Psoriasis

The effectiveness and safety of biosimilars for psoriasis appear to be similar to the originator biologics, reported the authors of a review of studies comparing the two.

“This systematic review found that there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators of adalimumab, etanercept, infliximab, and ustekinumab for the treatment of psoriasis,” senior study author and clinical lecturer Zenas Z. N. Yiu, MBChB, PhD, and his colleagues at the University of Manchester, England, wrote in JAMA Dermatology.“The biosimilars evaluated in this study could be considered alongside originators for biologic-naive patients to improve the accessibility of biological treatments,” they added. “Switching patients currently on originators to biosimilars could be considered where clinically appropriate to reduce treatment costs.”

Biologics versus biosimilars

In contrast to most chemically synthesized drugs, biologics are created from living organisms, and they have complex structures that can vary slightly from batch to batch, Luigi Naldi, MD, director of the department of dermatology of Ospedale San Bortolo, Vicenza, Italy, and Antonio Addis, PharmD, researcher in the department of epidemiology, Regione Lazio, in Rome, wrote in an accompanying editorial.

Once the patent on the “originator” biologic expires, U.S. and European regulators allow other manufacturers to develop similar molecules – biosimilars – through an abbreviated approval process. If the results of a limited number of equivalence or noninferiority clinical trials are acceptable, registration for all the indications of the originator is allowed for its biosimilars. Referring to the expense of biologics, Dr. Naldi and Dr. Addis noted that in the United States, “biologics comprise less than 3% of the volume of drugs on the market, but account for more than one-third of all drug spending.”

Systematic review

Dr. Yiu and his colleagues queried standard medical research databases in August 2022, and included 14 randomized clinical trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) in their review.

Twelve trials compared biosimilars vs. originators in originator-naive patients, and 11 trials compared switching from originators to biosimilars vs. continuous treatment with the originator.

The researchers found the following:

At week 16, mean PASI75 (Psoriasis Area and Severity Index) response rates ranges from 60.7% to 90.6% for adalimumab biosimilars, vs. 61.5% to 91.7% for the originator. Mean PASI75 responses for the two etanercept biosimilars were 56.1% and 76.7% vs. 55.5% and 73.4% for the originator. In the ustekinumab study, mean PASI75 responses were 86.1% for the biosimilar vs. 84.0% for the originator.

At week 52, mean PASI75 responses were between 86.3% and 92.8% for adalimumab biosimilars vs. 84.9% and 93.9% for the originator. In the one comparison of an etanercept biosimilar, mean PAS175 responses were 80.9% for the biosimilar vs. 82.9% for the originator.

In studies involving patients switching from the originator to a biosimilar vs. continuing treatment with the originator, 32-week response rates ranged from 87.0% to 91.3% for adalimumab biosimilars and from 88.2% to 93.2% for the originator. In the one ustekinumab study, the 32-week mean PASI75 response was 92.6% after switching from the originator to a biosimilar vs. 92.9% with continuous treatment with the originator.

At week 52, mean PASI75 responses to adalimumab were between 84.2% and 94.8% for patients who switched to biosimilars and between 88.1% and 93.9% for those who stayed on the originator.

At week 52, in all the randomized trials, the incidence of adverse events and serious adverse events among those who switched to the biosimilar and those who continued with the originator were similar. Two cohort studies showed similar safety outcomes between originators and biosimilars, but one reported more adverse events in patients who switched to adalimumab biosimilars (P = .04).

Three clinical trials showed low risk for bias, 11 had moderate risk, and all cohort studies had moderate to high risk for bias.

Experts weigh in

Asked to comment on the study, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., told this news organization that he expects that the results will affect patient care.

However, he added, “I believe the decision of whether to use a biosimilar instead of the originator biologic may be more in the hands of the insurers than in the hands of physicians and patients.

“Biologics for psoriasis are so complicated that even the originator products vary from batch to batch. A biosimilar is basically like another batch of the innovative product,” explained Dr. Feldman, who was not involved in the study. “If we’re comfortable with patients being on different batches of the innovator product, we probably should be comfortable with them being on a biosimilar, as we have more evidence for the similarity of the biosimilar than we do for the current batch of the originator product.”

Aída Lugo-Somolinos, MD, professor of dermatology and director of the Contact Dermatitis Clinic at the University of North Carolina, Chapel Hill, said that “biologics have become the treatment of choice for moderate to severe psoriasis, and the use of biosimilars may be an alternative to reduce psoriasis treatment costs.

“Unfortunately, this study included a comparison of the existing biosimilars, which are drugs that are not the first line of treatment for psoriasis any longer,” added Dr. Lugo-Somolinos, who was not involved in the study.

Neil J. Korman, MD, PhD, professor of dermatology and codirector of the Skin Study Center at Case Western Reserve University, Cleveland, said the study was an important systematic review.

“This is a very timely publication because in the United States, several biosimilars are reaching the market in 2023,” he said. “The costs of the originator biologics are extraordinarily high, and the promise of biosimilars is that their costs will be significantly lower.”

Because all the studies were short term, Dr. Korman, who was not involved in the study, joins the study authors in recommending further related research into the long-term safety and efficacy of these agents.

Dr. Feldman, as well as one study author and one editorial author, reported relevant relationships with various pharmaceutical companies, including those that develop biosimilars. The remaining study authors, as well as Dr. Lugo-Somolinos and Dr. Korman, reported no relevant relationships. The study was funded by the Psoriasis Association and supported by the NIHR (National Institute for Health and Care Research) Manchester Biomedical Research Centre. All outside experts commented by email.

The effectiveness and safety of biosimilars for psoriasis appear to be similar to the originator biologics, reported the authors of a review of studies comparing the two.

“This systematic review found that there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators of adalimumab, etanercept, infliximab, and ustekinumab for the treatment of psoriasis,” senior study author and clinical lecturer Zenas Z. N. Yiu, MBChB, PhD, and his colleagues at the University of Manchester, England, wrote in JAMA Dermatology.“The biosimilars evaluated in this study could be considered alongside originators for biologic-naive patients to improve the accessibility of biological treatments,” they added. “Switching patients currently on originators to biosimilars could be considered where clinically appropriate to reduce treatment costs.”

Biologics versus biosimilars

In contrast to most chemically synthesized drugs, biologics are created from living organisms, and they have complex structures that can vary slightly from batch to batch, Luigi Naldi, MD, director of the department of dermatology of Ospedale San Bortolo, Vicenza, Italy, and Antonio Addis, PharmD, researcher in the department of epidemiology, Regione Lazio, in Rome, wrote in an accompanying editorial.

Once the patent on the “originator” biologic expires, U.S. and European regulators allow other manufacturers to develop similar molecules – biosimilars – through an abbreviated approval process. If the results of a limited number of equivalence or noninferiority clinical trials are acceptable, registration for all the indications of the originator is allowed for its biosimilars. Referring to the expense of biologics, Dr. Naldi and Dr. Addis noted that in the United States, “biologics comprise less than 3% of the volume of drugs on the market, but account for more than one-third of all drug spending.”

Systematic review

Dr. Yiu and his colleagues queried standard medical research databases in August 2022, and included 14 randomized clinical trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) in their review.

Twelve trials compared biosimilars vs. originators in originator-naive patients, and 11 trials compared switching from originators to biosimilars vs. continuous treatment with the originator.

The researchers found the following:

At week 16, mean PASI75 (Psoriasis Area and Severity Index) response rates ranges from 60.7% to 90.6% for adalimumab biosimilars, vs. 61.5% to 91.7% for the originator. Mean PASI75 responses for the two etanercept biosimilars were 56.1% and 76.7% vs. 55.5% and 73.4% for the originator. In the ustekinumab study, mean PASI75 responses were 86.1% for the biosimilar vs. 84.0% for the originator.

At week 52, mean PASI75 responses were between 86.3% and 92.8% for adalimumab biosimilars vs. 84.9% and 93.9% for the originator. In the one comparison of an etanercept biosimilar, mean PAS175 responses were 80.9% for the biosimilar vs. 82.9% for the originator.

In studies involving patients switching from the originator to a biosimilar vs. continuing treatment with the originator, 32-week response rates ranged from 87.0% to 91.3% for adalimumab biosimilars and from 88.2% to 93.2% for the originator. In the one ustekinumab study, the 32-week mean PASI75 response was 92.6% after switching from the originator to a biosimilar vs. 92.9% with continuous treatment with the originator.

At week 52, mean PASI75 responses to adalimumab were between 84.2% and 94.8% for patients who switched to biosimilars and between 88.1% and 93.9% for those who stayed on the originator.

At week 52, in all the randomized trials, the incidence of adverse events and serious adverse events among those who switched to the biosimilar and those who continued with the originator were similar. Two cohort studies showed similar safety outcomes between originators and biosimilars, but one reported more adverse events in patients who switched to adalimumab biosimilars (P = .04).

Three clinical trials showed low risk for bias, 11 had moderate risk, and all cohort studies had moderate to high risk for bias.

Experts weigh in

Asked to comment on the study, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., told this news organization that he expects that the results will affect patient care.

However, he added, “I believe the decision of whether to use a biosimilar instead of the originator biologic may be more in the hands of the insurers than in the hands of physicians and patients.

“Biologics for psoriasis are so complicated that even the originator products vary from batch to batch. A biosimilar is basically like another batch of the innovative product,” explained Dr. Feldman, who was not involved in the study. “If we’re comfortable with patients being on different batches of the innovator product, we probably should be comfortable with them being on a biosimilar, as we have more evidence for the similarity of the biosimilar than we do for the current batch of the originator product.”

Aída Lugo-Somolinos, MD, professor of dermatology and director of the Contact Dermatitis Clinic at the University of North Carolina, Chapel Hill, said that “biologics have become the treatment of choice for moderate to severe psoriasis, and the use of biosimilars may be an alternative to reduce psoriasis treatment costs.

“Unfortunately, this study included a comparison of the existing biosimilars, which are drugs that are not the first line of treatment for psoriasis any longer,” added Dr. Lugo-Somolinos, who was not involved in the study.

Neil J. Korman, MD, PhD, professor of dermatology and codirector of the Skin Study Center at Case Western Reserve University, Cleveland, said the study was an important systematic review.

“This is a very timely publication because in the United States, several biosimilars are reaching the market in 2023,” he said. “The costs of the originator biologics are extraordinarily high, and the promise of biosimilars is that their costs will be significantly lower.”

Because all the studies were short term, Dr. Korman, who was not involved in the study, joins the study authors in recommending further related research into the long-term safety and efficacy of these agents.

Dr. Feldman, as well as one study author and one editorial author, reported relevant relationships with various pharmaceutical companies, including those that develop biosimilars. The remaining study authors, as well as Dr. Lugo-Somolinos and Dr. Korman, reported no relevant relationships. The study was funded by the Psoriasis Association and supported by the NIHR (National Institute for Health and Care Research) Manchester Biomedical Research Centre. All outside experts commented by email.

The effectiveness and safety of biosimilars for psoriasis appear to be similar to the originator biologics, reported the authors of a review of studies comparing the two.

“This systematic review found that there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators of adalimumab, etanercept, infliximab, and ustekinumab for the treatment of psoriasis,” senior study author and clinical lecturer Zenas Z. N. Yiu, MBChB, PhD, and his colleagues at the University of Manchester, England, wrote in JAMA Dermatology.“The biosimilars evaluated in this study could be considered alongside originators for biologic-naive patients to improve the accessibility of biological treatments,” they added. “Switching patients currently on originators to biosimilars could be considered where clinically appropriate to reduce treatment costs.”

Biologics versus biosimilars

In contrast to most chemically synthesized drugs, biologics are created from living organisms, and they have complex structures that can vary slightly from batch to batch, Luigi Naldi, MD, director of the department of dermatology of Ospedale San Bortolo, Vicenza, Italy, and Antonio Addis, PharmD, researcher in the department of epidemiology, Regione Lazio, in Rome, wrote in an accompanying editorial.

Once the patent on the “originator” biologic expires, U.S. and European regulators allow other manufacturers to develop similar molecules – biosimilars – through an abbreviated approval process. If the results of a limited number of equivalence or noninferiority clinical trials are acceptable, registration for all the indications of the originator is allowed for its biosimilars. Referring to the expense of biologics, Dr. Naldi and Dr. Addis noted that in the United States, “biologics comprise less than 3% of the volume of drugs on the market, but account for more than one-third of all drug spending.”

Systematic review

Dr. Yiu and his colleagues queried standard medical research databases in August 2022, and included 14 randomized clinical trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) in their review.

Twelve trials compared biosimilars vs. originators in originator-naive patients, and 11 trials compared switching from originators to biosimilars vs. continuous treatment with the originator.

The researchers found the following:

At week 16, mean PASI75 (Psoriasis Area and Severity Index) response rates ranges from 60.7% to 90.6% for adalimumab biosimilars, vs. 61.5% to 91.7% for the originator. Mean PASI75 responses for the two etanercept biosimilars were 56.1% and 76.7% vs. 55.5% and 73.4% for the originator. In the ustekinumab study, mean PASI75 responses were 86.1% for the biosimilar vs. 84.0% for the originator.

At week 52, mean PASI75 responses were between 86.3% and 92.8% for adalimumab biosimilars vs. 84.9% and 93.9% for the originator. In the one comparison of an etanercept biosimilar, mean PAS175 responses were 80.9% for the biosimilar vs. 82.9% for the originator.

In studies involving patients switching from the originator to a biosimilar vs. continuing treatment with the originator, 32-week response rates ranged from 87.0% to 91.3% for adalimumab biosimilars and from 88.2% to 93.2% for the originator. In the one ustekinumab study, the 32-week mean PASI75 response was 92.6% after switching from the originator to a biosimilar vs. 92.9% with continuous treatment with the originator.

At week 52, mean PASI75 responses to adalimumab were between 84.2% and 94.8% for patients who switched to biosimilars and between 88.1% and 93.9% for those who stayed on the originator.

At week 52, in all the randomized trials, the incidence of adverse events and serious adverse events among those who switched to the biosimilar and those who continued with the originator were similar. Two cohort studies showed similar safety outcomes between originators and biosimilars, but one reported more adverse events in patients who switched to adalimumab biosimilars (P = .04).

Three clinical trials showed low risk for bias, 11 had moderate risk, and all cohort studies had moderate to high risk for bias.

Experts weigh in

Asked to comment on the study, Steven R. Feldman, MD, PhD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., told this news organization that he expects that the results will affect patient care.

However, he added, “I believe the decision of whether to use a biosimilar instead of the originator biologic may be more in the hands of the insurers than in the hands of physicians and patients.

“Biologics for psoriasis are so complicated that even the originator products vary from batch to batch. A biosimilar is basically like another batch of the innovative product,” explained Dr. Feldman, who was not involved in the study. “If we’re comfortable with patients being on different batches of the innovator product, we probably should be comfortable with them being on a biosimilar, as we have more evidence for the similarity of the biosimilar than we do for the current batch of the originator product.”

Aída Lugo-Somolinos, MD, professor of dermatology and director of the Contact Dermatitis Clinic at the University of North Carolina, Chapel Hill, said that “biologics have become the treatment of choice for moderate to severe psoriasis, and the use of biosimilars may be an alternative to reduce psoriasis treatment costs.

“Unfortunately, this study included a comparison of the existing biosimilars, which are drugs that are not the first line of treatment for psoriasis any longer,” added Dr. Lugo-Somolinos, who was not involved in the study.

Neil J. Korman, MD, PhD, professor of dermatology and codirector of the Skin Study Center at Case Western Reserve University, Cleveland, said the study was an important systematic review.

“This is a very timely publication because in the United States, several biosimilars are reaching the market in 2023,” he said. “The costs of the originator biologics are extraordinarily high, and the promise of biosimilars is that their costs will be significantly lower.”

Because all the studies were short term, Dr. Korman, who was not involved in the study, joins the study authors in recommending further related research into the long-term safety and efficacy of these agents.

Dr. Feldman, as well as one study author and one editorial author, reported relevant relationships with various pharmaceutical companies, including those that develop biosimilars. The remaining study authors, as well as Dr. Lugo-Somolinos and Dr. Korman, reported no relevant relationships. The study was funded by the Psoriasis Association and supported by the NIHR (National Institute for Health and Care Research) Manchester Biomedical Research Centre. All outside experts commented by email.

