonder if some of this is also due to how overloaded most primary care offices are so that instead of stopping accepting new patients or shedding patients, it is just harder for existing patients to be seen,” said Dr. Barrett, who is a general internist and associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque. “Some of this could be from administrative burden – 2 hours per hour of clinic – and consequently reducing clinical time,” continued Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, which is affiliated with Family Practice News.

Other experts pointed to data showing an insufficient supply of PCPs as a potential explanation for the new study’s findings. The Health Resources and Services Organization, for example, reported that 83 million Americans live in primary care “health professional shortage areas,” as of Jan. 24, 2021, on their website.
 

New data

“The rate of any contact with a [PCP] for patients in the population over multiple 2-year periods decreased by 2.5% over the study period (adjusted odds ratio, 0.99 per panel; 95% [confidence interval], 0.98-0.99; P < .001),” wrote Dr. Johansen and Dr. Niforatos. The rate of contact for patients aged 18-39 years (aOR, 0.99 per panel; 95% CI, 0.98-0.99; P < .001) and patients aged 40-64 years (aOR, 0.99 per panel; 95% CI, 0.99-1.00; P = .002), specifically, also fell. These decreased contact rates correspond “to a predicted cumulative 5% absolute decrease for the younger group and a 2% absolute decrease for the older group,” the authors added.

“The number of contacts with a [PCP] decreased among individuals with any contact by 0.5 contacts over 2 years (P < .001). A decrease in the number of [PCP] contacts was observed across all age groups (P < .001 for all), with the largest absolute decrease among individuals with higher contact rates (aged less than 4 years and aged greater than 64 years),” according to the paper.

Outlook for PCPs

Physicians questioned about how concerning these data are for the future of PCPs and their ability to keep their practices running were hesitant to speculate, because of uncertainty about the causes of the study findings.

“A quote from the paper indicates that the respondents were interviewed five times over 2 years; however, without a copy of the questionnaire it is impossible to know what they were asked and not asked,” said Dr. Betton, who also serves on the editorial advisory board of Family Practice News and runs his own private practice. “In addition, it is impossible for the reader to know whether they understood what a primary care physician was to do.

“To draw a conclusion that PCP visits are falling off per patient per provider is only helpful if patients are opting out of the primary care model of practice and opting in for point-of-care [urgent] care,” Dr. Betton added.

Internist Alan Nelson, MD, said he was also undecided about whether the findings of the study are good or bad news for the physician specialty of primary care.

“Similar findings have been reported by the Medicare Payment Advisory Commission. They certainly merit further investigation,” noted Dr. Nelson, who is a member of the editorial advisory board of Internal Medicine News. “Is it because primary care physicians are too busy to see additional patients? Is it because nonphysician practitioners seem to be more caring? Should residency training be modified, and if so, how? In the meantime, I would not be surprised if the trend continues, at least in the short term.”

Ann Greiner, president and CEO of the Primary Care Collaborative, a nonprofit organization that advocates to strengthen primary care and make it more responsive to patient needs and preferences, on the other hand, reacted with a concerned outlook for primary care.

This study and others show that “the U.S. health care system is moving away from a primary care orientation, and that is concerning,” Ms. Greiner said in an interview. “Health systems that are more oriented toward primary care have better population health outcomes, do better on measures of equity across different population groups, and are less costly.”
 

Authors’ take

“Future research is needed to determine whether fewer contacts per patient resulted in clinically meaningful differences in outcomes across disease processes,” wrote Dr. Johansen, who is a family medicine doctor affiliated with OhioHealth Family Medicine Grant in Columbus and with the Heritage College of Osteopathic Medicine at Ohio University, Dublin, and Dr. Niforatos, who is affiliated with the department of emergency medicine at Johns Hopkins University, Baltimore.

The study’s limitations included reliance on self-reported categorization of PCP versus specialty care physician contact, insufficient accounting for nurse practitioner and physician assistant contact, and improved contact reporting having started in 2013, they said.
 

How to grow patient contact

For those PCPs looking to grow their visits and patient contact, Dr. Golden suggested they strengthen their medical home model in their practice.

“Medical home models help and transform practice operations. The Arkansas model is a multipayer model – private, Medicaid and CPC+ (Medicare),” said Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News. It includes community-based doctors, not Federally Qualified Health Centers, and “requires 24/7 live voice access that promotes regular contact with patients and can reduce dependency on ER and urgent care center visits.”

“Greater use of patient portals and email communications facilitate access and patient engagement with their PCP,” Dr. Golden explained.

 “Over the last 6 years, the Arkansas [patient-centered medical home] initiatives have altered culture and made our practice sites stronger to withstand COVID and other challenges. As our sites became more patient centered and incorporated behavioral health options, patients perceived greater value in the functionality of primary care” he said.

Dr. Barrett proposed PCPs participate in team-based care “for professional sustainability and also for patients to continue to experience high-quality, person-centered care.” She added that “telemedicine can also help practices maintain and increase patients, as it can lessen burden on patients and clinicians – if it is done right.”

“More flexible clinic hours is also key – after usual business hours and on weekends – but I would recommend in lieu of usual weekday hours and for those who can make it work with their family and other duties,” Dr. Barrett said. “Evening or Saturday morning clinic isn’t an option for everyone, but it is an option for many some of the time, and it would be great for access to care if it were available in more locations.”
 

