In this article, Gerard A. Silvestri, MD, MS, FCCP discusses guideline-recommended testing and multidisciplinary care for resectable non-small cell lung cancer.

Read More

Neither the editors of CHEST Physician® nor the Editorial Advisory Board nor the reporting staff contributed to this content.

In this article, Gerard A. Silvestri, MD, MS, FCCP discusses guideline-recommended testing and multidisciplinary care for resectable non-small cell lung cancer.

Read More

Neither the editors of CHEST Physician® nor the Editorial Advisory Board nor the reporting staff contributed to this content.

In this article, Gerard A. Silvestri, MD, MS, FCCP discusses guideline-recommended testing and multidisciplinary care for resectable non-small cell lung cancer.

Read More

Neither the editors of CHEST Physician® nor the Editorial Advisory Board nor the reporting staff contributed to this content.

Investigators in China have identified 14 immune-related genes associated with survival in osteosarcoma.

When they combined them into a risk score and added one additional factor – metastases at diagnosis – the model was an “excellent” predictor of 1-year survival, the team said (area under the curve, 0.947; 95% confidence interval, 0.832-0.972).

“The survival-associated” immune-related genes (IRGs) “examined in this study have potential for identifying prognosis in osteosarcoma and may be clinically useful as relevant clinical biomarkers and candidate targets for anticancer therapy,” said investigators led by Wangmi Liu, MD, of Zhejiang University in Hangzhou, China. The study was published in JAMA Network Open.

They explained that it’s often difficult to distinguish high- and low-risk patients at osteosarcoma diagnosis. To address the issue, they analyzed the genomic signatures of 84 patients in the Cancer Genome Atlas and their associated clinical information.

The team split their subjects evenly into high-risk and low-risk groups based on a score developed from their genetic signatures. A total of 26 patients in the high-risk group (61.9%) died over a median follow up of 4.1 years versus only 1 (2.4%) in the low-risk group.

The risk score also correlated positively with B-cell tumor infiltration, and negatively with infiltration of CD8 T cells and macrophages.

Overall, 16 genes were significantly up-regulated, and 187 genes were significantly down-regulated in the high-risk group, including three survival-associated IRGs: CCL2, CD79A, and FPR1.

The differentially expressed genes were most significantly associated with transmembrane signaling receptor activity and inflammatory response. The team noted that “it has been reported that inflammatory response plays a critical role in tumor initiation, promotion, malignant conversion, invasion, and metastases.”

Of the 14 survival-associated IRGs, 5 have been reported before in osteosarcoma. The other nine were deduced from computational analysis and may be potential treatment targets, including bone morphogenetic protein 8b (BMP8b). Another member of the BMP family, BMP9, has been shown to promote the proliferation of osteosarcoma cells, “which is similar to this study’s finding that BMP8b was a risk factor in osteosarcoma. Therefore, the role of BMP8b in osteosarcoma needs further research,” the team said.

“Because the database provides limited clinical information, other important factors, such as staging and grading, were not included in our analysis. Therefore, extrapolation based on the findings must be done very carefully,” they cautioned.

The work was supported by the National Natural Science Foundation of China and others. The investigators didn’t have any disclosures.

[email protected]

Investigators in China have identified 14 immune-related genes associated with survival in osteosarcoma.

When they combined them into a risk score and added one additional factor – metastases at diagnosis – the model was an “excellent” predictor of 1-year survival, the team said (area under the curve, 0.947; 95% confidence interval, 0.832-0.972).

“The survival-associated” immune-related genes (IRGs) “examined in this study have potential for identifying prognosis in osteosarcoma and may be clinically useful as relevant clinical biomarkers and candidate targets for anticancer therapy,” said investigators led by Wangmi Liu, MD, of Zhejiang University in Hangzhou, China. The study was published in JAMA Network Open.

They explained that it’s often difficult to distinguish high- and low-risk patients at osteosarcoma diagnosis. To address the issue, they analyzed the genomic signatures of 84 patients in the Cancer Genome Atlas and their associated clinical information.

The team split their subjects evenly into high-risk and low-risk groups based on a score developed from their genetic signatures. A total of 26 patients in the high-risk group (61.9%) died over a median follow up of 4.1 years versus only 1 (2.4%) in the low-risk group.

The risk score also correlated positively with B-cell tumor infiltration, and negatively with infiltration of CD8 T cells and macrophages.

Overall, 16 genes were significantly up-regulated, and 187 genes were significantly down-regulated in the high-risk group, including three survival-associated IRGs: CCL2, CD79A, and FPR1.

The differentially expressed genes were most significantly associated with transmembrane signaling receptor activity and inflammatory response. The team noted that “it has been reported that inflammatory response plays a critical role in tumor initiation, promotion, malignant conversion, invasion, and metastases.”

Of the 14 survival-associated IRGs, 5 have been reported before in osteosarcoma. The other nine were deduced from computational analysis and may be potential treatment targets, including bone morphogenetic protein 8b (BMP8b). Another member of the BMP family, BMP9, has been shown to promote the proliferation of osteosarcoma cells, “which is similar to this study’s finding that BMP8b was a risk factor in osteosarcoma. Therefore, the role of BMP8b in osteosarcoma needs further research,” the team said.

“Because the database provides limited clinical information, other important factors, such as staging and grading, were not included in our analysis. Therefore, extrapolation based on the findings must be done very carefully,” they cautioned.

The work was supported by the National Natural Science Foundation of China and others. The investigators didn’t have any disclosures.

[email protected]

Investigators in China have identified 14 immune-related genes associated with survival in osteosarcoma.

When they combined them into a risk score and added one additional factor – metastases at diagnosis – the model was an “excellent” predictor of 1-year survival, the team said (area under the curve, 0.947; 95% confidence interval, 0.832-0.972).

“The survival-associated” immune-related genes (IRGs) “examined in this study have potential for identifying prognosis in osteosarcoma and may be clinically useful as relevant clinical biomarkers and candidate targets for anticancer therapy,” said investigators led by Wangmi Liu, MD, of Zhejiang University in Hangzhou, China. The study was published in JAMA Network Open.

They explained that it’s often difficult to distinguish high- and low-risk patients at osteosarcoma diagnosis. To address the issue, they analyzed the genomic signatures of 84 patients in the Cancer Genome Atlas and their associated clinical information.

The team split their subjects evenly into high-risk and low-risk groups based on a score developed from their genetic signatures. A total of 26 patients in the high-risk group (61.9%) died over a median follow up of 4.1 years versus only 1 (2.4%) in the low-risk group.

The risk score also correlated positively with B-cell tumor infiltration, and negatively with infiltration of CD8 T cells and macrophages.

Overall, 16 genes were significantly up-regulated, and 187 genes were significantly down-regulated in the high-risk group, including three survival-associated IRGs: CCL2, CD79A, and FPR1.

The differentially expressed genes were most significantly associated with transmembrane signaling receptor activity and inflammatory response. The team noted that “it has been reported that inflammatory response plays a critical role in tumor initiation, promotion, malignant conversion, invasion, and metastases.”

Of the 14 survival-associated IRGs, 5 have been reported before in osteosarcoma. The other nine were deduced from computational analysis and may be potential treatment targets, including bone morphogenetic protein 8b (BMP8b). Another member of the BMP family, BMP9, has been shown to promote the proliferation of osteosarcoma cells, “which is similar to this study’s finding that BMP8b was a risk factor in osteosarcoma. Therefore, the role of BMP8b in osteosarcoma needs further research,” the team said.

“Because the database provides limited clinical information, other important factors, such as staging and grading, were not included in our analysis. Therefore, extrapolation based on the findings must be done very carefully,” they cautioned.

The work was supported by the National Natural Science Foundation of China and others. The investigators didn’t have any disclosures.

[email protected]

For women with extremely dense breasts, screening with MRI alone every 4 years is cost effective and delivers the greatest benefit, the first study of its kind indicates.

