A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

A woman who was born without a uterus has given birth to a boy in Alabama.

It’s the first time that a baby has been born to a woman with a transplanted uterus outside of a clinical trial. Officials from University of Alabama–Birmingham Hospital, where the 2-year process took place, said in a statement on July 24 that the birth sets its uterus transplant program on track to perhaps become covered under insurance plans.

The process of uterus transplant, in vitro fertilization, and pregnancy involves 50 medical providers and is open to women who have uterine factor infertility (UFI). The condition may affect up to 5% of reproductive-age women worldwide. Women with UFI cannot carry a pregnancy to term because they were either born without a uterus, had it removed via hysterectomy, or have a uterus that does not function properly.

The woman, whom the hospital identified as Mallory, moved with her family to the Birmingham area to enter the transplant program, which is one of four programs operating in the United States. Mallory learned when she was 17 years old that she was born without a uterus because of Mayer-Rokitansky-Küster-Hauser syndrome. Her first child, a daughter, was born after her sister carried the pregnancy as a surrogate.

Mallory received her uterus from a deceased donor. Her son was born in May.

“As with other types of organ transplants, the woman must take immunosuppressive medications to prevent the body from rejecting the transplanted uterus,” the transplant program’s website states. “After the baby is born and if the woman does not want more children, the transplanted uterus is removed with a hysterectomy procedure, and the woman no longer needs to take antirejection medications.”

“There are all different ways to grow your family if you have uterine factor infertility, but this [uterus transplantation] is what I feel like I knew that I was supposed to do,” Mallory said in a statement. “I mean, just hearing the cry at first was just, you know, mind blowing.”

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

TOPLINE:

The use of oral cancer drugs on Medicare Part D formularies requiring prior authorization has increased over the past decade, with the biggest rise occurring for nonspecialty brand drugs.

METHODOLOGY:  

• Researchers used Medicare Part D formulary files to identify insurance companies’ use of prior authorization and quantity limits for each drug-dose-formulary combination for oral cancer drugs.
• Drugs were identified using the 2021 Oncology Care Model drug list.
• Researchers categorized drugs as specialty – when monthly costs were higher than $600 in 2010-2016 and $670 in 2017-2020 – or nonspecialty and brand or generic.
• For each year in the study period, which spanned 2010-2020, researchers estimated the enrollment-weighted proportion of drug-dose-formulary combinations subject to administrative burdens. 
• Medicare Part D beneficiaries increased from 28,030,290 in 2010 to 47,337,020 in 2020.

TAKEAWAYS:

• In 2010, 333 formularies covered 62 oral cancer drugs – 26 specialty brands, zero specialty generics, 28 nonspecialty brands, and eight nonspecialty generics – compared with 548 formularies and 249 drugs in 2020 – 139 specialty brands, nine specialty generics, 86 nonspecialty brands, and 15 nonspecialty generics. 
• Unique drug-dose-formulary prescribing combinations increased from 19,004 to 122,173 between 2010 and 2020; the proportion of drug-dose-formulary combinations requiring prior authorization also increased in that time.
• For specialty brand drugs, the proportion requiring prior authorization increased from 72.8% to 95.4%; that proportion increased nearly fivefold, from 15.9% to 78.2%, for nonspecialty brand drugs, and eightfold, from 1% to 8%, for nonspecialty generic drugs.
• The proportion of drug-dose-formulary combinations for oral oncology drugs requiring quantity limits for specialty brand drugs doubled over the study period – from 31.4% to 62.5%. That proportion increased from 32.7% to 77.8% for specialty generic drugs between 2016 and 2020; and between 2010 and 2020, from 11.8% to 47.3% for nonspecialty brand drugs and from 9.7% to 18.8% for nonspecialty generic drugs.

IN PRACTICE:  

“Utilization management may be appropriate for some oncology drugs, such as those approved with provisional evidence of efficacy,” researchers wrote. “It is less clear why prior authorization is required for highly effective, first-line drugs such as generic imatinib.”

SOURCE:  

The analysis, led by Michael Anne Kyle, PhD, RN, was published online July 18 in JAMA Network Open.

LIMITATIONS:

The study focused on Medicare and oral oncology drugs, and future work could expand the scope.

DISCLOSURES:

The research was funded by a National Cancer Institute grant. Coauthors received funding from Arnold Ventures and the Commonwealth Fund.

Authors reported affiliations with the Robert Wood Johnson Foundation, Leukemia & Lymphoma Society, Institute for Clinical and Economic Review, West Health, Medicare Payment Advisory Commission, National Cancer Institute, and Centers for Medicare & Medicaid Services.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of oral cancer drugs on Medicare Part D formularies requiring prior authorization has increased over the past decade, with the biggest rise occurring for nonspecialty brand drugs.

METHODOLOGY:  

• Researchers used Medicare Part D formulary files to identify insurance companies’ use of prior authorization and quantity limits for each drug-dose-formulary combination for oral cancer drugs.
• Drugs were identified using the 2021 Oncology Care Model drug list.
• Researchers categorized drugs as specialty – when monthly costs were higher than $600 in 2010-2016 and $670 in 2017-2020 – or nonspecialty and brand or generic.
• For each year in the study period, which spanned 2010-2020, researchers estimated the enrollment-weighted proportion of drug-dose-formulary combinations subject to administrative burdens. 
• Medicare Part D beneficiaries increased from 28,030,290 in 2010 to 47,337,020 in 2020.

TAKEAWAYS:

• In 2010, 333 formularies covered 62 oral cancer drugs – 26 specialty brands, zero specialty generics, 28 nonspecialty brands, and eight nonspecialty generics – compared with 548 formularies and 249 drugs in 2020 – 139 specialty brands, nine specialty generics, 86 nonspecialty brands, and 15 nonspecialty generics. 
• Unique drug-dose-formulary prescribing combinations increased from 19,004 to 122,173 between 2010 and 2020; the proportion of drug-dose-formulary combinations requiring prior authorization also increased in that time.
• For specialty brand drugs, the proportion requiring prior authorization increased from 72.8% to 95.4%; that proportion increased nearly fivefold, from 15.9% to 78.2%, for nonspecialty brand drugs, and eightfold, from 1% to 8%, for nonspecialty generic drugs.
• The proportion of drug-dose-formulary combinations for oral oncology drugs requiring quantity limits for specialty brand drugs doubled over the study period – from 31.4% to 62.5%. That proportion increased from 32.7% to 77.8% for specialty generic drugs between 2016 and 2020; and between 2010 and 2020, from 11.8% to 47.3% for nonspecialty brand drugs and from 9.7% to 18.8% for nonspecialty generic drugs.

IN PRACTICE:  

“Utilization management may be appropriate for some oncology drugs, such as those approved with provisional evidence of efficacy,” researchers wrote. “It is less clear why prior authorization is required for highly effective, first-line drugs such as generic imatinib.”

SOURCE:  

The analysis, led by Michael Anne Kyle, PhD, RN, was published online July 18 in JAMA Network Open.

LIMITATIONS:

The study focused on Medicare and oral oncology drugs, and future work could expand the scope.

DISCLOSURES:

The research was funded by a National Cancer Institute grant. Coauthors received funding from Arnold Ventures and the Commonwealth Fund.

Authors reported affiliations with the Robert Wood Johnson Foundation, Leukemia & Lymphoma Society, Institute for Clinical and Economic Review, West Health, Medicare Payment Advisory Commission, National Cancer Institute, and Centers for Medicare & Medicaid Services.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of oral cancer drugs on Medicare Part D formularies requiring prior authorization has increased over the past decade, with the biggest rise occurring for nonspecialty brand drugs.

METHODOLOGY:  

• Researchers used Medicare Part D formulary files to identify insurance companies’ use of prior authorization and quantity limits for each drug-dose-formulary combination for oral cancer drugs.
• Drugs were identified using the 2021 Oncology Care Model drug list.
• Researchers categorized drugs as specialty – when monthly costs were higher than $600 in 2010-2016 and $670 in 2017-2020 – or nonspecialty and brand or generic.
• For each year in the study period, which spanned 2010-2020, researchers estimated the enrollment-weighted proportion of drug-dose-formulary combinations subject to administrative burdens. 
• Medicare Part D beneficiaries increased from 28,030,290 in 2010 to 47,337,020 in 2020.

TAKEAWAYS:

• In 2010, 333 formularies covered 62 oral cancer drugs – 26 specialty brands, zero specialty generics, 28 nonspecialty brands, and eight nonspecialty generics – compared with 548 formularies and 249 drugs in 2020 – 139 specialty brands, nine specialty generics, 86 nonspecialty brands, and 15 nonspecialty generics. 
• Unique drug-dose-formulary prescribing combinations increased from 19,004 to 122,173 between 2010 and 2020; the proportion of drug-dose-formulary combinations requiring prior authorization also increased in that time.
• For specialty brand drugs, the proportion requiring prior authorization increased from 72.8% to 95.4%; that proportion increased nearly fivefold, from 15.9% to 78.2%, for nonspecialty brand drugs, and eightfold, from 1% to 8%, for nonspecialty generic drugs.
• The proportion of drug-dose-formulary combinations for oral oncology drugs requiring quantity limits for specialty brand drugs doubled over the study period – from 31.4% to 62.5%. That proportion increased from 32.7% to 77.8% for specialty generic drugs between 2016 and 2020; and between 2010 and 2020, from 11.8% to 47.3% for nonspecialty brand drugs and from 9.7% to 18.8% for nonspecialty generic drugs.

IN PRACTICE:  

“Utilization management may be appropriate for some oncology drugs, such as those approved with provisional evidence of efficacy,” researchers wrote. “It is less clear why prior authorization is required for highly effective, first-line drugs such as generic imatinib.”

SOURCE:  

The analysis, led by Michael Anne Kyle, PhD, RN, was published online July 18 in JAMA Network Open.

LIMITATIONS:

The study focused on Medicare and oral oncology drugs, and future work could expand the scope.

DISCLOSURES:

The research was funded by a National Cancer Institute grant. Coauthors received funding from Arnold Ventures and the Commonwealth Fund.

Authors reported affiliations with the Robert Wood Johnson Foundation, Leukemia & Lymphoma Society, Institute for Clinical and Economic Review, West Health, Medicare Payment Advisory Commission, National Cancer Institute, and Centers for Medicare & Medicaid Services.

A version of this article appeared on Medscape.com.

Recently published conclusions from the first interim analysis of overall survival in the IMpower010 trial of adjuvant atezolizumab for non–small cell lung cancer (NSCLC) have met with some pushback on Twitter.

Here’s why.

At a median follow-up of 45.3 months, 127 of 507 patients (25%) in the atezolizumab group and 124 of 498 (24.9%) in the best supportive care group had died.

Among all 882 patients with stage II-IIIA disease, the investigators found no significant improvement in overall survival with atezolizumab, compared with best supportive care (hazard ratio, 0.95; 95% confidence interval, 0.74-1.24).

The researchers, however, concluded that the trial showed a “positive” trend favoring atezolizumab in PD-L1 subgroup analyses.

In a subgroup of 476 patients with tumor PD-L1 expression ≥ 1%, patients who received atezolizumab exhibited a nonsignificant 29% improvement in overall survival (HR, 0.71; 95% CI, 0.49-1.03). The best results were in the subgroup of 229 patients with tumor PD-L1 expression ≥ 50% – these patients exhibited a 57% improvement in overall survival with atezolizumab (HR, 0.43; 95% CI, 0.24-0.78). Those with PD-L1 expression 1%-49%, however, demonstrated no improvement in overall survival (HR, 0.95).

In a Twitter post, H. Jack West, MD, City of Hope Comprehensive Cancer Center, Duarte, Calif., urged caution in interpreting the study data: “Let’s be clear: OS results are neg for OS benefit in PD-L1+ NSCLC. If we’re going to rely on smaller subgroups to highlight HR of 0.43 for those w/high PD-L1, we should also note HR for OS was 0.95 (i.e., NO trend for OS benefit) for those w/PD-L1 1-49%.”

The tweet continued: “With favorable results driven entirely by a 30% subgroup, it’s understandable that Roche would want to also promote benefit in broader population. But we shouldn’t perpetuate misinformation that there’s a benefit for broad group of PD-L1+, even if the effort is to market it this way.”

In an interview, Dr. West elaborated on his tweet, explaining that the way the overall survival data are presented in the paper is “disingenuous and misleading.”

The paper clearly highlights that the drug was significantly beneficial for the narrower population who had high PD-L1 expression. But the hazard ratio of 0.95 for the entire population is like “where’s Waldo in this paper. It’s almost impossible to find, but it should have been prominently included in the figure of results by subgroup,” Dr. West said.

“This is something that should have been objected to by the oncologists on the paper and by the reviews and the editors,” Dr. West said.

Two other oncologists agreed.

Joel Grossman, MD, tweeted: “Bingo. I’m not sure we need cancer ground shots or lengthy treatises on common sense, but I am damn sure we need honest interpretation of clinical trial data as Jack shows here. We can’t tolerate over-broad borderline deception that leads to poor and wasteful decision-making.”

Jeff Ryckman, MD, tweeted: “Problem is, this is a routine FDA #CarteBlanche approval regardless of no benefit in PD-L1 1%-49%. This will be Rx’d to everyone.”
 

Regulatory ‘gamesmanship’

The results of the IMpower010 analysis were published online in Annals of Oncology. The interim overall survival data were first reported last year at the World Conference on Lung Cancer.