Pandemic effect

The data examined by Dr. Johansen and Dr. Niforatos predates the pandemic, but PCPs interviewed by this news organization have seen declining patient contact occur in 2020 as well.

In fact, a survey of 1,485 mostly physician primary care practitioners that began after the pandemic onset found that 43% of participants have fewer in-person visits, motivated largely by patient preferences (66%) and safety concerns (74%). This ongoing survey, which was conducted by the Larry Green Center in partnership with the Primary Care Collaborative, also indicated that, while 25% of participants saw a total increase in patient volume, more than half of primary care practitioners reported that chronic and wellness visits are down, 53% and 55%, respectively.

“Sometimes we have to go looking for our patients when we have not seen them in a while,” Dr. Stewart noted. “We saw that with COVID because people were fearful of coming into our offices, and we had to have some outreach.”

The study authors had no conflicts of interest. Dr. Barrett, Dr. Betton, Dr. Golden, Dr. Nelson, and Dr. Stewart had no relevant disclosures.

Jake Remaly contributed to this article.

[email protected]

Both patients in contact with primary care physicians and patient contact with these physicians in any form – including in office or over the phone – declined over 2-year periods occurring from 2002 to 2017.

The reasons for this less frequent contact and the ramifications for patients and doctors practicing primary care are unclear, according to various experts. But some offered possible explanations for the changes, with patients’ increased participation in high deductible plans and shortages in primary care physicians (PCPs) being among the most often cited.

The findings, which were published online Jan. 11 in Annals of Family Medicine, were derived from researchers using a repeated cross-sectional study of the 2002-2017 Medical Expenditure Panel Survey to characterize trends in primary care use. This survey, which collected information about medical care utilization from individuals and families, included 243,919 participants who were interviewed five times over 2 years. The authors defined primary care physician contact as “in-person visit or contact with a primary care physician (primarily telephone calls) with a reported specialty of family medicine, general internal medicine, geriatrics, general pediatrics, or general practice physician.” According to the paper, “the proportion of individuals with any primary care physician contact was determined for both the population and by age group using logistic regression models,” and negative binomial regression models were used to determine the number of contacts among people with visits during 2-year periods.

The study authors, Michael E. Johansen, MD, MS, and Joshua D. Niforatos, MD, MTS, said their study suggests that previously reported decreases in primary care contact was caused by fewer contacts per patient “as opposed to an absolute decrease in the number of patients in contact with primary care.”

Harold B. Betton, MD, PhD, who practices family medicine in Little Rock, Ark., questioned this claim.

"The paper draws observational conclusions and I fail to see the merit in the observation without knowing what the respondents were asked and not asked," he added. 

Other primary care physicians suggested patients’ participation in alternative pay models and high-deductible plans have played a factor in the declines.

Courtesy of Ada Stewart, MD

“Most of us have gone from fee-for-service, volume-based care to more value-based care,” Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. The data reflect that trend, “whereas we were rewarded more for the number of people we were seeing, now we are trying to get towards more of the value that we provide,” suggested Dr. Stewart, who also practices family medicine with Cooperative Health in Columbia, S.C.

“Given the rise of high-deductible plans and copays, it is not surprising that younger patients, a generally healthier population, might well decrease their visits to a primary care physician. I would suspect that data for patients over 50 might well be different,” William E. Golden, MD, who is medical director at the Arkansas Department of Health & Human Services, noted in an interview.

Eileen Barrett, MD, MPH, also cited greater participation in high-deductible plans as a possible factor that could be leading some patients to forgo visits, as well as increased financial insecurity, rendering it expensive to have the visit and also to take time from work for the visit.

“I would wonder if some of this is also due to how overloaded most primary care offices are so that instead of stopping accepting new patients or shedding patients, it is just harder for existing patients to be seen,” said Dr. Barrett, who is a general internist and associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque. “Some of this could be from administrative burden – 2 hours per hour of clinic – and consequently reducing clinical time,” continued Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, which is affiliated with Family Practice News.

Other experts pointed to data showing an insufficient supply of PCPs as a potential explanation for the new study’s findings. The Health Resources and Services Organization, for example, reported that 83 million Americans live in primary care “health professional shortage areas,” as of Jan. 24, 2021, on their website.
 

New data

“The rate of any contact with a [PCP] for patients in the population over multiple 2-year periods decreased by 2.5% over the study period (adjusted odds ratio, 0.99 per panel; 95% [confidence interval], 0.98-0.99; P < .001),” wrote Dr. Johansen and Dr. Niforatos. The rate of contact for patients aged 18-39 years (aOR, 0.99 per panel; 95% CI, 0.98-0.99; P < .001) and patients aged 40-64 years (aOR, 0.99 per panel; 95% CI, 0.99-1.00; P = .002), specifically, also fell. These decreased contact rates correspond “to a predicted cumulative 5% absolute decrease for the younger group and a 2% absolute decrease for the older group,” the authors added.

“The number of contacts with a [PCP] decreased among individuals with any contact by 0.5 contacts over 2 years (P < .001). A decrease in the number of [PCP] contacts was observed across all age groups (P < .001 for all), with the largest absolute decrease among individuals with higher contact rates (aged less than 4 years and aged greater than 64 years),” according to the paper.