The recent Food and Drug Administration approval of colchicine 0.5 mg (Lodoco) for use in atherosclerotic cardiovascular disease (ASCVD) prevention will possibly create opportunities to use the drug to treat residual risk for ASCVD in some patients with immune-mediated inflammatory diseases, particularly in rheumatology.

Potential in rheumatology

The 0.5-mg dose is just a shade under the 0.6-mg, twice daily dosing rheumatologists typically prescribe for gout, Christie Bartels, MD, MS, chief of rheumatology at the University of Wisconsin–Madison, said in an interview. Clinicians also use the 0.6-mg dose off-label for pseudogout or calcium pyrophosphate deposition disease (CPPD), Dr. Bartels noted.

University of Wisconsin

The new formulation opens the consideration for using colchicine more in patients with psoriatic arthritis, lupus, and rheumatoid arthritis, she said. “I think we could certainly discuss it, particularly, in secondary prevention patients who already had an event or who are at the highest risk and already on optimal traditional agents,” she said.

She cited previous comments by Paul Ridker, MD, director of the center for cardiovascular disease prevention at Brigham and Women’s Hospital in Boston, and developer of the high-sensitivity C-reactive protein (hsCRP) test for measuring inflammatory markers. “We might not know the answer because Dr. Ridker pointed out he used colchicine 0.5 mg in patients that had a high-sensitivity CRP that was high; we need patients who have had inflammation of unknown origin, so those patients presumably weren’t already on another anti-inflammatory,” she said, noting that hydroxychloroquine, methotrexate, and some biologics provide some protection from cardiovascular risks.

However, a potential role for long-term colchicine 0.5 mg in ASCVD prevention may cause consideration for changing the drug’s role in gout treatment, Dr. Bartels said. “In gout, where we do have an FDA-approved indication for colchicine, we used to use it only for the first 6 months while we were getting patients to goal on allopurinol, which was usually then monotherapy after the first 6 months,” she said. “I think this will likely change how I treat gout patients in that I may also offer to continue both medications [colchicine and allopurinol] if they are tolerating them well.

“And then in patients where I’m using it off-label in CPPD, I might again share with them that in addition to possibly helping their CPPD, there may be this added benefit to reduce inflammation just in discussing the risks and benefits of the medicine.”

However, rheumatologists must be careful in using colchicine beyond the typical 6-month cycle, Dr. Bartels said. “One of the tricky things with colchicine, and part of the reason we did not traditionally continue it specifically past the first 6 months, was that it can cause myopathies or cytopenias, so we still have to counsel patients regarding these risks and monitor that,” she said.

Additionally, colchicine can have drug interactions with statins or calcium channel blockers that can change colchicine levels. “I think the dose here is so low, the 0.5 mg, that it’s probably still safe, but again, it’s something that we have to take a look at in the patient’s whole picture and the rest of their burden of their meds in order to make a decision with them,” Dr. Bartels said.

Possibilities in dermatology

The LoDoCo2 trial one of two major randomized trials that supported approval of colchicine 0.5 mg, reported that treated patients had a 60% lower rate of gout than the placebo group (1.4% vs. 3.4%). Joel Gelfand, MD, MSCE, the James J. Leyden professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, pointed to this in evaluating the dermatologic implications of the drug’s approval. “This may be of particular interest as people with psoriasis have an increased risk of gout,” he said in emailed comments.

University of Pennsylvania

Colchicine’s mechanism of action to reduce inflammation parallels that of tumor necrosis factor (TNF) inhibitors used for dermatologic indications, namely by inhibiting leukocyte adhesion to disrupt the downregulation of TNF receptors, Dr. Gelfand said.

“Interestingly, observational data suggests biologics that target TNF such as adalimumab, etanercept, etc., are associated with a reduction in CV events, and in placebo-controlled trials we conducted in psoriasis patients, it reduced key inflammatory mediators of cardiovascular disease, including IL [interleukin]-6,” he said. “Randomized clinical trials to evaluate the ability of TNF inhibitors, which are now available as biosimilars, to prevent cardiovascular events in high-risk patients, should be conducted, and more work is needed to identify which additional immune-targeted treatments may lower CV risk with an acceptable safety profile.”

Colchicine currently has few indications for rare conditions in dermatology, Dr. Gelfand said, including Sweets syndrome, subcorneal pustular dermatosis, and cutaneous vasculitis. “There are some reports to suggest it may help psoriatic disease, but current data are limited and insufficient to recommend its use for psoriasis and/or psoriatic arthritis,” he said.

The approval of colchicine 0.5 mg for ASCVD could be meaningful for people with psoriasis who are also being treated for CV risk factors, Dr. Gelfand said. “Additional considerations such as signs of residual inflammation (elevated hsCRP) and CV imaging findings may be used to further guide shared decision-making for optimal use,” he said.

Another consideration he noted: “This is also a novel 0.5-mg formulation, and thus cost may be an issue.”
 

Would side effects bar use in gastroenterology?

Colchicine 0.5 mg may not move the needle much for expanding treatment of ASCVD in patients with inflammatory bowel disease (IBD) and potentially other gastrointestinal conditions, Edward Loftus Jr., MD, the Maxine and Jack Zarrow Family professor of gastroenterology specifically for IBD at the Mayo Clinic in Rochester, Minn., told MDEdge in emailed comments. “Given the GI side effect profile [of colchicine], I am not sure I would go there,” he said.

Mayo Clinic

“Hopefully, the prescribers of this low-dose formulation are aware of the gastrointestinal side effects, such as diarrhea and nausea, and educate patients about these side effects so that a proper risk-benefit discussion can ensue,” he said.

Dr. Bartels reporting a previous financial relationship with Pfizer. Dr. Gelfand said he has financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, GlaxoSmithKline, Twill, Lilly, Leo, Moonlake, Janssen Biologics, Novartis, Pfizer, UCB, Neuroderm, and Veolia North America. Dr. Loftus disclosed relationships with AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Receptos, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iterative Health, Janssen, KSL Diagnostics, Morphic, Ono, Pfizer, Sun, Surrozen, Takeda, Theravance, and UCB.
 

The recent Food and Drug Administration approval of colchicine 0.5 mg (Lodoco) for use in atherosclerotic cardiovascular disease (ASCVD) prevention will possibly create opportunities to use the drug to treat residual risk for ASCVD in some patients with immune-mediated inflammatory diseases, particularly in rheumatology.

Potential in rheumatology

The 0.5-mg dose is just a shade under the 0.6-mg, twice daily dosing rheumatologists typically prescribe for gout, Christie Bartels, MD, MS, chief of rheumatology at the University of Wisconsin–Madison, said in an interview. Clinicians also use the 0.6-mg dose off-label for pseudogout or calcium pyrophosphate deposition disease (CPPD), Dr. Bartels noted.

University of Wisconsin

The new formulation opens the consideration for using colchicine more in patients with psoriatic arthritis, lupus, and rheumatoid arthritis, she said. “I think we could certainly discuss it, particularly, in secondary prevention patients who already had an event or who are at the highest risk and already on optimal traditional agents,” she said.

She cited previous comments by Paul Ridker, MD, director of the center for cardiovascular disease prevention at Brigham and Women’s Hospital in Boston, and developer of the high-sensitivity C-reactive protein (hsCRP) test for measuring inflammatory markers. “We might not know the answer because Dr. Ridker pointed out he used colchicine 0.5 mg in patients that had a high-sensitivity CRP that was high; we need patients who have had inflammation of unknown origin, so those patients presumably weren’t already on another anti-inflammatory,” she said, noting that hydroxychloroquine, methotrexate, and some biologics provide some protection from cardiovascular risks.

However, a potential role for long-term colchicine 0.5 mg in ASCVD prevention may cause consideration for changing the drug’s role in gout treatment, Dr. Bartels said. “In gout, where we do have an FDA-approved indication for colchicine, we used to use it only for the first 6 months while we were getting patients to goal on allopurinol, which was usually then monotherapy after the first 6 months,” she said. “I think this will likely change how I treat gout patients in that I may also offer to continue both medications [colchicine and allopurinol] if they are tolerating them well.

“And then in patients where I’m using it off-label in CPPD, I might again share with them that in addition to possibly helping their CPPD, there may be this added benefit to reduce inflammation just in discussing the risks and benefits of the medicine.”

However, rheumatologists must be careful in using colchicine beyond the typical 6-month cycle, Dr. Bartels said. “One of the tricky things with colchicine, and part of the reason we did not traditionally continue it specifically past the first 6 months, was that it can cause myopathies or cytopenias, so we still have to counsel patients regarding these risks and monitor that,” she said.

Additionally, colchicine can have drug interactions with statins or calcium channel blockers that can change colchicine levels. “I think the dose here is so low, the 0.5 mg, that it’s probably still safe, but again, it’s something that we have to take a look at in the patient’s whole picture and the rest of their burden of their meds in order to make a decision with them,” Dr. Bartels said.

Possibilities in dermatology

The LoDoCo2 trial one of two major randomized trials that supported approval of colchicine 0.5 mg, reported that treated patients had a 60% lower rate of gout than the placebo group (1.4% vs. 3.4%). Joel Gelfand, MD, MSCE, the James J. Leyden professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, pointed to this in evaluating the dermatologic implications of the drug’s approval. “This may be of particular interest as people with psoriasis have an increased risk of gout,” he said in emailed comments.

University of Pennsylvania

Colchicine’s mechanism of action to reduce inflammation parallels that of tumor necrosis factor (TNF) inhibitors used for dermatologic indications, namely by inhibiting leukocyte adhesion to disrupt the downregulation of TNF receptors, Dr. Gelfand said.

“Interestingly, observational data suggests biologics that target TNF such as adalimumab, etanercept, etc., are associated with a reduction in CV events, and in placebo-controlled trials we conducted in psoriasis patients, it reduced key inflammatory mediators of cardiovascular disease, including IL [interleukin]-6,” he said. “Randomized clinical trials to evaluate the ability of TNF inhibitors, which are now available as biosimilars, to prevent cardiovascular events in high-risk patients, should be conducted, and more work is needed to identify which additional immune-targeted treatments may lower CV risk with an acceptable safety profile.”

Colchicine currently has few indications for rare conditions in dermatology, Dr. Gelfand said, including Sweets syndrome, subcorneal pustular dermatosis, and cutaneous vasculitis. “There are some reports to suggest it may help psoriatic disease, but current data are limited and insufficient to recommend its use for psoriasis and/or psoriatic arthritis,” he said.

The approval of colchicine 0.5 mg for ASCVD could be meaningful for people with psoriasis who are also being treated for CV risk factors, Dr. Gelfand said. “Additional considerations such as signs of residual inflammation (elevated hsCRP) and CV imaging findings may be used to further guide shared decision-making for optimal use,” he said.

Another consideration he noted: “This is also a novel 0.5-mg formulation, and thus cost may be an issue.”
 

Would side effects bar use in gastroenterology?

Colchicine 0.5 mg may not move the needle much for expanding treatment of ASCVD in patients with inflammatory bowel disease (IBD) and potentially other gastrointestinal conditions, Edward Loftus Jr., MD, the Maxine and Jack Zarrow Family professor of gastroenterology specifically for IBD at the Mayo Clinic in Rochester, Minn., told MDEdge in emailed comments. “Given the GI side effect profile [of colchicine], I am not sure I would go there,” he said.

Mayo Clinic

“Hopefully, the prescribers of this low-dose formulation are aware of the gastrointestinal side effects, such as diarrhea and nausea, and educate patients about these side effects so that a proper risk-benefit discussion can ensue,” he said.

Dr. Bartels reporting a previous financial relationship with Pfizer. Dr. Gelfand said he has financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, GlaxoSmithKline, Twill, Lilly, Leo, Moonlake, Janssen Biologics, Novartis, Pfizer, UCB, Neuroderm, and Veolia North America. Dr. Loftus disclosed relationships with AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Receptos, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iterative Health, Janssen, KSL Diagnostics, Morphic, Ono, Pfizer, Sun, Surrozen, Takeda, Theravance, and UCB.
 

The recent Food and Drug Administration approval of colchicine 0.5 mg (Lodoco) for use in atherosclerotic cardiovascular disease (ASCVD) prevention will possibly create opportunities to use the drug to treat residual risk for ASCVD in some patients with immune-mediated inflammatory diseases, particularly in rheumatology.

Potential in rheumatology

The 0.5-mg dose is just a shade under the 0.6-mg, twice daily dosing rheumatologists typically prescribe for gout, Christie Bartels, MD, MS, chief of rheumatology at the University of Wisconsin–Madison, said in an interview. Clinicians also use the 0.6-mg dose off-label for pseudogout or calcium pyrophosphate deposition disease (CPPD), Dr. Bartels noted.

University of Wisconsin

The new formulation opens the consideration for using colchicine more in patients with psoriatic arthritis, lupus, and rheumatoid arthritis, she said. “I think we could certainly discuss it, particularly, in secondary prevention patients who already had an event or who are at the highest risk and already on optimal traditional agents,” she said.

She cited previous comments by Paul Ridker, MD, director of the center for cardiovascular disease prevention at Brigham and Women’s Hospital in Boston, and developer of the high-sensitivity C-reactive protein (hsCRP) test for measuring inflammatory markers. “We might not know the answer because Dr. Ridker pointed out he used colchicine 0.5 mg in patients that had a high-sensitivity CRP that was high; we need patients who have had inflammation of unknown origin, so those patients presumably weren’t already on another anti-inflammatory,” she said, noting that hydroxychloroquine, methotrexate, and some biologics provide some protection from cardiovascular risks.

However, a potential role for long-term colchicine 0.5 mg in ASCVD prevention may cause consideration for changing the drug’s role in gout treatment, Dr. Bartels said. “In gout, where we do have an FDA-approved indication for colchicine, we used to use it only for the first 6 months while we were getting patients to goal on allopurinol, which was usually then monotherapy after the first 6 months,” she said. “I think this will likely change how I treat gout patients in that I may also offer to continue both medications [colchicine and allopurinol] if they are tolerating them well.

“And then in patients where I’m using it off-label in CPPD, I might again share with them that in addition to possibly helping their CPPD, there may be this added benefit to reduce inflammation just in discussing the risks and benefits of the medicine.”

However, rheumatologists must be careful in using colchicine beyond the typical 6-month cycle, Dr. Bartels said. “One of the tricky things with colchicine, and part of the reason we did not traditionally continue it specifically past the first 6 months, was that it can cause myopathies or cytopenias, so we still have to counsel patients regarding these risks and monitor that,” she said.

Additionally, colchicine can have drug interactions with statins or calcium channel blockers that can change colchicine levels. “I think the dose here is so low, the 0.5 mg, that it’s probably still safe, but again, it’s something that we have to take a look at in the patient’s whole picture and the rest of their burden of their meds in order to make a decision with them,” Dr. Bartels said.

Possibilities in dermatology

The LoDoCo2 trial one of two major randomized trials that supported approval of colchicine 0.5 mg, reported that treated patients had a 60% lower rate of gout than the placebo group (1.4% vs. 3.4%). Joel Gelfand, MD, MSCE, the James J. Leyden professor of dermatology and epidemiology at the University of Pennsylvania, Philadelphia, pointed to this in evaluating the dermatologic implications of the drug’s approval. “This may be of particular interest as people with psoriasis have an increased risk of gout,” he said in emailed comments.

University of Pennsylvania

Colchicine’s mechanism of action to reduce inflammation parallels that of tumor necrosis factor (TNF) inhibitors used for dermatologic indications, namely by inhibiting leukocyte adhesion to disrupt the downregulation of TNF receptors, Dr. Gelfand said.

“Interestingly, observational data suggests biologics that target TNF such as adalimumab, etanercept, etc., are associated with a reduction in CV events, and in placebo-controlled trials we conducted in psoriasis patients, it reduced key inflammatory mediators of cardiovascular disease, including IL [interleukin]-6,” he said. “Randomized clinical trials to evaluate the ability of TNF inhibitors, which are now available as biosimilars, to prevent cardiovascular events in high-risk patients, should be conducted, and more work is needed to identify which additional immune-targeted treatments may lower CV risk with an acceptable safety profile.”

Colchicine currently has few indications for rare conditions in dermatology, Dr. Gelfand said, including Sweets syndrome, subcorneal pustular dermatosis, and cutaneous vasculitis. “There are some reports to suggest it may help psoriatic disease, but current data are limited and insufficient to recommend its use for psoriasis and/or psoriatic arthritis,” he said.