IMpower010 was a global, randomized, open-label trial of 1,280 patients with completely resected stage IB (tumors ≥ 4 cm) through stage IIIA NSCLC for whom tissue samples were available for PD-L1 analysis.

All patients received four cycles of chemotherapy with cisplatin plus either pemetrexed, gemcitabine, docetaxel, or vinorelbine and were randomly assigned in a 1:1 ratio to receive either 16 cycles of atezolizumab or best supportive care.

Interim disease-free survival (DFS) results from IMpower010, presented at ASCO 2021, showed that patients with PD-L1 expression ≥ 1% experienced a 34% improvement in DFS, equating to a 21% improvement across all randomly assigned patients with stage II-IIIA disease.

On the basis of DFS findings, in 2021, the U.S. Food and Drug Administration granted atezolizumab a new indication – the adjuvant treatment following resection and platinum-based chemotherapy for patients with stage II-IIIA NSCLC whose tumors have PD-L1 expression ≥ 1%.

Looking at the big picture, Dr. West noted that regulatory approval for a drug allows for a certain amount of “gamesmanship.”

“It behooves a company to work with FDA to get approval for a broader population than it should be, relative to where the true clinical benefit lies,” he explained.

To this end, Dr. West noted that progression-free survival is increasingly being used as a primary endpoint in trials, but long-term data indicate that this surrogate endpoint is often not tethered to an overall survival benefit. However, drugs are often being approved now on the basis of a progression-free survival benefit.

“Unfortunately, that’s the system we live in today, with a bias toward, ‘If it could plausibly be interpreted as beneficial, we’ll wave it through for the broadest population possible,” Dr. West said.

The IMpower010 study and Annals of Oncology manuscript were funded by F. Hoffmann-La Roche. Several authors have disclosed relationships with the company. Dr. West has a regular column on Medscape.com and reported personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article appeared on Medscape.com.

Recently published conclusions from the first interim analysis of overall survival in the IMpower010 trial of adjuvant atezolizumab for non–small cell lung cancer (NSCLC) have met with some pushback on Twitter.

Here’s why.

At a median follow-up of 45.3 months, 127 of 507 patients (25%) in the atezolizumab group and 124 of 498 (24.9%) in the best supportive care group had died.

Among all 882 patients with stage II-IIIA disease, the investigators found no significant improvement in overall survival with atezolizumab, compared with best supportive care (hazard ratio, 0.95; 95% confidence interval, 0.74-1.24).

The researchers, however, concluded that the trial showed a “positive” trend favoring atezolizumab in PD-L1 subgroup analyses.

In a subgroup of 476 patients with tumor PD-L1 expression ≥ 1%, patients who received atezolizumab exhibited a nonsignificant 29% improvement in overall survival (HR, 0.71; 95% CI, 0.49-1.03). The best results were in the subgroup of 229 patients with tumor PD-L1 expression ≥ 50% – these patients exhibited a 57% improvement in overall survival with atezolizumab (HR, 0.43; 95% CI, 0.24-0.78). Those with PD-L1 expression 1%-49%, however, demonstrated no improvement in overall survival (HR, 0.95).

In a Twitter post, H. Jack West, MD, City of Hope Comprehensive Cancer Center, Duarte, Calif., urged caution in interpreting the study data: “Let’s be clear: OS results are neg for OS benefit in PD-L1+ NSCLC. If we’re going to rely on smaller subgroups to highlight HR of 0.43 for those w/high PD-L1, we should also note HR for OS was 0.95 (i.e., NO trend for OS benefit) for those w/PD-L1 1-49%.”

The tweet continued: “With favorable results driven entirely by a 30% subgroup, it’s understandable that Roche would want to also promote benefit in broader population. But we shouldn’t perpetuate misinformation that there’s a benefit for broad group of PD-L1+, even if the effort is to market it this way.”

In an interview, Dr. West elaborated on his tweet, explaining that the way the overall survival data are presented in the paper is “disingenuous and misleading.”

The paper clearly highlights that the drug was significantly beneficial for the narrower population who had high PD-L1 expression. But the hazard ratio of 0.95 for the entire population is like “where’s Waldo in this paper. It’s almost impossible to find, but it should have been prominently included in the figure of results by subgroup,” Dr. West said.

“This is something that should have been objected to by the oncologists on the paper and by the reviews and the editors,” Dr. West said.

Two other oncologists agreed.

Joel Grossman, MD, tweeted: “Bingo. I’m not sure we need cancer ground shots or lengthy treatises on common sense, but I am damn sure we need honest interpretation of clinical trial data as Jack shows here. We can’t tolerate over-broad borderline deception that leads to poor and wasteful decision-making.”

Jeff Ryckman, MD, tweeted: “Problem is, this is a routine FDA #CarteBlanche approval regardless of no benefit in PD-L1 1%-49%. This will be Rx’d to everyone.”
 

Regulatory ‘gamesmanship’

The results of the IMpower010 analysis were published online in Annals of Oncology. The interim overall survival data were first reported last year at the World Conference on Lung Cancer.

IMpower010 was a global, randomized, open-label trial of 1,280 patients with completely resected stage IB (tumors ≥ 4 cm) through stage IIIA NSCLC for whom tissue samples were available for PD-L1 analysis.

All patients received four cycles of chemotherapy with cisplatin plus either pemetrexed, gemcitabine, docetaxel, or vinorelbine and were randomly assigned in a 1:1 ratio to receive either 16 cycles of atezolizumab or best supportive care.

Interim disease-free survival (DFS) results from IMpower010, presented at ASCO 2021, showed that patients with PD-L1 expression ≥ 1% experienced a 34% improvement in DFS, equating to a 21% improvement across all randomly assigned patients with stage II-IIIA disease.

On the basis of DFS findings, in 2021, the U.S. Food and Drug Administration granted atezolizumab a new indication – the adjuvant treatment following resection and platinum-based chemotherapy for patients with stage II-IIIA NSCLC whose tumors have PD-L1 expression ≥ 1%.

Looking at the big picture, Dr. West noted that regulatory approval for a drug allows for a certain amount of “gamesmanship.”

“It behooves a company to work with FDA to get approval for a broader population than it should be, relative to where the true clinical benefit lies,” he explained.

To this end, Dr. West noted that progression-free survival is increasingly being used as a primary endpoint in trials, but long-term data indicate that this surrogate endpoint is often not tethered to an overall survival benefit. However, drugs are often being approved now on the basis of a progression-free survival benefit.

“Unfortunately, that’s the system we live in today, with a bias toward, ‘If it could plausibly be interpreted as beneficial, we’ll wave it through for the broadest population possible,” Dr. West said.

The IMpower010 study and Annals of Oncology manuscript were funded by F. Hoffmann-La Roche. Several authors have disclosed relationships with the company. Dr. West has a regular column on Medscape.com and reported personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article appeared on Medscape.com.

Recently published conclusions from the first interim analysis of overall survival in the IMpower010 trial of adjuvant atezolizumab for non–small cell lung cancer (NSCLC) have met with some pushback on Twitter.

Here’s why.

At a median follow-up of 45.3 months, 127 of 507 patients (25%) in the atezolizumab group and 124 of 498 (24.9%) in the best supportive care group had died.

Among all 882 patients with stage II-IIIA disease, the investigators found no significant improvement in overall survival with atezolizumab, compared with best supportive care (hazard ratio, 0.95; 95% confidence interval, 0.74-1.24).

The researchers, however, concluded that the trial showed a “positive” trend favoring atezolizumab in PD-L1 subgroup analyses.

In a subgroup of 476 patients with tumor PD-L1 expression ≥ 1%, patients who received atezolizumab exhibited a nonsignificant 29% improvement in overall survival (HR, 0.71; 95% CI, 0.49-1.03). The best results were in the subgroup of 229 patients with tumor PD-L1 expression ≥ 50% – these patients exhibited a 57% improvement in overall survival with atezolizumab (HR, 0.43; 95% CI, 0.24-0.78). Those with PD-L1 expression 1%-49%, however, demonstrated no improvement in overall survival (HR, 0.95).

In a Twitter post, H. Jack West, MD, City of Hope Comprehensive Cancer Center, Duarte, Calif., urged caution in interpreting the study data: “Let’s be clear: OS results are neg for OS benefit in PD-L1+ NSCLC. If we’re going to rely on smaller subgroups to highlight HR of 0.43 for those w/high PD-L1, we should also note HR for OS was 0.95 (i.e., NO trend for OS benefit) for those w/PD-L1 1-49%.”

The tweet continued: “With favorable results driven entirely by a 30% subgroup, it’s understandable that Roche would want to also promote benefit in broader population. But we shouldn’t perpetuate misinformation that there’s a benefit for broad group of PD-L1+, even if the effort is to market it this way.”

In an interview, Dr. West elaborated on his tweet, explaining that the way the overall survival data are presented in the paper is “disingenuous and misleading.”

The paper clearly highlights that the drug was significantly beneficial for the narrower population who had high PD-L1 expression. But the hazard ratio of 0.95 for the entire population is like “where’s Waldo in this paper. It’s almost impossible to find, but it should have been prominently included in the figure of results by subgroup,” Dr. West said.

“This is something that should have been objected to by the oncologists on the paper and by the reviews and the editors,” Dr. West said.

Two other oncologists agreed.

Joel Grossman, MD, tweeted: “Bingo. I’m not sure we need cancer ground shots or lengthy treatises on common sense, but I am damn sure we need honest interpretation of clinical trial data as Jack shows here. We can’t tolerate over-broad borderline deception that leads to poor and wasteful decision-making.”

Jeff Ryckman, MD, tweeted: “Problem is, this is a routine FDA #CarteBlanche approval regardless of no benefit in PD-L1 1%-49%. This will be Rx’d to everyone.”
 

Regulatory ‘gamesmanship’

The results of the IMpower010 analysis were published online in Annals of Oncology. The interim overall survival data were first reported last year at the World Conference on Lung Cancer.

IMpower010 was a global, randomized, open-label trial of 1,280 patients with completely resected stage IB (tumors ≥ 4 cm) through stage IIIA NSCLC for whom tissue samples were available for PD-L1 analysis.

All patients received four cycles of chemotherapy with cisplatin plus either pemetrexed, gemcitabine, docetaxel, or vinorelbine and were randomly assigned in a 1:1 ratio to receive either 16 cycles of atezolizumab or best supportive care.

Interim disease-free survival (DFS) results from IMpower010, presented at ASCO 2021, showed that patients with PD-L1 expression ≥ 1% experienced a 34% improvement in DFS, equating to a 21% improvement across all randomly assigned patients with stage II-IIIA disease.

On the basis of DFS findings, in 2021, the U.S. Food and Drug Administration granted atezolizumab a new indication – the adjuvant treatment following resection and platinum-based chemotherapy for patients with stage II-IIIA NSCLC whose tumors have PD-L1 expression ≥ 1%.

Looking at the big picture, Dr. West noted that regulatory approval for a drug allows for a certain amount of “gamesmanship.”

“It behooves a company to work with FDA to get approval for a broader population than it should be, relative to where the true clinical benefit lies,” he explained.

To this end, Dr. West noted that progression-free survival is increasingly being used as a primary endpoint in trials, but long-term data indicate that this surrogate endpoint is often not tethered to an overall survival benefit. However, drugs are often being approved now on the basis of a progression-free survival benefit.

“Unfortunately, that’s the system we live in today, with a bias toward, ‘If it could plausibly be interpreted as beneficial, we’ll wave it through for the broadest population possible,” Dr. West said.

The IMpower010 study and Annals of Oncology manuscript were funded by F. Hoffmann-La Roche. Several authors have disclosed relationships with the company. Dr. West has a regular column on Medscape.com and reported personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Chronic pancreatitis raises the risk for pregnancy complications, including gestational diabetes, gestational hypertensive complications, and preterm labor, according to a large study.

METHODOLOGY:

• A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted.
• The sample included 3,094 pregnancies with chronic pancreatitis and roughly 40.8 million pregnancies without this condition.
• The study focused on primary maternal outcomes and primary perinatal outcomes in pregnancies affected by chronic pancreatitis after accounting for relevant covariates.

TAKEAWAY:

• Chronic pancreatitis pregnancies had elevated rates of gestational diabetes (adjusted odds ratio, 1.63), gestational hypertensive complications (aOR, 2.48), preterm labor (aOR, 3.10), and small size for gestational age (aOR, 2.40).
• Women with chronic pancreatitis and a history of renal failure were more prone to gestational hypertensive complications (aOR, 20.09).
• Women with alcohol-induced chronic pancreatitis had a 17-fold higher risk for fetal death (aOR, 17.15).
• Pregnancies with chronic pancreatitis were associated with longer hospital stays and higher hospital costs.

IN PRACTICE:

“Our study provides novel insights into the impact of chronic pancreatitis on maternal and fetal health. The implications of our findings are critical for health care professionals, particularly those involved in preconception counseling. Pregnant women with chronic pancreatitis should be under the care of a multidisciplinary team of health care providers,” the authors advise.

SOURCE:

The study was led by Chengu Niu, MD, with Rochester General Hospital, Rochester, N.Y. It was published online July 18 in Digestive and Liver Disease. The study had no specific funding.

LIMITATIONS:

The authors note potential inaccuracies because of coding in the National Inpatient Sample database, a lack of detailed information regarding medication use, and a lack of follow-up clinical information. The findings are specific to the United States and may not be applicable to other countries.