Outlook for PCPs

Physicians questioned about how concerning these data are for the future of PCPs and their ability to keep their practices running were hesitant to speculate, because of uncertainty about the causes of the study findings.

“A quote from the paper indicates that the respondents were interviewed five times over 2 years; however, without a copy of the questionnaire it is impossible to know what they were asked and not asked,” said Dr. Betton, who also serves on the editorial advisory board of Family Practice News and runs his own private practice. “In addition, it is impossible for the reader to know whether they understood what a primary care physician was to do.

“To draw a conclusion that PCP visits are falling off per patient per provider is only helpful if patients are opting out of the primary care model of practice and opting in for point-of-care [urgent] care,” Dr. Betton added.

Internist Alan Nelson, MD, said he was also undecided about whether the findings of the study are good or bad news for the physician specialty of primary care.

“Similar findings have been reported by the Medicare Payment Advisory Commission. They certainly merit further investigation,” noted Dr. Nelson, who is a member of the editorial advisory board of Internal Medicine News. “Is it because primary care physicians are too busy to see additional patients? Is it because nonphysician practitioners seem to be more caring? Should residency training be modified, and if so, how? In the meantime, I would not be surprised if the trend continues, at least in the short term.”

Ann Greiner, president and CEO of the Primary Care Collaborative, a nonprofit organization that advocates to strengthen primary care and make it more responsive to patient needs and preferences, on the other hand, reacted with a concerned outlook for primary care.

This study and others show that “the U.S. health care system is moving away from a primary care orientation, and that is concerning,” Ms. Greiner said in an interview. “Health systems that are more oriented toward primary care have better population health outcomes, do better on measures of equity across different population groups, and are less costly.”
 

Authors’ take

“Future research is needed to determine whether fewer contacts per patient resulted in clinically meaningful differences in outcomes across disease processes,” wrote Dr. Johansen, who is a family medicine doctor affiliated with OhioHealth Family Medicine Grant in Columbus and with the Heritage College of Osteopathic Medicine at Ohio University, Dublin, and Dr. Niforatos, who is affiliated with the department of emergency medicine at Johns Hopkins University, Baltimore.

The study’s limitations included reliance on self-reported categorization of PCP versus specialty care physician contact, insufficient accounting for nurse practitioner and physician assistant contact, and improved contact reporting having started in 2013, they said.
 

How to grow patient contact

For those PCPs looking to grow their visits and patient contact, Dr. Golden suggested they strengthen their medical home model in their practice.

“Medical home models help and transform practice operations. The Arkansas model is a multipayer model – private, Medicaid and CPC+ (Medicare),” said Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News. It includes community-based doctors, not Federally Qualified Health Centers, and “requires 24/7 live voice access that promotes regular contact with patients and can reduce dependency on ER and urgent care center visits.”

“Greater use of patient portals and email communications facilitate access and patient engagement with their PCP,” Dr. Golden explained.

 “Over the last 6 years, the Arkansas [patient-centered medical home] initiatives have altered culture and made our practice sites stronger to withstand COVID and other challenges. As our sites became more patient centered and incorporated behavioral health options, patients perceived greater value in the functionality of primary care” he said.

Dr. Barrett proposed PCPs participate in team-based care “for professional sustainability and also for patients to continue to experience high-quality, person-centered care.” She added that “telemedicine can also help practices maintain and increase patients, as it can lessen burden on patients and clinicians – if it is done right.”

“More flexible clinic hours is also key – after usual business hours and on weekends – but I would recommend in lieu of usual weekday hours and for those who can make it work with their family and other duties,” Dr. Barrett said. “Evening or Saturday morning clinic isn’t an option for everyone, but it is an option for many some of the time, and it would be great for access to care if it were available in more locations.”
 

Pandemic effect

The data examined by Dr. Johansen and Dr. Niforatos predates the pandemic, but PCPs interviewed by this news organization have seen declining patient contact occur in 2020 as well.

In fact, a survey of 1,485 mostly physician primary care practitioners that began after the pandemic onset found that 43% of participants have fewer in-person visits, motivated largely by patient preferences (66%) and safety concerns (74%). This ongoing survey, which was conducted by the Larry Green Center in partnership with the Primary Care Collaborative, also indicated that, while 25% of participants saw a total increase in patient volume, more than half of primary care practitioners reported that chronic and wellness visits are down, 53% and 55%, respectively.

“Sometimes we have to go looking for our patients when we have not seen them in a while,” Dr. Stewart noted. “We saw that with COVID because people were fearful of coming into our offices, and we had to have some outreach.”

The study authors had no conflicts of interest. Dr. Barrett, Dr. Betton, Dr. Golden, Dr. Nelson, and Dr. Stewart had no relevant disclosures.

Jake Remaly contributed to this article.

[email protected]

Both patients in contact with primary care physicians and patient contact with these physicians in any form – including in office or over the phone – declined over 2-year periods occurring from 2002 to 2017.

The reasons for this less frequent contact and the ramifications for patients and doctors practicing primary care are unclear, according to various experts. But some offered possible explanations for the changes, with patients’ increased participation in high deductible plans and shortages in primary care physicians (PCPs) being among the most often cited.

