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Ustekinumab’s ‘Egregious’ Medicare Part B and D Pricing Differences Led to Federal Intervention

Article Type
Changed
Fri, 08/30/2024 - 14:48

 

A US government report showed how a Medicare policy change made the drug ustekinumab (Stelara) for autoimmune diseases much more expensive, a finding that experts say illustrates the need for reforms created by the Inflation Reduction Act of 2022 (IRA).

The topline findings of an August report from the Department of Health and Human Services (HHS) about ustekinumab may seem somewhat surprising and a bit counterintuitive.

Ustekinumab costs spiked as Medicare pushed patients to get their supply through the Part D pharmacy program. The aim of Part D is to make medicines more affordable and accessible for patients. It runs on a model of insurers to negotiate deals for pharmaceuticals.

Earlier, many patients who needed ustekinumab had the drug covered by Medicare Part B. For many years, Medicare Part B has been largely a passive purchaser of medicines. Part B covers drugs administered by physicians. Its longtime model has been to add a premium of 6% to the reported average sales price to reimburse physicians who buy and administer the drug for patients.

But it was Part D, the Medicare program based on insurers’ negotiating clout, that saw a spike in ustekinumab costs after patients were shifted out of Part B coverage, where the cost of the medicine fell.

The average reported Part B cost for an ustekinumab injection slipped from $14,450 in 2016 to $12,912 by 2023, according to the report from HHS’ Office of Inspector General (OIG).

The Part D cost jumped in the same period. It rose by 84% from $17,717 in 2016 to $32,559 by 2023.

The IRA is intended to curb these kinds of increases in the future for drugs covered by Medicare, said Stacie B. Dusetzina, PhD, professor of health policy at Vanderbilt University School of Medicine, Nashville, Tennessee. The law demands companies pay rebates to Medicare if they increase drug prices faster than consumer inflation.

“That should at least help with some of this price growth that over time has seemed quite egregious,” Dr. Dusetzina told this news organization.

The IRA contains several provisions intended to curb rising drug costs for people enrolled in Medicare, including allowing the federal government to directly negotiate on some medicines.

Ustekinumab is one of the first 10 medicines that are subject to negotiations. Medicare will select as many as 15 additional drugs covered under Part D for negotiation in 2025, another 15 Part B and D drugs in 2026, and up to 20 drugs every year after that.

Earlier in August, the Centers for Medicare & Medicaid Services (CMS) announced the results of its first drug negotiations, with prices set to take effect in 2026. The Part D price for a 30-day supply of ustekinumab will be $4695 in 2026, a 66% reduction from the list price last year of $13,836.

Even at the negotiated price, ustekinumab’s cost will be high enough to trigger a new cap on out-of-pocket Part D spending, Dr. Dusetzina said.

Starting in 2025, Part D will have a cap of $2000 on individuals’ out-of-pocket costs, with annual adjustments in future years.

“It may not be better for someone who was filling this on Part B, who had a supplement [that covered their share of the ustekinumab cost], but it will be better for a lot of people that it’s covered under Part D,” Dr. Dusetzina said. “The good news is that at least from a beneficiary affordability standpoint, they’re going to have some price protection.”

OIG noted that the US Food and Drug Administration has approved three competing biosimilar versions of ustekinumab. These could also potentially work to lower costs.
 

 

 

‘A Complicated and Not Particularly Transparent Process’

OIG said it expects to release a report later this year with more detail about the decision that shifted ustekinumab coverage from Part B to Part D.

First cleared for US sales in 2009, ustekinumab is approved for psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. It can be given subcutaneously or intravenously.

Part B does not generally cover self-administered drugs. The infused version of ustekinumab has been covered under Medicare Part B since it reached the market.

“However, Part B coverage of the subcutaneous versions has been less straightforward,” OIG said in the report.

In 2020, Medicare administrative contractors — the units or affiliates of insurers that for decades have processed Part B claims for the traditional Medicare programs — determined that subcutaneous ustekinumab did not meet the criteria for coverage under Part B. Implementation of this change was delayed due to the COVID public health emergency but has since taken effect.

The shift in ustekinumab coverage to Part D eroded financial protections of many people on Medicare when Part B covered the drug.

Almost 9 in 10 people enrolled in Medicare Part B have supplemental insurance such as Medigap, employer coverage, or Medicaid to fully or partially cover their cost-sharing requirements, the OIG report said. That means Part B coverage shielded many patients from high ustekinumab costs. 

In contrast, patients who self-administered the drug at home under Part D coverage paid an average of almost $6000 out of pocket if they did not receive any type of financial assistance, OIG said.

“From a financial standpoint, as long as you have Part B coinsurance, it would be much cheaper to get the drug in your doctor’s office than getting it through a pharmacy, unless you qualify for the low-income subsidy,” OIG Regional Inspector General David Tawes, who supervised the team that produced the report, told this news organization.

OIG has previously reported that post–point-of-sale rebates paid by manufacturers sometimes lower the costs incurred by Part D plans by a significant margin. But this was not the case with ustekinumab. Instead, OIG said the gap between initial and actual costs of ustekinumab was reduced by less than one third even with rebates. Rebate information is considered confidential.

“The whole negotiation structure is a complicated and not particularly transparent process,” Mr. Tawes said.
 

Backchannel Discounts, Top-Line Prices

The IRA is bringing some more transparency to the process through negotiations, said Mariana P. Socal, MD, associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore. Patients who buy medicines that have been through the CMS negotiation process will be able to see if they are being charged correctly.

Dr. Socal noted that there’s something of a disconnect in discussions of Part D between how insurers and consumers view prices. 

For Part D plans, the list prices represent the beginning of negotiations. They get rebates from drugmakers’ list prices for medicines, which insurers say work to lower premium costs. 

“For plans, those prices are unrealistic. They are simply a sticker price. But for patients, for the Medicare beneficiaries, these prices are very real” because they are used to set copays, Dr. Socal said.

Dr. Dusetzina reported receiving funding from Arnold Ventures and the Commonwealth Fund for research related to drug pricing. Dr. Socal reported receiving funding from Arnold Ventures. 

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

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A US government report showed how a Medicare policy change made the drug ustekinumab (Stelara) for autoimmune diseases much more expensive, a finding that experts say illustrates the need for reforms created by the Inflation Reduction Act of 2022 (IRA).