DISCLOSURES:

The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

Optimism about new opportunities to treat alopecia areata can be derived not only from a recently approved Janus kinase (JAK) inhibitor in older children but promising results with the monoclonal antibody dupilumab alone or in combination with additional treatments, such as minoxidil or corticosteroids, in children with AA and concomitant atopy.

It was only a little over a year ago that the JAK inhibitor baricitinib became the first systemic therapy approved by the Food and Drug Administration for AA in adults. In June 2023, the JAK inhibitor ritlecitinib was approved for severe AA in patients as young as 12 years of age, but there is accumulating evidence that dupilumab, which binds to the interleukin-4 receptor, might be an option for even younger children with AA.

Of those who have worked with dupilumab for controlling AA in children, Brittany Craiglow, MD, an adjunct associate professor of dermatology at Yale University, New Haven, Conn., updated a case series at the recent MedscapeLive! Annual Women’s and Pediatric Dermatology Seminar in Baltimore. A series of six children with AA treated with dupilumab was published 2 years ago in JAAD Case Reports.

Even in 2021, her case series was not the first report of benefit from dupilumab in children with AA, but instead contributed to a “growing body of literature” supporting the potential benefit in the setting of concomitant atopy, Dr. Craiglow, one of the authors of the series, said in an interview.

Of the six patients in that series, five had improvement and four had complete regrowth with dupilumab, whether as a monotherapy or in combination with other agents. The children ranged in age from 7 to 12 years. The age range at the time of AA onset was 3-11 years. All had atopic dermatitis (AD) and most had additional atopic conditions, such as food allergies or asthma.

Since publication, Dr. Craiglow has successfully treated many more patients with dupilumab, either as monotherapy or in combination with oral minoxidil, corticosteroids, and/or a topical JAK inhibitor. Dupilumab, which is approved for the treatment of AD in children as young as 6 months of age, has been well tolerated.

“Oral minoxidil is often a great adjuvant treatment in patients with AA and should be used unless there are contraindications,” based on the initial and subsequent experience treating AA with dupilumab, said Dr. Craiglow.

“Topical steroids can be used in combination with dupilumab and minoxidil, but in general dupilumab should not be combined with an oral JAK inhibitor,” she added.

Now, with the approval of ritlecitinib, Dr. Craiglow said this JAK inhibitor will become a first-line therapy in children 12 years or older with severe, persistent AA, but she considers a trial of dupilumab reasonable in younger children, given the controlled studies of safety for atopic diseases.

“I would say that dupilumab could be considered in the following clinical scenarios: children under 12 with AA and concomitant atopy, such as atopic dermatitis, asthma, allergies, and/or elevated IgE; and children over the age of 12 with concomitant atopy who either have a contraindication to a JAK inhibitor or whose families have reservations about or are unwilling to take one,” Dr. Craiglow said.

In older children, she believes that dupilumab has “a much lower chance of being effective” than an oral JAK inhibitor like ritlecitinib, but it circumvents the potential safety issues of JAK inhibitors that have been observed in adults.

With ritlecitinib providing an on-label option for AA in older children, Dr. Craiglow suggested it might be easier to obtain third-party coverage for dupilumab as an alternative to a JAK inhibitor for AA in patients younger than 12, particularly when there is an indication for a concomitant atopic condition and a rationale, such as a concern about relative safety.

Two years ago, when Dr. Craiglow and her coinvestigator published their six-patient case series, a second case series was published about the same time by investigators at the University of Pennsylvania, Philadelphia, in the Journal of the American Academy of Dermatology. This series of 16 pediatric patients with AA on dupilumab was more heterogeneous, but four of six patients with active disease and more than 4 months of follow-up had improvement in AA, including total regrowth. The improvement was concentrated in patients with moderate to severe AD at the time of treatment.

Based on this series, the authors, led by Leslie Castelo-Soccio, MD, PhD, who is now an attending physician in the Dermatology Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md., concluded that dupilumab “may be a therapeutic option for AA” when traditional therapies have failed, “especially in patients with concurrent AD or asthma, for which the benefits of dupilumab are clear.”

When contacted about where this therapy might fit on the basis of her case series and the update on Dr. Craiglow’s experience, Dr. Castelo-Soccio, like Dr. Craiglow, stressed the importance of employing this therapy selectively.

“I do think that dupilumab is a reasonable option for AA in children with atopy and IgE levels greater than 200 IU/mL, especially if treatment is for atopic dermatitis or asthma as well,” she said.

Many clinicians, including Dr. Craiglow, have experience with oral JAK inhibitors in children younger than 12. Indeed, a recently published case study associated oral abrocitinib, a JAK inhibitor approved for moderate to severe AD in patients ages 12 and older, with hair regrowth in an 11-year-old child who had persistent AA for more than 6 years despite numerous conventional therapies.

However, the advantage of dupilumab in younger children is the greater evidence of safety, providing a level of reassurance for a treatment that is commonly used for severe atopic diseases but does not have a specific indication for AA, according to Dr. Craiglow.

Dr. Craiglow disclosed being a speaker for AbbVie and a speaker and consultant for Eli Lilly, Incyte, Pfizer, Regeneron, and Sanofi Genzyme. Dr. Castelo-Soccio had no disclosures.

Optimism about new opportunities to treat alopecia areata can be derived not only from a recently approved Janus kinase (JAK) inhibitor in older children but promising results with the monoclonal antibody dupilumab alone or in combination with additional treatments, such as minoxidil or corticosteroids, in children with AA and concomitant atopy.

It was only a little over a year ago that the JAK inhibitor baricitinib became the first systemic therapy approved by the Food and Drug Administration for AA in adults. In June 2023, the JAK inhibitor ritlecitinib was approved for severe AA in patients as young as 12 years of age, but there is accumulating evidence that dupilumab, which binds to the interleukin-4 receptor, might be an option for even younger children with AA.

Of those who have worked with dupilumab for controlling AA in children, Brittany Craiglow, MD, an adjunct associate professor of dermatology at Yale University, New Haven, Conn., updated a case series at the recent MedscapeLive! Annual Women’s and Pediatric Dermatology Seminar in Baltimore. A series of six children with AA treated with dupilumab was published 2 years ago in JAAD Case Reports.

Even in 2021, her case series was not the first report of benefit from dupilumab in children with AA, but instead contributed to a “growing body of literature” supporting the potential benefit in the setting of concomitant atopy, Dr. Craiglow, one of the authors of the series, said in an interview.

Of the six patients in that series, five had improvement and four had complete regrowth with dupilumab, whether as a monotherapy or in combination with other agents. The children ranged in age from 7 to 12 years. The age range at the time of AA onset was 3-11 years. All had atopic dermatitis (AD) and most had additional atopic conditions, such as food allergies or asthma.

Since publication, Dr. Craiglow has successfully treated many more patients with dupilumab, either as monotherapy or in combination with oral minoxidil, corticosteroids, and/or a topical JAK inhibitor. Dupilumab, which is approved for the treatment of AD in children as young as 6 months of age, has been well tolerated.

“Oral minoxidil is often a great adjuvant treatment in patients with AA and should be used unless there are contraindications,” based on the initial and subsequent experience treating AA with dupilumab, said Dr. Craiglow.

“Topical steroids can be used in combination with dupilumab and minoxidil, but in general dupilumab should not be combined with an oral JAK inhibitor,” she added.

Now, with the approval of ritlecitinib, Dr. Craiglow said this JAK inhibitor will become a first-line therapy in children 12 years or older with severe, persistent AA, but she considers a trial of dupilumab reasonable in younger children, given the controlled studies of safety for atopic diseases.

“I would say that dupilumab could be considered in the following clinical scenarios: children under 12 with AA and concomitant atopy, such as atopic dermatitis, asthma, allergies, and/or elevated IgE; and children over the age of 12 with concomitant atopy who either have a contraindication to a JAK inhibitor or whose families have reservations about or are unwilling to take one,” Dr. Craiglow said.

In older children, she believes that dupilumab has “a much lower chance of being effective” than an oral JAK inhibitor like ritlecitinib, but it circumvents the potential safety issues of JAK inhibitors that have been observed in adults.

With ritlecitinib providing an on-label option for AA in older children, Dr. Craiglow suggested it might be easier to obtain third-party coverage for dupilumab as an alternative to a JAK inhibitor for AA in patients younger than 12, particularly when there is an indication for a concomitant atopic condition and a rationale, such as a concern about relative safety.

Two years ago, when Dr. Craiglow and her coinvestigator published their six-patient case series, a second case series was published about the same time by investigators at the University of Pennsylvania, Philadelphia, in the Journal of the American Academy of Dermatology. This series of 16 pediatric patients with AA on dupilumab was more heterogeneous, but four of six patients with active disease and more than 4 months of follow-up had improvement in AA, including total regrowth. The improvement was concentrated in patients with moderate to severe AD at the time of treatment.

Based on this series, the authors, led by Leslie Castelo-Soccio, MD, PhD, who is now an attending physician in the Dermatology Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md., concluded that dupilumab “may be a therapeutic option for AA” when traditional therapies have failed, “especially in patients with concurrent AD or asthma, for which the benefits of dupilumab are clear.”

When contacted about where this therapy might fit on the basis of her case series and the update on Dr. Craiglow’s experience, Dr. Castelo-Soccio, like Dr. Craiglow, stressed the importance of employing this therapy selectively.

“I do think that dupilumab is a reasonable option for AA in children with atopy and IgE levels greater than 200 IU/mL, especially if treatment is for atopic dermatitis or asthma as well,” she said.

Many clinicians, including Dr. Craiglow, have experience with oral JAK inhibitors in children younger than 12. Indeed, a recently published case study associated oral abrocitinib, a JAK inhibitor approved for moderate to severe AD in patients ages 12 and older, with hair regrowth in an 11-year-old child who had persistent AA for more than 6 years despite numerous conventional therapies.

However, the advantage of dupilumab in younger children is the greater evidence of safety, providing a level of reassurance for a treatment that is commonly used for severe atopic diseases but does not have a specific indication for AA, according to Dr. Craiglow.

Dr. Craiglow disclosed being a speaker for AbbVie and a speaker and consultant for Eli Lilly, Incyte, Pfizer, Regeneron, and Sanofi Genzyme. Dr. Castelo-Soccio had no disclosures.

Optimism about new opportunities to treat alopecia areata can be derived not only from a recently approved Janus kinase (JAK) inhibitor in older children but promising results with the monoclonal antibody dupilumab alone or in combination with additional treatments, such as minoxidil or corticosteroids, in children with AA and concomitant atopy.

It was only a little over a year ago that the JAK inhibitor baricitinib became the first systemic therapy approved by the Food and Drug Administration for AA in adults. In June 2023, the JAK inhibitor ritlecitinib was approved for severe AA in patients as young as 12 years of age, but there is accumulating evidence that dupilumab, which binds to the interleukin-4 receptor, might be an option for even younger children with AA.

Of those who have worked with dupilumab for controlling AA in children, Brittany Craiglow, MD, an adjunct associate professor of dermatology at Yale University, New Haven, Conn., updated a case series at the recent MedscapeLive! Annual Women’s and Pediatric Dermatology Seminar in Baltimore. A series of six children with AA treated with dupilumab was published 2 years ago in JAAD Case Reports.

Even in 2021, her case series was not the first report of benefit from dupilumab in children with AA, but instead contributed to a “growing body of literature” supporting the potential benefit in the setting of concomitant atopy, Dr. Craiglow, one of the authors of the series, said in an interview.

Of the six patients in that series, five had improvement and four had complete regrowth with dupilumab, whether as a monotherapy or in combination with other agents. The children ranged in age from 7 to 12 years. The age range at the time of AA onset was 3-11 years. All had atopic dermatitis (AD) and most had additional atopic conditions, such as food allergies or asthma.

Since publication, Dr. Craiglow has successfully treated many more patients with dupilumab, either as monotherapy or in combination with oral minoxidil, corticosteroids, and/or a topical JAK inhibitor. Dupilumab, which is approved for the treatment of AD in children as young as 6 months of age, has been well tolerated.

“Oral minoxidil is often a great adjuvant treatment in patients with AA and should be used unless there are contraindications,” based on the initial and subsequent experience treating AA with dupilumab, said Dr. Craiglow.

“Topical steroids can be used in combination with dupilumab and minoxidil, but in general dupilumab should not be combined with an oral JAK inhibitor,” she added.

Now, with the approval of ritlecitinib, Dr. Craiglow said this JAK inhibitor will become a first-line therapy in children 12 years or older with severe, persistent AA, but she considers a trial of dupilumab reasonable in younger children, given the controlled studies of safety for atopic diseases.

“I would say that dupilumab could be considered in the following clinical scenarios: children under 12 with AA and concomitant atopy, such as atopic dermatitis, asthma, allergies, and/or elevated IgE; and children over the age of 12 with concomitant atopy who either have a contraindication to a JAK inhibitor or whose families have reservations about or are unwilling to take one,” Dr. Craiglow said.

In older children, she believes that dupilumab has “a much lower chance of being effective” than an oral JAK inhibitor like ritlecitinib, but it circumvents the potential safety issues of JAK inhibitors that have been observed in adults.

With ritlecitinib providing an on-label option for AA in older children, Dr. Craiglow suggested it might be easier to obtain third-party coverage for dupilumab as an alternative to a JAK inhibitor for AA in patients younger than 12, particularly when there is an indication for a concomitant atopic condition and a rationale, such as a concern about relative safety.