The findings, which were published online Jan. 11 in Annals of Family Medicine, were derived from researchers using a repeated cross-sectional study of the 2002-2017 Medical Expenditure Panel Survey to characterize trends in primary care use. This survey, which collected information about medical care utilization from individuals and families, included 243,919 participants who were interviewed five times over 2 years. The authors defined primary care physician contact as “in-person visit or contact with a primary care physician (primarily telephone calls) with a reported specialty of family medicine, general internal medicine, geriatrics, general pediatrics, or general practice physician.” According to the paper, “the proportion of individuals with any primary care physician contact was determined for both the population and by age group using logistic regression models,” and negative binomial regression models were used to determine the number of contacts among people with visits during 2-year periods.

The study authors, Michael E. Johansen, MD, MS, and Joshua D. Niforatos, MD, MTS, said their study suggests that previously reported decreases in primary care contact was caused by fewer contacts per patient “as opposed to an absolute decrease in the number of patients in contact with primary care.”

Harold B. Betton, MD, PhD, who practices family medicine in Little Rock, Ark., questioned this claim.

"The paper draws observational conclusions and I fail to see the merit in the observation without knowing what the respondents were asked and not asked," he added. 

Other primary care physicians suggested patients’ participation in alternative pay models and high-deductible plans have played a factor in the declines.

Courtesy of Ada Stewart, MD

“Most of us have gone from fee-for-service, volume-based care to more value-based care,” Ada D. Stewart, MD, president of the American Academy of Family Physicians, said in an interview. The data reflect that trend, “whereas we were rewarded more for the number of people we were seeing, now we are trying to get towards more of the value that we provide,” suggested Dr. Stewart, who also practices family medicine with Cooperative Health in Columbia, S.C.

“Given the rise of high-deductible plans and copays, it is not surprising that younger patients, a generally healthier population, might well decrease their visits to a primary care physician. I would suspect that data for patients over 50 might well be different,” William E. Golden, MD, who is medical director at the Arkansas Department of Health & Human Services, noted in an interview.

Eileen Barrett, MD, MPH, also cited greater participation in high-deductible plans as a possible factor that could be leading some patients to forgo visits, as well as increased financial insecurity, rendering it expensive to have the visit and also to take time from work for the visit.

“I would wonder if some of this is also due to how overloaded most primary care offices are so that instead of stopping accepting new patients or shedding patients, it is just harder for existing patients to be seen,” said Dr. Barrett, who is a general internist and associate professor in the division of hospital medicine, department of internal medicine, at the University of New Mexico, Albuquerque. “Some of this could be from administrative burden – 2 hours per hour of clinic – and consequently reducing clinical time,” continued Dr. Barrett, who also serves on the editorial advisory board of Internal Medicine News, which is affiliated with Family Practice News.

Other experts pointed to data showing an insufficient supply of PCPs as a potential explanation for the new study’s findings. The Health Resources and Services Organization, for example, reported that 83 million Americans live in primary care “health professional shortage areas,” as of Jan. 24, 2021, on their website.
 

New data

“The rate of any contact with a [PCP] for patients in the population over multiple 2-year periods decreased by 2.5% over the study period (adjusted odds ratio, 0.99 per panel; 95% [confidence interval], 0.98-0.99; P < .001),” wrote Dr. Johansen and Dr. Niforatos. The rate of contact for patients aged 18-39 years (aOR, 0.99 per panel; 95% CI, 0.98-0.99; P < .001) and patients aged 40-64 years (aOR, 0.99 per panel; 95% CI, 0.99-1.00; P = .002), specifically, also fell. These decreased contact rates correspond “to a predicted cumulative 5% absolute decrease for the younger group and a 2% absolute decrease for the older group,” the authors added.

“The number of contacts with a [PCP] decreased among individuals with any contact by 0.5 contacts over 2 years (P < .001). A decrease in the number of [PCP] contacts was observed across all age groups (P < .001 for all), with the largest absolute decrease among individuals with higher contact rates (aged less than 4 years and aged greater than 64 years),” according to the paper.

Outlook for PCPs

Physicians questioned about how concerning these data are for the future of PCPs and their ability to keep their practices running were hesitant to speculate, because of uncertainty about the causes of the study findings.

“A quote from the paper indicates that the respondents were interviewed five times over 2 years; however, without a copy of the questionnaire it is impossible to know what they were asked and not asked,” said Dr. Betton, who also serves on the editorial advisory board of Family Practice News and runs his own private practice. “In addition, it is impossible for the reader to know whether they understood what a primary care physician was to do.

“To draw a conclusion that PCP visits are falling off per patient per provider is only helpful if patients are opting out of the primary care model of practice and opting in for point-of-care [urgent] care,” Dr. Betton added.

Internist Alan Nelson, MD, said he was also undecided about whether the findings of the study are good or bad news for the physician specialty of primary care.

“Similar findings have been reported by the Medicare Payment Advisory Commission. They certainly merit further investigation,” noted Dr. Nelson, who is a member of the editorial advisory board of Internal Medicine News. “Is it because primary care physicians are too busy to see additional patients? Is it because nonphysician practitioners seem to be more caring? Should residency training be modified, and if so, how? In the meantime, I would not be surprised if the trend continues, at least in the short term.”