Alternatively, if a woman worries that the 4-year screening interval is too long, screening mammography may be offered every 2 years, with MRI screening offered for the second 2-year interval, according to the findings. This strategy would still require the patient to undergo MRI breast cancer screening every 4 years.

“MRI is more effective not only for selected patients. It is actually more effective than mammography for all women,” editorialist Christiane Kuhl, MD, PhD, University of Aachen (Germany), said in an interview.

“But the superior diagnostic accuracy of MRI is more often needed for women who are at higher risk for breast cancer, and therefore the cost-effectiveness is easier to achieve in women who are at higher risk,” she added.

The study was published online Sept. 29 in the Journal of the National Cancer Institute.
 

DENSE trial

The simulation model used for the study was based on results from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which showed that additional MRI screening for women with extremely dense breast tissue led to significantly fewer interval cancers in comparison with mammography alone (P < .001). In the DENSE trial, MRI participants underwent mammography plus MRI at 2-year intervals; the control group underwent mammography alone at 2-year intervals.

In the current study, “screening strategies varied in the number of MRIs and mammograms offered to women aged 50-75 years,” explains Amarens Geuzinge, MSc, University Medical Center, Rotterdam, the Netherlands, and colleagues, “and incremental cost-effectiveness ratios (ICERs) were calculated ... with a willingness-to-pay threshold of 22,000 euros (>$25,000 U.S.),” the investigators add.

Analyses indicated that screening every 2 years with mammography alone cost the least of all strategies that were evaluated, but it also resulted in the lowest number of quality-adjusted life years (QALYs) – in other words, it delivered the least amount of benefit for patients, coauthor Eveline Heijnsdijk, PhD, University Medical Center, Rotterdam, the Netherlands, explained to this news organization.

Offering an additional MRI every 2 years resulted in the highest costs but not the highest number of QALYs and was inferior to the other screening strategies analyzed, she added. Alternating mammography with MRI breast cancer screening, each conducted every 2 years, came close to providing the same benefits to patients as the every-4-year MRI screening strategy, Dr. Heijnsdijk noted.

However, when the authors applied the National Institute for Health and Care Excellence (NICE) threshold, MRI screening every 4 years yielded the highest acceptable incremental cost-effectiveness ratio (ICER), at 15,620 euros per QALYs, whereas screening every 3 years with MRI alone yielded an ICER of 37,181 euros per QALY.

If decision-makers are willing to pay more than 22,000 euros per QALY gained, “MRI every 2 or 3 years can also become cost effective,” the authors add.

Asked how acceptable MRI screening might be if performed only once every 4 years, Dr. Heijnsdijk noted that, in another of their studies, most of the women who had undergone MRI screening for breast cancer said that they would do so again. “MRI is not a pleasant test, but mammography is also not a pleasant test,” she said.

“So many women prefer MRI above mammography, especially because the detection rate with MRI is better than mammography,” she noted. Dr. Heijnsdijk also said that the percentage of women with extremely dense breasts who would be candidates for MRI screening is small – no more than 10% of women.

At a unit cost of slightly under 300 euros for MRI screening – compared with about 100 euros for screening mammography in the Netherlands – the cost of offering 10% of women MRI instead of mammography might increase, but any additional screening costs could be offset by reductions in the need to treat late-stage breast cancer more aggressively.
 

‘Interval’ cancers

Commenting further on the study, Dr. Kuhl pointed out that from 25% to 45% of cancers that occur in women who have undergone screening mammography are diagnosed as “interval” cancers, even among women who participate in the best mammography programs. “For a long time, people argued that these interval cancers developed only after the last respective mammogram, but that’s not true at all, because we know that with MRI screening, we can reduce the interval cancer rate down to zero,” Dr. Kuhl emphasized.

This is partially explained by the fact that mammography is “particularly blind” when it comes to detecting rapidly growing tumors. “The fact is that mammography has a modality-inherent tendency to preferentially detect slow-growing cancers, whereas rapidly growing tumors are indistinguishable from ubiquitous benign changes like cysts. [This] is why women who undergo screening mammography are frequently not diagnosed with the cancers that we really need to find,” she said.

Although there is ample talk about overdiagnosis when it comes to screening mammography, the overwhelmingly important problem is underdiagnosis. Even in exemplary mammography screening programs, at least 20% of tumors that are diagnosed on mammography have already advanced to a stage that is too late, Dr. Kuhl noted.

This means that at least half of women do not benefit from screening mammography nearly to the extent that they – and their health care practitioners – believe they should, she added. Dr. Kuhl underscored that this does not mean that clinicians should abandon screening mammography.

What it does mean is that physicians need to abandon the one-size-fits-all approach to screening mammography and start stratifying women on the basis of their individual risk of developing breast cancer by taking a family or personal history. Most women do undergo screening mammography at least once, Dr. Kuhl pointed out. From that mammogram, physicians can use information on breast density and breast architecture to better determine individual risk.

“We have good ideas about how to achieve risk stratification, but we’re not using them, because as long as mammography is the answer for everybody, there isn’t much motivation to dig deeper into the issue of how to determine risk,” Dr. Kuhl said.

“But we have to ensure the early diagnosis of aggressive cancers, and it’s exactly MRI that can do this, and we should start with women with very dense breasts because they are doubly underserved by mammography,” she said.

The study was supported by the University Medical Center Utrecht, Bayer HealthCare Medical Care, Matakina, and others. Ms. Geuzinge, Dr. Heijnsdijk, and Dr. Kuhl have disclosed no relevant financial relationships.

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

For women with extremely dense breasts, screening with MRI alone every 4 years is cost effective and delivers the greatest benefit, the first study of its kind indicates.

Alternatively, if a woman worries that the 4-year screening interval is too long, screening mammography may be offered every 2 years, with MRI screening offered for the second 2-year interval, according to the findings. This strategy would still require the patient to undergo MRI breast cancer screening every 4 years.

“MRI is more effective not only for selected patients. It is actually more effective than mammography for all women,” editorialist Christiane Kuhl, MD, PhD, University of Aachen (Germany), said in an interview.

“But the superior diagnostic accuracy of MRI is more often needed for women who are at higher risk for breast cancer, and therefore the cost-effectiveness is easier to achieve in women who are at higher risk,” she added.

The study was published online Sept. 29 in the Journal of the National Cancer Institute.
 

DENSE trial

The simulation model used for the study was based on results from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which showed that additional MRI screening for women with extremely dense breast tissue led to significantly fewer interval cancers in comparison with mammography alone (P < .001). In the DENSE trial, MRI participants underwent mammography plus MRI at 2-year intervals; the control group underwent mammography alone at 2-year intervals.

In the current study, “screening strategies varied in the number of MRIs and mammograms offered to women aged 50-75 years,” explains Amarens Geuzinge, MSc, University Medical Center, Rotterdam, the Netherlands, and colleagues, “and incremental cost-effectiveness ratios (ICERs) were calculated ... with a willingness-to-pay threshold of 22,000 euros (>$25,000 U.S.),” the investigators add.

Analyses indicated that screening every 2 years with mammography alone cost the least of all strategies that were evaluated, but it also resulted in the lowest number of quality-adjusted life years (QALYs) – in other words, it delivered the least amount of benefit for patients, coauthor Eveline Heijnsdijk, PhD, University Medical Center, Rotterdam, the Netherlands, explained to this news organization.

Offering an additional MRI every 2 years resulted in the highest costs but not the highest number of QALYs and was inferior to the other screening strategies analyzed, she added. Alternating mammography with MRI breast cancer screening, each conducted every 2 years, came close to providing the same benefits to patients as the every-4-year MRI screening strategy, Dr. Heijnsdijk noted.

However, when the authors applied the National Institute for Health and Care Excellence (NICE) threshold, MRI screening every 4 years yielded the highest acceptable incremental cost-effectiveness ratio (ICER), at 15,620 euros per QALYs, whereas screening every 3 years with MRI alone yielded an ICER of 37,181 euros per QALY.