The approval of colchicine 0.5 mg for ASCVD could be meaningful for people with psoriasis who are also being treated for CV risk factors, Dr. Gelfand said. “Additional considerations such as signs of residual inflammation (elevated hsCRP) and CV imaging findings may be used to further guide shared decision-making for optimal use,” he said.

Another consideration he noted: “This is also a novel 0.5-mg formulation, and thus cost may be an issue.”
 

Would side effects bar use in gastroenterology?

Colchicine 0.5 mg may not move the needle much for expanding treatment of ASCVD in patients with inflammatory bowel disease (IBD) and potentially other gastrointestinal conditions, Edward Loftus Jr., MD, the Maxine and Jack Zarrow Family professor of gastroenterology specifically for IBD at the Mayo Clinic in Rochester, Minn., told MDEdge in emailed comments. “Given the GI side effect profile [of colchicine], I am not sure I would go there,” he said.

Mayo Clinic

“Hopefully, the prescribers of this low-dose formulation are aware of the gastrointestinal side effects, such as diarrhea and nausea, and educate patients about these side effects so that a proper risk-benefit discussion can ensue,” he said.

Dr. Bartels reporting a previous financial relationship with Pfizer. Dr. Gelfand said he has financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Celldex, GlaxoSmithKline, Twill, Lilly, Leo, Moonlake, Janssen Biologics, Novartis, Pfizer, UCB, Neuroderm, and Veolia North America. Dr. Loftus disclosed relationships with AbbVie, Alvotech, Amgen, Arena, Avalo, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene/Receptos, Celltrion Healthcare, Eli Lilly, Fresenius Kabi, Genentech, Gilead, GlaxoSmithKline, Gossamer Bio, Iterative Health, Janssen, KSL Diagnostics, Morphic, Ono, Pfizer, Sun, Surrozen, Takeda, Theravance, and UCB.
 

TOPLINE:

Methotrexate (MTX) is not associated with testicular toxicity, so therapy can be safety started in men pursuing parenthood, a small study finds.

METHODOLOGY:

• Lack of evidence regarding MTX’s effect on sperm quality has resulted in inconsistent recommendations for men actively pursuing parenthood.
• Researchers enrolled 20 men aged 18 years or older with an immune-mediated inflammatory disease (IMID) who were about to begin MTX therapy and 25 healthy men as controls.
• Participants provided semen samples prior to beginning MTX therapy and 13 weeks after beginning therapy.
• Researchers tested samples in both groups for markers of testicular toxicity.
• Also evaluated whether MTX polyglutamates could be detected in sperm of seminal fluid, as a secondary outcome.

TAKEAWAY:

• Found no significant differences in conventional semen parameters, sperm DNA damage, or male reproductive endocrine axis between the MTX group and controls.
• The concentration of MTX polyglutamates is low in both sperm and seminal fluid and is particularly low in sperm.

IN PRACTICE:

“Therapy with MTX can be safely started or continued in men diagnosed with an IMID and with an active wish to become a father,” the authors write.

STUDY DETAILS:

Luis Fernando Perez-Garcia, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the research. The study was published online in Annals of the Rheumatic Diseases on June 1, 2023.

LIMITATIONS:

The small number of participants and that the study included only MTX starters and not those who have taken MTX longer term.

DISCLOSURES:

Grants from the Dutch Arthritis Foundation, The Netherlands Organization for Health Research and Development, and Consejo Nacional de Ciencia y Tecnologia funded the project. Researchers disclosed financial relationships with Galapagos NV and UCB.

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

TOPLINE:

Methotrexate (MTX) is not associated with testicular toxicity, so therapy can be safety started in men pursuing parenthood, a small study finds.

METHODOLOGY:

• Lack of evidence regarding MTX’s effect on sperm quality has resulted in inconsistent recommendations for men actively pursuing parenthood.
• Researchers enrolled 20 men aged 18 years or older with an immune-mediated inflammatory disease (IMID) who were about to begin MTX therapy and 25 healthy men as controls.
• Participants provided semen samples prior to beginning MTX therapy and 13 weeks after beginning therapy.
• Researchers tested samples in both groups for markers of testicular toxicity.
• Also evaluated whether MTX polyglutamates could be detected in sperm of seminal fluid, as a secondary outcome.

TAKEAWAY:

• Found no significant differences in conventional semen parameters, sperm DNA damage, or male reproductive endocrine axis between the MTX group and controls.
• The concentration of MTX polyglutamates is low in both sperm and seminal fluid and is particularly low in sperm.

IN PRACTICE:

“Therapy with MTX can be safely started or continued in men diagnosed with an IMID and with an active wish to become a father,” the authors write.

STUDY DETAILS:

Luis Fernando Perez-Garcia, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the research. The study was published online in Annals of the Rheumatic Diseases on June 1, 2023.

LIMITATIONS:

The small number of participants and that the study included only MTX starters and not those who have taken MTX longer term.

DISCLOSURES:

Grants from the Dutch Arthritis Foundation, The Netherlands Organization for Health Research and Development, and Consejo Nacional de Ciencia y Tecnologia funded the project. Researchers disclosed financial relationships with Galapagos NV and UCB.

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

TOPLINE:

Methotrexate (MTX) is not associated with testicular toxicity, so therapy can be safety started in men pursuing parenthood, a small study finds.

METHODOLOGY:

• Lack of evidence regarding MTX’s effect on sperm quality has resulted in inconsistent recommendations for men actively pursuing parenthood.
• Researchers enrolled 20 men aged 18 years or older with an immune-mediated inflammatory disease (IMID) who were about to begin MTX therapy and 25 healthy men as controls.
• Participants provided semen samples prior to beginning MTX therapy and 13 weeks after beginning therapy.
• Researchers tested samples in both groups for markers of testicular toxicity.
• Also evaluated whether MTX polyglutamates could be detected in sperm of seminal fluid, as a secondary outcome.

TAKEAWAY:

• Found no significant differences in conventional semen parameters, sperm DNA damage, or male reproductive endocrine axis between the MTX group and controls.
• The concentration of MTX polyglutamates is low in both sperm and seminal fluid and is particularly low in sperm.

IN PRACTICE:

“Therapy with MTX can be safely started or continued in men diagnosed with an IMID and with an active wish to become a father,” the authors write.

STUDY DETAILS:

Luis Fernando Perez-Garcia, MD, Erasmus Medical Center, Rotterdam, the Netherlands, led the research. The study was published online in Annals of the Rheumatic Diseases on June 1, 2023.

LIMITATIONS:

The small number of participants and that the study included only MTX starters and not those who have taken MTX longer term.

DISCLOSURES:

Grants from the Dutch Arthritis Foundation, The Netherlands Organization for Health Research and Development, and Consejo Nacional de Ciencia y Tecnologia funded the project. Researchers disclosed financial relationships with Galapagos NV and UCB.

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

Adalimumab, sold under the brand name Humira, enjoyed a long run as one of the world’s best-selling medicines. But its 20-year, competition-free period has ended, and despite its best efforts to delay their arrival, drug manufacturer AbbVie now faces increasing competition from biosimilars entering the marketplace.
 

But one biosimilar about to be launched may be something of a game changer. Coherus BioSciences has announced plans to market its biosimilar Yusimry (adalimumab-aqvh) at a cost of $995 for two autoinjectors. This represents an approximate 85% discount over Humira’s sale list price of $6922.

This price, however, is slated to plunge even further as Coherus has also revealed that it will work with the Mark Cuban Cost Plus Drug Company (MCCPDC) to offer an even lower price. When Yusimry launches in July, it will sell for about $579 for two autoinjectors, making it the lowest-priced adalimumab biosimilar on the market.

“Coherus and Cost Plus Drug Company share a common mission, to increase access to high-quality medicine for patients at an affordable price,” said Dennis Lanfear, MBA, president, CEO and chairman of Coherus. “Mark Cuban and his team offer innovative solutions to health care problems, and Coherus is also a highly innovative company focused on unmet patient needs.”

He noted that, with adalimumab biosimilar pricing, this translates to a low list price approach. “We are pleased that Yusimry will be a part of that, as the first biologic they carry,” Mr. Lanfear said.

MCCPDC prices are based on the cost of ingredients and manufacturing plus 15% margin, a $3 pharmacy dispensing fee, and a $5 shipping fee. The company has expanded its inventory from 100 generics to more than 350 medications since it launched in January 2022. While MCCPDC is primarily directed to people who are paying cash for drugs, it does take insurance from select plans. And even for people who are covered by other insurers, the cost of drugs from Mr. Cuban’s company may be less than their out-of-pocket costs if they did go through their payer.

The low pricing of Yusimry is welcome, said Marcus Snow, MD, an assistant professor in the division of rheumatology at the University of Nebraska Medical Center, Omaha, but he pointed out that it is still a very expensive drug. “For patients who can’t afford Humira due to poor insurance coverage and high out-of-pocket costs, it is a welcome option. But it’s also unclear how many patients who lack adequate health insurance coverage can afford to pay $579 a month out of their own pockets.”
 

The biosimilars are coming

By early December 2022, the Food and Drug Administration had approved seven Humira biosimilars, and Amgen launched the first biosimilar to come on the market, Amjevita, soon afterward. By July 2023, half a dozen more are expected to enter the marketplace, said Steven Horvitz, managing director of EMC Analytics Group, a pharmaceutical research firm.

Mr. Horvitz agrees that the system is out of control, but it is unclear how much of an effect the low price tag on the Coherus product will have. “Some insurers may say, ‘we want the lowest price, and we don’t care about rebates,’ and will go with it,” he said. “PBMs [pharmacy benefit managers] are all about economics, so we have to see how many of their major clients will ask for the lowest price.”

Amgen has more or less followed the status quo on pricing for its biosimilar, but with a twist. It›s being offered at two different prices: $85,494 a year, which is only a 5% discount from Humira’s list price, or at $40,497 a year, a 55% discount. However, to date, the lower price has generally not been granted favorable formulary placement by PBMs. The plans that adopt the higher-priced biosimilar will get bigger rebates, but patients with coinsurance and deductibles will pay more out of pocket.

It is yet unknown how the pricing on Yusimry will affect the biosimilars ready to launch. “Will it give them pause for thought or not make any difference?” Mr. Horvitz said. “The companies do not reveal their pricing before the fact, so we have to wait and see.”

Large PBMs have not jumped at the opportunity to offer the Coherus biosimilar, but SmithRx, which bills itself as “next-generation pharmacy benefits management,” announced that it will offer Yusimry to its members at a discount of more than 90%.

“Unlike traditional PBMs, SmithRx prioritizes transparency and up-front cost savings. Humira is often an employer’s top drug expense so offering a low-cost alternative will have significant impact,” Jake Frenz, CEO and founder of SmithRx, said in a statement. “We’re excited to work with Cost Plus Drugs to bring this biosimilar to our members – and significantly reduce costs for them and their employers.”

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

Adalimumab, sold under the brand name Humira, enjoyed a long run as one of the world’s best-selling medicines. But its 20-year, competition-free period has ended, and despite its best efforts to delay their arrival, drug manufacturer AbbVie now faces increasing competition from biosimilars entering the marketplace.
 

But one biosimilar about to be launched may be something of a game changer. Coherus BioSciences has announced plans to market its biosimilar Yusimry (adalimumab-aqvh) at a cost of $995 for two autoinjectors. This represents an approximate 85% discount over Humira’s sale list price of $6922.

This price, however, is slated to plunge even further as Coherus has also revealed that it will work with the Mark Cuban Cost Plus Drug Company (MCCPDC) to offer an even lower price. When Yusimry launches in July, it will sell for about $579 for two autoinjectors, making it the lowest-priced adalimumab biosimilar on the market.

“Coherus and Cost Plus Drug Company share a common mission, to increase access to high-quality medicine for patients at an affordable price,” said Dennis Lanfear, MBA, president, CEO and chairman of Coherus. “Mark Cuban and his team offer innovative solutions to health care problems, and Coherus is also a highly innovative company focused on unmet patient needs.”

He noted that, with adalimumab biosimilar pricing, this translates to a low list price approach. “We are pleased that Yusimry will be a part of that, as the first biologic they carry,” Mr. Lanfear said.

MCCPDC prices are based on the cost of ingredients and manufacturing plus 15% margin, a $3 pharmacy dispensing fee, and a $5 shipping fee. The company has expanded its inventory from 100 generics to more than 350 medications since it launched in January 2022. While MCCPDC is primarily directed to people who are paying cash for drugs, it does take insurance from select plans. And even for people who are covered by other insurers, the cost of drugs from Mr. Cuban’s company may be less than their out-of-pocket costs if they did go through their payer.

The low pricing of Yusimry is welcome, said Marcus Snow, MD, an assistant professor in the division of rheumatology at the University of Nebraska Medical Center, Omaha, but he pointed out that it is still a very expensive drug. “For patients who can’t afford Humira due to poor insurance coverage and high out-of-pocket costs, it is a welcome option. But it’s also unclear how many patients who lack adequate health insurance coverage can afford to pay $579 a month out of their own pockets.”
 

The biosimilars are coming

By early December 2022, the Food and Drug Administration had approved seven Humira biosimilars, and Amgen launched the first biosimilar to come on the market, Amjevita, soon afterward. By July 2023, half a dozen more are expected to enter the marketplace, said Steven Horvitz, managing director of EMC Analytics Group, a pharmaceutical research firm.

Mr. Horvitz agrees that the system is out of control, but it is unclear how much of an effect the low price tag on the Coherus product will have. “Some insurers may say, ‘we want the lowest price, and we don’t care about rebates,’ and will go with it,” he said. “PBMs [pharmacy benefit managers] are all about economics, so we have to see how many of their major clients will ask for the lowest price.”

Amgen has more or less followed the status quo on pricing for its biosimilar, but with a twist. It›s being offered at two different prices: $85,494 a year, which is only a 5% discount from Humira’s list price, or at $40,497 a year, a 55% discount. However, to date, the lower price has generally not been granted favorable formulary placement by PBMs. The plans that adopt the higher-priced biosimilar will get bigger rebates, but patients with coinsurance and deductibles will pay more out of pocket.

It is yet unknown how the pricing on Yusimry will affect the biosimilars ready to launch. “Will it give them pause for thought or not make any difference?” Mr. Horvitz said. “The companies do not reveal their pricing before the fact, so we have to wait and see.”

Large PBMs have not jumped at the opportunity to offer the Coherus biosimilar, but SmithRx, which bills itself as “next-generation pharmacy benefits management,” announced that it will offer Yusimry to its members at a discount of more than 90%.

“Unlike traditional PBMs, SmithRx prioritizes transparency and up-front cost savings. Humira is often an employer’s top drug expense so offering a low-cost alternative will have significant impact,” Jake Frenz, CEO and founder of SmithRx, said in a statement. “We’re excited to work with Cost Plus Drugs to bring this biosimilar to our members – and significantly reduce costs for them and their employers.”

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

Adalimumab, sold under the brand name Humira, enjoyed a long run as one of the world’s best-selling medicines. But its 20-year, competition-free period has ended, and despite its best efforts to delay their arrival, drug manufacturer AbbVie now faces increasing competition from biosimilars entering the marketplace.
 

But one biosimilar about to be launched may be something of a game changer. Coherus BioSciences has announced plans to market its biosimilar Yusimry (adalimumab-aqvh) at a cost of $995 for two autoinjectors. This represents an approximate 85% discount over Humira’s sale list price of $6922.

This price, however, is slated to plunge even further as Coherus has also revealed that it will work with the Mark Cuban Cost Plus Drug Company (MCCPDC) to offer an even lower price. When Yusimry launches in July, it will sell for about $579 for two autoinjectors, making it the lowest-priced adalimumab biosimilar on the market.

“Coherus and Cost Plus Drug Company share a common mission, to increase access to high-quality medicine for patients at an affordable price,” said Dennis Lanfear, MBA, president, CEO and chairman of Coherus. “Mark Cuban and his team offer innovative solutions to health care problems, and Coherus is also a highly innovative company focused on unmet patient needs.”

He noted that, with adalimumab biosimilar pricing, this translates to a low list price approach. “We are pleased that Yusimry will be a part of that, as the first biologic they carry,” Mr. Lanfear said.