Ann Greiner, president and CEO of the Primary Care Collaborative, a nonprofit organization that advocates to strengthen primary care and make it more responsive to patient needs and preferences, on the other hand, reacted with a concerned outlook for primary care.

This study and others show that “the U.S. health care system is moving away from a primary care orientation, and that is concerning,” Ms. Greiner said in an interview. “Health systems that are more oriented toward primary care have better population health outcomes, do better on measures of equity across different population groups, and are less costly.”
 

Authors’ take

“Future research is needed to determine whether fewer contacts per patient resulted in clinically meaningful differences in outcomes across disease processes,” wrote Dr. Johansen, who is a family medicine doctor affiliated with OhioHealth Family Medicine Grant in Columbus and with the Heritage College of Osteopathic Medicine at Ohio University, Dublin, and Dr. Niforatos, who is affiliated with the department of emergency medicine at Johns Hopkins University, Baltimore.

The study’s limitations included reliance on self-reported categorization of PCP versus specialty care physician contact, insufficient accounting for nurse practitioner and physician assistant contact, and improved contact reporting having started in 2013, they said.
 

How to grow patient contact

For those PCPs looking to grow their visits and patient contact, Dr. Golden suggested they strengthen their medical home model in their practice.

“Medical home models help and transform practice operations. The Arkansas model is a multipayer model – private, Medicaid and CPC+ (Medicare),” said Dr. Golden, who also serves on the editorial advisory board of Internal Medicine News. It includes community-based doctors, not Federally Qualified Health Centers, and “requires 24/7 live voice access that promotes regular contact with patients and can reduce dependency on ER and urgent care center visits.”

“Greater use of patient portals and email communications facilitate access and patient engagement with their PCP,” Dr. Golden explained.

 “Over the last 6 years, the Arkansas [patient-centered medical home] initiatives have altered culture and made our practice sites stronger to withstand COVID and other challenges. As our sites became more patient centered and incorporated behavioral health options, patients perceived greater value in the functionality of primary care” he said.

Dr. Barrett proposed PCPs participate in team-based care “for professional sustainability and also for patients to continue to experience high-quality, person-centered care.” She added that “telemedicine can also help practices maintain and increase patients, as it can lessen burden on patients and clinicians – if it is done right.”

“More flexible clinic hours is also key – after usual business hours and on weekends – but I would recommend in lieu of usual weekday hours and for those who can make it work with their family and other duties,” Dr. Barrett said. “Evening or Saturday morning clinic isn’t an option for everyone, but it is an option for many some of the time, and it would be great for access to care if it were available in more locations.”
 

Pandemic effect

The data examined by Dr. Johansen and Dr. Niforatos predates the pandemic, but PCPs interviewed by this news organization have seen declining patient contact occur in 2020 as well.

In fact, a survey of 1,485 mostly physician primary care practitioners that began after the pandemic onset found that 43% of participants have fewer in-person visits, motivated largely by patient preferences (66%) and safety concerns (74%). This ongoing survey, which was conducted by the Larry Green Center in partnership with the Primary Care Collaborative, also indicated that, while 25% of participants saw a total increase in patient volume, more than half of primary care practitioners reported that chronic and wellness visits are down, 53% and 55%, respectively.

“Sometimes we have to go looking for our patients when we have not seen them in a while,” Dr. Stewart noted. “We saw that with COVID because people were fearful of coming into our offices, and we had to have some outreach.”

The study authors had no conflicts of interest. Dr. Barrett, Dr. Betton, Dr. Golden, Dr. Nelson, and Dr. Stewart had no relevant disclosures.

Jake Remaly contributed to this article.

[email protected]

Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.

The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.

In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

[email protected]

Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.

The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.

In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

[email protected]

Fully half of patients with moderate to severe psoriasis who achieve complete clearance after their first four doses of guselkumab (Tremfya) continue to maintain a PASI 90 response nearly 6 months after withdrawal of the biologic, according to a post hoc analysis of the pivotal phase 3 VOYAGE 2 trial.

“That’s impressive maintenance of efficacy,” said Curdin Conrad, MD, who presented the data at the virtual annual congress of the European Academy of Dermatology and Venereology.

“These findings are reassuring when you have to interrupt guselkumab therapy: For example, due to acute infection, pregnancy, or surgery. But it might also help when considering in the future a flexible dosing interval, particularly for patients who had complete clearance,” added Dr. Conrad, professor of dermatology and head of the polyclinic and the Center of Excellence for Psoriasis at Lausanne (Switzerland) University Hospital.

The intriguing implication from VOYAGE 2 that guselkumab might lend itself to flexible dosing featuring lengthy drug-free intervals is being prospectively examined in the ongoing phase 3b GUIDE trial. This is a double-blind, placebo-controlled trial including 888 French and German patients with moderate to severe psoriasis and a study hypothesis that those who have a Psoriasis Area and Severity Index score of 0 at weeks 20 and 28 in response to on-label dosing – the so-called ‘super responders’ – will maintain disease control until week 68 if their dosing is reduced to 100 mg of guselkumab every 16 weeks instead of the standard 8-week intervals.