The topline findings of an August report from the Department of Health and Human Services (HHS) about ustekinumab may seem somewhat surprising and a bit counterintuitive.

Ustekinumab costs spiked as Medicare pushed patients to get their supply through the Part D pharmacy program. The aim of Part D is to make medicines more affordable and accessible for patients. It runs on a model of insurers to negotiate deals for pharmaceuticals.

Earlier, many patients who needed ustekinumab had the drug covered by Medicare Part B. For many years, Medicare Part B has been largely a passive purchaser of medicines. Part B covers drugs administered by physicians. Its longtime model has been to add a premium of 6% to the reported average sales price to reimburse physicians who buy and administer the drug for patients.

But it was Part D, the Medicare program based on insurers’ negotiating clout, that saw a spike in ustekinumab costs after patients were shifted out of Part B coverage, where the cost of the medicine fell.

The average reported Part B cost for an ustekinumab injection slipped from $14,450 in 2016 to $12,912 by 2023, according to the report from HHS’ Office of Inspector General (OIG).

The Part D cost jumped in the same period. It rose by 84% from $17,717 in 2016 to $32,559 by 2023.

The IRA is intended to curb these kinds of increases in the future for drugs covered by Medicare, said Stacie B. Dusetzina, PhD, professor of health policy at Vanderbilt University School of Medicine, Nashville, Tennessee. The law demands companies pay rebates to Medicare if they increase drug prices faster than consumer inflation.

“That should at least help with some of this price growth that over time has seemed quite egregious,” Dr. Dusetzina told this news organization.

The IRA contains several provisions intended to curb rising drug costs for people enrolled in Medicare, including allowing the federal government to directly negotiate on some medicines.

Ustekinumab is one of the first 10 medicines that are subject to negotiations. Medicare will select as many as 15 additional drugs covered under Part D for negotiation in 2025, another 15 Part B and D drugs in 2026, and up to 20 drugs every year after that.

Earlier in August, the Centers for Medicare & Medicaid Services (CMS) announced the results of its first drug negotiations, with prices set to take effect in 2026. The Part D price for a 30-day supply of ustekinumab will be $4695 in 2026, a 66% reduction from the list price last year of $13,836.

Even at the negotiated price, ustekinumab’s cost will be high enough to trigger a new cap on out-of-pocket Part D spending, Dr. Dusetzina said.

Starting in 2025, Part D will have a cap of $2000 on individuals’ out-of-pocket costs, with annual adjustments in future years.

“It may not be better for someone who was filling this on Part B, who had a supplement [that covered their share of the ustekinumab cost], but it will be better for a lot of people that it’s covered under Part D,” Dr. Dusetzina said. “The good news is that at least from a beneficiary affordability standpoint, they’re going to have some price protection.”

OIG noted that the US Food and Drug Administration has approved three competing biosimilar versions of ustekinumab. These could also potentially work to lower costs.
 

 

 

‘A Complicated and Not Particularly Transparent Process’

OIG said it expects to release a report later this year with more detail about the decision that shifted ustekinumab coverage from Part B to Part D.

First cleared for US sales in 2009, ustekinumab is approved for psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. It can be given subcutaneously or intravenously.

Part B does not generally cover self-administered drugs. The infused version of ustekinumab has been covered under Medicare Part B since it reached the market.

“However, Part B coverage of the subcutaneous versions has been less straightforward,” OIG said in the report.

In 2020, Medicare administrative contractors — the units or affiliates of insurers that for decades have processed Part B claims for the traditional Medicare programs — determined that subcutaneous ustekinumab did not meet the criteria for coverage under Part B. Implementation of this change was delayed due to the COVID public health emergency but has since taken effect.

The shift in ustekinumab coverage to Part D eroded financial protections of many people on Medicare when Part B covered the drug.

Almost 9 in 10 people enrolled in Medicare Part B have supplemental insurance such as Medigap, employer coverage, or Medicaid to fully or partially cover their cost-sharing requirements, the OIG report said. That means Part B coverage shielded many patients from high ustekinumab costs. 

In contrast, patients who self-administered the drug at home under Part D coverage paid an average of almost $6000 out of pocket if they did not receive any type of financial assistance, OIG said.

“From a financial standpoint, as long as you have Part B coinsurance, it would be much cheaper to get the drug in your doctor’s office than getting it through a pharmacy, unless you qualify for the low-income subsidy,” OIG Regional Inspector General David Tawes, who supervised the team that produced the report, told this news organization.

OIG has previously reported that post–point-of-sale rebates paid by manufacturers sometimes lower the costs incurred by Part D plans by a significant margin. But this was not the case with ustekinumab. Instead, OIG said the gap between initial and actual costs of ustekinumab was reduced by less than one third even with rebates. Rebate information is considered confidential.

“The whole negotiation structure is a complicated and not particularly transparent process,” Mr. Tawes said.
 

Backchannel Discounts, Top-Line Prices

The IRA is bringing some more transparency to the process through negotiations, said Mariana P. Socal, MD, associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore. Patients who buy medicines that have been through the CMS negotiation process will be able to see if they are being charged correctly.

Dr. Socal noted that there’s something of a disconnect in discussions of Part D between how insurers and consumers view prices. 

For Part D plans, the list prices represent the beginning of negotiations. They get rebates from drugmakers’ list prices for medicines, which insurers say work to lower premium costs. 

“For plans, those prices are unrealistic. They are simply a sticker price. But for patients, for the Medicare beneficiaries, these prices are very real” because they are used to set copays, Dr. Socal said.

Dr. Dusetzina reported receiving funding from Arnold Ventures and the Commonwealth Fund for research related to drug pricing. Dr. Socal reported receiving funding from Arnold Ventures. 

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

 

A US government report showed how a Medicare policy change made the drug ustekinumab (Stelara) for autoimmune diseases much more expensive, a finding that experts say illustrates the need for reforms created by the Inflation Reduction Act of 2022 (IRA).

The topline findings of an August report from the Department of Health and Human Services (HHS) about ustekinumab may seem somewhat surprising and a bit counterintuitive.

Ustekinumab costs spiked as Medicare pushed patients to get their supply through the Part D pharmacy program. The aim of Part D is to make medicines more affordable and accessible for patients. It runs on a model of insurers to negotiate deals for pharmaceuticals.