Two years ago, when Dr. Craiglow and her coinvestigator published their six-patient case series, a second case series was published about the same time by investigators at the University of Pennsylvania, Philadelphia, in the Journal of the American Academy of Dermatology. This series of 16 pediatric patients with AA on dupilumab was more heterogeneous, but four of six patients with active disease and more than 4 months of follow-up had improvement in AA, including total regrowth. The improvement was concentrated in patients with moderate to severe AD at the time of treatment.

Based on this series, the authors, led by Leslie Castelo-Soccio, MD, PhD, who is now an attending physician in the Dermatology Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md., concluded that dupilumab “may be a therapeutic option for AA” when traditional therapies have failed, “especially in patients with concurrent AD or asthma, for which the benefits of dupilumab are clear.”

When contacted about where this therapy might fit on the basis of her case series and the update on Dr. Craiglow’s experience, Dr. Castelo-Soccio, like Dr. Craiglow, stressed the importance of employing this therapy selectively.

“I do think that dupilumab is a reasonable option for AA in children with atopy and IgE levels greater than 200 IU/mL, especially if treatment is for atopic dermatitis or asthma as well,” she said.

Many clinicians, including Dr. Craiglow, have experience with oral JAK inhibitors in children younger than 12. Indeed, a recently published case study associated oral abrocitinib, a JAK inhibitor approved for moderate to severe AD in patients ages 12 and older, with hair regrowth in an 11-year-old child who had persistent AA for more than 6 years despite numerous conventional therapies.

However, the advantage of dupilumab in younger children is the greater evidence of safety, providing a level of reassurance for a treatment that is commonly used for severe atopic diseases but does not have a specific indication for AA, according to Dr. Craiglow.

Dr. Craiglow disclosed being a speaker for AbbVie and a speaker and consultant for Eli Lilly, Incyte, Pfizer, Regeneron, and Sanofi Genzyme. Dr. Castelo-Soccio had no disclosures.

“What if VA health care goes away?” That was the headline of a July 6, 2023, Disabled American Veterans news article to its members. The question was not hypothetical. Legislation currently under consideration by the US Congress may make it a strong probability.  

The US Senate Committee on Veterans’ Affairs recently held a hearing to discuss 2 bills that would drastically reshape the provision of private health care services through the Veterans Community Care Program. An unprecedented coalition of 10 organizations—made up of US Department of Veterans Affairs (VA) nurses, psychologists, physicians, dentists, social workers, optometrists, physician assistants, and nurse anesthetists, as well as the American Psychological Association, the Military and Veterans Committee of the Group for the Advancement of Psychiatry and the Veterans Healthcare Policy Institute—came together in a unified statement for the record highlighting how these proposed policies would open a Pandora’s box that could forever eliminate the Veterans Health Administration as we know it.

Over the past decade—and especially following the passage of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act—there has been a surge of veterans gaining eligibility for private care if a VA medical facility is too far away, does not offer the needed care, or the wait time for an appointment is too long.

Courtesy: Rasmussen P, Farmer CM. The Promise and Challenges of VA Community Care: Veterans' Issues in Focus. Rand Health Q. 2023;10(3):9.

Testifying before the House Committee on Veterans’ Affairs hearing last year, Miguel LaPuz, MD, MBA, then the acting Deputy Under Secretary for Health at the VA, warned that “VA is rapidly approaching a point where half of all care available in both settings is provided through community care.” He cautioned that leaders were bracing for “the potential of a spiral effect.”

Care that is rendered to veterans in the community must, of course, be paid for. When those community costs began to soar at the start of the Community Care program, Congress bailed out the VA by allocating extra funds. Today, escalating costs are drawn from local VA facility budgets. And to guarantee that private sector care is paid for out of VA facility funds, legislators are introducing language, such as in the Veterans Healthcare Freedom Act, which states: “No additional funds are authorized to be appropriated to carry out this section and the amendments made by this section, and this section and the amendments made by this section shall be carried out using amounts otherwise made available to the Veterans Health Administration.” The anticipated vicious cycle looms. More money pouring into the private sector will force reductions and closures of in-house VA staff, programs, clinics, and units. This will cause more veterans to obtain care in the community, which will further drain more money out of VA facilities, leading to more reductions, etc. Rural areas will likely be hit hardest.

The VA is nearing the tipping point of this ever-descending spiral. And that is even without expanding eligibility further. Three provisions in this pair of bills could, on their own, drastically open eligibility, eliminate remaining guardrails, and push VA over the edge:

(1) Veteran preference. Tucked into the HEALTH Act, introduced by the ranking Republican Member, Jerry Moran of Kansas, is language which would require VA to consider a “veteran’s preference” for obtaining their health care in the private sector.

This stipulation violates the intent of the VA MISSION Act. When MISSION passed, there was bipartisan agreement that the Community Care Program was meant, in numerous Senators’ words, to “supplement, not supplant” VA health care. A veteran would be offered the option of receiving health care outside of the VA under 6 narrowly defined criteria. Legislators understood that veterans would get the option to choose whether to receive care in the private sector or the VA if, and only if, they qualified under the 6 eligibility rules. As a well-researched document coauthored by Disabled American Veterans, Paralyzed Veterans of America, and the Veterans of Foreign Wars stated, “veteran convenience or preference” should never be used as a sole reason for referral.

Explicitly adding preference for the first time will create the expectation among veterans and lawmakers of a new allowance. Were this to pass, every veteran—100%—would become eligible for referral to the private sector, kicking off an unstoppable drainage of VA budget resources and threatening its viability. Hopefully, the Senate will follow the lead of the US House Committee on Veterans’ Affairs which, last week, amended its its own community care bill by deleting “veteran preference” as a possible new eligibility criterion.

(2) Self-referral. Also being deliberated is the Making Community Care Work for Veterans Act, a draft bill authored by the US Senate Committee on Veterans’ Affairs Democratic Chairman Senator Jon Tester of Montana. It calls for allowing self-initiated routine vaccinations and routine vision/hearing services in the community.

On the surface, Tester’s bill focuses on only a tiny sliver of care. But once self-referral is permitted for a few services, private sector interests will, in no time, push the door wide open and add more services to which veterans can self-refer. Testimony at the hearing confirmed that prediction, as the Veterans of Foreign Wars and America’s Warrior Partnership stated there is no reason to limit self-referral to only eye and ear examinations. They proposed that self-referral should extend to mental health, substance use, podiatry, prosthetics, laboratory services, dermatology, and diabetes. Like other perilous sections of these bills, seemingly innocuous language would quickly lead to crippling impacts.

(3) Pilot program for unfettered access. The HEALTH Act contains another provision in which veterans would be allowed to receive outpatient care without VA referral, authorization, or oversight. An enrolled veteran could simply make an appointment with any Veterans Community Care Program mental health or substance use disorder practitioner for care for any duration of time. VA’s only role would be to pay the invoice. Private sector interests have been pressing this sort of program for years, and when it was carefully studied by the Commission on Care, the costs were estimated to be 2 to 3 times the existing system. That would come from a combination of fee-for-service reimbursement structures that abet overuse and higher overall costs in the private sector. Were the pilot to pass, VA would convert from its primary role as a system providing health care to an insurance carrier.

In the name of offering more choices, health care options will diminish for veterans. When VA programs/clinics/facilities close, veterans—especially service-connected veterans who depend on VA for high-quality care tailored to their needs—will lose those choices. Moreover, a downsized VA will make it nearly impossible for the VA to continue to research veterans’ complex health conditions, educate future health care professionals (the majority of whom train at VA medical centers), or fulfill its Fourth Mission as a backup for national emergencies.

Senate Committee members indicated their intention to combine provisions of the Moran and Tester bills into a larger compromise bill in September. Legislators must slow down, contemplate the ramifications, and set aside the stipulations noted above. What is needed first is a projection of future veterans’ authorizations for community care (under current eligibility criteria and also with these new allowances), how much money would that pull out of VA facilities, and what is the tipping point of a doom cycle.

In the meantime, there are smart solutions to ensure veterans can access high-quality care, as Disabled American Veterans testified at the hearing: By “investing in VA's health care infrastructure and staffing… this is particularly true for veterans who live in rural and remote areas where VA is most likely to be a stable, long-term health care option for veterans.”

The VA administers the most successful health care system in the country. As a recent summary of research confirmed yet again, the quality of care delivered by the VA is as good as or better than the care veterans receive from VA-paid community care or the general public obtains through private care. There will always be a supplemental role for the community to play when VA cannot provide care in a timely or convenient manner. But community care must be fixed in ways that never starves VA facilities of essential funding. If there ever were a time to stand up for the sake of our veterans and the long-term viability of the VA, it is now.

“What if VA health care goes away?” That was the headline of a July 6, 2023, Disabled American Veterans news article to its members. The question was not hypothetical. Legislation currently under consideration by the US Congress may make it a strong probability.  

The US Senate Committee on Veterans’ Affairs recently held a hearing to discuss 2 bills that would drastically reshape the provision of private health care services through the Veterans Community Care Program. An unprecedented coalition of 10 organizations—made up of US Department of Veterans Affairs (VA) nurses, psychologists, physicians, dentists, social workers, optometrists, physician assistants, and nurse anesthetists, as well as the American Psychological Association, the Military and Veterans Committee of the Group for the Advancement of Psychiatry and the Veterans Healthcare Policy Institute—came together in a unified statement for the record highlighting how these proposed policies would open a Pandora’s box that could forever eliminate the Veterans Health Administration as we know it.

Over the past decade—and especially following the passage of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act—there has been a surge of veterans gaining eligibility for private care if a VA medical facility is too far away, does not offer the needed care, or the wait time for an appointment is too long.

Courtesy: Rasmussen P, Farmer CM. The Promise and Challenges of VA Community Care: Veterans' Issues in Focus. Rand Health Q. 2023;10(3):9.

Testifying before the House Committee on Veterans’ Affairs hearing last year, Miguel LaPuz, MD, MBA, then the acting Deputy Under Secretary for Health at the VA, warned that “VA is rapidly approaching a point where half of all care available in both settings is provided through community care.” He cautioned that leaders were bracing for “the potential of a spiral effect.”

Care that is rendered to veterans in the community must, of course, be paid for. When those community costs began to soar at the start of the Community Care program, Congress bailed out the VA by allocating extra funds. Today, escalating costs are drawn from local VA facility budgets. And to guarantee that private sector care is paid for out of VA facility funds, legislators are introducing language, such as in the Veterans Healthcare Freedom Act, which states: “No additional funds are authorized to be appropriated to carry out this section and the amendments made by this section, and this section and the amendments made by this section shall be carried out using amounts otherwise made available to the Veterans Health Administration.” The anticipated vicious cycle looms. More money pouring into the private sector will force reductions and closures of in-house VA staff, programs, clinics, and units. This will cause more veterans to obtain care in the community, which will further drain more money out of VA facilities, leading to more reductions, etc. Rural areas will likely be hit hardest.

The VA is nearing the tipping point of this ever-descending spiral. And that is even without expanding eligibility further. Three provisions in this pair of bills could, on their own, drastically open eligibility, eliminate remaining guardrails, and push VA over the edge:

(1) Veteran preference. Tucked into the HEALTH Act, introduced by the ranking Republican Member, Jerry Moran of Kansas, is language which would require VA to consider a “veteran’s preference” for obtaining their health care in the private sector.

This stipulation violates the intent of the VA MISSION Act. When MISSION passed, there was bipartisan agreement that the Community Care Program was meant, in numerous Senators’ words, to “supplement, not supplant” VA health care. A veteran would be offered the option of receiving health care outside of the VA under 6 narrowly defined criteria. Legislators understood that veterans would get the option to choose whether to receive care in the private sector or the VA if, and only if, they qualified under the 6 eligibility rules. As a well-researched document coauthored by Disabled American Veterans, Paralyzed Veterans of America, and the Veterans of Foreign Wars stated, “veteran convenience or preference” should never be used as a sole reason for referral.

Explicitly adding preference for the first time will create the expectation among veterans and lawmakers of a new allowance. Were this to pass, every veteran—100%—would become eligible for referral to the private sector, kicking off an unstoppable drainage of VA budget resources and threatening its viability. Hopefully, the Senate will follow the lead of the US House Committee on Veterans’ Affairs which, last week, amended its its own community care bill by deleting “veteran preference” as a possible new eligibility criterion.

(2) Self-referral. Also being deliberated is the Making Community Care Work for Veterans Act, a draft bill authored by the US Senate Committee on Veterans’ Affairs Democratic Chairman Senator Jon Tester of Montana. It calls for allowing self-initiated routine vaccinations and routine vision/hearing services in the community.

On the surface, Tester’s bill focuses on only a tiny sliver of care. But once self-referral is permitted for a few services, private sector interests will, in no time, push the door wide open and add more services to which veterans can self-refer. Testimony at the hearing confirmed that prediction, as the Veterans of Foreign Wars and America’s Warrior Partnership stated there is no reason to limit self-referral to only eye and ear examinations. They proposed that self-referral should extend to mental health, substance use, podiatry, prosthetics, laboratory services, dermatology, and diabetes. Like other perilous sections of these bills, seemingly innocuous language would quickly lead to crippling impacts.

(3) Pilot program for unfettered access. The HEALTH Act contains another provision in which veterans would be allowed to receive outpatient care without VA referral, authorization, or oversight. An enrolled veteran could simply make an appointment with any Veterans Community Care Program mental health or substance use disorder practitioner for care for any duration of time. VA’s only role would be to pay the invoice. Private sector interests have been pressing this sort of program for years, and when it was carefully studied by the Commission on Care, the costs were estimated to be 2 to 3 times the existing system. That would come from a combination of fee-for-service reimbursement structures that abet overuse and higher overall costs in the private sector. Were the pilot to pass, VA would convert from its primary role as a system providing health care to an insurance carrier.