MCCPDC prices are based on the cost of ingredients and manufacturing plus 15% margin, a $3 pharmacy dispensing fee, and a $5 shipping fee. The company has expanded its inventory from 100 generics to more than 350 medications since it launched in January 2022. While MCCPDC is primarily directed to people who are paying cash for drugs, it does take insurance from select plans. And even for people who are covered by other insurers, the cost of drugs from Mr. Cuban’s company may be less than their out-of-pocket costs if they did go through their payer.

The low pricing of Yusimry is welcome, said Marcus Snow, MD, an assistant professor in the division of rheumatology at the University of Nebraska Medical Center, Omaha, but he pointed out that it is still a very expensive drug. “For patients who can’t afford Humira due to poor insurance coverage and high out-of-pocket costs, it is a welcome option. But it’s also unclear how many patients who lack adequate health insurance coverage can afford to pay $579 a month out of their own pockets.”
 

The biosimilars are coming

By early December 2022, the Food and Drug Administration had approved seven Humira biosimilars, and Amgen launched the first biosimilar to come on the market, Amjevita, soon afterward. By July 2023, half a dozen more are expected to enter the marketplace, said Steven Horvitz, managing director of EMC Analytics Group, a pharmaceutical research firm.

Mr. Horvitz agrees that the system is out of control, but it is unclear how much of an effect the low price tag on the Coherus product will have. “Some insurers may say, ‘we want the lowest price, and we don’t care about rebates,’ and will go with it,” he said. “PBMs [pharmacy benefit managers] are all about economics, so we have to see how many of their major clients will ask for the lowest price.”

Amgen has more or less followed the status quo on pricing for its biosimilar, but with a twist. It›s being offered at two different prices: $85,494 a year, which is only a 5% discount from Humira’s list price, or at $40,497 a year, a 55% discount. However, to date, the lower price has generally not been granted favorable formulary placement by PBMs. The plans that adopt the higher-priced biosimilar will get bigger rebates, but patients with coinsurance and deductibles will pay more out of pocket.

It is yet unknown how the pricing on Yusimry will affect the biosimilars ready to launch. “Will it give them pause for thought or not make any difference?” Mr. Horvitz said. “The companies do not reveal their pricing before the fact, so we have to wait and see.”

Large PBMs have not jumped at the opportunity to offer the Coherus biosimilar, but SmithRx, which bills itself as “next-generation pharmacy benefits management,” announced that it will offer Yusimry to its members at a discount of more than 90%.

“Unlike traditional PBMs, SmithRx prioritizes transparency and up-front cost savings. Humira is often an employer’s top drug expense so offering a low-cost alternative will have significant impact,” Jake Frenz, CEO and founder of SmithRx, said in a statement. “We’re excited to work with Cost Plus Drugs to bring this biosimilar to our members – and significantly reduce costs for them and their employers.”

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

Women with moderate to severe psoriasis had a lower fertility rate, compared with age-matched peers without psoriasis, and overall, those with psoriasis had a slightly higher risk of pregnancy loss, compared with those who did not have the disease, in a U.K. cohort study.

Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.

“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”

To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.

Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.

The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.

Fertility, birth outcomes

When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.

As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.

In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.

However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.

“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”

They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”

Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.

This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.

“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”

The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.

Women with moderate to severe psoriasis had a lower fertility rate, compared with age-matched peers without psoriasis, and overall, those with psoriasis had a slightly higher risk of pregnancy loss, compared with those who did not have the disease, in a U.K. cohort study.

Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.

“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”

To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.

Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.

The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.

Fertility, birth outcomes

When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.

As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.

In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.

However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.

“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”

They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”

Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.

This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.

“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”

The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.

Women with moderate to severe psoriasis had a lower fertility rate, compared with age-matched peers without psoriasis, and overall, those with psoriasis had a slightly higher risk of pregnancy loss, compared with those who did not have the disease, in a U.K. cohort study.

Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.

“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”

To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.

Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.

The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.

Fertility, birth outcomes

When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.

As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.

In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.

However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.

“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”

They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”

Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.

This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.

“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”

The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.

The activity and clustering of certain cell types may distinguish mild and severe forms of psoriasis, with severe disease altering the cellular and metabolic composition of distal unaffected skin sites, according to a new analysis using single-cell transcriptomic technology.

On the surface, psoriasis severity is identified based on the visible lesions, Rochelle L. Castillo, MD, of the division of rheumatology and the NYU Psoriatic Arthritis Center, NYU Langone Health, New York, and colleagues wrote in their study, published in Science Immunology. Although cellular and molecular features of inflammatory skin diseases such as psoriasis have been characterized, activity at the tissue level and its systemic impact has not been explored.

“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” study co–senior investigator Jose Scher, MD, director of the Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity at NYU Langone Health, said in a press release accompanying the publication of the findings. “Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,”

In the study, the researchers used spatial transcriptomics, a technique that positions tissue sections onto genetic arrays to determine gene expression by cell type and histological location, helping to create a broad image-based map of where certain cell types are located in tissues and with what other cells they are communicating. They characterized the cell activity of skin samples from 11 men and women with mild to severe psoriasis/psoriatic arthritis, and three healthy adults who did not have psoriasis. They defined the cellular composition of 25 healthy skin biopsies and matched skin biopsies from psoriatic lesional and nonlesional skin, and identified 17 distinct clusters of cells, which they grouped into epidermal, dermis, pilosebaceous, and adipose categories.

The researchers found that cell activity associated with inflammation, as shown by clusters of fibroblasts and dermal macrophages, was more common in the upper layers of the skin in samples from patients with more severe psoriasis, compared with healthy control samples.

They also examined patterns of immune activity at the cellular level and found significant patterns around the upper follicle, around the perifollicular dermis, and within the hair follicle, where immune cells were enriched in healthy skin. Other cells enriched in these upper layer areas in healthy skin included dendritic cells, innate lymphoid cells, T helper cells, T cytotoxic cells, and myeloid cells.

Clusters of fibroblasts and macrophages, which are associated with inflammation, were clustered in psoriatic lesional skin, which also showed more inflammation at the dermal and suprabasal epidermal levels. B lymphocytes also were more prevalent in lesional skin.

The researchers then analyzed the skin samples according to disease severity; mild psoriasis was defined as a Psoriasis Area and Severity Index score less than 12; moderate to severe disease was defined as a PASI score of 12 or higher. The macrophage, fibroblast, and lymphatic endothelium–associated clusters distinguished mild and moderate to severe endotypes.

The pathology of moderate to severe psoriasis in lesional and nonlesional skin showed the extensive effects of psoriasis-related inflammation. Although nonlesional mild disease was clustered with healthy skin, in cases of moderate to severe disease, nonlesional and lesional groups were clustered together. This effect was segregated according to disease severity, independent of the presence of joint disease, and “was particularly evident in distal, nonlesional samples,” the researchers wrote.

The researchers also found evidence of increased gene activity in more than three dozen molecular pathways associated with metabolism and lipid levels in areas of lesional and nonlesional skin, Dr. Scher said.

The findings were limited by several factors including the small sample size and the limits of spatial transcriptomics technology resolution, the researchers wrote. “As this technology evolves, platforms with higher density, and by extension, resolution, of spatially barcoded beads will provide more granularity about cellular microenvironments in healthy and diseased states.”

The study was supported by the National Institutes of Health, the National Psoriasis Foundation, the NYU Colton Center for Autoimmunity, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the Beatrice Snyder Foundation, The Riley Family Foundation, the Rheumatology Research Foundation, and the NY Stem Cell Foundation. Dr. Castillo had no financial conflicts to disclose. Dr. Scher has served as a consultant for Janssen, Abbvie, Novartis, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb, and has received research funding from Janssen and Pfizer.

The activity and clustering of certain cell types may distinguish mild and severe forms of psoriasis, with severe disease altering the cellular and metabolic composition of distal unaffected skin sites, according to a new analysis using single-cell transcriptomic technology.

On the surface, psoriasis severity is identified based on the visible lesions, Rochelle L. Castillo, MD, of the division of rheumatology and the NYU Psoriatic Arthritis Center, NYU Langone Health, New York, and colleagues wrote in their study, published in Science Immunology. Although cellular and molecular features of inflammatory skin diseases such as psoriasis have been characterized, activity at the tissue level and its systemic impact has not been explored.

“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” study co–senior investigator Jose Scher, MD, director of the Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity at NYU Langone Health, said in a press release accompanying the publication of the findings. “Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,”

In the study, the researchers used spatial transcriptomics, a technique that positions tissue sections onto genetic arrays to determine gene expression by cell type and histological location, helping to create a broad image-based map of where certain cell types are located in tissues and with what other cells they are communicating. They characterized the cell activity of skin samples from 11 men and women with mild to severe psoriasis/psoriatic arthritis, and three healthy adults who did not have psoriasis. They defined the cellular composition of 25 healthy skin biopsies and matched skin biopsies from psoriatic lesional and nonlesional skin, and identified 17 distinct clusters of cells, which they grouped into epidermal, dermis, pilosebaceous, and adipose categories.

The researchers found that cell activity associated with inflammation, as shown by clusters of fibroblasts and dermal macrophages, was more common in the upper layers of the skin in samples from patients with more severe psoriasis, compared with healthy control samples.

They also examined patterns of immune activity at the cellular level and found significant patterns around the upper follicle, around the perifollicular dermis, and within the hair follicle, where immune cells were enriched in healthy skin. Other cells enriched in these upper layer areas in healthy skin included dendritic cells, innate lymphoid cells, T helper cells, T cytotoxic cells, and myeloid cells.

Clusters of fibroblasts and macrophages, which are associated with inflammation, were clustered in psoriatic lesional skin, which also showed more inflammation at the dermal and suprabasal epidermal levels. B lymphocytes also were more prevalent in lesional skin.

The researchers then analyzed the skin samples according to disease severity; mild psoriasis was defined as a Psoriasis Area and Severity Index score less than 12; moderate to severe disease was defined as a PASI score of 12 or higher. The macrophage, fibroblast, and lymphatic endothelium–associated clusters distinguished mild and moderate to severe endotypes.

The pathology of moderate to severe psoriasis in lesional and nonlesional skin showed the extensive effects of psoriasis-related inflammation. Although nonlesional mild disease was clustered with healthy skin, in cases of moderate to severe disease, nonlesional and lesional groups were clustered together. This effect was segregated according to disease severity, independent of the presence of joint disease, and “was particularly evident in distal, nonlesional samples,” the researchers wrote.

The researchers also found evidence of increased gene activity in more than three dozen molecular pathways associated with metabolism and lipid levels in areas of lesional and nonlesional skin, Dr. Scher said.

The findings were limited by several factors including the small sample size and the limits of spatial transcriptomics technology resolution, the researchers wrote. “As this technology evolves, platforms with higher density, and by extension, resolution, of spatially barcoded beads will provide more granularity about cellular microenvironments in healthy and diseased states.”

The study was supported by the National Institutes of Health, the National Psoriasis Foundation, the NYU Colton Center for Autoimmunity, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the Beatrice Snyder Foundation, The Riley Family Foundation, the Rheumatology Research Foundation, and the NY Stem Cell Foundation. Dr. Castillo had no financial conflicts to disclose. Dr. Scher has served as a consultant for Janssen, Abbvie, Novartis, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb, and has received research funding from Janssen and Pfizer.

The activity and clustering of certain cell types may distinguish mild and severe forms of psoriasis, with severe disease altering the cellular and metabolic composition of distal unaffected skin sites, according to a new analysis using single-cell transcriptomic technology.

On the surface, psoriasis severity is identified based on the visible lesions, Rochelle L. Castillo, MD, of the division of rheumatology and the NYU Psoriatic Arthritis Center, NYU Langone Health, New York, and colleagues wrote in their study, published in Science Immunology. Although cellular and molecular features of inflammatory skin diseases such as psoriasis have been characterized, activity at the tissue level and its systemic impact has not been explored.

“Our initial goal was to find measurable molecular signals that could tell us who is more likely to develop severe psoriasis, as well as who is at higher risk of developing related disorders that often accompany psoriasis, such as arthritis and cardiovascular disease,” study co–senior investigator Jose Scher, MD, director of the Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity at NYU Langone Health, said in a press release accompanying the publication of the findings. “Having found signals with potential systemic consequences, we are now working to understand how skin inflammation can lead to widespread disease affecting other organs,”

In the study, the researchers used spatial transcriptomics, a technique that positions tissue sections onto genetic arrays to determine gene expression by cell type and histological location, helping to create a broad image-based map of where certain cell types are located in tissues and with what other cells they are communicating. They characterized the cell activity of skin samples from 11 men and women with mild to severe psoriasis/psoriatic arthritis, and three healthy adults who did not have psoriasis. They defined the cellular composition of 25 healthy skin biopsies and matched skin biopsies from psoriatic lesional and nonlesional skin, and identified 17 distinct clusters of cells, which they grouped into epidermal, dermis, pilosebaceous, and adipose categories.

The researchers found that cell activity associated with inflammation, as shown by clusters of fibroblasts and dermal macrophages, was more common in the upper layers of the skin in samples from patients with more severe psoriasis, compared with healthy control samples.

They also examined patterns of immune activity at the cellular level and found significant patterns around the upper follicle, around the perifollicular dermis, and within the hair follicle, where immune cells were enriched in healthy skin. Other cells enriched in these upper layer areas in healthy skin included dendritic cells, innate lymphoid cells, T helper cells, T cytotoxic cells, and myeloid cells.

Clusters of fibroblasts and macrophages, which are associated with inflammation, were clustered in psoriatic lesional skin, which also showed more inflammation at the dermal and suprabasal epidermal levels. B lymphocytes also were more prevalent in lesional skin.

The researchers then analyzed the skin samples according to disease severity; mild psoriasis was defined as a Psoriasis Area and Severity Index score less than 12; moderate to severe disease was defined as a PASI score of 12 or higher. The macrophage, fibroblast, and lymphatic endothelium–associated clusters distinguished mild and moderate to severe endotypes.

The pathology of moderate to severe psoriasis in lesional and nonlesional skin showed the extensive effects of psoriasis-related inflammation. Although nonlesional mild disease was clustered with healthy skin, in cases of moderate to severe disease, nonlesional and lesional groups were clustered together. This effect was segregated according to disease severity, independent of the presence of joint disease, and “was particularly evident in distal, nonlesional samples,” the researchers wrote.

The researchers also found evidence of increased gene activity in more than three dozen molecular pathways associated with metabolism and lipid levels in areas of lesional and nonlesional skin, Dr. Scher said.

The findings were limited by several factors including the small sample size and the limits of spatial transcriptomics technology resolution, the researchers wrote. “As this technology evolves, platforms with higher density, and by extension, resolution, of spatially barcoded beads will provide more granularity about cellular microenvironments in healthy and diseased states.”

The study was supported by the National Institutes of Health, the National Psoriasis Foundation, the NYU Colton Center for Autoimmunity, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis, the Beatrice Snyder Foundation, The Riley Family Foundation, the Rheumatology Research Foundation, and the NY Stem Cell Foundation. Dr. Castillo had no financial conflicts to disclose. Dr. Scher has served as a consultant for Janssen, Abbvie, Novartis, Pfizer, Sanofi, UCB, and Bristol-Myers Squibb, and has received research funding from Janssen and Pfizer.

Nearly all dermatologists are aware that psoriatic arthritis (PsA) is one of the most prevalent comorbidities associated with psoriasis, yet we may lack the insight regarding how to utilize this information. After all, we specialize in the skin, not the joints, right?

When I graduated from residency in 2014, I began staffing our psoriasis clinic, where we care for the toughest, most complicated psoriasis patients, many of them struggling with both severe recalcitrant psoriasis as well as debilitating PsA. In 2016, we partnered with rheumatology to open a multidisciplinary psoriasis and PsA clinic, and I quickly began to appreciate how much PsA was being overlooked simply because patients with psoriasis were not being asked about their joints.

To start, let’s look at several facts:

1. One quarter of patients with psoriasis also have PsA.¹
2. Skin disease most commonly develops before PsA.¹
3. Fifteen percent of PsA cases go undiagnosed, which dramatically increases the risk for deformed joints, erosions, osteolysis, sacroiliitis, and arthritis mutilans² and also increases the cost of health care.³
4. Everyone is crazy busy—rheumatology wait lists often are months long.