Earlier, many patients who needed ustekinumab had the drug covered by Medicare Part B. For many years, Medicare Part B has been largely a passive purchaser of medicines. Part B covers drugs administered by physicians. Its longtime model has been to add a premium of 6% to the reported average sales price to reimburse physicians who buy and administer the drug for patients.

But it was Part D, the Medicare program based on insurers’ negotiating clout, that saw a spike in ustekinumab costs after patients were shifted out of Part B coverage, where the cost of the medicine fell.

The average reported Part B cost for an ustekinumab injection slipped from $14,450 in 2016 to $12,912 by 2023, according to the report from HHS’ Office of Inspector General (OIG).

The Part D cost jumped in the same period. It rose by 84% from $17,717 in 2016 to $32,559 by 2023.

The IRA is intended to curb these kinds of increases in the future for drugs covered by Medicare, said Stacie B. Dusetzina, PhD, professor of health policy at Vanderbilt University School of Medicine, Nashville, Tennessee. The law demands companies pay rebates to Medicare if they increase drug prices faster than consumer inflation.

“That should at least help with some of this price growth that over time has seemed quite egregious,” Dr. Dusetzina told this news organization.

The IRA contains several provisions intended to curb rising drug costs for people enrolled in Medicare, including allowing the federal government to directly negotiate on some medicines.

Ustekinumab is one of the first 10 medicines that are subject to negotiations. Medicare will select as many as 15 additional drugs covered under Part D for negotiation in 2025, another 15 Part B and D drugs in 2026, and up to 20 drugs every year after that.

Earlier in August, the Centers for Medicare & Medicaid Services (CMS) announced the results of its first drug negotiations, with prices set to take effect in 2026. The Part D price for a 30-day supply of ustekinumab will be $4695 in 2026, a 66% reduction from the list price last year of $13,836.

Even at the negotiated price, ustekinumab’s cost will be high enough to trigger a new cap on out-of-pocket Part D spending, Dr. Dusetzina said.

Starting in 2025, Part D will have a cap of $2000 on individuals’ out-of-pocket costs, with annual adjustments in future years.

“It may not be better for someone who was filling this on Part B, who had a supplement [that covered their share of the ustekinumab cost], but it will be better for a lot of people that it’s covered under Part D,” Dr. Dusetzina said. “The good news is that at least from a beneficiary affordability standpoint, they’re going to have some price protection.”

OIG noted that the US Food and Drug Administration has approved three competing biosimilar versions of ustekinumab. These could also potentially work to lower costs.
 

 

 

‘A Complicated and Not Particularly Transparent Process’

OIG said it expects to release a report later this year with more detail about the decision that shifted ustekinumab coverage from Part B to Part D.

First cleared for US sales in 2009, ustekinumab is approved for psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. It can be given subcutaneously or intravenously.

Part B does not generally cover self-administered drugs. The infused version of ustekinumab has been covered under Medicare Part B since it reached the market.

“However, Part B coverage of the subcutaneous versions has been less straightforward,” OIG said in the report.

In 2020, Medicare administrative contractors — the units or affiliates of insurers that for decades have processed Part B claims for the traditional Medicare programs — determined that subcutaneous ustekinumab did not meet the criteria for coverage under Part B. Implementation of this change was delayed due to the COVID public health emergency but has since taken effect.

The shift in ustekinumab coverage to Part D eroded financial protections of many people on Medicare when Part B covered the drug.

Almost 9 in 10 people enrolled in Medicare Part B have supplemental insurance such as Medigap, employer coverage, or Medicaid to fully or partially cover their cost-sharing requirements, the OIG report said. That means Part B coverage shielded many patients from high ustekinumab costs. 

In contrast, patients who self-administered the drug at home under Part D coverage paid an average of almost $6000 out of pocket if they did not receive any type of financial assistance, OIG said.

“From a financial standpoint, as long as you have Part B coinsurance, it would be much cheaper to get the drug in your doctor’s office than getting it through a pharmacy, unless you qualify for the low-income subsidy,” OIG Regional Inspector General David Tawes, who supervised the team that produced the report, told this news organization.

OIG has previously reported that post–point-of-sale rebates paid by manufacturers sometimes lower the costs incurred by Part D plans by a significant margin. But this was not the case with ustekinumab. Instead, OIG said the gap between initial and actual costs of ustekinumab was reduced by less than one third even with rebates. Rebate information is considered confidential.

“The whole negotiation structure is a complicated and not particularly transparent process,” Mr. Tawes said.
 

Backchannel Discounts, Top-Line Prices

The IRA is bringing some more transparency to the process through negotiations, said Mariana P. Socal, MD, associate professor at the Johns Hopkins Bloomberg School of Public Health in Baltimore. Patients who buy medicines that have been through the CMS negotiation process will be able to see if they are being charged correctly.

Dr. Socal noted that there’s something of a disconnect in discussions of Part D between how insurers and consumers view prices. 

For Part D plans, the list prices represent the beginning of negotiations. They get rebates from drugmakers’ list prices for medicines, which insurers say work to lower premium costs. 

“For plans, those prices are unrealistic. They are simply a sticker price. But for patients, for the Medicare beneficiaries, these prices are very real” because they are used to set copays, Dr. Socal said.

Dr. Dusetzina reported receiving funding from Arnold Ventures and the Commonwealth Fund for research related to drug pricing. Dr. Socal reported receiving funding from Arnold Ventures. 

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

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New Associations Identified Between IBD and Extraintestinal Manifestations

Article Type
Changed
Thu, 08/29/2024 - 13:07

Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center
Dr. Dermot McGovern

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

 

 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

Dr. David T. Rubin


“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”

In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.

“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”

The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.

A version of this article appeared on Medscape.com.

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Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center
Dr. Dermot McGovern

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

 

 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

Dr. David T. Rubin


“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”

In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.

“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”

The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Certain extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) have distinct clinical, serologic, and genetic associations that reveal underlying mechanisms and indicate targets for new or existing drugs, according to a recent study.

For instance, antinuclear cytoplastic antibody is associated with primary sclerosing cholangitis (PSC) in Crohn’s disease, and CPEB4 genetic variation is associated with skin manifestations.

“Up to 40% of people with IBD suffer with symptoms from inflammation that occurs outside the gut, particularly affecting the liver, skin, and joints. These symptoms can often have a bigger impact on quality of life than the gut inflammation itself and can actually be life-threatening,” said senior author Dermot McGovern, MD, PhD, AGAF, director of translational medicine at the F. Widjaja Foundation Inflammatory Bowel Disease and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles.