In the name of offering more choices, health care options will diminish for veterans. When VA programs/clinics/facilities close, veterans—especially service-connected veterans who depend on VA for high-quality care tailored to their needs—will lose those choices. Moreover, a downsized VA will make it nearly impossible for the VA to continue to research veterans’ complex health conditions, educate future health care professionals (the majority of whom train at VA medical centers), or fulfill its Fourth Mission as a backup for national emergencies.

Senate Committee members indicated their intention to combine provisions of the Moran and Tester bills into a larger compromise bill in September. Legislators must slow down, contemplate the ramifications, and set aside the stipulations noted above. What is needed first is a projection of future veterans’ authorizations for community care (under current eligibility criteria and also with these new allowances), how much money would that pull out of VA facilities, and what is the tipping point of a doom cycle.

In the meantime, there are smart solutions to ensure veterans can access high-quality care, as Disabled American Veterans testified at the hearing: By “investing in VA's health care infrastructure and staffing… this is particularly true for veterans who live in rural and remote areas where VA is most likely to be a stable, long-term health care option for veterans.”

The VA administers the most successful health care system in the country. As a recent summary of research confirmed yet again, the quality of care delivered by the VA is as good as or better than the care veterans receive from VA-paid community care or the general public obtains through private care. There will always be a supplemental role for the community to play when VA cannot provide care in a timely or convenient manner. But community care must be fixed in ways that never starves VA facilities of essential funding. If there ever were a time to stand up for the sake of our veterans and the long-term viability of the VA, it is now.

“What if VA health care goes away?” That was the headline of a July 6, 2023, Disabled American Veterans news article to its members. The question was not hypothetical. Legislation currently under consideration by the US Congress may make it a strong probability.  

The US Senate Committee on Veterans’ Affairs recently held a hearing to discuss 2 bills that would drastically reshape the provision of private health care services through the Veterans Community Care Program. An unprecedented coalition of 10 organizations—made up of US Department of Veterans Affairs (VA) nurses, psychologists, physicians, dentists, social workers, optometrists, physician assistants, and nurse anesthetists, as well as the American Psychological Association, the Military and Veterans Committee of the Group for the Advancement of Psychiatry and the Veterans Healthcare Policy Institute—came together in a unified statement for the record highlighting how these proposed policies would open a Pandora’s box that could forever eliminate the Veterans Health Administration as we know it.

Over the past decade—and especially following the passage of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act—there has been a surge of veterans gaining eligibility for private care if a VA medical facility is too far away, does not offer the needed care, or the wait time for an appointment is too long.

Courtesy: Rasmussen P, Farmer CM. The Promise and Challenges of VA Community Care: Veterans' Issues in Focus. Rand Health Q. 2023;10(3):9.

Testifying before the House Committee on Veterans’ Affairs hearing last year, Miguel LaPuz, MD, MBA, then the acting Deputy Under Secretary for Health at the VA, warned that “VA is rapidly approaching a point where half of all care available in both settings is provided through community care.” He cautioned that leaders were bracing for “the potential of a spiral effect.”

Care that is rendered to veterans in the community must, of course, be paid for. When those community costs began to soar at the start of the Community Care program, Congress bailed out the VA by allocating extra funds. Today, escalating costs are drawn from local VA facility budgets. And to guarantee that private sector care is paid for out of VA facility funds, legislators are introducing language, such as in the Veterans Healthcare Freedom Act, which states: “No additional funds are authorized to be appropriated to carry out this section and the amendments made by this section, and this section and the amendments made by this section shall be carried out using amounts otherwise made available to the Veterans Health Administration.” The anticipated vicious cycle looms. More money pouring into the private sector will force reductions and closures of in-house VA staff, programs, clinics, and units. This will cause more veterans to obtain care in the community, which will further drain more money out of VA facilities, leading to more reductions, etc. Rural areas will likely be hit hardest.

The VA is nearing the tipping point of this ever-descending spiral. And that is even without expanding eligibility further. Three provisions in this pair of bills could, on their own, drastically open eligibility, eliminate remaining guardrails, and push VA over the edge:

(1) Veteran preference. Tucked into the HEALTH Act, introduced by the ranking Republican Member, Jerry Moran of Kansas, is language which would require VA to consider a “veteran’s preference” for obtaining their health care in the private sector.

This stipulation violates the intent of the VA MISSION Act. When MISSION passed, there was bipartisan agreement that the Community Care Program was meant, in numerous Senators’ words, to “supplement, not supplant” VA health care. A veteran would be offered the option of receiving health care outside of the VA under 6 narrowly defined criteria. Legislators understood that veterans would get the option to choose whether to receive care in the private sector or the VA if, and only if, they qualified under the 6 eligibility rules. As a well-researched document coauthored by Disabled American Veterans, Paralyzed Veterans of America, and the Veterans of Foreign Wars stated, “veteran convenience or preference” should never be used as a sole reason for referral.

Explicitly adding preference for the first time will create the expectation among veterans and lawmakers of a new allowance. Were this to pass, every veteran—100%—would become eligible for referral to the private sector, kicking off an unstoppable drainage of VA budget resources and threatening its viability. Hopefully, the Senate will follow the lead of the US House Committee on Veterans’ Affairs which, last week, amended its its own community care bill by deleting “veteran preference” as a possible new eligibility criterion.

(2) Self-referral. Also being deliberated is the Making Community Care Work for Veterans Act, a draft bill authored by the US Senate Committee on Veterans’ Affairs Democratic Chairman Senator Jon Tester of Montana. It calls for allowing self-initiated routine vaccinations and routine vision/hearing services in the community.

On the surface, Tester’s bill focuses on only a tiny sliver of care. But once self-referral is permitted for a few services, private sector interests will, in no time, push the door wide open and add more services to which veterans can self-refer. Testimony at the hearing confirmed that prediction, as the Veterans of Foreign Wars and America’s Warrior Partnership stated there is no reason to limit self-referral to only eye and ear examinations. They proposed that self-referral should extend to mental health, substance use, podiatry, prosthetics, laboratory services, dermatology, and diabetes. Like other perilous sections of these bills, seemingly innocuous language would quickly lead to crippling impacts.

(3) Pilot program for unfettered access. The HEALTH Act contains another provision in which veterans would be allowed to receive outpatient care without VA referral, authorization, or oversight. An enrolled veteran could simply make an appointment with any Veterans Community Care Program mental health or substance use disorder practitioner for care for any duration of time. VA’s only role would be to pay the invoice. Private sector interests have been pressing this sort of program for years, and when it was carefully studied by the Commission on Care, the costs were estimated to be 2 to 3 times the existing system. That would come from a combination of fee-for-service reimbursement structures that abet overuse and higher overall costs in the private sector. Were the pilot to pass, VA would convert from its primary role as a system providing health care to an insurance carrier.

In the name of offering more choices, health care options will diminish for veterans. When VA programs/clinics/facilities close, veterans—especially service-connected veterans who depend on VA for high-quality care tailored to their needs—will lose those choices. Moreover, a downsized VA will make it nearly impossible for the VA to continue to research veterans’ complex health conditions, educate future health care professionals (the majority of whom train at VA medical centers), or fulfill its Fourth Mission as a backup for national emergencies.

Senate Committee members indicated their intention to combine provisions of the Moran and Tester bills into a larger compromise bill in September. Legislators must slow down, contemplate the ramifications, and set aside the stipulations noted above. What is needed first is a projection of future veterans’ authorizations for community care (under current eligibility criteria and also with these new allowances), how much money would that pull out of VA facilities, and what is the tipping point of a doom cycle.

In the meantime, there are smart solutions to ensure veterans can access high-quality care, as Disabled American Veterans testified at the hearing: By “investing in VA's health care infrastructure and staffing… this is particularly true for veterans who live in rural and remote areas where VA is most likely to be a stable, long-term health care option for veterans.”

The VA administers the most successful health care system in the country. As a recent summary of research confirmed yet again, the quality of care delivered by the VA is as good as or better than the care veterans receive from VA-paid community care or the general public obtains through private care. There will always be a supplemental role for the community to play when VA cannot provide care in a timely or convenient manner. But community care must be fixed in ways that never starves VA facilities of essential funding. If there ever were a time to stand up for the sake of our veterans and the long-term viability of the VA, it is now.

Doctors who treat patients with long COVID, hampered by a lack of federally approved treatments, are turning to off-label use of drugs designed for addiction, diabetes, and other conditions.

Those with long COVID for years now are engaging in robust online conversations about a range of treatments not formally approved by the Food and Drug Administration for the condition, reporting good and bad results.

High on the current list: low-dose naltrexone (LDN). A version of drug developed to help addicts has been shown to help some long COVID patients.

But evidence is building for other treatments, many of them targeted to treat brain fog or one of the other long-term symptoms in individuals 3 months or more after acute COVID infection.

Some patients are taking metformin, which studies have found to be effective at lowering long COVID risk. Paxlovid is being tested for long COVID.  Antivirals are also on the list.

Alba Azola, MD, said she has treated long COVID patients with brain fog and dizziness who have postural orthostatic tachycardia syndrome (POTS).

Dr. Azola said she asked the staff at Johns Hopkins Medicine in Baltimore, where she is a rehabilitation specialist, to teach her how to treat the condition. Since there is no approved treatment for POTS, that meant using off-label drugs, she said. 

“It was super scary as a provider to start doing that, but my patients were suffering so much,” she  said, noting the wait for patients to get into the POTS clinic at Hopkins was 2 years.

Dr. Azola was the lead author on guidelines published by the American Academy of Physical Medicine and Rehabilitation (AAPM&R) last September on how to treat autonomic dysfunction, a common symptom of long COVID. 

The guidelines she helped write include drugs designed for blood pressure – such as midodrine – and steroids.

Dr. Azola noted the medications are prescribed on a case-by-case basis because the same drug that works for one patient may have awful side effects for another patient, she said. At the same time, some of these drugs have helped her patients go back to living relatively normal lives.

The first time JD Davids of Brooklyn, N.Y., took LDN, it was for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and he couldn’t tolerate it. He had nightmares. But when he took it for long COVID, he started out at a low dose and worked his way up, at his doctor’s advice. 

“It’s been a game-changer,” said Mr. Davids, cofounder of Long COVID Justice, an activist group. He has ME/CFS and several other chronic conditions, including long COVID. But, since he started taking LDN for long COVID, Mr. Davids said he has more energy and less pain. 

Technically, evidence is required to show off-label drug use could be effective in treating conditions for which the drug is not formally approved. Research suggests that 20%-30% of drugs are prescribed off-label.

No formal data exist on how widespread the use of off-label drugs for long COVID may be. But LDN is a major topic of discussion on public patient groups on Facebook. 

A recent study in The Lancet Infectious Diseases suggested that the diabetes drug metformin could be helpful. (The same study found no benefit from ivermectin, a drug since dismissed as a possible COVID treatment.)

Patients who testified at a virtual FDA hearing on drug development in April reported using vitamins, herbal supplements, over-the-counter medications and off-label drugs such as gabapentin and beta-blockers. Both of those drugs were on a list of potential treatments published in a January Nature Review article, along with LDN and Paxlovid.

Currently, Paxlovid is approved for acute COVID, and is in clinical trials as a treatment for long COVID as part of the federal government’s RECOVER Initiative. While only small studies of LDN have been conducted for long COVID, doctors are already prescribing the treatment. Mr. Davids said his primary care doctor recommended it.

Some doctors, such as Michael Peluso, MD, are comparing the trend to the early days of the AIDS epidemic, when the federal government was slow to recognize the viral disease. Patients banded together to protest and gain access to experimental treatments. 

Dr. Peluso, who treats long COVID patients at the University of California, San Francisco, said that without any approved treatment, patients are turning to one another to find out what works.

“A lot of people experiencing long COVID are looking for ways to feel better now, rather than waiting for the science or the guidelines to catch up,” he said in an interview.

In some cases, the drugs are backed by small studies, he said. 

“While we still need clinical trials to prove what will work, the drugs tested in these trials are also being informed by anecdotes shared by patients,” Dr. Peluso said.

Gail Van Norman, MD, of the University of Washington, Seattle, also said the long COVID situation today is reminiscent of the AIDS movement, which was “one of the times in history where we saw a real response to patient advocacy groups in terms of access to drugs.” Since then, the FDA has set up multiple programs to expand access to experimental drugs, added Dr. Van Norman, author of a recent study on off-label drug use.

But off-label use needs to be supervised by a physician, she and others said. Many patients get their information from social media, which Dr. Van Norman sees as a double-edged sword. Patients can share information, do their own research online, and alert practitioners to new findings, she said. But social media also promotes misinformation.

“People with no expertise have the same level of voice, and they are magnified,” Dr. Van Norman said.

The FDA requires doctors to have some evidence to support off-label use, she said. Doctors should talk to patients who want to try-off label drugs about what has been studied and what has not been studied.

“If I had [long COVID], I would be asking questions about all these drugs,” Dr. Van Norman said.

Mr. Davids has been asking questions like this for years. Diagnosed in 2019 with ME/CFS, he developed long COVID during the pandemic. Once he began started taking LDN, he started feeling better.