If decision-makers are willing to pay more than 22,000 euros per QALY gained, “MRI every 2 or 3 years can also become cost effective,” the authors add.

Asked how acceptable MRI screening might be if performed only once every 4 years, Dr. Heijnsdijk noted that, in another of their studies, most of the women who had undergone MRI screening for breast cancer said that they would do so again. “MRI is not a pleasant test, but mammography is also not a pleasant test,” she said.

“So many women prefer MRI above mammography, especially because the detection rate with MRI is better than mammography,” she noted. Dr. Heijnsdijk also said that the percentage of women with extremely dense breasts who would be candidates for MRI screening is small – no more than 10% of women.

At a unit cost of slightly under 300 euros for MRI screening – compared with about 100 euros for screening mammography in the Netherlands – the cost of offering 10% of women MRI instead of mammography might increase, but any additional screening costs could be offset by reductions in the need to treat late-stage breast cancer more aggressively.
 

‘Interval’ cancers

Commenting further on the study, Dr. Kuhl pointed out that from 25% to 45% of cancers that occur in women who have undergone screening mammography are diagnosed as “interval” cancers, even among women who participate in the best mammography programs. “For a long time, people argued that these interval cancers developed only after the last respective mammogram, but that’s not true at all, because we know that with MRI screening, we can reduce the interval cancer rate down to zero,” Dr. Kuhl emphasized.

This is partially explained by the fact that mammography is “particularly blind” when it comes to detecting rapidly growing tumors. “The fact is that mammography has a modality-inherent tendency to preferentially detect slow-growing cancers, whereas rapidly growing tumors are indistinguishable from ubiquitous benign changes like cysts. [This] is why women who undergo screening mammography are frequently not diagnosed with the cancers that we really need to find,” she said.

Although there is ample talk about overdiagnosis when it comes to screening mammography, the overwhelmingly important problem is underdiagnosis. Even in exemplary mammography screening programs, at least 20% of tumors that are diagnosed on mammography have already advanced to a stage that is too late, Dr. Kuhl noted.

This means that at least half of women do not benefit from screening mammography nearly to the extent that they – and their health care practitioners – believe they should, she added. Dr. Kuhl underscored that this does not mean that clinicians should abandon screening mammography.

What it does mean is that physicians need to abandon the one-size-fits-all approach to screening mammography and start stratifying women on the basis of their individual risk of developing breast cancer by taking a family or personal history. Most women do undergo screening mammography at least once, Dr. Kuhl pointed out. From that mammogram, physicians can use information on breast density and breast architecture to better determine individual risk.

“We have good ideas about how to achieve risk stratification, but we’re not using them, because as long as mammography is the answer for everybody, there isn’t much motivation to dig deeper into the issue of how to determine risk,” Dr. Kuhl said.

“But we have to ensure the early diagnosis of aggressive cancers, and it’s exactly MRI that can do this, and we should start with women with very dense breasts because they are doubly underserved by mammography,” she said.

The study was supported by the University Medical Center Utrecht, Bayer HealthCare Medical Care, Matakina, and others. Ms. Geuzinge, Dr. Heijnsdijk, and Dr. Kuhl have disclosed no relevant financial relationships.

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

For women with extremely dense breasts, screening with MRI alone every 4 years is cost effective and delivers the greatest benefit, the first study of its kind indicates.

Alternatively, if a woman worries that the 4-year screening interval is too long, screening mammography may be offered every 2 years, with MRI screening offered for the second 2-year interval, according to the findings. This strategy would still require the patient to undergo MRI breast cancer screening every 4 years.

“MRI is more effective not only for selected patients. It is actually more effective than mammography for all women,” editorialist Christiane Kuhl, MD, PhD, University of Aachen (Germany), said in an interview.

“But the superior diagnostic accuracy of MRI is more often needed for women who are at higher risk for breast cancer, and therefore the cost-effectiveness is easier to achieve in women who are at higher risk,” she added.

The study was published online Sept. 29 in the Journal of the National Cancer Institute.
 

DENSE trial

The simulation model used for the study was based on results from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which showed that additional MRI screening for women with extremely dense breast tissue led to significantly fewer interval cancers in comparison with mammography alone (P < .001). In the DENSE trial, MRI participants underwent mammography plus MRI at 2-year intervals; the control group underwent mammography alone at 2-year intervals.

In the current study, “screening strategies varied in the number of MRIs and mammograms offered to women aged 50-75 years,” explains Amarens Geuzinge, MSc, University Medical Center, Rotterdam, the Netherlands, and colleagues, “and incremental cost-effectiveness ratios (ICERs) were calculated ... with a willingness-to-pay threshold of 22,000 euros (>$25,000 U.S.),” the investigators add.

Analyses indicated that screening every 2 years with mammography alone cost the least of all strategies that were evaluated, but it also resulted in the lowest number of quality-adjusted life years (QALYs) – in other words, it delivered the least amount of benefit for patients, coauthor Eveline Heijnsdijk, PhD, University Medical Center, Rotterdam, the Netherlands, explained to this news organization.

Offering an additional MRI every 2 years resulted in the highest costs but not the highest number of QALYs and was inferior to the other screening strategies analyzed, she added. Alternating mammography with MRI breast cancer screening, each conducted every 2 years, came close to providing the same benefits to patients as the every-4-year MRI screening strategy, Dr. Heijnsdijk noted.

However, when the authors applied the National Institute for Health and Care Excellence (NICE) threshold, MRI screening every 4 years yielded the highest acceptable incremental cost-effectiveness ratio (ICER), at 15,620 euros per QALYs, whereas screening every 3 years with MRI alone yielded an ICER of 37,181 euros per QALY.

If decision-makers are willing to pay more than 22,000 euros per QALY gained, “MRI every 2 or 3 years can also become cost effective,” the authors add.

Asked how acceptable MRI screening might be if performed only once every 4 years, Dr. Heijnsdijk noted that, in another of their studies, most of the women who had undergone MRI screening for breast cancer said that they would do so again. “MRI is not a pleasant test, but mammography is also not a pleasant test,” she said.

“So many women prefer MRI above mammography, especially because the detection rate with MRI is better than mammography,” she noted. Dr. Heijnsdijk also said that the percentage of women with extremely dense breasts who would be candidates for MRI screening is small – no more than 10% of women.

At a unit cost of slightly under 300 euros for MRI screening – compared with about 100 euros for screening mammography in the Netherlands – the cost of offering 10% of women MRI instead of mammography might increase, but any additional screening costs could be offset by reductions in the need to treat late-stage breast cancer more aggressively.
 

‘Interval’ cancers

Commenting further on the study, Dr. Kuhl pointed out that from 25% to 45% of cancers that occur in women who have undergone screening mammography are diagnosed as “interval” cancers, even among women who participate in the best mammography programs. “For a long time, people argued that these interval cancers developed only after the last respective mammogram, but that’s not true at all, because we know that with MRI screening, we can reduce the interval cancer rate down to zero,” Dr. Kuhl emphasized.

This is partially explained by the fact that mammography is “particularly blind” when it comes to detecting rapidly growing tumors. “The fact is that mammography has a modality-inherent tendency to preferentially detect slow-growing cancers, whereas rapidly growing tumors are indistinguishable from ubiquitous benign changes like cysts. [This] is why women who undergo screening mammography are frequently not diagnosed with the cancers that we really need to find,” she said.

Although there is ample talk about overdiagnosis when it comes to screening mammography, the overwhelmingly important problem is underdiagnosis. Even in exemplary mammography screening programs, at least 20% of tumors that are diagnosed on mammography have already advanced to a stage that is too late, Dr. Kuhl noted.

This means that at least half of women do not benefit from screening mammography nearly to the extent that they – and their health care practitioners – believe they should, she added. Dr. Kuhl underscored that this does not mean that clinicians should abandon screening mammography.