Dr. Conrad reported that in VOYAGE 2, 106 patients on standard-dose guselkumab who had a PASI score of 0 at weeks 20 and 28 were randomized to discontinue the interleukin-23 inhibitor after receiving their fourth dose at week 20. It took 25 weeks for 50% of them to lose their PASI 90 response as defined by regression to a PASI score of 1 or greater. Using a less stringent definition of maintenance of efficacy, the super responders’ median time off guselkumab until reaching a PASI score of 3 or more was 30.7 weeks, with a median of 35.4 weeks to a PASI score of 5 or more.

In addition, 34 other VOYAGE 2 participants who were almost clear on guselkumab at weeks 20 and 28, with a PASI score of more than 0 but less than 1, were randomized to guselkumab withdrawal after their week-20 dose. Median time to loss of their PASI 90 response was shorter than that of the super responders – not surprising since their mean PASI score when the biologic was halted was 0.5, rather than 0 as for the super responders. But Dr. Conrad said the maintenance of response was still impressive: A median of 16.2 weeks to reach a PASI score of 1 or more, 27.2 weeks for a PASI 3, and 33.7 weeks for a PASI score of 5.

He reported receiving research funding from and serving as a scientific adviser to Janssen, the study sponsor, as well as to more than a dozen other pharmaceutical companies.

[email protected]

The Food and Drug Administration has approved voclosporin (Lupkynis) for the treatment of lupus nephritis, according to a Jan. 22 press release from manufacturer Aurinia Pharmaceuticals.

Lupkynis is a calcineurin-inhibitor immunosuppressant, and is the first oral medication to show effectiveness in lupus nephritis, according to the company. The drug is indicated for the treatment of adult patients with active lupus nephritis in combination with a background immunosuppressive therapy regimen, according to the drug label, which also has a boxed warning describing the increased risk of infections and malignancies, including lymphoma.

The approval of voclosporin was based on data from two studies, the AURORA phase 3 study and the AURA-LV phase 2 study. The studies included 533 adults with lupus nephritis who were randomized to 23.7 mg or placebo of voclosporin twice daily in the form of oral capsules, or placebo capsules, in addition to standard of care (mycophenolate mofetil plus low-dose glucocorticoids).

In the AURORA phase 3 study of 357 patients, close to twice as many patients in the treatment group showed a complete renal response, compared with the placebo group after 1 year (40.8% vs. 22.5%). In addition, patients treated with voclosporin more quickly achieved a significant reduction in urine protein to creatinine ratio, compared with the placebo patients (169 days vs. 372 days).

Severe adverse events were similar between the groups, including the most common complication of infection (10.1% and 11.2% for voclosporin and control groups, respectively). Other adverse reactions reported in at least 3% of the study participants included a decrease in glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite, according to the company press release.

Full clinical trial information for the AURORA study is available here.

The Food and Drug Administration has approved voclosporin (Lupkynis) for the treatment of lupus nephritis, according to a Jan. 22 press release from manufacturer Aurinia Pharmaceuticals.

Lupkynis is a calcineurin-inhibitor immunosuppressant, and is the first oral medication to show effectiveness in lupus nephritis, according to the company. The drug is indicated for the treatment of adult patients with active lupus nephritis in combination with a background immunosuppressive therapy regimen, according to the drug label, which also has a boxed warning describing the increased risk of infections and malignancies, including lymphoma.

The approval of voclosporin was based on data from two studies, the AURORA phase 3 study and the AURA-LV phase 2 study. The studies included 533 adults with lupus nephritis who were randomized to 23.7 mg or placebo of voclosporin twice daily in the form of oral capsules, or placebo capsules, in addition to standard of care (mycophenolate mofetil plus low-dose glucocorticoids).

In the AURORA phase 3 study of 357 patients, close to twice as many patients in the treatment group showed a complete renal response, compared with the placebo group after 1 year (40.8% vs. 22.5%). In addition, patients treated with voclosporin more quickly achieved a significant reduction in urine protein to creatinine ratio, compared with the placebo patients (169 days vs. 372 days).

Severe adverse events were similar between the groups, including the most common complication of infection (10.1% and 11.2% for voclosporin and control groups, respectively). Other adverse reactions reported in at least 3% of the study participants included a decrease in glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite, according to the company press release.

Full clinical trial information for the AURORA study is available here.

The Food and Drug Administration has approved voclosporin (Lupkynis) for the treatment of lupus nephritis, according to a Jan. 22 press release from manufacturer Aurinia Pharmaceuticals.

Lupkynis is a calcineurin-inhibitor immunosuppressant, and is the first oral medication to show effectiveness in lupus nephritis, according to the company. The drug is indicated for the treatment of adult patients with active lupus nephritis in combination with a background immunosuppressive therapy regimen, according to the drug label, which also has a boxed warning describing the increased risk of infections and malignancies, including lymphoma.

The approval of voclosporin was based on data from two studies, the AURORA phase 3 study and the AURA-LV phase 2 study. The studies included 533 adults with lupus nephritis who were randomized to 23.7 mg or placebo of voclosporin twice daily in the form of oral capsules, or placebo capsules, in addition to standard of care (mycophenolate mofetil plus low-dose glucocorticoids).

In the AURORA phase 3 study of 357 patients, close to twice as many patients in the treatment group showed a complete renal response, compared with the placebo group after 1 year (40.8% vs. 22.5%). In addition, patients treated with voclosporin more quickly achieved a significant reduction in urine protein to creatinine ratio, compared with the placebo patients (169 days vs. 372 days).