As someone with multiple chronic illnesses, Mr. Davids has tried a lot of treatments – he’s currently on two intravenous drugs and two compounded drugs, including LDN. But when his doctor first suggested it, he was wary. 

“I’ve worked with her to help increase the dosage slowly over time,” he said. “It’s very important for many people to start low and slow and work their way up.”

He hears stories of people who can’t get it from their physicians. Some, he said, think it may be because of the association of the drug with opioid abuse. 

Mr. Davids said long COVID patients have no other choice but to turn to alternative treatments. 
 

“I think we’ve been ill-served by our research establishment,” he said. “It is not set up for complex chronic conditions.”

Mr. Davids said he doesn’t know if LDN helps with underlying conditions or treats the symptoms – such as pain and fatigue – that keep him from doing things such as typing. 

“My understanding is that it may be doing both,” he said. “I sure am happy that it allows me to do things like keep my job.”

Dr. Azola and others said patients need to be monitored closely if they are taking an off-label drug. She recommends primary care doctors become familiar with them so they can offer patients some relief.

“It’s about the relationship between the patient and the provider and the provider being comfortable,” she said. “l was very transparent with my patients.”
 

A version of this article appeared on Medscape.com.

Doctors who treat patients with long COVID, hampered by a lack of federally approved treatments, are turning to off-label use of drugs designed for addiction, diabetes, and other conditions.

Those with long COVID for years now are engaging in robust online conversations about a range of treatments not formally approved by the Food and Drug Administration for the condition, reporting good and bad results.

High on the current list: low-dose naltrexone (LDN). A version of drug developed to help addicts has been shown to help some long COVID patients.

But evidence is building for other treatments, many of them targeted to treat brain fog or one of the other long-term symptoms in individuals 3 months or more after acute COVID infection.

Some patients are taking metformin, which studies have found to be effective at lowering long COVID risk. Paxlovid is being tested for long COVID.  Antivirals are also on the list.

Alba Azola, MD, said she has treated long COVID patients with brain fog and dizziness who have postural orthostatic tachycardia syndrome (POTS).

Dr. Azola said she asked the staff at Johns Hopkins Medicine in Baltimore, where she is a rehabilitation specialist, to teach her how to treat the condition. Since there is no approved treatment for POTS, that meant using off-label drugs, she said. 

“It was super scary as a provider to start doing that, but my patients were suffering so much,” she  said, noting the wait for patients to get into the POTS clinic at Hopkins was 2 years.

Dr. Azola was the lead author on guidelines published by the American Academy of Physical Medicine and Rehabilitation (AAPM&R) last September on how to treat autonomic dysfunction, a common symptom of long COVID. 

The guidelines she helped write include drugs designed for blood pressure – such as midodrine – and steroids.

Dr. Azola noted the medications are prescribed on a case-by-case basis because the same drug that works for one patient may have awful side effects for another patient, she said. At the same time, some of these drugs have helped her patients go back to living relatively normal lives.

The first time JD Davids of Brooklyn, N.Y., took LDN, it was for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and he couldn’t tolerate it. He had nightmares. But when he took it for long COVID, he started out at a low dose and worked his way up, at his doctor’s advice. 

“It’s been a game-changer,” said Mr. Davids, cofounder of Long COVID Justice, an activist group. He has ME/CFS and several other chronic conditions, including long COVID. But, since he started taking LDN for long COVID, Mr. Davids said he has more energy and less pain. 

Technically, evidence is required to show off-label drug use could be effective in treating conditions for which the drug is not formally approved. Research suggests that 20%-30% of drugs are prescribed off-label.

No formal data exist on how widespread the use of off-label drugs for long COVID may be. But LDN is a major topic of discussion on public patient groups on Facebook. 

A recent study in The Lancet Infectious Diseases suggested that the diabetes drug metformin could be helpful. (The same study found no benefit from ivermectin, a drug since dismissed as a possible COVID treatment.)

Patients who testified at a virtual FDA hearing on drug development in April reported using vitamins, herbal supplements, over-the-counter medications and off-label drugs such as gabapentin and beta-blockers. Both of those drugs were on a list of potential treatments published in a January Nature Review article, along with LDN and Paxlovid.

Currently, Paxlovid is approved for acute COVID, and is in clinical trials as a treatment for long COVID as part of the federal government’s RECOVER Initiative. While only small studies of LDN have been conducted for long COVID, doctors are already prescribing the treatment. Mr. Davids said his primary care doctor recommended it.

Some doctors, such as Michael Peluso, MD, are comparing the trend to the early days of the AIDS epidemic, when the federal government was slow to recognize the viral disease. Patients banded together to protest and gain access to experimental treatments. 

Dr. Peluso, who treats long COVID patients at the University of California, San Francisco, said that without any approved treatment, patients are turning to one another to find out what works.

“A lot of people experiencing long COVID are looking for ways to feel better now, rather than waiting for the science or the guidelines to catch up,” he said in an interview.

In some cases, the drugs are backed by small studies, he said. 

“While we still need clinical trials to prove what will work, the drugs tested in these trials are also being informed by anecdotes shared by patients,” Dr. Peluso said.

Gail Van Norman, MD, of the University of Washington, Seattle, also said the long COVID situation today is reminiscent of the AIDS movement, which was “one of the times in history where we saw a real response to patient advocacy groups in terms of access to drugs.” Since then, the FDA has set up multiple programs to expand access to experimental drugs, added Dr. Van Norman, author of a recent study on off-label drug use.

But off-label use needs to be supervised by a physician, she and others said. Many patients get their information from social media, which Dr. Van Norman sees as a double-edged sword. Patients can share information, do their own research online, and alert practitioners to new findings, she said. But social media also promotes misinformation.

“People with no expertise have the same level of voice, and they are magnified,” Dr. Van Norman said.

The FDA requires doctors to have some evidence to support off-label use, she said. Doctors should talk to patients who want to try-off label drugs about what has been studied and what has not been studied.

“If I had [long COVID], I would be asking questions about all these drugs,” Dr. Van Norman said.

Mr. Davids has been asking questions like this for years. Diagnosed in 2019 with ME/CFS, he developed long COVID during the pandemic. Once he began started taking LDN, he started feeling better.

As someone with multiple chronic illnesses, Mr. Davids has tried a lot of treatments – he’s currently on two intravenous drugs and two compounded drugs, including LDN. But when his doctor first suggested it, he was wary. 

“I’ve worked with her to help increase the dosage slowly over time,” he said. “It’s very important for many people to start low and slow and work their way up.”

He hears stories of people who can’t get it from their physicians. Some, he said, think it may be because of the association of the drug with opioid abuse. 

Mr. Davids said long COVID patients have no other choice but to turn to alternative treatments. 
 

“I think we’ve been ill-served by our research establishment,” he said. “It is not set up for complex chronic conditions.”

Mr. Davids said he doesn’t know if LDN helps with underlying conditions or treats the symptoms – such as pain and fatigue – that keep him from doing things such as typing. 

“My understanding is that it may be doing both,” he said. “I sure am happy that it allows me to do things like keep my job.”

Dr. Azola and others said patients need to be monitored closely if they are taking an off-label drug. She recommends primary care doctors become familiar with them so they can offer patients some relief.

“It’s about the relationship between the patient and the provider and the provider being comfortable,” she said. “l was very transparent with my patients.”
 

A version of this article appeared on Medscape.com.

Doctors who treat patients with long COVID, hampered by a lack of federally approved treatments, are turning to off-label use of drugs designed for addiction, diabetes, and other conditions.

Those with long COVID for years now are engaging in robust online conversations about a range of treatments not formally approved by the Food and Drug Administration for the condition, reporting good and bad results.

High on the current list: low-dose naltrexone (LDN). A version of drug developed to help addicts has been shown to help some long COVID patients.

But evidence is building for other treatments, many of them targeted to treat brain fog or one of the other long-term symptoms in individuals 3 months or more after acute COVID infection.

Some patients are taking metformin, which studies have found to be effective at lowering long COVID risk. Paxlovid is being tested for long COVID.  Antivirals are also on the list.

Alba Azola, MD, said she has treated long COVID patients with brain fog and dizziness who have postural orthostatic tachycardia syndrome (POTS).

Dr. Azola said she asked the staff at Johns Hopkins Medicine in Baltimore, where she is a rehabilitation specialist, to teach her how to treat the condition. Since there is no approved treatment for POTS, that meant using off-label drugs, she said. 

“It was super scary as a provider to start doing that, but my patients were suffering so much,” she  said, noting the wait for patients to get into the POTS clinic at Hopkins was 2 years.

Dr. Azola was the lead author on guidelines published by the American Academy of Physical Medicine and Rehabilitation (AAPM&R) last September on how to treat autonomic dysfunction, a common symptom of long COVID. 

The guidelines she helped write include drugs designed for blood pressure – such as midodrine – and steroids.

Dr. Azola noted the medications are prescribed on a case-by-case basis because the same drug that works for one patient may have awful side effects for another patient, she said. At the same time, some of these drugs have helped her patients go back to living relatively normal lives.

The first time JD Davids of Brooklyn, N.Y., took LDN, it was for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and he couldn’t tolerate it. He had nightmares. But when he took it for long COVID, he started out at a low dose and worked his way up, at his doctor’s advice. 

“It’s been a game-changer,” said Mr. Davids, cofounder of Long COVID Justice, an activist group. He has ME/CFS and several other chronic conditions, including long COVID. But, since he started taking LDN for long COVID, Mr. Davids said he has more energy and less pain. 

Technically, evidence is required to show off-label drug use could be effective in treating conditions for which the drug is not formally approved. Research suggests that 20%-30% of drugs are prescribed off-label.

No formal data exist on how widespread the use of off-label drugs for long COVID may be. But LDN is a major topic of discussion on public patient groups on Facebook. 

A recent study in The Lancet Infectious Diseases suggested that the diabetes drug metformin could be helpful. (The same study found no benefit from ivermectin, a drug since dismissed as a possible COVID treatment.)

Patients who testified at a virtual FDA hearing on drug development in April reported using vitamins, herbal supplements, over-the-counter medications and off-label drugs such as gabapentin and beta-blockers. Both of those drugs were on a list of potential treatments published in a January Nature Review article, along with LDN and Paxlovid.

Currently, Paxlovid is approved for acute COVID, and is in clinical trials as a treatment for long COVID as part of the federal government’s RECOVER Initiative. While only small studies of LDN have been conducted for long COVID, doctors are already prescribing the treatment. Mr. Davids said his primary care doctor recommended it.

Some doctors, such as Michael Peluso, MD, are comparing the trend to the early days of the AIDS epidemic, when the federal government was slow to recognize the viral disease. Patients banded together to protest and gain access to experimental treatments. 

Dr. Peluso, who treats long COVID patients at the University of California, San Francisco, said that without any approved treatment, patients are turning to one another to find out what works.

“A lot of people experiencing long COVID are looking for ways to feel better now, rather than waiting for the science or the guidelines to catch up,” he said in an interview.

In some cases, the drugs are backed by small studies, he said. 

“While we still need clinical trials to prove what will work, the drugs tested in these trials are also being informed by anecdotes shared by patients,” Dr. Peluso said.

Gail Van Norman, MD, of the University of Washington, Seattle, also said the long COVID situation today is reminiscent of the AIDS movement, which was “one of the times in history where we saw a real response to patient advocacy groups in terms of access to drugs.” Since then, the FDA has set up multiple programs to expand access to experimental drugs, added Dr. Van Norman, author of a recent study on off-label drug use.

But off-label use needs to be supervised by a physician, she and others said. Many patients get their information from social media, which Dr. Van Norman sees as a double-edged sword. Patients can share information, do their own research online, and alert practitioners to new findings, she said. But social media also promotes misinformation.

“People with no expertise have the same level of voice, and they are magnified,” Dr. Van Norman said.

The FDA requires doctors to have some evidence to support off-label use, she said. Doctors should talk to patients who want to try-off label drugs about what has been studied and what has not been studied.

“If I had [long COVID], I would be asking questions about all these drugs,” Dr. Van Norman said.

Mr. Davids has been asking questions like this for years. Diagnosed in 2019 with ME/CFS, he developed long COVID during the pandemic. Once he began started taking LDN, he started feeling better.

As someone with multiple chronic illnesses, Mr. Davids has tried a lot of treatments – he’s currently on two intravenous drugs and two compounded drugs, including LDN. But when his doctor first suggested it, he was wary. 

“I’ve worked with her to help increase the dosage slowly over time,” he said. “It’s very important for many people to start low and slow and work their way up.”

He hears stories of people who can’t get it from their physicians. Some, he said, think it may be because of the association of the drug with opioid abuse. 

Mr. Davids said long COVID patients have no other choice but to turn to alternative treatments. 
 

“I think we’ve been ill-served by our research establishment,” he said. “It is not set up for complex chronic conditions.”

Mr. Davids said he doesn’t know if LDN helps with underlying conditions or treats the symptoms – such as pain and fatigue – that keep him from doing things such as typing. 

“My understanding is that it may be doing both,” he said. “I sure am happy that it allows me to do things like keep my job.”

Dr. Azola and others said patients need to be monitored closely if they are taking an off-label drug. She recommends primary care doctors become familiar with them so they can offer patients some relief.

“It’s about the relationship between the patient and the provider and the provider being comfortable,” she said. “l was very transparent with my patients.”
 

A version of this article appeared on Medscape.com.

An air monitor made by researchers at Washington University in St. Louis can detect COVID-19 in a room with an infected person within 5 minutes.