What it does mean is that physicians need to abandon the one-size-fits-all approach to screening mammography and start stratifying women on the basis of their individual risk of developing breast cancer by taking a family or personal history. Most women do undergo screening mammography at least once, Dr. Kuhl pointed out. From that mammogram, physicians can use information on breast density and breast architecture to better determine individual risk.

“We have good ideas about how to achieve risk stratification, but we’re not using them, because as long as mammography is the answer for everybody, there isn’t much motivation to dig deeper into the issue of how to determine risk,” Dr. Kuhl said.

“But we have to ensure the early diagnosis of aggressive cancers, and it’s exactly MRI that can do this, and we should start with women with very dense breasts because they are doubly underserved by mammography,” she said.

The study was supported by the University Medical Center Utrecht, Bayer HealthCare Medical Care, Matakina, and others. Ms. Geuzinge, Dr. Heijnsdijk, and Dr. Kuhl have disclosed no relevant financial relationships.

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

Ponatinib is most likely the most powerful tyrosine kinase inhibitor (TKI) approved for the relapsed or refractory chronic myeloid leukemia (CML) after two lines of therapy. In the original PACE study, ponatinib showed deep and durable responses, but arterial occlusive events (AOE) emerged as notable adverse events. Post hoc analyses indicated that AOEs were dose dependent and recommendations to lower the dose from 45 mg to 30 mg after achieving complete cytogenic response (CCR) and to 15 mg after achieving major molecular response (MMR) were used in an attempt to minimize the cardiovascular toxicities. The question remained regarding the optimal dose of ponatinib in terms of efficacy and toxicity. Cortes et al (Blood 2021 Aug 18.) reported the results of the OPTIC trial where patients with chronic phase CML (CP-CML), resistant/intolerant to at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1T315I mutation, were randomized 1:1:1 to receive 3 different doses of ponatinib daily (45, 30, or 15 mg). Patients who received 45 mg or 30 mg daily reduced their dose to 15 mg upon achievement of response (BCR-ABL1^IS transcript levels ≤1%). The primary endpoint (BCR-ABL1^IS transcript levels ≤1%) was achieved at 12 months in 44.1%, 29.0%, and 23.1% in the 3 cohorts, respectively. Independently confirmed grade 3/4 treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 3 cohorts, respectively. In conclusion, the optimal benefit:risk outcomes occurred with the 45 mg starting dose reduced to 15 mg upon achievement of response.

New drugs with alternative mechanisms of action are always welcome for the treatment of resistant or intolerant CP-CML. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with the potential to overcome resistance or intolerance to approved TKIs. Rea et al (Blood 2021 Aug 18) reported the results of the ASCEMBL trial that compare 40 mg twice daily asciminib vs. bosutinib in patients with CP-CML refractory to >2 previous lines of therapy. The rates of MMR at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). The bosutinib arm, compared to the asciminib arm, had a more frequent occurrence of grade 3 or higher adverse events (AE; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%). This will be another important alternative for CP-CML patients failing 2 lines of therapy; however, it is still unclear if the drug may be superior to ponatinib in the same setting.

In the new era of COVID-19, patients with hematologic malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and an adverse outcome. However, is unclear if this can be seen across the board in all type of hematologic malignancies, as a low mortality rate has been described in patients with CP-CML, suggesting that TKIs may have a protective role against severe COVID-19. Bonifacio et al (Cancer Med 2021 Aug 31) conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in 5 hematologic centers representative of 3 Italian regions. Interestingly, the serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population. The data confirm mild SARS-CoV-2 infection in patients with CML and suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2 similar to the general population.

Ponatinib is most likely the most powerful tyrosine kinase inhibitor (TKI) approved for the relapsed or refractory chronic myeloid leukemia (CML) after two lines of therapy. In the original PACE study, ponatinib showed deep and durable responses, but arterial occlusive events (AOE) emerged as notable adverse events. Post hoc analyses indicated that AOEs were dose dependent and recommendations to lower the dose from 45 mg to 30 mg after achieving complete cytogenic response (CCR) and to 15 mg after achieving major molecular response (MMR) were used in an attempt to minimize the cardiovascular toxicities. The question remained regarding the optimal dose of ponatinib in terms of efficacy and toxicity. Cortes et al (Blood 2021 Aug 18.) reported the results of the OPTIC trial where patients with chronic phase CML (CP-CML), resistant/intolerant to at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1T315I mutation, were randomized 1:1:1 to receive 3 different doses of ponatinib daily (45, 30, or 15 mg). Patients who received 45 mg or 30 mg daily reduced their dose to 15 mg upon achievement of response (BCR-ABL1^IS transcript levels ≤1%). The primary endpoint (BCR-ABL1^IS transcript levels ≤1%) was achieved at 12 months in 44.1%, 29.0%, and 23.1% in the 3 cohorts, respectively. Independently confirmed grade 3/4 treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 3 cohorts, respectively. In conclusion, the optimal benefit:risk outcomes occurred with the 45 mg starting dose reduced to 15 mg upon achievement of response.

New drugs with alternative mechanisms of action are always welcome for the treatment of resistant or intolerant CP-CML. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with the potential to overcome resistance or intolerance to approved TKIs. Rea et al (Blood 2021 Aug 18) reported the results of the ASCEMBL trial that compare 40 mg twice daily asciminib vs. bosutinib in patients with CP-CML refractory to >2 previous lines of therapy. The rates of MMR at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). The bosutinib arm, compared to the asciminib arm, had a more frequent occurrence of grade 3 or higher adverse events (AE; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%). This will be another important alternative for CP-CML patients failing 2 lines of therapy; however, it is still unclear if the drug may be superior to ponatinib in the same setting.

In the new era of COVID-19, patients with hematologic malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and an adverse outcome. However, is unclear if this can be seen across the board in all type of hematologic malignancies, as a low mortality rate has been described in patients with CP-CML, suggesting that TKIs may have a protective role against severe COVID-19. Bonifacio et al (Cancer Med 2021 Aug 31) conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in 5 hematologic centers representative of 3 Italian regions. Interestingly, the serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population. The data confirm mild SARS-CoV-2 infection in patients with CML and suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2 similar to the general population.

Ponatinib is most likely the most powerful tyrosine kinase inhibitor (TKI) approved for the relapsed or refractory chronic myeloid leukemia (CML) after two lines of therapy. In the original PACE study, ponatinib showed deep and durable responses, but arterial occlusive events (AOE) emerged as notable adverse events. Post hoc analyses indicated that AOEs were dose dependent and recommendations to lower the dose from 45 mg to 30 mg after achieving complete cytogenic response (CCR) and to 15 mg after achieving major molecular response (MMR) were used in an attempt to minimize the cardiovascular toxicities. The question remained regarding the optimal dose of ponatinib in terms of efficacy and toxicity. Cortes et al (Blood 2021 Aug 18.) reported the results of the OPTIC trial where patients with chronic phase CML (CP-CML), resistant/intolerant to at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1T315I mutation, were randomized 1:1:1 to receive 3 different doses of ponatinib daily (45, 30, or 15 mg). Patients who received 45 mg or 30 mg daily reduced their dose to 15 mg upon achievement of response (BCR-ABL1^IS transcript levels ≤1%). The primary endpoint (BCR-ABL1^IS transcript levels ≤1%) was achieved at 12 months in 44.1%, 29.0%, and 23.1% in the 3 cohorts, respectively. Independently confirmed grade 3/4 treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 3 cohorts, respectively. In conclusion, the optimal benefit:risk outcomes occurred with the 45 mg starting dose reduced to 15 mg upon achievement of response.

New drugs with alternative mechanisms of action are always welcome for the treatment of resistant or intolerant CP-CML. Asciminib is a first-in-class STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor with the potential to overcome resistance or intolerance to approved TKIs. Rea et al (Blood 2021 Aug 18) reported the results of the ASCEMBL trial that compare 40 mg twice daily asciminib vs. bosutinib in patients with CP-CML refractory to >2 previous lines of therapy. The rates of MMR at week 24 in patients receiving asciminib and bosutinib were 25.5% and 13.2%, respectively (difference 12.2%; P = .029). The bosutinib arm, compared to the asciminib arm, had a more frequent occurrence of grade 3 or higher adverse events (AE; 60.5% vs. 50.6%) and AEs leading to treatment discontinuation (21.1% vs. 5.8%). This will be another important alternative for CP-CML patients failing 2 lines of therapy; however, it is still unclear if the drug may be superior to ponatinib in the same setting.

