Good results from two studies, but questions remain

Researchers of two recent studies — from Denmark and the U.S. — sought to determine whether biosimilars are as effective as their biologic originators in the treatment of psoriasis and of hidradenitis suppurativa.

In the first study, published in JAMA Dermatology, researchers from Denmark concluded that the biosimilar for adalimumab may be as effective as adalimumab originator for the treatment of patients with psoriasis. Patients who switched to an adalimumab biosimilar had similar drug retention as adalimumab originator, but more dermatologic adverse events.

“In Denmark, a national guideline dictated a nonmedical mandatory switch of all adults with psoriasis treated with adalimumab originator to GP2017 in the Eastern part of Denmark and SB5 in the Western part of Denmark by November 2018 and a switch from adalimumab originator to ABP 501 for children by November 2018. This guideline provided a unique opportunity to assess real-world data on a mandatory switch of adalimumab originator to adalimumab biosimilars,” wrote Nikolai Loft, MD, of The University of Copenhagen, Hellerup, Denmark, and colleagues.

Using the Biological Treatment in Danish Dermatology (DERMBIO) registry, Loft and colleagues identified 348 patients (mean age: 52.2 years; 72.1% male) with psoriasis who had been switched to an adalimumab biosimilar and compared them with 378 patients who remained on adalimumab originator (mean age: 51.1 years; 72.0% male).

After one year of treatment, the drug retention rate in those switched to the adalimumab biosimilar was 92.0%, compared with 92.1% in those who remained on the adalimumab originator. The number of patients who experienced adverse events after switching to adalimumab biosimilars was significantly higher compared with those treated with adalimumab originator (6.6% versus 0.8%, respectively; P˂0.001).

Crude hazard ratios for all cases of drug discontinuation were 1.02 (95% CI: 0.61-1.70; P=0.94), and for insufficient effect 0.82 (95% CI: 0.39-1.73; P=0.60). When discontinuation for adverse events was analyzed, the crude hazard ratio was 1.41 in those switching to the adalimumab biosimilar compared with patients treated with adalimumab originator (95% CI: 0.52-3.77; P=0.50).

In a second study, researchers from the University of North Carolina at Chapel Hill found similar and significant disease improvement after treatment with both infliximab and infliximab-abda in patients with hidradenitis suppurativa and concluded that infliximab-abda may be a viable treatment option for the disease.

Christopher John Sayed, MD, and colleagues conducted a retrospective study in 34 patients with hidradenitis suppurativa, who received continuous doses of infliximab or infliximab-abda for at least 10 weeks. The primary outcome was Hidradenitis Suppurative Clinical Response, defined as an at least 50% decrease in inflammatory nodule counts with no increase in the number of abscesses or draining sinuses.

Twenty patients were treated with infliximab (mean age: 42.2 years; 85% women), and 14 with infliximab-abda (mean age: 35.5 years; 93% women). In all, 71% of patients treated with infliximab-abda achieve a Hidradenitis Suppurative Clinical Response, compared with 60% patients treated with infliximab (P=0.47).

Limitations of the study from Loft et al include the inclusion of only Danish patients, the inability to assess individual adverse events and less rigorous surveillance of them, the inability to assess the efficacy of individual adalimumab biosimilar versions, and missing data.

Limitations of the study from Sayed and colleagues include its small sample size and retrospective nature, the use of concomitant medications by some patients, and the risk of selection bias.

“The hope for biosimilars is that they will markedly lower the cost of treatment and make these expensive therapies more accessible so that we may treat more patients with psoriasis, psoriatic arthritis, hidradenitis, or other dermatologic conditions responsive to these therapies. But are biosimilars equal in effectiveness and safety to their originator drugs?” queried Mark Lebwohl, MD, of the Icahn School of Medicine at Mount Sinai, New York, in an editorial accompanying the two studies.

Regarding the equivalence of the biosimilar and its originator drug in the study from Loft and colleagues, Lebwohl wrote: “The 2 studies in this issue of JAMA Dermatology and many other published trials would argue that they are, but the pharmaceutical manufacturers of the originator drugs may legitimately contend that results reported for rheumatoid arthritis do not necessarily predict results in psoriasis.”

He also noted the small size of the second study from Sayed et al, and the significantly larger proportion of patients treated with the originator drug who showed improvement compared with the biosimilar (71% versus 60%, respectively).

“This result may lead skeptics to question the bioequivalence of the 2 agents tested. Other questions arise regarding the interchangeability of originator and biosimilar drugs. There are concerns about increased immunogenicity when switching back and forth between originator drugs and biosimilars, but that concern has not been substantiated in some trials. And even the data reported in the Danish nationwide study showed an increase in adverse events with the biosimilar compared with the originator drug,” wrote Lebwohl.

Ultimately, he concluded, more studies are needed and many factors need to be considered before biosimilars prove their worth in the treatment of dermatologic disorders like psoriasis and hidradenitis suppurativa.

  1. In a study from Danish researchers, patients who switched to an adalimumab biosimilar had similar drug retention as adalimumab originator, but they also suffered more dermatologic adverse events.

  2. In a second study, U.S. researchers documented similar and significant disease improvement after treatment with both infliximab and infliximab-abda in patients with hidradenitis suppurativa and concluded that infliximab-abda may be a viable treatment option for hidradenitis suppurativa.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

The Biological Treatment in Danish Dermatology (DERMBIO) registry has entered into agreements with Abbvie, Eli Lily, Almirall, UCB, Novartis, Janssen, and Leo Pharma. They received postmarketing data but had no influence on the data collection, statistical analyses, manuscript preparation, or decision to submit.

Loft has received personal fee from Eli Lilly and Janssen outside the submitted work.

The study from Sayed and colleagues was supported by a grant from the National Institute of Health Public Health Service Ruth L. Kirschstein National Research Service Award.

Sayed has received personal fees or personal fees paid to the institution from AbbVie, Novartis, Chemocentryx, GlaxoSmithKline, Incyte, InflaRx, and UCB.

Lebwohl is an employee of Mount Sinai; receiving research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant, Eli Lilly and Company, Incyte, Janssen Research & Development, Ortho Dermatologics, Regeneron, and UCB; and receiving personal fees from Aditum Bio, AnaptysBio, Almirall, Arcutis, Aristea, Arrive technology, Avotres Therapeutics, BioMx, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Dr. Reddy’s, Evelo, Evommune, Facilitate International Dermatologic Education, Forte, Foundation for Research and Education in Dermatology, Helsinn, LEO Pharma, Meiji, Mindera, Pfizer, and Verrica outside the submitted work.

Cat ID: 10

Topic ID: 75,10,730,10,105,192,925