Cedars-Sinai Medical Center
Dr. Dermot McGovern

“With the advances in therapies for IBD, including availability of gut-selective agents, treatment choices often incorporate whether a patient has one of these manifestations or not,” he said. “We need to understand who is at increased risk of these and why.”

The study was published in Gastroenterology .
 

Analyzing Associations

Dr. McGovern and colleagues analyzed data for 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs across four cohorts in the Cedars-Sinai Medical Center IBD Research Repository, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease.

In particular, the researchers looked at EIM phenotypes such as ankylosing spondylitis and sacroiliitis, PSC, peripheral arthritis, and skin and ocular manifestations. They analyzed clinical and serologic parameters through regression analyses using a mixed-effects model, as well as within-case logistic regression for genetic associations.

Overall, 14% of patients had at least one EIM. Contrary to previous reports, only 2% had multiple EIMs, and most co-occurrences were negatively correlated. Nearly all EIMs were more common in Crohn’s disease, except for PSC, which was more common in ulcerative colitis.

In general, EIMs occurred more often in women, particularly with Crohn’s disease and colonic disease location, and in patients who required surgery. Jewish ancestry was associated with psoriasis and overall skin manifestations.

Smoking increased the risk for multiple EIMs, except for PSC, where there appeared to be a “protective” effect. Older age at diagnosis and a family history of IBD were associated with increased risk for certain EIMs as well.

In addition, the research team noted multiple serologic associations, such as immunoglobulin (Ig) G and IgA, perinuclear antinuclear cytoplastic antibodies, and anti–Pseudomonas fluorescens–associated sequences with any EIM, as well as particular associations with PSC, such as anti-Saccharomyces cerevisiae antibodies and anti-flagellin.

There were also genome-wide significant associations within the major histocompatibility complex and CPEB4. Genetic associations implicated tumor necrosis factor, Janus kinase-signal transducer and activator of transcription, and interleukin 6 as potential targets for EIMs.

“We are working with colleagues across the world to increase the sample size, as we believe there is more to find,” Dr. McGovern said. “Importantly, this includes non-European ancestry subjects, as there is an urgent need to increase the diversity of populations we study so advances in clinical care are available to all communities.”
 

 

 

Considering Target Therapies

As medicine becomes more specialized, physicians should remember to consider the whole patient while choosing treatment strategies.

“Sometimes doctors wear blinders to the whole person, and it’s important to be aware of a holistic approach, where a gastroenterologist also asks about potential joint inflammation or a rheumatologist asks about bowel inflammation,” said David Rubin, MD, AGAF, chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine, Chicago.

Dr. Rubin, who wasn’t involved with this study, has researched and published on EIMs in IBD. He and colleagues analyzed the prevalence, pathophysiology, and clinical presentation of EIMs to better understand possibilities for disease management.

Dr. David T. Rubin


“As we’ve gotten a better understanding of the immune system, we’ve learned that an EIM can sometimes provide a clue to the treatment we might use,” he said. “Given a similar amount of bowel inflammation, if one patient also has joint pain and another doesn’t, we might choose different treatments based on the immune pathway that might be involved.”

In future studies, researchers may consider whether these genetic or serologic markers could predict EIM manifestation before it occurs clinically, Dr. Rubin said. He and colleagues are also studying the links between IBD and mental health associations.

“So far, we don’t have a blood test or biopsy test that tells you which treatment is more or less likely to work, so we need to think carefully as clinicians and look to other organ systems for clues,” he said. “It’s not only more efficient to pick a single therapy to treat both the skin and bowel, but it may actually be more effective if both have a particular dominant pathway.”

The study was supported by internal funds from the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. Several authors reported consultant roles or other associations with pharmaceutical companies. Dr. Rubin reported no relevant disclosures.

A version of this article appeared on Medscape.com.

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TYK2 Inhibitor Effective for Psoriasis in Phase 2 Study

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Changed
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TOPLINE:

Zasocitinib, a tyrosine kinase 2 (TYK2) inhibitor, at oral doses of ≥ 5 mg led to greater skin clearance than placebo over a period of 12 weeks, in a phase 2b study.
 

METHODOLOGY:

  • Researchers performed a phase 2b, randomized, double-blind trial to assess the efficacy, safety, and tolerability of different doses of zasocitinib in adults with moderate to severe psoriasis (mean age, 47 years; 32% women) at 47 centers in the United States and eight centers in Canada. Most (83%) were White, 7% were Black, and 8% were Asian.
  • A total of 287 patients were randomly assigned to receive one of the four oral doses of zasocitinib (2 mg, 5 mg, 15 mg, or 30 mg, once daily) or a matched placebo for 12 weeks, followed by a 4-week safety monitoring period.
  • The primary outcome was the proportion of patients achieving a ≥ 75% improvement in the Psoriasis Area and Severity Index score (PASI 75) from baseline at week 12.

TAKEAWAY:

  • At week 12, PASI 75 was achieved by 18%, 44%, 68%, and 67% of patients receiving zasocitinib at doses of 2 mg, 5 mg, 15 mg, and 30 mg, respectively, vs 6% of patients receiving placebo.
  • PASI 90 was achieved in 8%, 21%, 45%, and 46% of patients receiving zasocitinib at 2 mg, 5 mg, 15 mg, and 30 mg, respectively, and in no patients in the placebo group.
  • At week 12, 10%, 27%, 49%, and 52% of patients receiving zasocitinib at 2 mg, 5 mg, 15 mg, and 30 mg, respectively, had no or mild disease (a score of 0 or 1) according to the Physician Global Assessment tool vs 4% in the placebo group.
  • Treatment-emergent adverse events occurred in 53%-62% of patients in the zasocitinib groups compared with 44% in the placebo group. The most common were COVID-19, acne/acneiform dermatitis, and diarrhea. There were no reports of major adverse cardiovascular events, thromboembolic events, or opportunistic infections.

IN PRACTICE:

“Zasocitinib, an advanced, potent, and highly selective oral TYK2 inhibitor bioengineered to optimize target coverage and functional selectivity, achieved biologic-level efficacy with complete skin clearance observed after only a 12-week treatment period in up to one third of patients, with a low incidence of known tolerability issues and absence of serious toxic effects that are characteristic of [Janus kinase] 1-3 inhibition,” the authors wrote.