The project was a collaboration among researchers from the university’s engineering and medical schools; the results were published in Nature Communications.

One of the challenges the team had to overcome is that detecting the virus in a roomful of air “is like finding a needle in a haystack,” researcher and associate engineering professor Rajan Chakrabarty, PhD, said in a statement.

The team overcame that challenge using a technology called wet cyclone that samples the equivalent of 176 cubic feet of air in 5 minutes. A light on the device turns from green to red when the virus is detected, which the researchers said indicates that increased air circulation is needed. 

The device stands just 10 inches tall and 1 foot wide and is considered a proof of concept. The next step would be to implement the technology into a prototype to see how a commercial or household design could be achieved. The researchers foresee potential for the device to be used in hospitals and schools, as well as to be able to detect other respiratory viruses such as influenza and respiratory syncytial virus.

Current methods used for detecting viruses in the air take between 1 and 24 hours to collect and analyze samples. The existing methods usually require skilled labor, resulting in a process that doesn’t allow for real-time information that could translate into reducing risk or the spread of the virus, the researchers wrote.

The team tested their device both in laboratory experiments where they released aerosolized SARS-CoV-2 into a room-sized chamber, as well as in the apartments of two people who were COVID positive.

“There is nothing at the moment that tells us how safe a room is,” Washington University neurology professor John Cirrito, PhD, said in a statement. “If you are in a room with 100 people, you don’t want to find out 5 days later whether you could be sick or not. The idea with this device is that you can know essentially in real time, or every 5 minutes, if there is a live virus in the air.”

Their goal is to develop a commercially available air quality monitor, the researchers said. 

The study authors reported that they had no conflicts of interest.

A version of this article appeared on WebMD.com.

An air monitor made by researchers at Washington University in St. Louis can detect COVID-19 in a room with an infected person within 5 minutes.

The project was a collaboration among researchers from the university’s engineering and medical schools; the results were published in Nature Communications.

One of the challenges the team had to overcome is that detecting the virus in a roomful of air “is like finding a needle in a haystack,” researcher and associate engineering professor Rajan Chakrabarty, PhD, said in a statement.

The team overcame that challenge using a technology called wet cyclone that samples the equivalent of 176 cubic feet of air in 5 minutes. A light on the device turns from green to red when the virus is detected, which the researchers said indicates that increased air circulation is needed. 

The device stands just 10 inches tall and 1 foot wide and is considered a proof of concept. The next step would be to implement the technology into a prototype to see how a commercial or household design could be achieved. The researchers foresee potential for the device to be used in hospitals and schools, as well as to be able to detect other respiratory viruses such as influenza and respiratory syncytial virus.

Current methods used for detecting viruses in the air take between 1 and 24 hours to collect and analyze samples. The existing methods usually require skilled labor, resulting in a process that doesn’t allow for real-time information that could translate into reducing risk or the spread of the virus, the researchers wrote.

The team tested their device both in laboratory experiments where they released aerosolized SARS-CoV-2 into a room-sized chamber, as well as in the apartments of two people who were COVID positive.

“There is nothing at the moment that tells us how safe a room is,” Washington University neurology professor John Cirrito, PhD, said in a statement. “If you are in a room with 100 people, you don’t want to find out 5 days later whether you could be sick or not. The idea with this device is that you can know essentially in real time, or every 5 minutes, if there is a live virus in the air.”

Their goal is to develop a commercially available air quality monitor, the researchers said. 

The study authors reported that they had no conflicts of interest.

A version of this article appeared on WebMD.com.

An air monitor made by researchers at Washington University in St. Louis can detect COVID-19 in a room with an infected person within 5 minutes.

The project was a collaboration among researchers from the university’s engineering and medical schools; the results were published in Nature Communications.

One of the challenges the team had to overcome is that detecting the virus in a roomful of air “is like finding a needle in a haystack,” researcher and associate engineering professor Rajan Chakrabarty, PhD, said in a statement.

The team overcame that challenge using a technology called wet cyclone that samples the equivalent of 176 cubic feet of air in 5 minutes. A light on the device turns from green to red when the virus is detected, which the researchers said indicates that increased air circulation is needed. 

The device stands just 10 inches tall and 1 foot wide and is considered a proof of concept. The next step would be to implement the technology into a prototype to see how a commercial or household design could be achieved. The researchers foresee potential for the device to be used in hospitals and schools, as well as to be able to detect other respiratory viruses such as influenza and respiratory syncytial virus.

Current methods used for detecting viruses in the air take between 1 and 24 hours to collect and analyze samples. The existing methods usually require skilled labor, resulting in a process that doesn’t allow for real-time information that could translate into reducing risk or the spread of the virus, the researchers wrote.

The team tested their device both in laboratory experiments where they released aerosolized SARS-CoV-2 into a room-sized chamber, as well as in the apartments of two people who were COVID positive.

“There is nothing at the moment that tells us how safe a room is,” Washington University neurology professor John Cirrito, PhD, said in a statement. “If you are in a room with 100 people, you don’t want to find out 5 days later whether you could be sick or not. The idea with this device is that you can know essentially in real time, or every 5 minutes, if there is a live virus in the air.”

Their goal is to develop a commercially available air quality monitor, the researchers said. 

The study authors reported that they had no conflicts of interest.

A version of this article appeared on WebMD.com.

A new practice guideline is setting a standard for doctors who use lasers to treat cutaneous vascular anomalies.

Poor treatment has been an issue in this field because no uniform guidelines existed to inform practice, according to a press release from the American Society for Laser Medicine and Surgery.

The laser treatment settings can vary based on the type and location of the birthmark and also the patient’s skin type, which has resulted in an inconsistent approach from clinicians, according to the release.

“For decades, I have observed adverse outcomes from the improper laser treatment of vascular birthmarks,” Linda Rozell-Shannon, PhD, president and founder of the Vascular Birthmarks Foundation said in a statement from ASLMS. “As a result of these guidelines, patient outcomes will be improved.”

The guideline, published on the ASLMS website along with supporting videos, was jointly developed by ASLMS, VBF, and an international group of clinicians, marking the first consensus guideline on laser treatments for cutaneous vascular anomalies. It details 32 best practice directives for various scenarios, including advice on safety considerations, additional testing, and when to refer.

“It is important to realize that just because someone is board certified does not mean they are skilled in treating all conditions or using all lasers,” Paul Friedman, MD, a dermatologist in Houston, and former president of ASLMS, said in the ASLMS statement.

Vascular birthmarks are a common condition affecting up to 14% of children, according to VBF. Most are hemangiomas, a buildup of blood vessels that usually appears at birth or within a month after birth. Laser therapy reduces the size and color of the anomalies.

Support for this initiative was provided by Candela Medical.

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

A new practice guideline is setting a standard for doctors who use lasers to treat cutaneous vascular anomalies.

Poor treatment has been an issue in this field because no uniform guidelines existed to inform practice, according to a press release from the American Society for Laser Medicine and Surgery.

The laser treatment settings can vary based on the type and location of the birthmark and also the patient’s skin type, which has resulted in an inconsistent approach from clinicians, according to the release.

“For decades, I have observed adverse outcomes from the improper laser treatment of vascular birthmarks,” Linda Rozell-Shannon, PhD, president and founder of the Vascular Birthmarks Foundation said in a statement from ASLMS. “As a result of these guidelines, patient outcomes will be improved.”

The guideline, published on the ASLMS website along with supporting videos, was jointly developed by ASLMS, VBF, and an international group of clinicians, marking the first consensus guideline on laser treatments for cutaneous vascular anomalies. It details 32 best practice directives for various scenarios, including advice on safety considerations, additional testing, and when to refer.

“It is important to realize that just because someone is board certified does not mean they are skilled in treating all conditions or using all lasers,” Paul Friedman, MD, a dermatologist in Houston, and former president of ASLMS, said in the ASLMS statement.

Vascular birthmarks are a common condition affecting up to 14% of children, according to VBF. Most are hemangiomas, a buildup of blood vessels that usually appears at birth or within a month after birth. Laser therapy reduces the size and color of the anomalies.

Support for this initiative was provided by Candela Medical.

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

A new practice guideline is setting a standard for doctors who use lasers to treat cutaneous vascular anomalies.

Poor treatment has been an issue in this field because no uniform guidelines existed to inform practice, according to a press release from the American Society for Laser Medicine and Surgery.

The laser treatment settings can vary based on the type and location of the birthmark and also the patient’s skin type, which has resulted in an inconsistent approach from clinicians, according to the release.

“For decades, I have observed adverse outcomes from the improper laser treatment of vascular birthmarks,” Linda Rozell-Shannon, PhD, president and founder of the Vascular Birthmarks Foundation said in a statement from ASLMS. “As a result of these guidelines, patient outcomes will be improved.”

The guideline, published on the ASLMS website along with supporting videos, was jointly developed by ASLMS, VBF, and an international group of clinicians, marking the first consensus guideline on laser treatments for cutaneous vascular anomalies. It details 32 best practice directives for various scenarios, including advice on safety considerations, additional testing, and when to refer.

“It is important to realize that just because someone is board certified does not mean they are skilled in treating all conditions or using all lasers,” Paul Friedman, MD, a dermatologist in Houston, and former president of ASLMS, said in the ASLMS statement.

Vascular birthmarks are a common condition affecting up to 14% of children, according to VBF. Most are hemangiomas, a buildup of blood vessels that usually appears at birth or within a month after birth. Laser therapy reduces the size and color of the anomalies.

Support for this initiative was provided by Candela Medical.

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

ASHEVILLE, N.C. – Epidermolysis bullosa (EB), a heterogeneous congenital condition of skin fragility, received its first U.S. Food and Drug Association–approved gene therapy only a few months ago, but accelerated progress across multiple treatment strategies predicts additional important and perhaps dramatic further progress, according to a prominent EB researcher.

Not only are recent developments in EB “exciting,” the progress on multiple fronts for control of disease or its symptoms suggests “we are on the cusp of a new era,” Jemima Mellerio, BSc, MD, a consultant dermatologist, St. John’s Institute of Dermatology, London, said at the annual meeting of the Society for Pediatric Dermatology.

Published clinical studies of cell therapies and gene therapies date back at least 15 years, according to a review by Dr. Mellerio on why developments are starting to move so quickly. The difference now is that many obstacles to routine use of these options are being resolved so that viable strategies have reached or are reaching phase 3 trials.

In addition to cell therapies and gene therapies, Dr. Mellerio discussed progress in three additional areas: gene editing, protein therapy, and drug repurposing.

Summarizing progress in each, she described improvement in levels of collagen VII, an important deficit in most types of EB, that were achieved with fibroblast injections that improved levels of collagen VII and anchoring fibrils in a study published in the Journal of Investigative Dermatology. Injection of mesenchymal stromal cells (MSC) have been associated with reduced pain and itch in a series of studies, one of the earliest of which was published in the New England Journal of Medicine.

Since that time, there have been several approaches using MSC.

Of these approaches, intravenous injection of ABCB5+ MSCs might be the first to gain regulatory approval. According to Dr. Mellerio, there is an ongoing phase 3 crossover trial evaluating this approach, which followed several earlier phase studies that demonstrated adequate safety and tolerability while reducing severity scores, relieving pain and itch, and improving wound closure in patients with EB.

In 2006, correction of junctional EB (JEB) was achieved by transplantation of genetically modified epidermal cells to replace the LAMB3 gene, thereby restoring production of laminin 332, which is an essential component of the dermal-epidermal junction, according to Dr. Mellerio, citing a study in Nature Medicine.

The next attempt with this approach did not take place until 2015, resurrected to save the life of a 7-year-old Syrian boy – to generate epidermal sheets that eventually covered 80% of his body. The success is supporting further work on this approach but has also been an inspiration to other gene therapies, including a topical gene therapy recently approved in the United States.

Topically applied beremagene geperpavec (Vyjuvek, formerly known as B-VEC) was approved by the FDA in May for treating wounds in patients 6 months of age and older, with recessive or dominant dystrophic EB, on the basis of a phase 3 trial published in the New England Journal of Medicine, but others are coming. Dr. Mellerio also described a recently completed phase 3 trial with introduction of ex vivo gene-corrected keratinocytes, which has been associated with long-term improvements among patients with recessive dystrophic EB (RDEB). The responses in early phase studies included wound healing and reduction in pain and itch.

Perhaps less advanced but still promising, protein therapy, gene editing, and repurposing of existing therapies are all approaches that are moving forward. Many are supported by at least some clinical data, according to Dr. Mellerio.

As an example of protein therapy, a completed phase I/II trial associated recombinant human collagen with wound healing and pain reduction in RDEB. This study provided proof of principle for a therapy that could be applied topically or intravenously. Further development is anticipated.

Multiple platforms for gene editing have been described with the goal of simply excising pathogenic mutations or antisense oligonucleotides for sustained or permanent control of EB expression. Clinical evidence is limited, but Dr. Mellerio suggested that the theoretical potential for eliminating the source of abnormal transcription is the restoration of functional proteins essential for reversing skin fragility.

In some cases, existing drugs have the same potential. Dr. Mellerio described efforts to use an aminoglycoside to circumvent nonsense mutations that produce messenger RNA decay and impaired production of the proteins that prevent EB. In a pilot study evaluating topical gentamicin in RDEB, there were substantial improvements at 1 month and 3 months in several measures of skin fragility and encouraged studies that are now ongoing in both RDEB and JEB.