Severe adverse events were similar between the groups, including the most common complication of infection (10.1% and 11.2% for voclosporin and control groups, respectively). Other adverse reactions reported in at least 3% of the study participants included a decrease in glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, upper abdominal pain, dyspepsia, alopecia, renal impairment, abdominal pain, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite, according to the company press release.

Full clinical trial information for the AURORA study is available here.

Overutilization and low-value care are important clinical and policy problems. Their measurement is challenging because it requires detailed clinical information. Additionally, there are inherent difficulties in identifying discretionary services likely to be inappropriate or low-value and demonstrating that certain services produce little/no health benefit. Quantifying “ideal” expected testing rates—ones that would reflect minimization of inappropriate/low-value care without excluding essential, high-yield diagnostic services—presents additional challenges. Consequently, of 521 unique measures specified by national measurement programs and professional guidelines, 91.6% targeted underuse, while only 6.5% targeted overuse.¹

The potential for unintended consequences of implementing measures to eliminate overuse are a barrier to incorporating such measures into practice.² For example, measuring, reporting, and penalizing overuse of inappropriate bone scanning may lead to underuse in patients for whom scanning is crucial.² Most overuse measures based on inappropriate or low-value indications relate to imaging and medications.¹ However, there is increasing interest in overutilization measures based on a broad set of health services. Identifying low-value testing or treatments often requires a substantial degree of clinical detail to avoid the damaging inclusion of beneficial services, which may lead to unintended negative outcomes, creating skepticism among clinicians. Ultimately, getting measurement of low-value care wrong would undermine adoption of interventions to reduce overuse.

To reduce low-value care through expansive measures of provider ordering behavior,³ Ellenbogen et al⁴ derived a novel index to identify hospitals with high rates of low-yield diagnostic testing. This index is based on the concept that, in the presence of nonspecific, symptom-based principal diagnoses, a substantial proportion of (apparently) non-diagnostic related studies were probably ordered despite a low pretest probability of serious disease. Since such symptom-based diagnoses reflect the absence of a more specific diagnosis, the examinations observed are markers of physician-driven decisions leading to discretionary utilization likely to be of low-value to patients. This study fills a critical gap in dual measures of appropriateness and yield, rather than simply utilization, to advance the Choosing Wisely campaign.³

Advantages of this overuse index include its derivation from administrative data, obviating the need for electronic health records, and incorporation of diagnostic yield at the inpatient-encounter level. One study selected procedures identifiable solely with claims from a set deemed overused by professional/consumer groups.⁵ However, the yield of physician decisions in specific cases was not measured. In contrast, this novel index is derived from an assessment of diagnostic yield.⁴ Although test results are not known with certainty, the absence of a specific discharge diagnosis serves as a test result proxy. Measurement of diagnostic examination yield at the patient-level (aggregated to the hospital-level) may be applicable across hospitals with varied patient populations, which include large differences in patient and/or family preferences to seek medical attention and engage in shared decision-making. The role that patient preferences play in decisions creates a limitation in this index—while decisions for the candidate diagnostic tests are physician driven, patient demand may be a confounding factor. This index cannot therefore be considered purely a measure of physician-induced intensity of diagnostic services. Patient-reported data would enhance future analyses by more fully capturing all dimensions of care necessary to identify low-value services. Subjective outcomes are critical in completely measuring the aggregate benefits of tests and interventions judged low-value based on objective metrics. Such data would also aid in quantifying the relative contributions of patient and physician preferences in driving discretionary utilization.

Finally, the derived index is restricted to diagnostic decision-making and may not be applicable to treatment-related practice patterns. However, the literature suggests strong correlations between diagnostic and therapeutic intensity. Application of this novel index will play an important role in reducing low-value discretionary utilization.

Overutilization and low-value care are important clinical and policy problems. Their measurement is challenging because it requires detailed clinical information. Additionally, there are inherent difficulties in identifying discretionary services likely to be inappropriate or low-value and demonstrating that certain services produce little/no health benefit. Quantifying “ideal” expected testing rates—ones that would reflect minimization of inappropriate/low-value care without excluding essential, high-yield diagnostic services—presents additional challenges. Consequently, of 521 unique measures specified by national measurement programs and professional guidelines, 91.6% targeted underuse, while only 6.5% targeted overuse.¹

The potential for unintended consequences of implementing measures to eliminate overuse are a barrier to incorporating such measures into practice.² For example, measuring, reporting, and penalizing overuse of inappropriate bone scanning may lead to underuse in patients for whom scanning is crucial.² Most overuse measures based on inappropriate or low-value indications relate to imaging and medications.¹ However, there is increasing interest in overutilization measures based on a broad set of health services. Identifying low-value testing or treatments often requires a substantial degree of clinical detail to avoid the damaging inclusion of beneficial services, which may lead to unintended negative outcomes, creating skepticism among clinicians. Ultimately, getting measurement of low-value care wrong would undermine adoption of interventions to reduce overuse.