SOURCE:

The study was led by April W. Armstrong, MD, MPH, University of California, Los Angeles, and was published online on August 21, 2024, in JAMA Dermatology.
 

LIMITATIONS:

The study was limited by a relatively small sample size and a short duration. In addition, the inclusion of predominantly White patients may limit the generalizability of findings to a diverse population.
 

DISCLOSURES:

The study was funded by Nimbus Discovery, which includes Nimbus Therapeutics and Nimbus Lakshmi. Dr. Armstrong’s disclosures included receiving grants and/or personal fees from various pharmaceutical companies, including Nimbus Therapeutics and Nimbus. Three authors were employees of and reported holding equity, stocks, or shares in Nimbus. Several authors had disclosures related to pharmaceutical companies, including Nimbus.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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TOPLINE:

Zasocitinib, a tyrosine kinase 2 (TYK2) inhibitor, at oral doses of ≥ 5 mg led to greater skin clearance than placebo over a period of 12 weeks, in a phase 2b study.
 

METHODOLOGY:

  • Researchers performed a phase 2b, randomized, double-blind trial to assess the efficacy, safety, and tolerability of different doses of zasocitinib in adults with moderate to severe psoriasis (mean age, 47 years; 32% women) at 47 centers in the United States and eight centers in Canada. Most (83%) were White, 7% were Black, and 8% were Asian.
  • A total of 287 patients were randomly assigned to receive one of the four oral doses of zasocitinib (2 mg, 5 mg, 15 mg, or 30 mg, once daily) or a matched placebo for 12 weeks, followed by a 4-week safety monitoring period.
  • The primary outcome was the proportion of patients achieving a ≥ 75% improvement in the Psoriasis Area and Severity Index score (PASI 75) from baseline at week 12.

TAKEAWAY:

  • At week 12, PASI 75 was achieved by 18%, 44%, 68%, and 67% of patients receiving zasocitinib at doses of 2 mg, 5 mg, 15 mg, and 30 mg, respectively, vs 6% of patients receiving placebo.
  • PASI 90 was achieved in 8%, 21%, 45%, and 46% of patients receiving zasocitinib at 2 mg, 5 mg, 15 mg, and 30 mg, respectively, and in no patients in the placebo group.
  • At week 12, 10%, 27%, 49%, and 52% of patients receiving zasocitinib at 2 mg, 5 mg, 15 mg, and 30 mg, respectively, had no or mild disease (a score of 0 or 1) according to the Physician Global Assessment tool vs 4% in the placebo group.
  • Treatment-emergent adverse events occurred in 53%-62% of patients in the zasocitinib groups compared with 44% in the placebo group. The most common were COVID-19, acne/acneiform dermatitis, and diarrhea. There were no reports of major adverse cardiovascular events, thromboembolic events, or opportunistic infections.

IN PRACTICE:

“Zasocitinib, an advanced, potent, and highly selective oral TYK2 inhibitor bioengineered to optimize target coverage and functional selectivity, achieved biologic-level efficacy with complete skin clearance observed after only a 12-week treatment period in up to one third of patients, with a low incidence of known tolerability issues and absence of serious toxic effects that are characteristic of [Janus kinase] 1-3 inhibition,” the authors wrote.

SOURCE:

The study was led by April W. Armstrong, MD, MPH, University of California, Los Angeles, and was published online on August 21, 2024, in JAMA Dermatology.
 

LIMITATIONS:

The study was limited by a relatively small sample size and a short duration. In addition, the inclusion of predominantly White patients may limit the generalizability of findings to a diverse population.
 

DISCLOSURES:

The study was funded by Nimbus Discovery, which includes Nimbus Therapeutics and Nimbus Lakshmi. Dr. Armstrong’s disclosures included receiving grants and/or personal fees from various pharmaceutical companies, including Nimbus Therapeutics and Nimbus. Three authors were employees of and reported holding equity, stocks, or shares in Nimbus. Several authors had disclosures related to pharmaceutical companies, including Nimbus.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

 

TOPLINE:

Zasocitinib, a tyrosine kinase 2 (TYK2) inhibitor, at oral doses of ≥ 5 mg led to greater skin clearance than placebo over a period of 12 weeks, in a phase 2b study.
 

METHODOLOGY:

  • Researchers performed a phase 2b, randomized, double-blind trial to assess the efficacy, safety, and tolerability of different doses of zasocitinib in adults with moderate to severe psoriasis (mean age, 47 years; 32% women) at 47 centers in the United States and eight centers in Canada. Most (83%) were White, 7% were Black, and 8% were Asian.
  • A total of 287 patients were randomly assigned to receive one of the four oral doses of zasocitinib (2 mg, 5 mg, 15 mg, or 30 mg, once daily) or a matched placebo for 12 weeks, followed by a 4-week safety monitoring period.
  • The primary outcome was the proportion of patients achieving a ≥ 75% improvement in the Psoriasis Area and Severity Index score (PASI 75) from baseline at week 12.

TAKEAWAY:

  • At week 12, PASI 75 was achieved by 18%, 44%, 68%, and 67% of patients receiving zasocitinib at doses of 2 mg, 5 mg, 15 mg, and 30 mg, respectively, vs 6% of patients receiving placebo.
  • PASI 90 was achieved in 8%, 21%, 45%, and 46% of patients receiving zasocitinib at 2 mg, 5 mg, 15 mg, and 30 mg, respectively, and in no patients in the placebo group.
  • At week 12, 10%, 27%, 49%, and 52% of patients receiving zasocitinib at 2 mg, 5 mg, 15 mg, and 30 mg, respectively, had no or mild disease (a score of 0 or 1) according to the Physician Global Assessment tool vs 4% in the placebo group.
  • Treatment-emergent adverse events occurred in 53%-62% of patients in the zasocitinib groups compared with 44% in the placebo group. The most common were COVID-19, acne/acneiform dermatitis, and diarrhea. There were no reports of major adverse cardiovascular events, thromboembolic events, or opportunistic infections.

IN PRACTICE:

“Zasocitinib, an advanced, potent, and highly selective oral TYK2 inhibitor bioengineered to optimize target coverage and functional selectivity, achieved biologic-level efficacy with complete skin clearance observed after only a 12-week treatment period in up to one third of patients, with a low incidence of known tolerability issues and absence of serious toxic effects that are characteristic of [Janus kinase] 1-3 inhibition,” the authors wrote.