Given that dermatologists are the ones who already are seeing the majority of patients who develop PsA, we play a key role in screening for this debilitating comorbidity and starting therapy for patients with both psoriasis and PsA. We, too, are crazy busy; therefore, we need to make this process quick and efficient but also reliable. Fortunately, the Psoriasis Epidemiology Screening Tool (PEST) is effective, fast, and very easy. With only 5 questions and a sensitivity and specificity of around 70%,⁴ this short and simple questionnaire can be incorporated into an intake form or rooming note or can just be asked during the visit. The questions include whether the patient currently has or has had a swollen joint, nail pits, heel pain, and/or dactylitis, as well as if they have been told by a physician that they have arthritis. A score of 3 or higher is considered positive and a referral to rheumatology should be considered. At the bare minimum, I highly encourage all dermatologists to incorporate the PEST screening tool into their practice.

During the physical examination itself, be sure to look at the patient’s nails and also look for joint swelling and redness, especially in the hands. When palpating a swollen joint, the presence of inflammatory arthritis will feel spongy or boggy, while the osteophytes associated with osteoarthritis will feel hard. Radiography of the affected joint may be helpful, but keep in mind that bone changes are latter sequelae of PsA, and negative radiographs do not rule out PsA.

If you highly suspect PsA after using the PEST screening tool and palpating any swollen joints, then a rheumatology referral certainly is warranted. Medication that covers both psoriasis and PsA also can be initiated. Although methotrexate often is used for joints, higher doses (ie, >15 mg/wk) usually are needed. A 2019 Cochrane review found that low-dose methotrexate (ie, ≤15 mg/wk) may be only slightly more effective then placebo⁵—certainly not a ringing endorsement for its use in PsA. Additionally, quality data demonstrating methotrexate’s efficacy for enthesitis or axial spondyloarthritis is lacking, and methotrexate has not demonstrated an ability to slow the radiographic progression of joints. In contrast, the anti–tumor necrosis factor agents, including adalimumab, infliximab, etanercept, and certolizumab, as well as ustekinumab and the anti–IL-17 biologics secukinumab and ixekizumab have demonstrated efficacy in American College of Rheumatology (ACR) scores, enthesitis, dactylitis, and prevention of radiographic progression of joints.^6,7 Although brodalumab, an anti–IL-17 receptor inhibitor, demonstrated improvement in ACR scores, enthesitis, and dactylitis, data on its effects on radiographic progression of joints were inconclusive given the phase III trial’s premature ending due to suicidal ideation and behavior in participants.⁸ Several of the anti–IL-23 agents also may help PsA, with trials demonstrating improvements in ACR scores, enthesitis, and dactylitis; however, only guselkumab 100 mg every 4 weeks decreased radiographic progression of joints.⁹ Additionally, with the age of the Janus kinase (JAK) inhibitor upon us, there are several JAK/TYK2 inhibitors that are approved by the US Food and Drug Administration for psoriasis (deucravacitinib) as well as for PsA (tofacitinib, upadacitinib), and there are more JAK inhibitors in the pipeline. These medications are effective; however, I do encourage caution and careful consideration in selecting the appropriate patient, as data demonstrated an increased risk for major adverse cardiovascular events and cancer in older (>50 years) rheumatoid arthritis patients who had at least 1 cardiovascular risk factor and were treated with tofacitinib.¹⁰ Although several other trials have not demonstrated this increased risk, further data are needed to determine risk for both pan-JAK inhibitors as well as selective JAK inhibitors and TYK2 inhibitors. Additionally, given psoriasis already is closely linked with many cardiovascular risk factors including heart disease, obesity, hypertension, hyperlipidemia, and diabetes mellitus,¹¹ it will be important to have long-term safety information for JAK inhibitors in the psoriasis and PsA population.

Dermatologists are in a pivotal position to identify patients affected by PsA and start an appropriate systemic medication. We can help make an enormous impact on our patients’ lives as well as help decrease the economic impact of untreated disease. Let’s join the effort to save the joints!

Nearly all dermatologists are aware that psoriatic arthritis (PsA) is one of the most prevalent comorbidities associated with psoriasis, yet we may lack the insight regarding how to utilize this information. After all, we specialize in the skin, not the joints, right?

When I graduated from residency in 2014, I began staffing our psoriasis clinic, where we care for the toughest, most complicated psoriasis patients, many of them struggling with both severe recalcitrant psoriasis as well as debilitating PsA. In 2016, we partnered with rheumatology to open a multidisciplinary psoriasis and PsA clinic, and I quickly began to appreciate how much PsA was being overlooked simply because patients with psoriasis were not being asked about their joints.

To start, let’s look at several facts:

1. One quarter of patients with psoriasis also have PsA.¹
2. Skin disease most commonly develops before PsA.¹
3. Fifteen percent of PsA cases go undiagnosed, which dramatically increases the risk for deformed joints, erosions, osteolysis, sacroiliitis, and arthritis mutilans² and also increases the cost of health care.³
4. Everyone is crazy busy—rheumatology wait lists often are months long.

Given that dermatologists are the ones who already are seeing the majority of patients who develop PsA, we play a key role in screening for this debilitating comorbidity and starting therapy for patients with both psoriasis and PsA. We, too, are crazy busy; therefore, we need to make this process quick and efficient but also reliable. Fortunately, the Psoriasis Epidemiology Screening Tool (PEST) is effective, fast, and very easy. With only 5 questions and a sensitivity and specificity of around 70%,⁴ this short and simple questionnaire can be incorporated into an intake form or rooming note or can just be asked during the visit. The questions include whether the patient currently has or has had a swollen joint, nail pits, heel pain, and/or dactylitis, as well as if they have been told by a physician that they have arthritis. A score of 3 or higher is considered positive and a referral to rheumatology should be considered. At the bare minimum, I highly encourage all dermatologists to incorporate the PEST screening tool into their practice.

During the physical examination itself, be sure to look at the patient’s nails and also look for joint swelling and redness, especially in the hands. When palpating a swollen joint, the presence of inflammatory arthritis will feel spongy or boggy, while the osteophytes associated with osteoarthritis will feel hard. Radiography of the affected joint may be helpful, but keep in mind that bone changes are latter sequelae of PsA, and negative radiographs do not rule out PsA.

If you highly suspect PsA after using the PEST screening tool and palpating any swollen joints, then a rheumatology referral certainly is warranted. Medication that covers both psoriasis and PsA also can be initiated. Although methotrexate often is used for joints, higher doses (ie, >15 mg/wk) usually are needed. A 2019 Cochrane review found that low-dose methotrexate (ie, ≤15 mg/wk) may be only slightly more effective then placebo⁵—certainly not a ringing endorsement for its use in PsA. Additionally, quality data demonstrating methotrexate’s efficacy for enthesitis or axial spondyloarthritis is lacking, and methotrexate has not demonstrated an ability to slow the radiographic progression of joints. In contrast, the anti–tumor necrosis factor agents, including adalimumab, infliximab, etanercept, and certolizumab, as well as ustekinumab and the anti–IL-17 biologics secukinumab and ixekizumab have demonstrated efficacy in American College of Rheumatology (ACR) scores, enthesitis, dactylitis, and prevention of radiographic progression of joints.^6,7 Although brodalumab, an anti–IL-17 receptor inhibitor, demonstrated improvement in ACR scores, enthesitis, and dactylitis, data on its effects on radiographic progression of joints were inconclusive given the phase III trial’s premature ending due to suicidal ideation and behavior in participants.⁸ Several of the anti–IL-23 agents also may help PsA, with trials demonstrating improvements in ACR scores, enthesitis, and dactylitis; however, only guselkumab 100 mg every 4 weeks decreased radiographic progression of joints.⁹ Additionally, with the age of the Janus kinase (JAK) inhibitor upon us, there are several JAK/TYK2 inhibitors that are approved by the US Food and Drug Administration for psoriasis (deucravacitinib) as well as for PsA (tofacitinib, upadacitinib), and there are more JAK inhibitors in the pipeline. These medications are effective; however, I do encourage caution and careful consideration in selecting the appropriate patient, as data demonstrated an increased risk for major adverse cardiovascular events and cancer in older (>50 years) rheumatoid arthritis patients who had at least 1 cardiovascular risk factor and were treated with tofacitinib.¹⁰ Although several other trials have not demonstrated this increased risk, further data are needed to determine risk for both pan-JAK inhibitors as well as selective JAK inhibitors and TYK2 inhibitors. Additionally, given psoriasis already is closely linked with many cardiovascular risk factors including heart disease, obesity, hypertension, hyperlipidemia, and diabetes mellitus,¹¹ it will be important to have long-term safety information for JAK inhibitors in the psoriasis and PsA population.

Dermatologists are in a pivotal position to identify patients affected by PsA and start an appropriate systemic medication. We can help make an enormous impact on our patients’ lives as well as help decrease the economic impact of untreated disease. Let’s join the effort to save the joints!

Nearly all dermatologists are aware that psoriatic arthritis (PsA) is one of the most prevalent comorbidities associated with psoriasis, yet we may lack the insight regarding how to utilize this information. After all, we specialize in the skin, not the joints, right?

When I graduated from residency in 2014, I began staffing our psoriasis clinic, where we care for the toughest, most complicated psoriasis patients, many of them struggling with both severe recalcitrant psoriasis as well as debilitating PsA. In 2016, we partnered with rheumatology to open a multidisciplinary psoriasis and PsA clinic, and I quickly began to appreciate how much PsA was being overlooked simply because patients with psoriasis were not being asked about their joints.

To start, let’s look at several facts:

1. One quarter of patients with psoriasis also have PsA.¹
2. Skin disease most commonly develops before PsA.¹
3. Fifteen percent of PsA cases go undiagnosed, which dramatically increases the risk for deformed joints, erosions, osteolysis, sacroiliitis, and arthritis mutilans² and also increases the cost of health care.³
4. Everyone is crazy busy—rheumatology wait lists often are months long.

Given that dermatologists are the ones who already are seeing the majority of patients who develop PsA, we play a key role in screening for this debilitating comorbidity and starting therapy for patients with both psoriasis and PsA. We, too, are crazy busy; therefore, we need to make this process quick and efficient but also reliable. Fortunately, the Psoriasis Epidemiology Screening Tool (PEST) is effective, fast, and very easy. With only 5 questions and a sensitivity and specificity of around 70%,⁴ this short and simple questionnaire can be incorporated into an intake form or rooming note or can just be asked during the visit. The questions include whether the patient currently has or has had a swollen joint, nail pits, heel pain, and/or dactylitis, as well as if they have been told by a physician that they have arthritis. A score of 3 or higher is considered positive and a referral to rheumatology should be considered. At the bare minimum, I highly encourage all dermatologists to incorporate the PEST screening tool into their practice.

During the physical examination itself, be sure to look at the patient’s nails and also look for joint swelling and redness, especially in the hands. When palpating a swollen joint, the presence of inflammatory arthritis will feel spongy or boggy, while the osteophytes associated with osteoarthritis will feel hard. Radiography of the affected joint may be helpful, but keep in mind that bone changes are latter sequelae of PsA, and negative radiographs do not rule out PsA.

If you highly suspect PsA after using the PEST screening tool and palpating any swollen joints, then a rheumatology referral certainly is warranted. Medication that covers both psoriasis and PsA also can be initiated. Although methotrexate often is used for joints, higher doses (ie, >15 mg/wk) usually are needed. A 2019 Cochrane review found that low-dose methotrexate (ie, ≤15 mg/wk) may be only slightly more effective then placebo⁵—certainly not a ringing endorsement for its use in PsA. Additionally, quality data demonstrating methotrexate’s efficacy for enthesitis or axial spondyloarthritis is lacking, and methotrexate has not demonstrated an ability to slow the radiographic progression of joints. In contrast, the anti–tumor necrosis factor agents, including adalimumab, infliximab, etanercept, and certolizumab, as well as ustekinumab and the anti–IL-17 biologics secukinumab and ixekizumab have demonstrated efficacy in American College of Rheumatology (ACR) scores, enthesitis, dactylitis, and prevention of radiographic progression of joints.^6,7 Although brodalumab, an anti–IL-17 receptor inhibitor, demonstrated improvement in ACR scores, enthesitis, and dactylitis, data on its effects on radiographic progression of joints were inconclusive given the phase III trial’s premature ending due to suicidal ideation and behavior in participants.⁸ Several of the anti–IL-23 agents also may help PsA, with trials demonstrating improvements in ACR scores, enthesitis, and dactylitis; however, only guselkumab 100 mg every 4 weeks decreased radiographic progression of joints.⁹ Additionally, with the age of the Janus kinase (JAK) inhibitor upon us, there are several JAK/TYK2 inhibitors that are approved by the US Food and Drug Administration for psoriasis (deucravacitinib) as well as for PsA (tofacitinib, upadacitinib), and there are more JAK inhibitors in the pipeline. These medications are effective; however, I do encourage caution and careful consideration in selecting the appropriate patient, as data demonstrated an increased risk for major adverse cardiovascular events and cancer in older (>50 years) rheumatoid arthritis patients who had at least 1 cardiovascular risk factor and were treated with tofacitinib.¹⁰ Although several other trials have not demonstrated this increased risk, further data are needed to determine risk for both pan-JAK inhibitors as well as selective JAK inhibitors and TYK2 inhibitors. Additionally, given psoriasis already is closely linked with many cardiovascular risk factors including heart disease, obesity, hypertension, hyperlipidemia, and diabetes mellitus,¹¹ it will be important to have long-term safety information for JAK inhibitors in the psoriasis and PsA population.

Dermatologists are in a pivotal position to identify patients affected by PsA and start an appropriate systemic medication. We can help make an enormous impact on our patients’ lives as well as help decrease the economic impact of untreated disease. Let’s join the effort to save the joints!

The U.S. Food and Drug Administration has approved the biosimilar adalimumab-aaty (Yuflyma) in a citrate-free, high-concentration formulation, the manufacturer, Celltrion USA, announced today. It is the ninth biosimilar of adalimumab (Humira) to be approved in the United States.
 

Yuflyma is approved for the treatment of adult patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa. It is also approved for polyarticular juvenile idiopathic arthritis for patients aged 2 years or older, as well as for Crohn’s disease in adults and in pediatric patients aged 6 years or older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The formulation was approved on the basis of a comprehensive data package of analytic, preclinical, and clinical studies, according to Celltrion USA, “demonstrating that Yuflyma is comparable to the reference product Humira in terms of efficacy, safety, pharmacokinetics, and immunogenicity up to 24 weeks and 1 year following treatment.”

The company conducted a double-blind, randomized phase 3 trial that compared switching from reference adalimumab to Yuflyma with continuing either reference adalimumab or Yuflyma for patients with active rheumatoid arthritis. In that trial, the efficacy, pharmacokinetics, safety, and immunogenicity of Yuflyma and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to Yuflyma.

“Currently, more than 80% of patients treated with Humira in the United States rely on a high-concentration and citrate-free formulation of this medication. The availability of a high-concentration and citrate-free formulation adalimumab biosimilar provides an important treatment option for patients with inflammatory diseases who benefit from this effective therapy,” said Jonathan Kay, MD, of the University of Massachusetts, Worcester, in the press release.

The citrate-free formulation is thought to lead to less pain on injection.

Yuflyma will be available in prefilled syringe and autoinjector administration options.

Celltrion USA plans to market the drug in the United States in July 2023. Following the initial launch of 40 mg/0.4 mL, the company plans to launch dose forms of 80 mg/0.8 mL and 20 mg/0.2 mL.

Celltrion USA is also seeking an interchangeability designation from the FDA following the completion of an interchangeability trial of 366 patients with chronic plaque psoriasis. The interchangeability designation would mean that patients successfully switched from Humira to Yuflyma multiple times in the trial. The interchangeability designation would allow pharmacists to autosubstitute Humira with Yuflyma. In these cases, individual state laws control how and whether physicians will be notified of this switch.

If interchangeability is approved for Yuflyma, which the company tentatively expects in the fourth quarter of 2024, it would be just the third interchangeable biosimilar approved by the FDA overall and the second adalimumab biosimilar to be designated as such, after adalimumab-adbm (Cyltezo) in October 2021.

Yuflyma was approved in Canada in December 2021 for 10 indications: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, adult ulcerative colitis, hidradenitis suppurativa, plaque psoriasis, adult uveitis, and pediatric uveitis.

In February 2022, the European Commission granted marketing authorization for Yuflyma across those 10 indications, as well as for nonradiographic axial spondyloarthritis, pediatric plaque psoriasis, and pediatric Crohn’s disease.