In the new era of COVID-19, patients with hematologic malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and an adverse outcome. However, is unclear if this can be seen across the board in all type of hematologic malignancies, as a low mortality rate has been described in patients with CP-CML, suggesting that TKIs may have a protective role against severe COVID-19. Bonifacio et al (Cancer Med 2021 Aug 31) conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in 5 hematologic centers representative of 3 Italian regions. Interestingly, the serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population. The data confirm mild SARS-CoV-2 infection in patients with CML and suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2 similar to the general population.

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

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

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

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

Irish dermatologists are reporting two more cases of a rare skin ulcer known as reactive infectious mucocutaneous eruption (RIME) in teenage males who were infected with COVID-19. A similar case in an adolescent, also with ulcers affecting the mouth and penis, was reported earlier in 2021 in the United States.

“Our cases show that a swab for COVID-19 can be added to the list of investigations for mucosal and cutaneous rashes in children and probably adults,” said dermatologist Stephanie Bowe, MD, of South Infirmary-Victoria University Hospital in Cork, Ireland, in an interview. “Our patients seemed to improve with IV steroids, but there is not enough data to recommend them to all patients or for use in the different cutaneous presentations associated with COVID-19.”

The new case reports were presented at the 2021 meeting of the World Congress of Pediatric Dermatology and published in Pediatric Dermatology.

Researchers have noted that skin disorders linked to COVID-19 infection are different than those in adults. In children, the conditions include morbilliform rash, pernio-like acral lesions, urticaria, macular erythema, vesicular eruption, papulosquamous eruption, and retiform purpura. “The pathogenesis of each is not fully understood but likely related to the inflammatory response to COVID-19 and the various pathways within the body, which become activated,” Dr. Bowe said.

The first patient, a 17-year-old boy, presented at clinic 6 days after he’d been confirmed to be infected with COVID-19 and 8 days after developing fever and cough. “He had a 2-day history of conjunctivitis and ulceration of his oral mucosa, erythematous circumferential erosions of the glans penis with no other cutaneous findings,” the authors write in the report.

The boy “was distressed and embarrassed about his genital ulceration and also found eating very painful due to his oral ulceration,” Dr. Bowe said.

The second patient, a 14-year-old boy, was hospitalized 7 days after a positive COVID-19 test and 9 days after developing cough and fever. “He had a 5-day history of ulceration of the oral mucosa with mild conjunctivitis,” the authors wrote. “Ulceration of the glans penis developed on day 2 of admission.”

The 14-year-old was sicker than the 17-year-old boy, Dr. Bowe said. “He was unable to tolerate an oral diet for several days and had exquisite pain and vomiting with his coughing fits.”

This patient had a history of recurrent herpes labialis, but it’s unclear whether herpes simplex virus (HSV) played a role in the COVID-19–related case. “There is a possibility that the patient was more susceptible to viral cutaneous reactions during COVID-19 infection, but we didn’t have any definite history of HSV infection at the time of mucositis,” Dr. Bowe said. “We also didn’t have any swabs positive for HSV even though several were done at the time.”

Both patients received IV steroids – hydrocortisone at 100 mg 3 times daily for 3 days. This treatment was used “because of deterioration in symptoms and COVID-19 infection,” Dr. Bowe said. “IV steroids were used for respiratory symptoms of COVID-19, so we felt these cutaneous symptoms may have also been caused by an inflammatory response and might benefit from steroids. There was very little literature about this specific situation, though.”

She added that intravenous steroids wouldn’t be appropriate for most pediatric patients, and noted that “their use is controversial in the literature for erythema multiforme and RIME.”

In addition, the patients received betamethasone valerate 0.1% ointment once daily, hydrocortisone 2.5 mg buccal tablets 4 times daily, analgesia with acetaminophen and ibuprofen, and intravenous hydration. The first patient also received prednisolone 1% eye drops, while the second patient was given lidocaine hydrochloride mouthwash and total parenteral nutrition for 5 days.

The patients were discharged after 4 and 14 days, respectively.

Dermatologists in Massachusetts reported a similar case earlier in 2021 in a 17-year-old boy who was positive for COVID-19 and presented with “shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities.”

The patient received betamethasone valerate 0.1% ointment for the lips and penis, intraoral dexamethasone solution, viscous lidocaine, acetaminophen, and ibuprofen. He also received oral prednisone at approximately 1 mg/kg daily for 4 consecutive days after worsening oral pain. A recurrence of oral pain 3 months later was resolved with a higher and longer treatment with oral prednisone.

Dermatologists have also reported cases of erythema multiforme lesions of the mucosa in adults with COVID-19. One case was reported in Iran, and the other in France.

The authors report no study funding and disclosed no relevant financial relationships.

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

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Antibody levels may wane after 7 months for people who got the Pfizer-BioNTech vaccine, according to a new study published on the bioRxiv preprint server.

In the study, which hasn’t yet been peer-reviewed or formally published in a medical journal, researchers analyzed blood samples from 46 healthy young or middle-aged adults after receiving two doses, and then 6 months after the second dose.

“Our study shows vaccination with the Pfizer-BioNTech vaccine induces high levels of neutralizing antibodies against the original vaccine strain, but these levels drop by nearly 10-fold by 7 months,” the researchers told Reuters.

In about half of the adults, neutralizing antibodies were undetectable at 6 months after the second dose, particularly against coronavirus variants such as Delta, Beta, and Mu.

Neutralizing antibodies only make up part of the body’s immune defense against the virus, Reuters noted, but they are still “critically important” in protecting against coronavirus infections.

“These findings suggest that administering a booster dose at around 6 to 7 months following the initial immunization will likely enhance protection,” the study authors wrote.

BioNTech said a new vaccine formula will likely be needed by mid-2022 to protect against future mutations of the virus, according to the Financial Times.

“This year, [a different vaccine] is completely unneeded, but by mid-next year, it could be a different situation,” Ugur Sahin, MD, cofounder and CEO of BioNTech, told the news outlet.

Current variants, namely the Delta variant, are more contagious than the original coronavirus strain but not different enough to evade current vaccines, he said. But new strains may be able to evade boosters.

“This virus will stay, and the virus will further adapt,” Dr. Sahin said. “This is a continuous evolution, and that evolution has just started.”

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

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

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

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

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

Serious adverse events remained rare and skin remained largely clear in adolescents treated with dupilumab for moderate to severe atopic dermatitis (AD) for up to 52 weeks in a phase 3, open-label extension trial, researchers reported.

At 1 year, 86% of 50 remaining patients with weights under 60 kg (132 lb) had achieved 75% improvement on the Eczema Area and Severity Index (EASI-75, and 77% of 51 remaining patients with weights over 60 kg reached that level of clearance. Only 5 (1.7%) of 294 patients had serious treatment-emergent adverse events (TEAEs).

The findings back up a perception that patients can stay on dupilumab for some time instead of having to switch from one biologic to another after a few years, study coauthor Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, said in an interview. He added that the drug’s long-term safety profile is “very reassuring.”

The industry-funded findings of the study were released in a poster at the 2021 meeting of the World Congress of Pediatric Dermatology.

The FDA approved dupilumab (Dupixent), an interleukin-4 receptor alpha antagonist, for treating AD in adults in 2017; it is now approved for treating patients ages 6 years and older with moderate to severe atopic dermatitis whose disease is not adequately controlled with topicals.

The new study tracked patients who received at least 300 mg dupilumab subcutaneously every 4 weeks. The dose could be increased if needed to improve clinical response to once every 2 weeks (200 mg if baseline weight was <60 kg; 300 mg if ≥60 kg).