SOURCE:

The study was led by April W. Armstrong, MD, MPH, University of California, Los Angeles, and was published online on August 21, 2024, in JAMA Dermatology.
 

LIMITATIONS:

The study was limited by a relatively small sample size and a short duration. In addition, the inclusion of predominantly White patients may limit the generalizability of findings to a diverse population.
 

DISCLOSURES:

The study was funded by Nimbus Discovery, which includes Nimbus Therapeutics and Nimbus Lakshmi. Dr. Armstrong’s disclosures included receiving grants and/or personal fees from various pharmaceutical companies, including Nimbus Therapeutics and Nimbus. Three authors were employees of and reported holding equity, stocks, or shares in Nimbus. Several authors had disclosures related to pharmaceutical companies, including Nimbus.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

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Commentary: Targeted Therapies in PsA, September 2024

Article Type
Changed
Wed, 09/11/2024 - 15:45
Dr. Chandran scans the journals, so you don't have to!
Vinod Chandran, MBBS, MD, DM, PhD

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

 

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

 

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

 

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

Author and Disclosure Information

Vinod Chandran MBBS, MD, DM, PhD, FRCPC

Staff Physician, Department of Medicine/Rheumatology, University Health Network, Toronto, ON, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships: Member of the board of directors of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Received research grant from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly. Received income in an amount equal to or greater than $250 from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; UCB.
Spousal employment: AstraZeneca

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Author and Disclosure Information

Vinod Chandran MBBS, MD, DM, PhD, FRCPC

Staff Physician, Department of Medicine/Rheumatology, University Health Network, Toronto, ON, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships: Member of the board of directors of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Received research grant from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly. Received income in an amount equal to or greater than $250 from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; UCB.
Spousal employment: AstraZeneca

Author and Disclosure Information

Vinod Chandran MBBS, MD, DM, PhD, FRCPC

Staff Physician, Department of Medicine/Rheumatology, University Health Network, Toronto, ON, Canada

Vinod Chandran, MBBS, MD, DM, PhD, has disclosed the following relevant financial relationships: Member of the board of directors of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Received research grant from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly. Received income in an amount equal to or greater than $250 from: Amgen; AbbVie; Bristol-Myers Squibb; Eli Lilly; Janssen; Novartis; UCB.
Spousal employment: AstraZeneca

Dr. Chandran scans the journals, so you don't have to!
Dr. Chandran scans the journals, so you don't have to!
Vinod Chandran, MBBS, MD, DM, PhD

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

 

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

 

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

 

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

Vinod Chandran, MBBS, MD, DM, PhD

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

 

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

 

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

 

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

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Patients With Immune-Mediated Inflammatory Diseases, Type 2 Diabetes Reap GLP-1 Receptor Agonist Benefits, Too

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Changed
Fri, 08/23/2024 - 12:40

 

TOPLINE:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

  • GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
  • Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
  • They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
  • The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
  • The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

  • The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
  • Additionally, patients initiating DPP-4 inhibitors.
  • In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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TOPLINE:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

  • GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
  • Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
  • They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
  • The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
  • The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

  • The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
  • Additionally, patients initiating DPP-4 inhibitors.
  • In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

 

TOPLINE:

Compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a lower risk for all-cause mortality and major adverse cardiovascular events (MACE) in patients with immune-mediated inflammatory diseases (IMIDs) and type 2 diabetes (T2D).

METHODOLOGY:

  • GLP-1 RAs reduce the risk for all-cause mortality, cardiovascular mortality, and stroke in patients with diabetes. However, previous trials have excluded those with IMIDs, leaving a gap in understanding the cardioprotective effects of GLP-1 RAs in this population.
  • Researchers conducted a population-based cohort study to assess if patients with an IMID derive greater benefits from GLP-1 RAs than DPP-4 inhibitors.
  • They used administrative health data from British Columbia, Canada, to include 10,855 patients with IMIDs (rheumatoid arthritis, psoriatic disease, ankylosing spondylitis, inflammatory bowel disease, or systemic autoimmune rheumatic disease) and T2D who initiated either GLP-1 RA (n = 3570) or DPP-4 inhibitor (n = 7285).
  • The mean follow-up was 1.46 and 1.88 years in the GLP-1 RA and DPP-4 inhibitor cohorts, respectively.
  • The primary outcome was all-cause mortality, and the secondary outcome was MACE, including cardiovascular death, myocardial infarction, and ischemic stroke.

TAKEAWAY:

  • The risk for all-cause mortality was 52% lower in patients who initiated GLP-1 RAs than in those who initiated DPP-4 inhibitors (weighted hazard ratio [HR], 0.48; 95% CI, 0.31-0.75).
  • Additionally, patients initiating DPP-4 inhibitors.
  • In the subgroup of patients with GLP-1 RAs had a significantly lower risk for MACE (weighted HR, 0.66; 95% CI, 0.50-0.88), particularly myocardial infarction (weighted HR, 0.62; 95% CI, 0.40-0.96), than those initiating rheumatoid arthritis and T2D, those who initiated GLP-1 RAs had a 55% lower risk for all-cause mortality and 61% lower risk for MACE than those who initiated DPP-4 inhibitors.

IN PRACTICE:

“This corresponds to nine fewer deaths and 11 fewer MACE per 1000 person-years, respectively, supporting the hypothesis that these agents have a cardioprotective effect in this high-risk population,” the authors wrote.

SOURCE:

This study was led by Derin Karacabeyli, MD, Division of Rheumatology, Department of Medicine, University of British Columbia, Vancouver, Canada, and was published online on August 8, 2024, in PLOS ONE.

LIMITATIONS:

The study’s dependence on administrative health data might have resulted in incomplete capture of comorbidities, particularly obesity. The mean follow-up period was relatively short, which might have limited the long-term applicability of these findings. The accuracy of the case definitions for IMIDs and T2D, according to International Classification of Diseases codes, could not be fully ascertained.