To reduce low-value care through expansive measures of provider ordering behavior,³ Ellenbogen et al⁴ derived a novel index to identify hospitals with high rates of low-yield diagnostic testing. This index is based on the concept that, in the presence of nonspecific, symptom-based principal diagnoses, a substantial proportion of (apparently) non-diagnostic related studies were probably ordered despite a low pretest probability of serious disease. Since such symptom-based diagnoses reflect the absence of a more specific diagnosis, the examinations observed are markers of physician-driven decisions leading to discretionary utilization likely to be of low-value to patients. This study fills a critical gap in dual measures of appropriateness and yield, rather than simply utilization, to advance the Choosing Wisely campaign.³

Advantages of this overuse index include its derivation from administrative data, obviating the need for electronic health records, and incorporation of diagnostic yield at the inpatient-encounter level. One study selected procedures identifiable solely with claims from a set deemed overused by professional/consumer groups.⁵ However, the yield of physician decisions in specific cases was not measured. In contrast, this novel index is derived from an assessment of diagnostic yield.⁴ Although test results are not known with certainty, the absence of a specific discharge diagnosis serves as a test result proxy. Measurement of diagnostic examination yield at the patient-level (aggregated to the hospital-level) may be applicable across hospitals with varied patient populations, which include large differences in patient and/or family preferences to seek medical attention and engage in shared decision-making. The role that patient preferences play in decisions creates a limitation in this index—while decisions for the candidate diagnostic tests are physician driven, patient demand may be a confounding factor. This index cannot therefore be considered purely a measure of physician-induced intensity of diagnostic services. Patient-reported data would enhance future analyses by more fully capturing all dimensions of care necessary to identify low-value services. Subjective outcomes are critical in completely measuring the aggregate benefits of tests and interventions judged low-value based on objective metrics. Such data would also aid in quantifying the relative contributions of patient and physician preferences in driving discretionary utilization.

Finally, the derived index is restricted to diagnostic decision-making and may not be applicable to treatment-related practice patterns. However, the literature suggests strong correlations between diagnostic and therapeutic intensity. Application of this novel index will play an important role in reducing low-value discretionary utilization.

Overutilization and low-value care are important clinical and policy problems. Their measurement is challenging because it requires detailed clinical information. Additionally, there are inherent difficulties in identifying discretionary services likely to be inappropriate or low-value and demonstrating that certain services produce little/no health benefit. Quantifying “ideal” expected testing rates—ones that would reflect minimization of inappropriate/low-value care without excluding essential, high-yield diagnostic services—presents additional challenges. Consequently, of 521 unique measures specified by national measurement programs and professional guidelines, 91.6% targeted underuse, while only 6.5% targeted overuse.¹

The potential for unintended consequences of implementing measures to eliminate overuse are a barrier to incorporating such measures into practice.² For example, measuring, reporting, and penalizing overuse of inappropriate bone scanning may lead to underuse in patients for whom scanning is crucial.² Most overuse measures based on inappropriate or low-value indications relate to imaging and medications.¹ However, there is increasing interest in overutilization measures based on a broad set of health services. Identifying low-value testing or treatments often requires a substantial degree of clinical detail to avoid the damaging inclusion of beneficial services, which may lead to unintended negative outcomes, creating skepticism among clinicians. Ultimately, getting measurement of low-value care wrong would undermine adoption of interventions to reduce overuse.

To reduce low-value care through expansive measures of provider ordering behavior,³ Ellenbogen et al⁴ derived a novel index to identify hospitals with high rates of low-yield diagnostic testing. This index is based on the concept that, in the presence of nonspecific, symptom-based principal diagnoses, a substantial proportion of (apparently) non-diagnostic related studies were probably ordered despite a low pretest probability of serious disease. Since such symptom-based diagnoses reflect the absence of a more specific diagnosis, the examinations observed are markers of physician-driven decisions leading to discretionary utilization likely to be of low-value to patients. This study fills a critical gap in dual measures of appropriateness and yield, rather than simply utilization, to advance the Choosing Wisely campaign.³

Advantages of this overuse index include its derivation from administrative data, obviating the need for electronic health records, and incorporation of diagnostic yield at the inpatient-encounter level. One study selected procedures identifiable solely with claims from a set deemed overused by professional/consumer groups.⁵ However, the yield of physician decisions in specific cases was not measured. In contrast, this novel index is derived from an assessment of diagnostic yield.⁴ Although test results are not known with certainty, the absence of a specific discharge diagnosis serves as a test result proxy. Measurement of diagnostic examination yield at the patient-level (aggregated to the hospital-level) may be applicable across hospitals with varied patient populations, which include large differences in patient and/or family preferences to seek medical attention and engage in shared decision-making. The role that patient preferences play in decisions creates a limitation in this index—while decisions for the candidate diagnostic tests are physician driven, patient demand may be a confounding factor. This index cannot therefore be considered purely a measure of physician-induced intensity of diagnostic services. Patient-reported data would enhance future analyses by more fully capturing all dimensions of care necessary to identify low-value services. Subjective outcomes are critical in completely measuring the aggregate benefits of tests and interventions judged low-value based on objective metrics. Such data would also aid in quantifying the relative contributions of patient and physician preferences in driving discretionary utilization.

Finally, the derived index is restricted to diagnostic decision-making and may not be applicable to treatment-related practice patterns. However, the literature suggests strong correlations between diagnostic and therapeutic intensity. Application of this novel index will play an important role in reducing low-value discretionary utilization.