In April 2022, Celltrion USA signed a licensing agreement with AbbVie, the manufacturer of Humira. Under that agreement, Celltrion will pay royalties to AbbVie on sales of their individual biosimilars, and AbbVie agreed to drop all patent litigation.

The full prescribing information for Yuflyma is available here.

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

The U.S. Food and Drug Administration has approved the biosimilar adalimumab-aaty (Yuflyma) in a citrate-free, high-concentration formulation, the manufacturer, Celltrion USA, announced today. It is the ninth biosimilar of adalimumab (Humira) to be approved in the United States.
 

Yuflyma is approved for the treatment of adult patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa. It is also approved for polyarticular juvenile idiopathic arthritis for patients aged 2 years or older, as well as for Crohn’s disease in adults and in pediatric patients aged 6 years or older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The formulation was approved on the basis of a comprehensive data package of analytic, preclinical, and clinical studies, according to Celltrion USA, “demonstrating that Yuflyma is comparable to the reference product Humira in terms of efficacy, safety, pharmacokinetics, and immunogenicity up to 24 weeks and 1 year following treatment.”

The company conducted a double-blind, randomized phase 3 trial that compared switching from reference adalimumab to Yuflyma with continuing either reference adalimumab or Yuflyma for patients with active rheumatoid arthritis. In that trial, the efficacy, pharmacokinetics, safety, and immunogenicity of Yuflyma and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to Yuflyma.

“Currently, more than 80% of patients treated with Humira in the United States rely on a high-concentration and citrate-free formulation of this medication. The availability of a high-concentration and citrate-free formulation adalimumab biosimilar provides an important treatment option for patients with inflammatory diseases who benefit from this effective therapy,” said Jonathan Kay, MD, of the University of Massachusetts, Worcester, in the press release.

The citrate-free formulation is thought to lead to less pain on injection.

Yuflyma will be available in prefilled syringe and autoinjector administration options.

Celltrion USA plans to market the drug in the United States in July 2023. Following the initial launch of 40 mg/0.4 mL, the company plans to launch dose forms of 80 mg/0.8 mL and 20 mg/0.2 mL.

Celltrion USA is also seeking an interchangeability designation from the FDA following the completion of an interchangeability trial of 366 patients with chronic plaque psoriasis. The interchangeability designation would mean that patients successfully switched from Humira to Yuflyma multiple times in the trial. The interchangeability designation would allow pharmacists to autosubstitute Humira with Yuflyma. In these cases, individual state laws control how and whether physicians will be notified of this switch.

If interchangeability is approved for Yuflyma, which the company tentatively expects in the fourth quarter of 2024, it would be just the third interchangeable biosimilar approved by the FDA overall and the second adalimumab biosimilar to be designated as such, after adalimumab-adbm (Cyltezo) in October 2021.

Yuflyma was approved in Canada in December 2021 for 10 indications: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, adult ulcerative colitis, hidradenitis suppurativa, plaque psoriasis, adult uveitis, and pediatric uveitis.

In February 2022, the European Commission granted marketing authorization for Yuflyma across those 10 indications, as well as for nonradiographic axial spondyloarthritis, pediatric plaque psoriasis, and pediatric Crohn’s disease.

In April 2022, Celltrion USA signed a licensing agreement with AbbVie, the manufacturer of Humira. Under that agreement, Celltrion will pay royalties to AbbVie on sales of their individual biosimilars, and AbbVie agreed to drop all patent litigation.

The full prescribing information for Yuflyma is available here.

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

The U.S. Food and Drug Administration has approved the biosimilar adalimumab-aaty (Yuflyma) in a citrate-free, high-concentration formulation, the manufacturer, Celltrion USA, announced today. It is the ninth biosimilar of adalimumab (Humira) to be approved in the United States.
 

Yuflyma is approved for the treatment of adult patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, plaque psoriasis, and hidradenitis suppurativa. It is also approved for polyarticular juvenile idiopathic arthritis for patients aged 2 years or older, as well as for Crohn’s disease in adults and in pediatric patients aged 6 years or older.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The formulation was approved on the basis of a comprehensive data package of analytic, preclinical, and clinical studies, according to Celltrion USA, “demonstrating that Yuflyma is comparable to the reference product Humira in terms of efficacy, safety, pharmacokinetics, and immunogenicity up to 24 weeks and 1 year following treatment.”

The company conducted a double-blind, randomized phase 3 trial that compared switching from reference adalimumab to Yuflyma with continuing either reference adalimumab or Yuflyma for patients with active rheumatoid arthritis. In that trial, the efficacy, pharmacokinetics, safety, and immunogenicity of Yuflyma and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to Yuflyma.

“Currently, more than 80% of patients treated with Humira in the United States rely on a high-concentration and citrate-free formulation of this medication. The availability of a high-concentration and citrate-free formulation adalimumab biosimilar provides an important treatment option for patients with inflammatory diseases who benefit from this effective therapy,” said Jonathan Kay, MD, of the University of Massachusetts, Worcester, in the press release.

The citrate-free formulation is thought to lead to less pain on injection.

Yuflyma will be available in prefilled syringe and autoinjector administration options.

Celltrion USA plans to market the drug in the United States in July 2023. Following the initial launch of 40 mg/0.4 mL, the company plans to launch dose forms of 80 mg/0.8 mL and 20 mg/0.2 mL.

Celltrion USA is also seeking an interchangeability designation from the FDA following the completion of an interchangeability trial of 366 patients with chronic plaque psoriasis. The interchangeability designation would mean that patients successfully switched from Humira to Yuflyma multiple times in the trial. The interchangeability designation would allow pharmacists to autosubstitute Humira with Yuflyma. In these cases, individual state laws control how and whether physicians will be notified of this switch.

If interchangeability is approved for Yuflyma, which the company tentatively expects in the fourth quarter of 2024, it would be just the third interchangeable biosimilar approved by the FDA overall and the second adalimumab biosimilar to be designated as such, after adalimumab-adbm (Cyltezo) in October 2021.

Yuflyma was approved in Canada in December 2021 for 10 indications: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, adult ulcerative colitis, hidradenitis suppurativa, plaque psoriasis, adult uveitis, and pediatric uveitis.

In February 2022, the European Commission granted marketing authorization for Yuflyma across those 10 indications, as well as for nonradiographic axial spondyloarthritis, pediatric plaque psoriasis, and pediatric Crohn’s disease.

In April 2022, Celltrion USA signed a licensing agreement with AbbVie, the manufacturer of Humira. Under that agreement, Celltrion will pay royalties to AbbVie on sales of their individual biosimilars, and AbbVie agreed to drop all patent litigation.

The full prescribing information for Yuflyma is available here.

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

Psoriasis is an inflammatory autoimmune skin condition that affects approximately 125 million individuals worldwide, with approximately 8 million patients in the United States.¹ Psoriasis not only involves a cosmetic component but also comprises other comorbidities, such as psoriatic arthritis, cardiovascular disease, and psychiatric disorders, that can influence patient quality of life.^2-4 In addition, the costs associated with psoriasis are substantial, with an estimated economic burden of $35.2 billion in the United States in 2015.⁵ Given the prevalence of psoriasis and its many effects on patients, it is important that providers have high-quality evidence regarding efficacious treatment options.

Systematic reviews, which compile all available evidence on a subject to answer a specific question, represent the gold standard of research.⁶ However, studies have demonstrated that when referencing research literature, physicians tend to read only the abstract of a study rather than the entire article.^7,8 A study by Marcelo et al⁸ showed that residents at a tertiary care center answered clinical questions using only the abstract of a paper 69% of the time. Based on these findings, it is imperative that the results of systematic reviews be accurately reported in their abstracts because they can influence patient care.

Referencing only the abstracts of systematic reviews can be problematic if the abstract contains spin. Spin is a form of reporting that inappropriately highlights the benefits of a treatment with greater emphasis than what is shown by the results.⁹ Research has identified the presence of spin in the abstracts of randomized controlled trials.^10-12 For example, Cooper et al¹⁰ found that 70% (33/47) of abstracts in otolaryngology randomized controlled trials contained spin. Additionally, Arthur et al¹¹ and Austin et al¹² had similar findings within abstracts of orthopedic and obesity trials, where 44.8% (112/250) and 46.7% (21/45) contained spin, respectively. Ottwell et al¹³ found that the presence of spin in abstracts is not limited to randomized controlled trials; they demonstrated that the abstracts of nearly one-third (31% [11/36]) of systematic reviews focused on the treatment of acne vulgaris contained spin.

In our study, we aimed to evaluate the presence of spin in the abstracts of systematic reviews focused on the treatment of psoriasis.

Methods

Reproducibility and Reporting—Our study did not meet the regulatory definition for human subjects research per the US Code of Federal Regulations because the study did not involve human research subjects. The study also was not subject to review by the institutional review board. Our protocol, data set, analysis scripts, extraction forms, and other material related to the study have been placed on Open Science Framework to provide transparency and ensure reproducibility. To further allow for analytic reproducibility, our data set was given to an independent laboratory and reanalyzed with a masked approach. Our study was carried out alongside other studies assessing spin in systematic reviews regarding different specialties and disease states. Because these studies were similar in design, this methodology also has been reported elsewhere. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)¹⁴ and the guidelines for meta-epidemiological studies developed by Murad and Wang¹⁵ were used in drafting this article.

Search Strategy—The search strategies for the MEDLINE (Ovid) and Embase (Ovid) databases were created by a systematic review librarian (D.N.W.) to identify systematic reviews and meta-analyses regarding treatments for psoriasis (Figure 1). The searches were performed on June 2, 2020, and uploaded to Rayyan, a systematic review screening platform.¹⁶ After duplicates were removed, the records were screened for eligibility by 2 authors (C.H. and A.L.) using the titles and abstracts. Screening was conducted independently while each of these authors was masked to the other’s results; disagreements were resolved through discussion.

Eligibility Criteria—An article had to meet the following criteria for inclusion in our study: (1) be a systematic review with or without a meta-analysis; (2) relate to the treatment of psoriasis; and (3) be written in English and include human patients only. The PRISMA definition of systematic reviews and meta-analyses was applied.¹⁷

Training—Various training occurred throughout our study to ensure understanding of each step and mitigate subjectivity. Before beginning screening, 2 investigators (C.H. and A.L.) completed the Introduction to Systematic Review and Meta-Analysis course offered by Johns Hopkins University.¹⁸ They also underwent 2 days of online and in-person training on the definition and interpretation of the 9 most severe types of spin found in the abstracts of systematic reviews as defined by Yavchitz et al.⁹ Finally, they were trained to use A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) to appraise the methodological quality of each systematic review. Our protocol contained an outline of all training modules used.

Data Extraction—The investigators (C.H. and A.L.) analyzed included abstracts for the 9 most severe types of spin (Table 1). Data were extracted in a masked duplicate fashion using the Google form. AMSTAR-2 was used to assess systematic reviews for methodological quality. AMSTAR-2 is an appraisal tool consisting of a 16-item checklist for systematic reviews or meta-analyses. Scores range from critically low to high based on the methodological quality of the review. Interrater reliability of AMSTAR-2 scores has been moderate to high across studies. Construct validity coefficients have been high with the original AMSTAR instrument (r=0.91) and the Risk of Bias in Systematic Reviews instrument (r=0.84).¹⁹

During data extraction from each included systematic review, the following additional items were obtained: (1) the date the review was received; (2) intervention type (ie, pharmacologic, nonpharmacologic, surgery, light therapy, mixed); (3) the funding source(s) for each systematic review (ie, industry, private, public, none, not mentioned, hospital, a combination of funding not including industry, a combination of funding including industry, other); (4) whether the journal submission guidelines suggested adherence to PRISMA guidelines; (5) whether the review discussed adherence to PRISMA¹⁴ or PRISMA for Abstracts²⁰ (PRISMA-A); (6) the publishing journal’s 5-year impact factor; and (6) the country of the systematic review’s origin. When data extraction was complete, investigators (C.H. and A.L.) were unmasked and met to resolve any disagreements by discussion. Two authors (R.O. or M.V.) served as arbiters in the case that an agreement between C.H. and A.L. could not be reached.

Statistical Analysis—Frequencies and percentages were calculated to evaluate the most common types of spin found within systematic reviews and meta-analyses. One author (M.H.) prespecified the possibility of a binary logistic regression and calculated a power analysis to determine sample size, as stated in our protocol. Our final sample size of 173 was not powered to perform the multivariable logistic regression; therefore, we calculated unadjusted odds ratios to enable assessing relationships between the presence of spin in abstracts and the various study characteristics. We used Stata 16.1 for all analyses, and all analytic decisions can be found in our protocol.

Results

General Characteristics—Our systematic search of MEDLINE and Embase returned 3200 articles, of which 665 were duplicates that were removed. An additional 2253 articles were excluded during initial abstract and title screening, and full-text screening led to the exclusion of another 109 articles. In total, 173 systematic reviews were included for data extraction. Figure 2 illustrates the screening process with the rationale for all exclusions.

Of the 173 included systematic reviews and meta-analyses, 150 (86.7%) focused on pharmacologic interventions. The majority of studies did not mention adhering to PRISMA guidelines (125/173 [72.3%]), and the publishing journals recommended their authors adhere to PRISMA for only 66 (38.2%) of the included articles. For the articles that received funding (90/173 [52.0%]), industry sources were the most common funding source (40/90 [44.4%]), followed by private (27/90 [30%]) and public funding sources (23/90 [25.6%]). Of the remaining studies, 46 articles did not include a funding statement (46/83 [55.4%]), and 37 studies were not funded (37/83 [44.6%]). The average (SD) 5-year impact factor of our included journals was 4.68 (4.64). Systematic reviews were from 31 different countries. All studies were received by their respective journals between the years 2000 and 2020 (Table 2).

Abstracts Containing Spin—We found that 37 (21.4%) of the abstracts of systematic reviews focused on psoriasis treatments contained at least 1 type of spin. Some abstracts had more than 1 type; thus, a total of 51 different instances of spin were detected. Spin type 6—selective reporting of or overemphasis on harm outcomes or analysis favoring the safety of the experimental intervention—was the most common type ofspin, found in 19 of 173 abstracts (11.0%). The most severe type of spin—type 1 (conclusion contains recommendations for clinical practice not supported by the findings)—occurred in only 1 abstract (0.6%). Spin type 8 did not occur in any of the abstracts (Table 1). There was no statistically significant association between the presence of spin and any of the study characteristics (Table 2).

AMSTAR Ratings—After using AMSTAR-2 to appraise the included systematic reviews, we found that 6 (3.5%) of the 173 studies could be rated as high; 36 (20.8%) as moderate; 25 (14.5%) as low; and 106 (61.3%) as critically low. Of the 37 abstracts containing spin, 2 (5.4%) had an AMSTAR-2 rating of high, 10 (27%) had a rating of moderate, 6 (16.2%) had a rating of low, and 19 (51.4%) had a rating of critically low (Table 2). No statistically significant associations were seen between abstracts found to have spin and the AMSTAR-2 rating of the review.

Nearly all (160/173 [92.5%]) of the included reviews were compliant with the inclusion of Population, Intervention, Comparison, and Outcome (PICO) method. Only 17 of 173 (9.8%) reviews reported funding sources for the studies included. See Table 3 for all AMSTAR-2 items.

Comment

Primary Findings—We evaluated the abstracts of systematic reviews for the treatment of psoriasis and found that more than one-fifth of them contained spin. Our study contributes to the existing literature surrounding spin. Spin in randomized controlled trials is well documented across several fields of medicine, including otolaryngology,¹⁰ obesity medicine,¹² dermatology,²¹ anesthesiology,²² psychiatry,²³ orthopedics,²⁴ emergency medicine,²⁵ oncology,²⁶ and cardiology.²⁷ More recently, studies have emerged evaluating the presence of spin in systematic reviews. Specific to dermatology, one study found that 74% (84/113) of systematic reviews related to atopic dermatitis treatment contained spin.²⁸ Additionally, Ottwell et al¹³ identified spin in 31% (11/36) of the systematic reviews related to the treatment of acne vulgaris, which is similar to our results for systematic reviews focused on psoriasis treatments. When comparing the presence of spin in abstracts of systematic reviews from the field of dermatology with other specialties, dermatology-focused systematic reviews appear to contain more spin in the abstract than systematic reviews focused on tinnitus and glaucoma therapies.^29,30 However, systematic reviews from the field of dermatology appear to contain less spin than systematic reviews focused on therapies for lower back pain.³¹ For example, Nascimento et al³¹ found that 80% (53/66) of systematic reviews focused on low-back pain treatments contained spin.