At 52 weeks, 37% of 52 patients with weights under 60 kg reached an Investigator Global Assessment (IGA) of 0/1, a level that had been fairly steady since week 16 (n = 146). Among 51 heavier patients, 49% reached an IGA of 0/1 at 52 weeks; this percentage grew steadily since baseline.

The mean percentage change in EASI was –87% in the lower-weight group (n = 50) at 52 weeks and –80.1% in the larger-weight group (n = 51). The majority of the reduction in EASI occurred in the first 4 weeks of treatment.

At 52 weeks, the mean Children’s Dermatology Life Quality Index level, which judges the effect of AD on life, was judged as “small” (low) in 71 patients. At baseline, the mean level among 189 patients was “moderate.” The levels dipped below “moderate” at week 4 and never rose above “small” after that.

“Treatment-emergent adverse events reported in ≥5% of patients were nasopharyngitis (21.1%), AD (19.4%), upper respiratory tract infection (12.4%), headache (9.4%), and oropharyngeal pain (5.7%),” the investigators wrote in the poster. They add that 6.7% of patients experienced injection-site reactions, and 8.7% of patients experienced treatment-emergent “narrow conjunctivitis,” which includes conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, and atopic keratoconjunctivitis.

Dr. Simpson noted that cases of conjunctivitis fell over time. It’s not clear why this adverse effect appears, he said.

He said that the findings reflect his own experience in clinic. Many of his adolescent patients took part in early dupilumab trials, he said, and dozens have been taking the drug for more than 5 years. “They just seem to get better and better,” he said.

University of Minnesota, Minneapolis, dermatologist Sheilagh Maguiness, MD, who wasn’t involved with the study, said in an interview that dupilumab remains “the safest, most effective and evidence-based therapy we had for children with moderate to severe atopic dermatitis.”

The new study’s findings are “very reassuring,” she said, and similar to those in a 2021 report that tracked long-term use of the drug in children aged 6-11.

Like Dr. Simpson, Dr. Maguiness said many pediatric patients at her clinic have stayed on the drug for more than 5 years. They still have “sustained improvement in skin disease and in their quality of life as well”

There are, however, still questions about dupilumab treatment. “For children who have responded well, when could we consider dose reduction or discontinuation? I have done this successfully just a handful of times, but I would love to see data about what percentage of pediatric patients experience rebound disease after coming off the drug and after what duration of treatment,” she said. “Another mystery that will be very interesting to unravel is the question as to whether or not early treatment with dupilumab may attenuate other atopic diseases.”

Dr. Maguiness added that “another issue specific to pediatric use of dupilumab is the recommendation surrounding vaccinations. This is an issue that should be studied in terms of antibody response and safety surrounding vaccinations, particularly as we are eagerly awaiting a pediatric FDA approval for the COVID-19 vaccine in children.”

She also urged colleagues to push back against insurers who resist paying for dupilumab. “Whether prescribing this medication on or off label, insurance companies are often requiring patients to try and fail other traditional immunosuppressive medications such as methotrexate, cyclosporine, or to pursue phototherapy,” she said. “Oftentimes, these are not practical or even safe options for children for a multitude of reasons. Don’t be shy about advocating for your patients by second- or even third-level appeals to try and gain approval for children who are in need of treatment.”

The study was funded by Sanofi Genzyme and Regeneron Pharmaceuticals. The study authors reported various disclosures. Dr. Simpson reported investigator and consultant fee relationships from various pharmaceutical companies. Dr. Maguiness was an investigator for one of the initial pediatric dupilumab trials.

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

There is a narrative being pushed now about health care professionals being “frustrated” and “tired” in the midst of this current delta COVID wave. This stems from the idea that this current wave was potentially preventable if everyone received the COVID vaccines when they were made available.

Courtesy of Sound Physicians

I certainly understand this frustration and am tired of dealing with COVID restrictions and wearing masks. Above all I’m tired of talking about it. But frustration and fatigue are nothing new for those in the health care profession. Part of our training is that we should care for everyone, no matter what. Compassion for the ill should not be restricted to patients with a certain financial status, immigration status, race, gender, sexual orientation, or education level. Socially and politically, we are having a reckoning with how we treat people and how we need to do better to create a more just society. A key virtue in all of this is tolerance.

If we are going to have a free society, tolerance is essential. This is because in a free society people are going to, well, be free. In medicine we tolerate people who are morbidly obese, drink alcohol excessively, smoke, refuse to take their medications, won’t exercise, won’t sleep, and do drugs. The overwhelming majority of these people know that what they are doing is bad for their health. Not only do we tolerate them, we are taught to treat them indiscriminately. When someone who is morbidly obese has a heart attack, we treat them, give them medicine, and tell them the importance of losing weight. We do not tell them, “you shouldn’t have eaten so much and gotten so fat,” or “don’t you wish you didn’t get so fat?”

What I am trying to circle back to here is that if you could force people into doing everything they could for their health and eliminate all “preventable” diseases, then the need for health care in this country – including doctors, nurses, hospitals, and pharmaceuticals, just to name a few – would be cut dramatically. While the frustration for the continued COVID surges is understandable, I urge people to remember that in the business of health care we deal with preventable diseases all the time, every day. We are taught to show compassion for everyone, and for good reason. We have no idea what many people’s backstories are, we just know that they are sick and need help.

I urge everyone to put the unvaccinated under the same umbrella you put other people with preventable diseases, which, sadly, is a lot of patients. Continue to educate those about the vaccine as you should about every other aspect of their health. Education is part of our job as health care professionals but judgment is not.

Dr. Matuszak works for Sound Physicians and is a nocturnist at a hospital in the San Francisco Bay Area.

There is a narrative being pushed now about health care professionals being “frustrated” and “tired” in the midst of this current delta COVID wave. This stems from the idea that this current wave was potentially preventable if everyone received the COVID vaccines when they were made available.

Courtesy of Sound Physicians

I certainly understand this frustration and am tired of dealing with COVID restrictions and wearing masks. Above all I’m tired of talking about it. But frustration and fatigue are nothing new for those in the health care profession. Part of our training is that we should care for everyone, no matter what. Compassion for the ill should not be restricted to patients with a certain financial status, immigration status, race, gender, sexual orientation, or education level. Socially and politically, we are having a reckoning with how we treat people and how we need to do better to create a more just society. A key virtue in all of this is tolerance.

If we are going to have a free society, tolerance is essential. This is because in a free society people are going to, well, be free. In medicine we tolerate people who are morbidly obese, drink alcohol excessively, smoke, refuse to take their medications, won’t exercise, won’t sleep, and do drugs. The overwhelming majority of these people know that what they are doing is bad for their health. Not only do we tolerate them, we are taught to treat them indiscriminately. When someone who is morbidly obese has a heart attack, we treat them, give them medicine, and tell them the importance of losing weight. We do not tell them, “you shouldn’t have eaten so much and gotten so fat,” or “don’t you wish you didn’t get so fat?”

What I am trying to circle back to here is that if you could force people into doing everything they could for their health and eliminate all “preventable” diseases, then the need for health care in this country – including doctors, nurses, hospitals, and pharmaceuticals, just to name a few – would be cut dramatically. While the frustration for the continued COVID surges is understandable, I urge people to remember that in the business of health care we deal with preventable diseases all the time, every day. We are taught to show compassion for everyone, and for good reason. We have no idea what many people’s backstories are, we just know that they are sick and need help.

I urge everyone to put the unvaccinated under the same umbrella you put other people with preventable diseases, which, sadly, is a lot of patients. Continue to educate those about the vaccine as you should about every other aspect of their health. Education is part of our job as health care professionals but judgment is not.

Dr. Matuszak works for Sound Physicians and is a nocturnist at a hospital in the San Francisco Bay Area.

