Not All Biologics Equally Safe for Patients With Psoriasis

Lara C. Pullen, PhD

May 19, 2015

A report of results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) suggests that treatment with adalimumab and infliximab are associated with a higher risk for serious infections than nonmethotrexate and nonbiologic therapies. The registry found no increased risk from treatment with ustekinumab and etanercept.

Robert E. Kalb, MD, from the State University of New York at Buffalo, and colleagues published their analysis of the multicenter, longitudinal disease registry online May 13 in JAMA Dermatology. The PSOLAR enrolled 11,466 patients, 9154 of whom were treated with biologic agents.

The registry was designed to characterize the relative risks for serious infection in patients with psoriasis who were treated with various systemic therapies. Because PSOLAR was a registry and not a randomized trial, treatment was chosen entirely by the prescriber. The registry opened in June 2007, and data were collected through August 2013.

The cumulative incidence rate of serious infections was 1.45 per 100 patient years across all treatment groups.

Table. Cumulative Incidence Rate of Serious Infection by Treatment Group

Treatment Serious Infection per 100 Patient-Years
Ustekinumab 0.83
Etanercept 1.47
Adalimumab 1.97
Infliximab 2.49
Nonmethotrexate/nonbiologics 1.05
Methotrexate/biologics 1.28

In a multivariable analysis, the researchers found that serious infection risk was significantly higher in patients treated with infliximab (hazard ratio, 2.51; 95% confidence interval, 1.45 - 4.33; P < .001) or adalimumab (hazard ratio, 2.13; 95% confidence interval, 1.33 - 3.41; P = .002) compared with patients treated with nonmethotrexate or nonbiologics. The risk was not significantly elevated for those taking ustekinumab or etanercept.

"This article does a good job of comparing the infection risk of the most used psoriatic biologic agents across patients," explained Lisa Zaba, MD, PhD, from Stanford School of Medicine in Palo Alto, California, to Medscape Medical News. "As a first-line agent for psoriatic arthritis, I will preferentially use etanercept over adalimumab, which dermatologists currently tend to view as comparable-risk medications," she added.

The investigators note that the results are consistent with previous studies that have documented an association between the use of tumor necrosis factor (TNF) inhibitors and serious infection.

Other factors that were significantly associated with infection included increasing age, diabetes mellitus, history of significant infection, and the use of tobacco. Presence of psoriatic arthritis was not significantly associated with serious infection risk.

When asked about the differences between the medications, Dr Zaba explained to Medscape Medical News, "The most obvious difference in mechanism is between the anti-TNF agents and ustekinumab. Ustekinumab targets the common p40 subunit, which is shared between interleukin 12 and interleukin 23 cytokines, which are specifically involved in psoriasis pathogenesis. TNF, on the other hand, is a more global cytokine, which is involved in many pathways of inflammation, including pathways of arthritis and atherosclerosis."

She also explained that etanercept is a low-affinity TNF receptor fusion protein. Adalimumab and infliximab are high-affinity anti-TNF monoclonal antibodies. Differences between adalimumab and infliximab may be result from differences in affinity or more subtle differences in the interaction of the constant portion of the antibodies with other immune cells.

This study was sponsored by Janssen Scientific Affairs, LLC. Dr Kalb reported being a consultant for AbbVie, Amgen, Celgene, Janssen Biotech, Leo Pharma, Pfizer, and Taro Pharmaceuticals; reported serving on the dermatology safety monitoring board for ApoPharma and Eli Lilly; and reported receiving grants for clinical research from AbbVie, Amgen, Janssen Biotech, and Merck. Several coauthors reported various financial relationships with Johnson & Johnson, AbGenomics, AbbVie, Amgen, Canfite Biopharma, Celgene, Coronado Biosciences, Dermipsor, Eli Lilly, Forward Pharma, GSK-Stiefel, Janssen Biotech, Leo Pharma, Maruho, Meda, Merck, Novartis, Pfizer, Taro Pharmaceuticals, UCB Pharma, Incyte, Dexcel, Medison, Neopharm, Perrigo, Rafa, Dermira, Boehringer-Ingleheim, Sandoz, Anacor, Coherus, Galderma, Stiefel, and Tolmar. Dr Zaba has disclosed no relevant financial relationships.

JAMA Dermatol. Published online May 13, 2015. Full text

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