Examples of Spin—The most common type of spin found in our study was type 6.⁹ An example of spin type 6 can be found in an article by Bai et al³² that investigated the short-term efficacy and safety of multiple interleukin inhibitors for the treatment of plaque psoriasis. The conclusion of the abstract states, “Risankizumab appeared to have relatively high efficacy and low risk.” However, in the results section, the authors showed that risankizumab had the highest risk of serious adverse events and was ranked highest for discontinuation because of adverse events when compared with other interleukin inhibitors. Here, the presence of spin in the abstract may mislead the reader to accept the “low risk” of risankizumab without understanding the study’s full results.³²

Another example of selective reporting of harm outcomes in a systematic review can be found in the article by Wu et al,³³ which focused on assessing IL-17 antagonists for the treatment of plaque psoriasis. The conclusion of the abstract indicated that IL-17 antagonists should be accepted as safe; however, in the results section, the authors discussed serious safety concerns with brodalumab, including the death of 4 patients from suicide.³³ This example of spin type 6 highlights how the overgeneralization of a drug’s safety profile neglects serious harm outcomes that are critical to patient safety. In fact, against the safety claims of Wu et al,³³ brodalumab later received a boxed warning from the US Food and Drug Administration after 6 patients died from suicide while receiving the drug, which led to early discontinuation of the trials.^34,35 Although studies suggest this relationship is not causal,^34-36 the purpose of our study was not to investigate this association but to highlight the importance of this finding. Thus, with this example of spin in mind, we offer recommendations that we believe will improve reporting in abstracts as well as quality of patient care.

Recommendations for Reporting in Abstracts—Regarding the boxed warning³⁷ for brodalumab because of suicidal ideation and behavior, the US Food and Drug Administration recommends that prior to prescribing brodalumab, clinicians consider the potential benefits and risks in patients with a history of depression and/or suicidal ideation or behavior. However, a clinician would not adequately assess the full risks and benefits when an abstract, such as that for the article by Wu et al,³³ contains spin through selectively reporting harm outcomes. Arguably, clinicians could just read the full text; however, research confirms that abstracts often are utilized by clinicians and commonly are used to guide clinical decisions.^7,38 It is reasonable that clinicians would use abstracts in this fashion because they provide a quick synopsis of the full article’s findings and are widely available to clinicians who may not have access to article databases. Initiatives are in place to improve the quality of reporting in an abstract, such as PRISMA-A,²⁰ but even this fails to address spin. In fact, it may suggest spin because checklist item 10 of PRISMA-A advises authors of systematic reviews to provide a “general interpretation of the results and important implications.” This item is concerning because it suggests that the authors interpret importance rather than the clinician who prescribes the drug and is ultimately responsible for patient safety. Therefore, we recommend a reform to abstract reporting and an update to PRISMA-A that leads authors to report all benefits and risks encountered instead of reporting what the authors define as important.

Strengths and Limitations—Our study has several strengths as well as limitations. One of these strengths is that our protocol was strictly adhered to; any deviations were noted and added as an amendment. Our protocol, data, and all study artifacts were made freely available online on the Open Science Framework to strengthen reproducibility (https://osf.io/zrxh8/). Investigators underwent training to ensure comprehension of spin and systematic review designs. All data were extracted in masked duplicate fashion per the Cochrane Handbook for Systematic Reviews of Interventions.³⁹

Regarding limitations, only 2 databases were searched—MEDLINE and Embase. Therefore, our screening process may not have included every available systematic review on the treatment of psoriasis. Journal impact factors may be inaccurate for the systematic reviews that were published earlier in our data date range; however, we attempted to negate this limitation by using a 5-year average. Our study characteristic regarding PRISMA adherence did not account for studies published before the PRISMA statement release; we also could not access prior submission guidelines to determine when a journal began recommending PRISMA adherence. Another limitation of our study was the intrinsic subjectivity behind spin. Some may disagree with our classifications. Finally, our cross-sectional design should not be generalized to study types that are not systematic reviews or published in other journals during different periods.

Conclusion

Evidence of spin was present in many of the abstracts of systematic reviews pertaining to the treatment of psoriasis. Future clinical research should investigate any reporting of spin and search for ways to better reduce spin within literature. Continued research is necessary to evaluate the presence of spin within dermatology and other specialties.

Psoriasis is an inflammatory autoimmune skin condition that affects approximately 125 million individuals worldwide, with approximately 8 million patients in the United States.¹ Psoriasis not only involves a cosmetic component but also comprises other comorbidities, such as psoriatic arthritis, cardiovascular disease, and psychiatric disorders, that can influence patient quality of life.^2-4 In addition, the costs associated with psoriasis are substantial, with an estimated economic burden of $35.2 billion in the United States in 2015.⁵ Given the prevalence of psoriasis and its many effects on patients, it is important that providers have high-quality evidence regarding efficacious treatment options.

Systematic reviews, which compile all available evidence on a subject to answer a specific question, represent the gold standard of research.⁶ However, studies have demonstrated that when referencing research literature, physicians tend to read only the abstract of a study rather than the entire article.^7,8 A study by Marcelo et al⁸ showed that residents at a tertiary care center answered clinical questions using only the abstract of a paper 69% of the time. Based on these findings, it is imperative that the results of systematic reviews be accurately reported in their abstracts because they can influence patient care.

Referencing only the abstracts of systematic reviews can be problematic if the abstract contains spin. Spin is a form of reporting that inappropriately highlights the benefits of a treatment with greater emphasis than what is shown by the results.⁹ Research has identified the presence of spin in the abstracts of randomized controlled trials.^10-12 For example, Cooper et al¹⁰ found that 70% (33/47) of abstracts in otolaryngology randomized controlled trials contained spin. Additionally, Arthur et al¹¹ and Austin et al¹² had similar findings within abstracts of orthopedic and obesity trials, where 44.8% (112/250) and 46.7% (21/45) contained spin, respectively. Ottwell et al¹³ found that the presence of spin in abstracts is not limited to randomized controlled trials; they demonstrated that the abstracts of nearly one-third (31% [11/36]) of systematic reviews focused on the treatment of acne vulgaris contained spin.

In our study, we aimed to evaluate the presence of spin in the abstracts of systematic reviews focused on the treatment of psoriasis.

Methods

Reproducibility and Reporting—Our study did not meet the regulatory definition for human subjects research per the US Code of Federal Regulations because the study did not involve human research subjects. The study also was not subject to review by the institutional review board. Our protocol, data set, analysis scripts, extraction forms, and other material related to the study have been placed on Open Science Framework to provide transparency and ensure reproducibility. To further allow for analytic reproducibility, our data set was given to an independent laboratory and reanalyzed with a masked approach. Our study was carried out alongside other studies assessing spin in systematic reviews regarding different specialties and disease states. Because these studies were similar in design, this methodology also has been reported elsewhere. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)¹⁴ and the guidelines for meta-epidemiological studies developed by Murad and Wang¹⁵ were used in drafting this article.

Search Strategy—The search strategies for the MEDLINE (Ovid) and Embase (Ovid) databases were created by a systematic review librarian (D.N.W.) to identify systematic reviews and meta-analyses regarding treatments for psoriasis (Figure 1). The searches were performed on June 2, 2020, and uploaded to Rayyan, a systematic review screening platform.¹⁶ After duplicates were removed, the records were screened for eligibility by 2 authors (C.H. and A.L.) using the titles and abstracts. Screening was conducted independently while each of these authors was masked to the other’s results; disagreements were resolved through discussion.

Eligibility Criteria—An article had to meet the following criteria for inclusion in our study: (1) be a systematic review with or without a meta-analysis; (2) relate to the treatment of psoriasis; and (3) be written in English and include human patients only. The PRISMA definition of systematic reviews and meta-analyses was applied.¹⁷

Training—Various training occurred throughout our study to ensure understanding of each step and mitigate subjectivity. Before beginning screening, 2 investigators (C.H. and A.L.) completed the Introduction to Systematic Review and Meta-Analysis course offered by Johns Hopkins University.¹⁸ They also underwent 2 days of online and in-person training on the definition and interpretation of the 9 most severe types of spin found in the abstracts of systematic reviews as defined by Yavchitz et al.⁹ Finally, they were trained to use A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) to appraise the methodological quality of each systematic review. Our protocol contained an outline of all training modules used.

Data Extraction—The investigators (C.H. and A.L.) analyzed included abstracts for the 9 most severe types of spin (Table 1). Data were extracted in a masked duplicate fashion using the Google form. AMSTAR-2 was used to assess systematic reviews for methodological quality. AMSTAR-2 is an appraisal tool consisting of a 16-item checklist for systematic reviews or meta-analyses. Scores range from critically low to high based on the methodological quality of the review. Interrater reliability of AMSTAR-2 scores has been moderate to high across studies. Construct validity coefficients have been high with the original AMSTAR instrument (r=0.91) and the Risk of Bias in Systematic Reviews instrument (r=0.84).¹⁹

During data extraction from each included systematic review, the following additional items were obtained: (1) the date the review was received; (2) intervention type (ie, pharmacologic, nonpharmacologic, surgery, light therapy, mixed); (3) the funding source(s) for each systematic review (ie, industry, private, public, none, not mentioned, hospital, a combination of funding not including industry, a combination of funding including industry, other); (4) whether the journal submission guidelines suggested adherence to PRISMA guidelines; (5) whether the review discussed adherence to PRISMA¹⁴ or PRISMA for Abstracts²⁰ (PRISMA-A); (6) the publishing journal’s 5-year impact factor; and (6) the country of the systematic review’s origin. When data extraction was complete, investigators (C.H. and A.L.) were unmasked and met to resolve any disagreements by discussion. Two authors (R.O. or M.V.) served as arbiters in the case that an agreement between C.H. and A.L. could not be reached.

Statistical Analysis—Frequencies and percentages were calculated to evaluate the most common types of spin found within systematic reviews and meta-analyses. One author (M.H.) prespecified the possibility of a binary logistic regression and calculated a power analysis to determine sample size, as stated in our protocol. Our final sample size of 173 was not powered to perform the multivariable logistic regression; therefore, we calculated unadjusted odds ratios to enable assessing relationships between the presence of spin in abstracts and the various study characteristics. We used Stata 16.1 for all analyses, and all analytic decisions can be found in our protocol.

Results

General Characteristics—Our systematic search of MEDLINE and Embase returned 3200 articles, of which 665 were duplicates that were removed. An additional 2253 articles were excluded during initial abstract and title screening, and full-text screening led to the exclusion of another 109 articles. In total, 173 systematic reviews were included for data extraction. Figure 2 illustrates the screening process with the rationale for all exclusions.

Of the 173 included systematic reviews and meta-analyses, 150 (86.7%) focused on pharmacologic interventions. The majority of studies did not mention adhering to PRISMA guidelines (125/173 [72.3%]), and the publishing journals recommended their authors adhere to PRISMA for only 66 (38.2%) of the included articles. For the articles that received funding (90/173 [52.0%]), industry sources were the most common funding source (40/90 [44.4%]), followed by private (27/90 [30%]) and public funding sources (23/90 [25.6%]). Of the remaining studies, 46 articles did not include a funding statement (46/83 [55.4%]), and 37 studies were not funded (37/83 [44.6%]). The average (SD) 5-year impact factor of our included journals was 4.68 (4.64). Systematic reviews were from 31 different countries. All studies were received by their respective journals between the years 2000 and 2020 (Table 2).

Abstracts Containing Spin—We found that 37 (21.4%) of the abstracts of systematic reviews focused on psoriasis treatments contained at least 1 type of spin. Some abstracts had more than 1 type; thus, a total of 51 different instances of spin were detected. Spin type 6—selective reporting of or overemphasis on harm outcomes or analysis favoring the safety of the experimental intervention—was the most common type ofspin, found in 19 of 173 abstracts (11.0%). The most severe type of spin—type 1 (conclusion contains recommendations for clinical practice not supported by the findings)—occurred in only 1 abstract (0.6%). Spin type 8 did not occur in any of the abstracts (Table 1). There was no statistically significant association between the presence of spin and any of the study characteristics (Table 2).

AMSTAR Ratings—After using AMSTAR-2 to appraise the included systematic reviews, we found that 6 (3.5%) of the 173 studies could be rated as high; 36 (20.8%) as moderate; 25 (14.5%) as low; and 106 (61.3%) as critically low. Of the 37 abstracts containing spin, 2 (5.4%) had an AMSTAR-2 rating of high, 10 (27%) had a rating of moderate, 6 (16.2%) had a rating of low, and 19 (51.4%) had a rating of critically low (Table 2). No statistically significant associations were seen between abstracts found to have spin and the AMSTAR-2 rating of the review.

Nearly all (160/173 [92.5%]) of the included reviews were compliant with the inclusion of Population, Intervention, Comparison, and Outcome (PICO) method. Only 17 of 173 (9.8%) reviews reported funding sources for the studies included. See Table 3 for all AMSTAR-2 items.

Comment

Primary Findings—We evaluated the abstracts of systematic reviews for the treatment of psoriasis and found that more than one-fifth of them contained spin. Our study contributes to the existing literature surrounding spin. Spin in randomized controlled trials is well documented across several fields of medicine, including otolaryngology,¹⁰ obesity medicine,¹² dermatology,²¹ anesthesiology,²² psychiatry,²³ orthopedics,²⁴ emergency medicine,²⁵ oncology,²⁶ and cardiology.²⁷ More recently, studies have emerged evaluating the presence of spin in systematic reviews. Specific to dermatology, one study found that 74% (84/113) of systematic reviews related to atopic dermatitis treatment contained spin.²⁸ Additionally, Ottwell et al¹³ identified spin in 31% (11/36) of the systematic reviews related to the treatment of acne vulgaris, which is similar to our results for systematic reviews focused on psoriasis treatments. When comparing the presence of spin in abstracts of systematic reviews from the field of dermatology with other specialties, dermatology-focused systematic reviews appear to contain more spin in the abstract than systematic reviews focused on tinnitus and glaucoma therapies.^29,30 However, systematic reviews from the field of dermatology appear to contain less spin than systematic reviews focused on therapies for lower back pain.³¹ For example, Nascimento et al³¹ found that 80% (53/66) of systematic reviews focused on low-back pain treatments contained spin.

Examples of Spin—The most common type of spin found in our study was type 6.⁹ An example of spin type 6 can be found in an article by Bai et al³² that investigated the short-term efficacy and safety of multiple interleukin inhibitors for the treatment of plaque psoriasis. The conclusion of the abstract states, “Risankizumab appeared to have relatively high efficacy and low risk.” However, in the results section, the authors showed that risankizumab had the highest risk of serious adverse events and was ranked highest for discontinuation because of adverse events when compared with other interleukin inhibitors. Here, the presence of spin in the abstract may mislead the reader to accept the “low risk” of risankizumab without understanding the study’s full results.³²

Another example of selective reporting of harm outcomes in a systematic review can be found in the article by Wu et al,³³ which focused on assessing IL-17 antagonists for the treatment of plaque psoriasis. The conclusion of the abstract indicated that IL-17 antagonists should be accepted as safe; however, in the results section, the authors discussed serious safety concerns with brodalumab, including the death of 4 patients from suicide.³³ This example of spin type 6 highlights how the overgeneralization of a drug’s safety profile neglects serious harm outcomes that are critical to patient safety. In fact, against the safety claims of Wu et al,³³ brodalumab later received a boxed warning from the US Food and Drug Administration after 6 patients died from suicide while receiving the drug, which led to early discontinuation of the trials.^34,35 Although studies suggest this relationship is not causal,^34-36 the purpose of our study was not to investigate this association but to highlight the importance of this finding. Thus, with this example of spin in mind, we offer recommendations that we believe will improve reporting in abstracts as well as quality of patient care.