More than promising, a multinational randomized phase 3 study with birch bark extract recently published in the British Journal of Dermatology, associated treatment with this topical gel, known as Oleogel-S10, with higher rates of complete wound closure at 45 days (41.3% vs. 28.9% in the control vehicle arm) and a low risk of adverse events.

“This therapy is now approved in Europe and the United Kingdom, although, unfortunately, it is not yet available in the United States,” Dr. Mellerio noted.

Importantly, none of these therapies are necessarily effective across subtypes of EB, which often have different underlying pathogenic mechanisms, she said. However, the growing sophistication with which the pathophysiology of these subtypes is understood makes the numerous treatments in the pipeline “exciting.”

“We are at a point where we can really start to think of personalized medicine in EB,” Dr. Mellerio said. With the clinical advances already available and those expected, she suggested the recently approved treatment options are just the beginning. She expects the treatment landscape to evolve quickly over the next few years.

This does not appear to be a personal opinion. Another prominent researcher in EB, M. Peter Marinkovich, MD, director of the Stanford Bullous Disease and Psoriasis Clinics at Stanford (Calif.) University, is seeing the same real-world promise of therapies that have been in gestation for a decade or more.

“Dr. Mellerio is right. This is an exciting time for EB patients,” Dr. Marinkovich said in an interview. While the approval of B-VEC, the first gene therapy for EB, is the proof, Dr. Marinkovich, the lead author of the NEJM paper on B-VEC, noted that “many other potential EB therapies are being studied right now.” Based on promise in earlier clinical studies with many of these agents, he, like Dr. Mellerio, expects progress in real-world treatments for EB to accelerate.

Dr. Mellerio reported financial relationships with Amryt Pharma and Krystal Biotech. Dr. Marinkovich receives research support from Abeona Therapeutics, Castle Creek Pharmaceuticals, Krystal Biotech, Phoenix Tissue Repair, and WINGS Therapeutics.

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

ASHEVILLE, N.C. – Epidermolysis bullosa (EB), a heterogeneous congenital condition of skin fragility, received its first U.S. Food and Drug Association–approved gene therapy only a few months ago, but accelerated progress across multiple treatment strategies predicts additional important and perhaps dramatic further progress, according to a prominent EB researcher.

Not only are recent developments in EB “exciting,” the progress on multiple fronts for control of disease or its symptoms suggests “we are on the cusp of a new era,” Jemima Mellerio, BSc, MD, a consultant dermatologist, St. John’s Institute of Dermatology, London, said at the annual meeting of the Society for Pediatric Dermatology.

Published clinical studies of cell therapies and gene therapies date back at least 15 years, according to a review by Dr. Mellerio on why developments are starting to move so quickly. The difference now is that many obstacles to routine use of these options are being resolved so that viable strategies have reached or are reaching phase 3 trials.

In addition to cell therapies and gene therapies, Dr. Mellerio discussed progress in three additional areas: gene editing, protein therapy, and drug repurposing.

Summarizing progress in each, she described improvement in levels of collagen VII, an important deficit in most types of EB, that were achieved with fibroblast injections that improved levels of collagen VII and anchoring fibrils in a study published in the Journal of Investigative Dermatology. Injection of mesenchymal stromal cells (MSC) have been associated with reduced pain and itch in a series of studies, one of the earliest of which was published in the New England Journal of Medicine.

Since that time, there have been several approaches using MSC.

Of these approaches, intravenous injection of ABCB5+ MSCs might be the first to gain regulatory approval. According to Dr. Mellerio, there is an ongoing phase 3 crossover trial evaluating this approach, which followed several earlier phase studies that demonstrated adequate safety and tolerability while reducing severity scores, relieving pain and itch, and improving wound closure in patients with EB.

In 2006, correction of junctional EB (JEB) was achieved by transplantation of genetically modified epidermal cells to replace the LAMB3 gene, thereby restoring production of laminin 332, which is an essential component of the dermal-epidermal junction, according to Dr. Mellerio, citing a study in Nature Medicine.

The next attempt with this approach did not take place until 2015, resurrected to save the life of a 7-year-old Syrian boy – to generate epidermal sheets that eventually covered 80% of his body. The success is supporting further work on this approach but has also been an inspiration to other gene therapies, including a topical gene therapy recently approved in the United States.

Topically applied beremagene geperpavec (Vyjuvek, formerly known as B-VEC) was approved by the FDA in May for treating wounds in patients 6 months of age and older, with recessive or dominant dystrophic EB, on the basis of a phase 3 trial published in the New England Journal of Medicine, but others are coming. Dr. Mellerio also described a recently completed phase 3 trial with introduction of ex vivo gene-corrected keratinocytes, which has been associated with long-term improvements among patients with recessive dystrophic EB (RDEB). The responses in early phase studies included wound healing and reduction in pain and itch.

Perhaps less advanced but still promising, protein therapy, gene editing, and repurposing of existing therapies are all approaches that are moving forward. Many are supported by at least some clinical data, according to Dr. Mellerio.

As an example of protein therapy, a completed phase I/II trial associated recombinant human collagen with wound healing and pain reduction in RDEB. This study provided proof of principle for a therapy that could be applied topically or intravenously. Further development is anticipated.

Multiple platforms for gene editing have been described with the goal of simply excising pathogenic mutations or antisense oligonucleotides for sustained or permanent control of EB expression. Clinical evidence is limited, but Dr. Mellerio suggested that the theoretical potential for eliminating the source of abnormal transcription is the restoration of functional proteins essential for reversing skin fragility.

In some cases, existing drugs have the same potential. Dr. Mellerio described efforts to use an aminoglycoside to circumvent nonsense mutations that produce messenger RNA decay and impaired production of the proteins that prevent EB. In a pilot study evaluating topical gentamicin in RDEB, there were substantial improvements at 1 month and 3 months in several measures of skin fragility and encouraged studies that are now ongoing in both RDEB and JEB.

More than promising, a multinational randomized phase 3 study with birch bark extract recently published in the British Journal of Dermatology, associated treatment with this topical gel, known as Oleogel-S10, with higher rates of complete wound closure at 45 days (41.3% vs. 28.9% in the control vehicle arm) and a low risk of adverse events.

“This therapy is now approved in Europe and the United Kingdom, although, unfortunately, it is not yet available in the United States,” Dr. Mellerio noted.

Importantly, none of these therapies are necessarily effective across subtypes of EB, which often have different underlying pathogenic mechanisms, she said. However, the growing sophistication with which the pathophysiology of these subtypes is understood makes the numerous treatments in the pipeline “exciting.”

“We are at a point where we can really start to think of personalized medicine in EB,” Dr. Mellerio said. With the clinical advances already available and those expected, she suggested the recently approved treatment options are just the beginning. She expects the treatment landscape to evolve quickly over the next few years.

This does not appear to be a personal opinion. Another prominent researcher in EB, M. Peter Marinkovich, MD, director of the Stanford Bullous Disease and Psoriasis Clinics at Stanford (Calif.) University, is seeing the same real-world promise of therapies that have been in gestation for a decade or more.

“Dr. Mellerio is right. This is an exciting time for EB patients,” Dr. Marinkovich said in an interview. While the approval of B-VEC, the first gene therapy for EB, is the proof, Dr. Marinkovich, the lead author of the NEJM paper on B-VEC, noted that “many other potential EB therapies are being studied right now.” Based on promise in earlier clinical studies with many of these agents, he, like Dr. Mellerio, expects progress in real-world treatments for EB to accelerate.

Dr. Mellerio reported financial relationships with Amryt Pharma and Krystal Biotech. Dr. Marinkovich receives research support from Abeona Therapeutics, Castle Creek Pharmaceuticals, Krystal Biotech, Phoenix Tissue Repair, and WINGS Therapeutics.

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

ASHEVILLE, N.C. – Epidermolysis bullosa (EB), a heterogeneous congenital condition of skin fragility, received its first U.S. Food and Drug Association–approved gene therapy only a few months ago, but accelerated progress across multiple treatment strategies predicts additional important and perhaps dramatic further progress, according to a prominent EB researcher.

Not only are recent developments in EB “exciting,” the progress on multiple fronts for control of disease or its symptoms suggests “we are on the cusp of a new era,” Jemima Mellerio, BSc, MD, a consultant dermatologist, St. John’s Institute of Dermatology, London, said at the annual meeting of the Society for Pediatric Dermatology.

Published clinical studies of cell therapies and gene therapies date back at least 15 years, according to a review by Dr. Mellerio on why developments are starting to move so quickly. The difference now is that many obstacles to routine use of these options are being resolved so that viable strategies have reached or are reaching phase 3 trials.

In addition to cell therapies and gene therapies, Dr. Mellerio discussed progress in three additional areas: gene editing, protein therapy, and drug repurposing.

Summarizing progress in each, she described improvement in levels of collagen VII, an important deficit in most types of EB, that were achieved with fibroblast injections that improved levels of collagen VII and anchoring fibrils in a study published in the Journal of Investigative Dermatology. Injection of mesenchymal stromal cells (MSC) have been associated with reduced pain and itch in a series of studies, one of the earliest of which was published in the New England Journal of Medicine.

Since that time, there have been several approaches using MSC.

Of these approaches, intravenous injection of ABCB5+ MSCs might be the first to gain regulatory approval. According to Dr. Mellerio, there is an ongoing phase 3 crossover trial evaluating this approach, which followed several earlier phase studies that demonstrated adequate safety and tolerability while reducing severity scores, relieving pain and itch, and improving wound closure in patients with EB.

In 2006, correction of junctional EB (JEB) was achieved by transplantation of genetically modified epidermal cells to replace the LAMB3 gene, thereby restoring production of laminin 332, which is an essential component of the dermal-epidermal junction, according to Dr. Mellerio, citing a study in Nature Medicine.

The next attempt with this approach did not take place until 2015, resurrected to save the life of a 7-year-old Syrian boy – to generate epidermal sheets that eventually covered 80% of his body. The success is supporting further work on this approach but has also been an inspiration to other gene therapies, including a topical gene therapy recently approved in the United States.

Topically applied beremagene geperpavec (Vyjuvek, formerly known as B-VEC) was approved by the FDA in May for treating wounds in patients 6 months of age and older, with recessive or dominant dystrophic EB, on the basis of a phase 3 trial published in the New England Journal of Medicine, but others are coming. Dr. Mellerio also described a recently completed phase 3 trial with introduction of ex vivo gene-corrected keratinocytes, which has been associated with long-term improvements among patients with recessive dystrophic EB (RDEB). The responses in early phase studies included wound healing and reduction in pain and itch.

Perhaps less advanced but still promising, protein therapy, gene editing, and repurposing of existing therapies are all approaches that are moving forward. Many are supported by at least some clinical data, according to Dr. Mellerio.

As an example of protein therapy, a completed phase I/II trial associated recombinant human collagen with wound healing and pain reduction in RDEB. This study provided proof of principle for a therapy that could be applied topically or intravenously. Further development is anticipated.

Multiple platforms for gene editing have been described with the goal of simply excising pathogenic mutations or antisense oligonucleotides for sustained or permanent control of EB expression. Clinical evidence is limited, but Dr. Mellerio suggested that the theoretical potential for eliminating the source of abnormal transcription is the restoration of functional proteins essential for reversing skin fragility.

In some cases, existing drugs have the same potential. Dr. Mellerio described efforts to use an aminoglycoside to circumvent nonsense mutations that produce messenger RNA decay and impaired production of the proteins that prevent EB. In a pilot study evaluating topical gentamicin in RDEB, there were substantial improvements at 1 month and 3 months in several measures of skin fragility and encouraged studies that are now ongoing in both RDEB and JEB.

More than promising, a multinational randomized phase 3 study with birch bark extract recently published in the British Journal of Dermatology, associated treatment with this topical gel, known as Oleogel-S10, with higher rates of complete wound closure at 45 days (41.3% vs. 28.9% in the control vehicle arm) and a low risk of adverse events.

“This therapy is now approved in Europe and the United Kingdom, although, unfortunately, it is not yet available in the United States,” Dr. Mellerio noted.

Importantly, none of these therapies are necessarily effective across subtypes of EB, which often have different underlying pathogenic mechanisms, she said. However, the growing sophistication with which the pathophysiology of these subtypes is understood makes the numerous treatments in the pipeline “exciting.”

“We are at a point where we can really start to think of personalized medicine in EB,” Dr. Mellerio said. With the clinical advances already available and those expected, she suggested the recently approved treatment options are just the beginning. She expects the treatment landscape to evolve quickly over the next few years.

This does not appear to be a personal opinion. Another prominent researcher in EB, M. Peter Marinkovich, MD, director of the Stanford Bullous Disease and Psoriasis Clinics at Stanford (Calif.) University, is seeing the same real-world promise of therapies that have been in gestation for a decade or more.

“Dr. Mellerio is right. This is an exciting time for EB patients,” Dr. Marinkovich said in an interview. While the approval of B-VEC, the first gene therapy for EB, is the proof, Dr. Marinkovich, the lead author of the NEJM paper on B-VEC, noted that “many other potential EB therapies are being studied right now.” Based on promise in earlier clinical studies with many of these agents, he, like Dr. Mellerio, expects progress in real-world treatments for EB to accelerate.

Dr. Mellerio reported financial relationships with Amryt Pharma and Krystal Biotech. Dr. Marinkovich receives research support from Abeona Therapeutics, Castle Creek Pharmaceuticals, Krystal Biotech, Phoenix Tissue Repair, and WINGS Therapeutics.

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