There is a narrative being pushed now about health care professionals being “frustrated” and “tired” in the midst of this current delta COVID wave. This stems from the idea that this current wave was potentially preventable if everyone received the COVID vaccines when they were made available.

Courtesy of Sound Physicians

I certainly understand this frustration and am tired of dealing with COVID restrictions and wearing masks. Above all I’m tired of talking about it. But frustration and fatigue are nothing new for those in the health care profession. Part of our training is that we should care for everyone, no matter what. Compassion for the ill should not be restricted to patients with a certain financial status, immigration status, race, gender, sexual orientation, or education level. Socially and politically, we are having a reckoning with how we treat people and how we need to do better to create a more just society. A key virtue in all of this is tolerance.

If we are going to have a free society, tolerance is essential. This is because in a free society people are going to, well, be free. In medicine we tolerate people who are morbidly obese, drink alcohol excessively, smoke, refuse to take their medications, won’t exercise, won’t sleep, and do drugs. The overwhelming majority of these people know that what they are doing is bad for their health. Not only do we tolerate them, we are taught to treat them indiscriminately. When someone who is morbidly obese has a heart attack, we treat them, give them medicine, and tell them the importance of losing weight. We do not tell them, “you shouldn’t have eaten so much and gotten so fat,” or “don’t you wish you didn’t get so fat?”

What I am trying to circle back to here is that if you could force people into doing everything they could for their health and eliminate all “preventable” diseases, then the need for health care in this country – including doctors, nurses, hospitals, and pharmaceuticals, just to name a few – would be cut dramatically. While the frustration for the continued COVID surges is understandable, I urge people to remember that in the business of health care we deal with preventable diseases all the time, every day. We are taught to show compassion for everyone, and for good reason. We have no idea what many people’s backstories are, we just know that they are sick and need help.

I urge everyone to put the unvaccinated under the same umbrella you put other people with preventable diseases, which, sadly, is a lot of patients. Continue to educate those about the vaccine as you should about every other aspect of their health. Education is part of our job as health care professionals but judgment is not.

Dr. Matuszak works for Sound Physicians and is a nocturnist at a hospital in the San Francisco Bay Area.

Marconi et al report out the results of the COV-Barrier study, a phase 3 randomized placebo controlled (RCT) trial with baricitinib, a JAK-STAT pathway inhibitor generally used to suppress proinflammatory cytokine production and systemic inflammation in rheumatoid arthritis, in hospitalized COVID-19 patients. The 1525 participants equally divided between placebo and baricitinib in an intention to treat analysis, were recruited from 12 countries, and most were on systemic corticosteroids (79.3%) and about one fifth received the antiviral, remdesivir. The study did not show a difference in the primary outcome (a composite of progression to more severe disease including need for high flow oxygen, non-invasive or invasive mechanical ventilation or death by 28 days), but did note a 5% absolute reduction in mortality at 28 days. Based on this results, Baricitinib may have a role similar role in the care of COVID-19 patients as tocilizumab (an IL-6 inhibitor) when given in combination with steroids, but may be used in the care of patients earlier in their disease including those on high flow or noninvasive oxygen as well as those requiring invasive mechanical ventilation, compared to tocilizumab, which is currently preferred by many clinicians in those on more intensive respiratory support and within 24-48 hours of ICU admission.  Like other immunomodulators, there is a concern for increased secondary infections with the use of this therapy, but JAK inhibitors also carry a risk for increase in venous thromboembolic events. Interestingly, in this trial, there was no difference in the incidence of either of these adverse effects between the placebo and treatment groups.

The results of a phase 3 RCT with Canakinumab, an anti-interleukin-1B monoclonal antibody, on the other hand, did not show a benefit in primary outcome of survival without need for mechanical ventilation day 3 to day 29, or recovery time, in hospitalized patients who had elevated C-reactive protein and ferritin but were not yet intubated. Canakinumab was evaluated because IL-1B has been identified as one of the signature elevated cytokines in a maladaptive immune response to SARS-CoV-2 infection and because had shown some promise in small and retrospective studies. 

Lastly, on the prevention side, a study of Regeneron’s anti-SARS-CoV-2 monoclonal antibody cocktail (casirivimab and imdevimab) was evaluated in a double blind placebo controlled RCT in prevention of development of symptomatic SARS-CoV-2 infection within 28 days among household contacts who did not have prior immunity. In the study, 1.5% of those who received the monoclonal therapy subcutaneously versus 7.8% of those who received placebo met the primary endpoint. Additionally, those who received the therapy and were symptomatic, resolved their symptoms two weeks earlier. The real-world utility of the results, however, maybe limited to specific groups, given that need for early identification of contacts, the need to access medical facility for administration, as well as the cost of the drug. There may be a role in high risk and immunocompromised contacts who do not develop adequate immune response to vaccination.

Marconi et al report out the results of the COV-Barrier study, a phase 3 randomized placebo controlled (RCT) trial with baricitinib, a JAK-STAT pathway inhibitor generally used to suppress proinflammatory cytokine production and systemic inflammation in rheumatoid arthritis, in hospitalized COVID-19 patients. The 1525 participants equally divided between placebo and baricitinib in an intention to treat analysis, were recruited from 12 countries, and most were on systemic corticosteroids (79.3%) and about one fifth received the antiviral, remdesivir. The study did not show a difference in the primary outcome (a composite of progression to more severe disease including need for high flow oxygen, non-invasive or invasive mechanical ventilation or death by 28 days), but did note a 5% absolute reduction in mortality at 28 days. Based on this results, Baricitinib may have a role similar role in the care of COVID-19 patients as tocilizumab (an IL-6 inhibitor) when given in combination with steroids, but may be used in the care of patients earlier in their disease including those on high flow or noninvasive oxygen as well as those requiring invasive mechanical ventilation, compared to tocilizumab, which is currently preferred by many clinicians in those on more intensive respiratory support and within 24-48 hours of ICU admission.  Like other immunomodulators, there is a concern for increased secondary infections with the use of this therapy, but JAK inhibitors also carry a risk for increase in venous thromboembolic events. Interestingly, in this trial, there was no difference in the incidence of either of these adverse effects between the placebo and treatment groups.

The results of a phase 3 RCT with Canakinumab, an anti-interleukin-1B monoclonal antibody, on the other hand, did not show a benefit in primary outcome of survival without need for mechanical ventilation day 3 to day 29, or recovery time, in hospitalized patients who had elevated C-reactive protein and ferritin but were not yet intubated. Canakinumab was evaluated because IL-1B has been identified as one of the signature elevated cytokines in a maladaptive immune response to SARS-CoV-2 infection and because had shown some promise in small and retrospective studies. 

Lastly, on the prevention side, a study of Regeneron’s anti-SARS-CoV-2 monoclonal antibody cocktail (casirivimab and imdevimab) was evaluated in a double blind placebo controlled RCT in prevention of development of symptomatic SARS-CoV-2 infection within 28 days among household contacts who did not have prior immunity. In the study, 1.5% of those who received the monoclonal therapy subcutaneously versus 7.8% of those who received placebo met the primary endpoint. Additionally, those who received the therapy and were symptomatic, resolved their symptoms two weeks earlier. The real-world utility of the results, however, maybe limited to specific groups, given that need for early identification of contacts, the need to access medical facility for administration, as well as the cost of the drug. There may be a role in high risk and immunocompromised contacts who do not develop adequate immune response to vaccination.