Recommendations for Reporting in Abstracts—Regarding the boxed warning³⁷ for brodalumab because of suicidal ideation and behavior, the US Food and Drug Administration recommends that prior to prescribing brodalumab, clinicians consider the potential benefits and risks in patients with a history of depression and/or suicidal ideation or behavior. However, a clinician would not adequately assess the full risks and benefits when an abstract, such as that for the article by Wu et al,³³ contains spin through selectively reporting harm outcomes. Arguably, clinicians could just read the full text; however, research confirms that abstracts often are utilized by clinicians and commonly are used to guide clinical decisions.^7,38 It is reasonable that clinicians would use abstracts in this fashion because they provide a quick synopsis of the full article’s findings and are widely available to clinicians who may not have access to article databases. Initiatives are in place to improve the quality of reporting in an abstract, such as PRISMA-A,²⁰ but even this fails to address spin. In fact, it may suggest spin because checklist item 10 of PRISMA-A advises authors of systematic reviews to provide a “general interpretation of the results and important implications.” This item is concerning because it suggests that the authors interpret importance rather than the clinician who prescribes the drug and is ultimately responsible for patient safety. Therefore, we recommend a reform to abstract reporting and an update to PRISMA-A that leads authors to report all benefits and risks encountered instead of reporting what the authors define as important.

Strengths and Limitations—Our study has several strengths as well as limitations. One of these strengths is that our protocol was strictly adhered to; any deviations were noted and added as an amendment. Our protocol, data, and all study artifacts were made freely available online on the Open Science Framework to strengthen reproducibility (https://osf.io/zrxh8/). Investigators underwent training to ensure comprehension of spin and systematic review designs. All data were extracted in masked duplicate fashion per the Cochrane Handbook for Systematic Reviews of Interventions.³⁹

Regarding limitations, only 2 databases were searched—MEDLINE and Embase. Therefore, our screening process may not have included every available systematic review on the treatment of psoriasis. Journal impact factors may be inaccurate for the systematic reviews that were published earlier in our data date range; however, we attempted to negate this limitation by using a 5-year average. Our study characteristic regarding PRISMA adherence did not account for studies published before the PRISMA statement release; we also could not access prior submission guidelines to determine when a journal began recommending PRISMA adherence. Another limitation of our study was the intrinsic subjectivity behind spin. Some may disagree with our classifications. Finally, our cross-sectional design should not be generalized to study types that are not systematic reviews or published in other journals during different periods.

Conclusion

Evidence of spin was present in many of the abstracts of systematic reviews pertaining to the treatment of psoriasis. Future clinical research should investigate any reporting of spin and search for ways to better reduce spin within literature. Continued research is necessary to evaluate the presence of spin within dermatology and other specialties.

Psoriasis is an inflammatory autoimmune skin condition that affects approximately 125 million individuals worldwide, with approximately 8 million patients in the United States.¹ Psoriasis not only involves a cosmetic component but also comprises other comorbidities, such as psoriatic arthritis, cardiovascular disease, and psychiatric disorders, that can influence patient quality of life.^2-4 In addition, the costs associated with psoriasis are substantial, with an estimated economic burden of $35.2 billion in the United States in 2015.⁵ Given the prevalence of psoriasis and its many effects on patients, it is important that providers have high-quality evidence regarding efficacious treatment options.

Systematic reviews, which compile all available evidence on a subject to answer a specific question, represent the gold standard of research.⁶ However, studies have demonstrated that when referencing research literature, physicians tend to read only the abstract of a study rather than the entire article.^7,8 A study by Marcelo et al⁸ showed that residents at a tertiary care center answered clinical questions using only the abstract of a paper 69% of the time. Based on these findings, it is imperative that the results of systematic reviews be accurately reported in their abstracts because they can influence patient care.

Referencing only the abstracts of systematic reviews can be problematic if the abstract contains spin. Spin is a form of reporting that inappropriately highlights the benefits of a treatment with greater emphasis than what is shown by the results.⁹ Research has identified the presence of spin in the abstracts of randomized controlled trials.^10-12 For example, Cooper et al¹⁰ found that 70% (33/47) of abstracts in otolaryngology randomized controlled trials contained spin. Additionally, Arthur et al¹¹ and Austin et al¹² had similar findings within abstracts of orthopedic and obesity trials, where 44.8% (112/250) and 46.7% (21/45) contained spin, respectively. Ottwell et al¹³ found that the presence of spin in abstracts is not limited to randomized controlled trials; they demonstrated that the abstracts of nearly one-third (31% [11/36]) of systematic reviews focused on the treatment of acne vulgaris contained spin.

In our study, we aimed to evaluate the presence of spin in the abstracts of systematic reviews focused on the treatment of psoriasis.

Methods

Reproducibility and Reporting—Our study did not meet the regulatory definition for human subjects research per the US Code of Federal Regulations because the study did not involve human research subjects. The study also was not subject to review by the institutional review board. Our protocol, data set, analysis scripts, extraction forms, and other material related to the study have been placed on Open Science Framework to provide transparency and ensure reproducibility. To further allow for analytic reproducibility, our data set was given to an independent laboratory and reanalyzed with a masked approach. Our study was carried out alongside other studies assessing spin in systematic reviews regarding different specialties and disease states. Because these studies were similar in design, this methodology also has been reported elsewhere. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)¹⁴ and the guidelines for meta-epidemiological studies developed by Murad and Wang¹⁵ were used in drafting this article.

Search Strategy—The search strategies for the MEDLINE (Ovid) and Embase (Ovid) databases were created by a systematic review librarian (D.N.W.) to identify systematic reviews and meta-analyses regarding treatments for psoriasis (Figure 1). The searches were performed on June 2, 2020, and uploaded to Rayyan, a systematic review screening platform.¹⁶ After duplicates were removed, the records were screened for eligibility by 2 authors (C.H. and A.L.) using the titles and abstracts. Screening was conducted independently while each of these authors was masked to the other’s results; disagreements were resolved through discussion.

Eligibility Criteria—An article had to meet the following criteria for inclusion in our study: (1) be a systematic review with or without a meta-analysis; (2) relate to the treatment of psoriasis; and (3) be written in English and include human patients only. The PRISMA definition of systematic reviews and meta-analyses was applied.¹⁷

Training—Various training occurred throughout our study to ensure understanding of each step and mitigate subjectivity. Before beginning screening, 2 investigators (C.H. and A.L.) completed the Introduction to Systematic Review and Meta-Analysis course offered by Johns Hopkins University.¹⁸ They also underwent 2 days of online and in-person training on the definition and interpretation of the 9 most severe types of spin found in the abstracts of systematic reviews as defined by Yavchitz et al.⁹ Finally, they were trained to use A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) to appraise the methodological quality of each systematic review. Our protocol contained an outline of all training modules used.

Data Extraction—The investigators (C.H. and A.L.) analyzed included abstracts for the 9 most severe types of spin (Table 1). Data were extracted in a masked duplicate fashion using the Google form. AMSTAR-2 was used to assess systematic reviews for methodological quality. AMSTAR-2 is an appraisal tool consisting of a 16-item checklist for systematic reviews or meta-analyses. Scores range from critically low to high based on the methodological quality of the review. Interrater reliability of AMSTAR-2 scores has been moderate to high across studies. Construct validity coefficients have been high with the original AMSTAR instrument (r=0.91) and the Risk of Bias in Systematic Reviews instrument (r=0.84).¹⁹

During data extraction from each included systematic review, the following additional items were obtained: (1) the date the review was received; (2) intervention type (ie, pharmacologic, nonpharmacologic, surgery, light therapy, mixed); (3) the funding source(s) for each systematic review (ie, industry, private, public, none, not mentioned, hospital, a combination of funding not including industry, a combination of funding including industry, other); (4) whether the journal submission guidelines suggested adherence to PRISMA guidelines; (5) whether the review discussed adherence to PRISMA¹⁴ or PRISMA for Abstracts²⁰ (PRISMA-A); (6) the publishing journal’s 5-year impact factor; and (6) the country of the systematic review’s origin. When data extraction was complete, investigators (C.H. and A.L.) were unmasked and met to resolve any disagreements by discussion. Two authors (R.O. or M.V.) served as arbiters in the case that an agreement between C.H. and A.L. could not be reached.

Statistical Analysis—Frequencies and percentages were calculated to evaluate the most common types of spin found within systematic reviews and meta-analyses. One author (M.H.) prespecified the possibility of a binary logistic regression and calculated a power analysis to determine sample size, as stated in our protocol. Our final sample size of 173 was not powered to perform the multivariable logistic regression; therefore, we calculated unadjusted odds ratios to enable assessing relationships between the presence of spin in abstracts and the various study characteristics. We used Stata 16.1 for all analyses, and all analytic decisions can be found in our protocol.

Results

General Characteristics—Our systematic search of MEDLINE and Embase returned 3200 articles, of which 665 were duplicates that were removed. An additional 2253 articles were excluded during initial abstract and title screening, and full-text screening led to the exclusion of another 109 articles. In total, 173 systematic reviews were included for data extraction. Figure 2 illustrates the screening process with the rationale for all exclusions.

Of the 173 included systematic reviews and meta-analyses, 150 (86.7%) focused on pharmacologic interventions. The majority of studies did not mention adhering to PRISMA guidelines (125/173 [72.3%]), and the publishing journals recommended their authors adhere to PRISMA for only 66 (38.2%) of the included articles. For the articles that received funding (90/173 [52.0%]), industry sources were the most common funding source (40/90 [44.4%]), followed by private (27/90 [30%]) and public funding sources (23/90 [25.6%]). Of the remaining studies, 46 articles did not include a funding statement (46/83 [55.4%]), and 37 studies were not funded (37/83 [44.6%]). The average (SD) 5-year impact factor of our included journals was 4.68 (4.64). Systematic reviews were from 31 different countries. All studies were received by their respective journals between the years 2000 and 2020 (Table 2).

Abstracts Containing Spin—We found that 37 (21.4%) of the abstracts of systematic reviews focused on psoriasis treatments contained at least 1 type of spin. Some abstracts had more than 1 type; thus, a total of 51 different instances of spin were detected. Spin type 6—selective reporting of or overemphasis on harm outcomes or analysis favoring the safety of the experimental intervention—was the most common type ofspin, found in 19 of 173 abstracts (11.0%). The most severe type of spin—type 1 (conclusion contains recommendations for clinical practice not supported by the findings)—occurred in only 1 abstract (0.6%). Spin type 8 did not occur in any of the abstracts (Table 1). There was no statistically significant association between the presence of spin and any of the study characteristics (Table 2).

AMSTAR Ratings—After using AMSTAR-2 to appraise the included systematic reviews, we found that 6 (3.5%) of the 173 studies could be rated as high; 36 (20.8%) as moderate; 25 (14.5%) as low; and 106 (61.3%) as critically low. Of the 37 abstracts containing spin, 2 (5.4%) had an AMSTAR-2 rating of high, 10 (27%) had a rating of moderate, 6 (16.2%) had a rating of low, and 19 (51.4%) had a rating of critically low (Table 2). No statistically significant associations were seen between abstracts found to have spin and the AMSTAR-2 rating of the review.

Nearly all (160/173 [92.5%]) of the included reviews were compliant with the inclusion of Population, Intervention, Comparison, and Outcome (PICO) method. Only 17 of 173 (9.8%) reviews reported funding sources for the studies included. See Table 3 for all AMSTAR-2 items.

Comment

Primary Findings—We evaluated the abstracts of systematic reviews for the treatment of psoriasis and found that more than one-fifth of them contained spin. Our study contributes to the existing literature surrounding spin. Spin in randomized controlled trials is well documented across several fields of medicine, including otolaryngology,¹⁰ obesity medicine,¹² dermatology,²¹ anesthesiology,²² psychiatry,²³ orthopedics,²⁴ emergency medicine,²⁵ oncology,²⁶ and cardiology.²⁷ More recently, studies have emerged evaluating the presence of spin in systematic reviews. Specific to dermatology, one study found that 74% (84/113) of systematic reviews related to atopic dermatitis treatment contained spin.²⁸ Additionally, Ottwell et al¹³ identified spin in 31% (11/36) of the systematic reviews related to the treatment of acne vulgaris, which is similar to our results for systematic reviews focused on psoriasis treatments. When comparing the presence of spin in abstracts of systematic reviews from the field of dermatology with other specialties, dermatology-focused systematic reviews appear to contain more spin in the abstract than systematic reviews focused on tinnitus and glaucoma therapies.^29,30 However, systematic reviews from the field of dermatology appear to contain less spin than systematic reviews focused on therapies for lower back pain.³¹ For example, Nascimento et al³¹ found that 80% (53/66) of systematic reviews focused on low-back pain treatments contained spin.

Examples of Spin—The most common type of spin found in our study was type 6.⁹ An example of spin type 6 can be found in an article by Bai et al³² that investigated the short-term efficacy and safety of multiple interleukin inhibitors for the treatment of plaque psoriasis. The conclusion of the abstract states, “Risankizumab appeared to have relatively high efficacy and low risk.” However, in the results section, the authors showed that risankizumab had the highest risk of serious adverse events and was ranked highest for discontinuation because of adverse events when compared with other interleukin inhibitors. Here, the presence of spin in the abstract may mislead the reader to accept the “low risk” of risankizumab without understanding the study’s full results.³²

Another example of selective reporting of harm outcomes in a systematic review can be found in the article by Wu et al,³³ which focused on assessing IL-17 antagonists for the treatment of plaque psoriasis. The conclusion of the abstract indicated that IL-17 antagonists should be accepted as safe; however, in the results section, the authors discussed serious safety concerns with brodalumab, including the death of 4 patients from suicide.³³ This example of spin type 6 highlights how the overgeneralization of a drug’s safety profile neglects serious harm outcomes that are critical to patient safety. In fact, against the safety claims of Wu et al,³³ brodalumab later received a boxed warning from the US Food and Drug Administration after 6 patients died from suicide while receiving the drug, which led to early discontinuation of the trials.^34,35 Although studies suggest this relationship is not causal,^34-36 the purpose of our study was not to investigate this association but to highlight the importance of this finding. Thus, with this example of spin in mind, we offer recommendations that we believe will improve reporting in abstracts as well as quality of patient care.

Recommendations for Reporting in Abstracts—Regarding the boxed warning³⁷ for brodalumab because of suicidal ideation and behavior, the US Food and Drug Administration recommends that prior to prescribing brodalumab, clinicians consider the potential benefits and risks in patients with a history of depression and/or suicidal ideation or behavior. However, a clinician would not adequately assess the full risks and benefits when an abstract, such as that for the article by Wu et al,³³ contains spin through selectively reporting harm outcomes. Arguably, clinicians could just read the full text; however, research confirms that abstracts often are utilized by clinicians and commonly are used to guide clinical decisions.^7,38 It is reasonable that clinicians would use abstracts in this fashion because they provide a quick synopsis of the full article’s findings and are widely available to clinicians who may not have access to article databases. Initiatives are in place to improve the quality of reporting in an abstract, such as PRISMA-A,²⁰ but even this fails to address spin. In fact, it may suggest spin because checklist item 10 of PRISMA-A advises authors of systematic reviews to provide a “general interpretation of the results and important implications.” This item is concerning because it suggests that the authors interpret importance rather than the clinician who prescribes the drug and is ultimately responsible for patient safety. Therefore, we recommend a reform to abstract reporting and an update to PRISMA-A that leads authors to report all benefits and risks encountered instead of reporting what the authors define as important.

Strengths and Limitations—Our study has several strengths as well as limitations. One of these strengths is that our protocol was strictly adhered to; any deviations were noted and added as an amendment. Our protocol, data, and all study artifacts were made freely available online on the Open Science Framework to strengthen reproducibility (https://osf.io/zrxh8/). Investigators underwent training to ensure comprehension of spin and systematic review designs. All data were extracted in masked duplicate fashion per the Cochrane Handbook for Systematic Reviews of Interventions.³⁹

Regarding limitations, only 2 databases were searched—MEDLINE and Embase. Therefore, our screening process may not have included every available systematic review on the treatment of psoriasis. Journal impact factors may be inaccurate for the systematic reviews that were published earlier in our data date range; however, we attempted to negate this limitation by using a 5-year average. Our study characteristic regarding PRISMA adherence did not account for studies published before the PRISMA statement release; we also could not access prior submission guidelines to determine when a journal began recommending PRISMA adherence. Another limitation of our study was the intrinsic subjectivity behind spin. Some may disagree with our classifications. Finally, our cross-sectional design should not be generalized to study types that are not systematic reviews or published in other journals during different periods.

Conclusion

Evidence of spin was present in many of the abstracts of systematic reviews pertaining to the treatment of psoriasis. Future clinical research should investigate any reporting of spin and search for ways to better reduce spin within literature. Continued research is necessary to evaluate the presence of spin within dermatology and other specialties.

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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