DISCLOSURES:

The study was supported by grants from the Canadian Institutes of Health Research. Two authors declared receiving research support, consulting fees, or participating in advisory boards outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

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Do You Have Patients With JAKne — JAK Inhibitor–Associated Acne? Here’s What to Know

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Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital
Dr. Arash Mostaghimi

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School
Dr. Janelle Nassim

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

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Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital
Dr. Arash Mostaghimi

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School
Dr. Janelle Nassim

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital
Dr. Arash Mostaghimi

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School
Dr. Janelle Nassim

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

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Genetic Study Reveals Increased Mutual Risk Between PsA and Ulcerative Colitis

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Fri, 08/16/2024 - 12:14

Key clinical point: A Mendelian randomization analysis revealed that psoriatic arthritis (PsA) was a significant risk factor for ulcerative colitis (UC) and vice versa.

Major finding: UC was associated with a 45.8% increased risk for PsA (odds ratio [OR] 1.458; P = .0013); conversely, PsA was associated with a 32.9% increased risk for UC (OR 1.329; P < .001).

Study details: This Mendelian randomization study evaluated the causal association between PsA, UC, and psoriasis using 123 single nucleotide polymorphisms from genome-wide association studies as genetic instrumental variables.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Pan J, Lv Y, Wang L, et al. Mendelian randomization analysis of psoriasis and psoriatic arthritis associated with risks of ulcerative colitis. Skin Res Technol. 2024;30:e13795 (Jul 12). Doi: 10.3390/jcm13154567 Source

 

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Key clinical point: A Mendelian randomization analysis revealed that psoriatic arthritis (PsA) was a significant risk factor for ulcerative colitis (UC) and vice versa.

Major finding: UC was associated with a 45.8% increased risk for PsA (odds ratio [OR] 1.458; P = .0013); conversely, PsA was associated with a 32.9% increased risk for UC (OR 1.329; P < .001).

Study details: This Mendelian randomization study evaluated the causal association between PsA, UC, and psoriasis using 123 single nucleotide polymorphisms from genome-wide association studies as genetic instrumental variables.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Pan J, Lv Y, Wang L, et al. Mendelian randomization analysis of psoriasis and psoriatic arthritis associated with risks of ulcerative colitis. Skin Res Technol. 2024;30:e13795 (Jul 12). Doi: 10.3390/jcm13154567 Source

 

Key clinical point: A Mendelian randomization analysis revealed that psoriatic arthritis (PsA) was a significant risk factor for ulcerative colitis (UC) and vice versa.

Major finding: UC was associated with a 45.8% increased risk for PsA (odds ratio [OR] 1.458; P = .0013); conversely, PsA was associated with a 32.9% increased risk for UC (OR 1.329; P < .001).

Study details: This Mendelian randomization study evaluated the causal association between PsA, UC, and psoriasis using 123 single nucleotide polymorphisms from genome-wide association studies as genetic instrumental variables.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Pan J, Lv Y, Wang L, et al. Mendelian randomization analysis of psoriasis and psoriatic arthritis associated with risks of ulcerative colitis. Skin Res Technol. 2024;30:e13795 (Jul 12). Doi: 10.3390/jcm13154567 Source

 

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Ultrasound Can Detect Disease Activity in PsA Patients Apparently Within Treatment Target

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Key clinical point: Ultrasound detected active enthesitis and synovitis in a non-negligible proportion of patients with psoriatic arthritis (PsA) who achieved remission or low disease activity with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD).

Major finding: Despite achieving the Disease Activity Index for Psoriatic Arthritis (DAPSA) treatment target, 21.6% patients had at least one painful enthesis on clinical examination. Ultrasound showed evidence of active enthesitis in 19.6% and active synovitis in 15.7% patients.

Study details: This cross-sectional study included 51 patients with PsA who met the DAPSA treatment target after at least 6 months of therapy with b/tsDMARD and underwent bilateral ultrasound and clinical examination of entheses and joints.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interests.

Source: Agache M, Popescu CC, Enache L, et al. Additional value of ultrasound in patients with psoriatic arthritis within treatment target. J Clin Med. 2024;13(5):4567 (Aug 5). Doi: 10.3390/jcm13154567 Source

 

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Key clinical point: Ultrasound detected active enthesitis and synovitis in a non-negligible proportion of patients with psoriatic arthritis (PsA) who achieved remission or low disease activity with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD).

Major finding: Despite achieving the Disease Activity Index for Psoriatic Arthritis (DAPSA) treatment target, 21.6% patients had at least one painful enthesis on clinical examination. Ultrasound showed evidence of active enthesitis in 19.6% and active synovitis in 15.7% patients.

Study details: This cross-sectional study included 51 patients with PsA who met the DAPSA treatment target after at least 6 months of therapy with b/tsDMARD and underwent bilateral ultrasound and clinical examination of entheses and joints.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interests.

Source: Agache M, Popescu CC, Enache L, et al. Additional value of ultrasound in patients with psoriatic arthritis within treatment target. J Clin Med. 2024;13(5):4567 (Aug 5). Doi: 10.3390/jcm13154567 Source

 

Key clinical point: Ultrasound detected active enthesitis and synovitis in a non-negligible proportion of patients with psoriatic arthritis (PsA) who achieved remission or low disease activity with biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD).

Major finding: Despite achieving the Disease Activity Index for Psoriatic Arthritis (DAPSA) treatment target, 21.6% patients had at least one painful enthesis on clinical examination. Ultrasound showed evidence of active enthesitis in 19.6% and active synovitis in 15.7% patients.

Study details: This cross-sectional study included 51 patients with PsA who met the DAPSA treatment target after at least 6 months of therapy with b/tsDMARD and underwent bilateral ultrasound and clinical examination of entheses and joints.

Disclosures: This study did not receive any external funding. The authors declared no conflicts of interests.

Source: Agache M, Popescu CC, Enache L, et al. Additional value of ultrasound in patients with psoriatic arthritis within treatment target. J Clin Med. 2024;13(5):4567 (Aug 5). Doi: 10.3390/jcm13154567 Source

 

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Exercise and Mediterranean Diet Benefit Skin and Joints in PsA

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Key clinical point: Exercise and a Mediterranean diet improved disease activity outcomes pertaining to skin and joints in patients with psoriatic arthritis (PsA), indicating that combining lifestyle changes with conventional medical treatment can benefit patients with PsA.

Major finding: High vs low levels of exercise were associated with lower median values of Disease Activity in PsA Score (10.6 vs 28.5; P = .004), erythrocyte sedimentation rate (9 vs 16; P = .001), and fewer tender (1.5 vs 10; P = .003) and swollen (1.5 vs 9; P = .016) joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index (0.9 vs 1.5; P = .001) and body surface area (1 vs 2; P = .009).