Marconi et al report out the results of the COV-Barrier study, a phase 3 randomized placebo controlled (RCT) trial with baricitinib, a JAK-STAT pathway inhibitor generally used to suppress proinflammatory cytokine production and systemic inflammation in rheumatoid arthritis, in hospitalized COVID-19 patients. The 1525 participants equally divided between placebo and baricitinib in an intention to treat analysis, were recruited from 12 countries, and most were on systemic corticosteroids (79.3%) and about one fifth received the antiviral, remdesivir. The study did not show a difference in the primary outcome (a composite of progression to more severe disease including need for high flow oxygen, non-invasive or invasive mechanical ventilation or death by 28 days), but did note a 5% absolute reduction in mortality at 28 days. Based on this results, Baricitinib may have a role similar role in the care of COVID-19 patients as tocilizumab (an IL-6 inhibitor) when given in combination with steroids, but may be used in the care of patients earlier in their disease including those on high flow or noninvasive oxygen as well as those requiring invasive mechanical ventilation, compared to tocilizumab, which is currently preferred by many clinicians in those on more intensive respiratory support and within 24-48 hours of ICU admission.  Like other immunomodulators, there is a concern for increased secondary infections with the use of this therapy, but JAK inhibitors also carry a risk for increase in venous thromboembolic events. Interestingly, in this trial, there was no difference in the incidence of either of these adverse effects between the placebo and treatment groups.

The results of a phase 3 RCT with Canakinumab, an anti-interleukin-1B monoclonal antibody, on the other hand, did not show a benefit in primary outcome of survival without need for mechanical ventilation day 3 to day 29, or recovery time, in hospitalized patients who had elevated C-reactive protein and ferritin but were not yet intubated. Canakinumab was evaluated because IL-1B has been identified as one of the signature elevated cytokines in a maladaptive immune response to SARS-CoV-2 infection and because had shown some promise in small and retrospective studies. 

Lastly, on the prevention side, a study of Regeneron’s anti-SARS-CoV-2 monoclonal antibody cocktail (casirivimab and imdevimab) was evaluated in a double blind placebo controlled RCT in prevention of development of symptomatic SARS-CoV-2 infection within 28 days among household contacts who did not have prior immunity. In the study, 1.5% of those who received the monoclonal therapy subcutaneously versus 7.8% of those who received placebo met the primary endpoint. Additionally, those who received the therapy and were symptomatic, resolved their symptoms two weeks earlier. The real-world utility of the results, however, maybe limited to specific groups, given that need for early identification of contacts, the need to access medical facility for administration, as well as the cost of the drug. There may be a role in high risk and immunocompromised contacts who do not develop adequate immune response to vaccination.

Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.

Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.

However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.

In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.

Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.

In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).

Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).

When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).

The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.

However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
 

Step up lead elimination efforts

“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.

The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
 

Elevated lead levels may be underreported

In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.

“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.

“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.

“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.

The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.

Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.

However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.

In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.

Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.

In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).

Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).

When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).

The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.

However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
 

Step up lead elimination efforts

“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.

The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
 

Elevated lead levels may be underreported

In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.

“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.

“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.

“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.

The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.

Lead poisoning remains a significant threat to the health of young children in the United States, based on data from blood tests of more than 1 million children.

Any level of lead is potentially harmful, although blood lead levels have decreased over the past several decades in part because of the elimination of lead from many consumer products, as well as from gas, paint, and plumbing fixtures, wrote Marissa Hauptman, MD, of Boston Children’s Hospital and colleagues.

However, “numerous environmental sources of legacy lead still exist,” and children living in poverty and in older housing in particular remain at increased risk for lead exposure, they noted.

In a study published in JAMA Pediatrics, the researchers analyzed deidentified results from blood lead tests performed at a single clinical laboratory for 1,141,441 children younger than 6 years between Oct. 1, 2018, and Feb. 29, 2020. The mean age of the children was 2.3 years; approximately half were boys.

Overall, 50.5% of the children tested (576,092 children) had detectable blood lead levels (BLLs), defined as 1.0 mcg/dL or higher, and 1.9% (21,172 children) had elevated BLLs, defined as 5.0 mcg/dL or higher.

In multivariate analysis, both detectable BLLs and elevated BLLs were significantly more common among children with public insurance (adjusted odds ratios, 2.01 and 1.08, respectively).

Children in the highest vs. lowest quintile of pre-1950s housing had significantly greater odds of both detectable and elevated BLLs (aOR, 1.65 and aOR, 3.06); those in the highest vs. lowest quintiles of poverty showed similarly increased risk of detectable and elevated BLLs (aOR, 1.89 and aOR, 1.99, respectively; P < .001 for all).

When the data were broken out by ZIP code, children in predominantly Black non-Hispanic and non-Latino neighborhoods were more likely than those living in other ZIP codes to have detectable BLLs (aOR, 1.13), but less likely to have elevated BLLs (aOR, 0.83). States with the highest overall proportions of children with detectable BLLs were Nebraska (83%), Missouri (82%), and Michigan (78%).

The study findings were limited by several factors, especially the potential for selection bias because of the use of a single reference laboratory (Quest Diagnostics), that does not perform all lead testing in the United States, the researchers noted. Other limitations included variability in testing at the state level, and the use of ZIP code–level data to estimate race, ethnicity, housing, and poverty, they said.

However, the results suggest that lead exposure remains a problem in young children, with significant disparities at the individual and community level, and national efforts must focus on further reductions of lead exposure in areas of highest risk, they concluded.
 

Step up lead elimination efforts

“The removal of lead from gasoline and new paint produced a precipitous decrease in blood lead levels from a population mean of 17 mcg/dL (all ages) in 1976 to 4 mcg/dL in the early 1990s to less than 2 mcg/dL today,” wrote Philip J. Landrigan, MD, of Boston College and David Bellinger, PhD, of Harvard University, Boston, in an accompanying editorial. However, “The findings from this study underscore the urgent need to eliminate all sources of lead exposure from U.S. children’s environments,” and highlight the persistent disparities in children’s lead exposure, they said.

The authors emphasized the need to remove existing lead paint from U.S. homes, as not only the paint itself, but the dust that enters the environment as the pain wears over time, continue to account for most detectable and elevated BLLs in children. A comprehensive lead paint removal effort would be an investment that would protect children now and would protect future generations, they emphasized. They proposed “creating a lead paint removal workforce through federally supported partnerships between city governments and major unions,” that would not only protect children from disease and disability, but could potentially provide jobs and vocational programs that would have a significant impact on communities.
 

Elevated lead levels may be underreported

In fact, the situation of children’s lead exposure in the United States may be more severe than indicated by the study findings, given the variation in testing at the state and local levels, said Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn.

“There are no available lead test kits in our offices, so I do worry that many elevated lead levels will be missed,” she said.

“The recent case of elevated lead levels in drinking water in Flint, Michigan, was largely detected through pediatric clinic screening and showed that elevated lead levels may remain a major issue in some communities,” said Tim Joos, MD, a clinician in combined internal medicine/pediatrics in Seattle, Wash., in an interview.

“It is important to highlight to what extent baseline and point-source lead contamination still exists, monitor progress towards lowering levels, and identify communities at high risk,” Dr. Joos emphasized. “The exact prevalence of elevated lead levels among the general pediatric populations is hard to estimate from this study because of the methodology, which looked at demographic characteristics of the subset of the pediatric population that had venous samples sent to Quest Lab,” he noted.

“As the authors pointed out, it is hard to know what biases went into deciding whether to screen or not, and whether these were confirmatory tests for elevated point of care testing done earlier in the clinic,” said Dr. Joos. “Nonetheless, it does point to the role of poverty and pre-1950s housing in elevated blood lead levels,” he added. “The study also highlights that, as the CDC considers lowering the level for what is considered an ‘elevated blood lead level’ from 5.0 to perhaps 3.5 mcg/dL, we still have a lot more work to do,” he said.

The study was funded by Quest Diagnostics and the company provided salaries to several coauthors during the study. Dr. Hauptmann disclosed support from the National Institutes of Health/National Institute of Environmental Health Sciences during the current study and support from the Agency for Toxic Substances and Disease Registry and the U.S. Environmental Protection Agency unrelated to the current study. Dr. Landrigan had no financial conflicts to disclose. Dr. Bellinger disclosed fees from attorneys for testimony in cases unrelated to the editorial. Dr. Kinsella had no financial conflicts to disclose, but serves on the Editorial Advisory Board of Pediatric News. Dr. Joos had no financial conflicts to disclose, but serves on the Pediatric News Editorial Advisory Board.