Study details: This cross-sectional study enrolled 355 patients with psoriatic disease (age > 18 years), including 279 patients with PsA and 76 patients with psoriasis.

Disclosures: No funding sources were declared for this study. The authors did not declare any conflicts of interest.

Source: Katsimbri P, Grivas A, Papadavid E, et al. Mediterranean diet and exercise are associated with better disease control in psoriatic arthritis. Clin Rheumatol. 2024 (Jul 25). Doi: 10.1007/s10067-024-07080-6 Source

 

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Key clinical point: Exercise and a Mediterranean diet improved disease activity outcomes pertaining to skin and joints in patients with psoriatic arthritis (PsA), indicating that combining lifestyle changes with conventional medical treatment can benefit patients with PsA.

Major finding: High vs low levels of exercise were associated with lower median values of Disease Activity in PsA Score (10.6 vs 28.5; P = .004), erythrocyte sedimentation rate (9 vs 16; P = .001), and fewer tender (1.5 vs 10; P = .003) and swollen (1.5 vs 9; P = .016) joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index (0.9 vs 1.5; P = .001) and body surface area (1 vs 2; P = .009).

Study details: This cross-sectional study enrolled 355 patients with psoriatic disease (age > 18 years), including 279 patients with PsA and 76 patients with psoriasis.

Disclosures: No funding sources were declared for this study. The authors did not declare any conflicts of interest.

Source: Katsimbri P, Grivas A, Papadavid E, et al. Mediterranean diet and exercise are associated with better disease control in psoriatic arthritis. Clin Rheumatol. 2024 (Jul 25). Doi: 10.1007/s10067-024-07080-6 Source

 

Key clinical point: Exercise and a Mediterranean diet improved disease activity outcomes pertaining to skin and joints in patients with psoriatic arthritis (PsA), indicating that combining lifestyle changes with conventional medical treatment can benefit patients with PsA.

Major finding: High vs low levels of exercise were associated with lower median values of Disease Activity in PsA Score (10.6 vs 28.5; P = .004), erythrocyte sedimentation rate (9 vs 16; P = .001), and fewer tender (1.5 vs 10; P = .003) and swollen (1.5 vs 9; P = .016) joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index (0.9 vs 1.5; P = .001) and body surface area (1 vs 2; P = .009).

Study details: This cross-sectional study enrolled 355 patients with psoriatic disease (age > 18 years), including 279 patients with PsA and 76 patients with psoriasis.

Disclosures: No funding sources were declared for this study. The authors did not declare any conflicts of interest.

Source: Katsimbri P, Grivas A, Papadavid E, et al. Mediterranean diet and exercise are associated with better disease control in psoriatic arthritis. Clin Rheumatol. 2024 (Jul 25). Doi: 10.1007/s10067-024-07080-6 Source

 

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Autoimmune Diseases Increase PsA Risk

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Key clinical point: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and certain other autoimmune diseases (AID) may have an increased risk of developing psoriatic arthritis (PsA).

Major finding: The risk factors for PsA included RA (inverse variance weighting odds ratio [ORIVW] 1.11; P = .0205), SLE (ORIVW 1.04; P = .0107), AS (ORIVW 2.18; P = .000155), Crohn's disease (CD; ORIVW 1.07; P = .01), Hashimoto's thyroiditis (HT; ORIVW 1.23; P = .00143), and vitiligo (ORIVW 1.27; P = .0000267). However, PsA did not increase the risk for these AID.

Study details: This bidirectional two-sample Mendelian randomization study used genome-wide association data for PsA (3186 cases and 240,862 control individuals and  an additional 5065 cases and 21,286 control individuals), psoriasis, and AID.

Disclosures: This study was supported by two research projects from China. The authors declared no conflicts of interest.

Source: Duan K, Wang J, Chen S, et al. Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: A bidirectional two-sample Mendelian randomization study. Front. Immunol. 2024;15:1422626 (Jul 24). Doi: 10.3389/fimmu.2024.1422626 Source

 

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Key clinical point: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and certain other autoimmune diseases (AID) may have an increased risk of developing psoriatic arthritis (PsA).

Major finding: The risk factors for PsA included RA (inverse variance weighting odds ratio [ORIVW] 1.11; P = .0205), SLE (ORIVW 1.04; P = .0107), AS (ORIVW 2.18; P = .000155), Crohn's disease (CD; ORIVW 1.07; P = .01), Hashimoto's thyroiditis (HT; ORIVW 1.23; P = .00143), and vitiligo (ORIVW 1.27; P = .0000267). However, PsA did not increase the risk for these AID.

Study details: This bidirectional two-sample Mendelian randomization study used genome-wide association data for PsA (3186 cases and 240,862 control individuals and  an additional 5065 cases and 21,286 control individuals), psoriasis, and AID.

Disclosures: This study was supported by two research projects from China. The authors declared no conflicts of interest.

Source: Duan K, Wang J, Chen S, et al. Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: A bidirectional two-sample Mendelian randomization study. Front. Immunol. 2024;15:1422626 (Jul 24). Doi: 10.3389/fimmu.2024.1422626 Source

 

Key clinical point: Patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and certain other autoimmune diseases (AID) may have an increased risk of developing psoriatic arthritis (PsA).

Major finding: The risk factors for PsA included RA (inverse variance weighting odds ratio [ORIVW] 1.11; P = .0205), SLE (ORIVW 1.04; P = .0107), AS (ORIVW 2.18; P = .000155), Crohn's disease (CD; ORIVW 1.07; P = .01), Hashimoto's thyroiditis (HT; ORIVW 1.23; P = .00143), and vitiligo (ORIVW 1.27; P = .0000267). However, PsA did not increase the risk for these AID.

Study details: This bidirectional two-sample Mendelian randomization study used genome-wide association data for PsA (3186 cases and 240,862 control individuals and  an additional 5065 cases and 21,286 control individuals), psoriasis, and AID.

Disclosures: This study was supported by two research projects from China. The authors declared no conflicts of interest.

Source: Duan K, Wang J, Chen S, et al. Causal associations between both psoriasis and psoriatic arthritis and multiple autoimmune diseases: A bidirectional two-sample Mendelian randomization study. Front. Immunol. 2024;15:1422626 (Jul 24). Doi: 10.3389/fimmu.2024.1422626 Source

 

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