Level 2: Mid-level evidence

The American Academy of Dermatology recommends oral methotrexate for severe psoriasis in patients with poor response to other therapies (J Am Acad Dermatol. 2009;60:643-659), but its efficacy is limited, it can be poorly tolerated and it has a long list of contraindications.

A recent trial compared the efficacy of briakinumab, an experimental human monoclonal antibody, and methotrexate in 317 patients with moderate or severe psoriasis (N Engl J Med. 2011;365:1586-1596). Patients were randomized to monthly subcutaneous injections of briakinumab vs. oral methotrexate plus folate for 52 weeks. Each group received placebos for the other intervention. The primary outcome was clinically meaningful response (defined as ≥ 75% improvement in score on Psoriasis Area-and-Severity Index [PASI-75]).

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A total of 151 patients (48%) completed the trial. Most of the dropouts in both groups were for lack of efficacy (22 of 48 for briakinumab and 95 of 118 for methotrexate). Missing data were classified as “no response” in an intention-to-treat analysis.

At 52 weeks, significantly more patients achieved PASI-75 in the briakinumab group (66.2% vs. 23.9%; P<0.001, NNT 3). Briakinumab was also associated with a greater rate of patients achieving a physician’s global assessment of either “no apparent disease” or “minimal disease” (63% vs. 20.2%; P<0.001; NNT 3) and with a greater rate of clinically meaningful improvement in quality of life (56.5% vs. 18.4%; P<0.001; NNT 3). Rates of serious adverse events (including infections and cancer) were higher in the briakinumab group, but the differences were not statistically significant. The pattern of results was similar at an interim analysis at 24 weeks.

In another recent trial, response rates at 12 weeks were significantly higher with briakinumab than with etanercept or placebo (Br J Dermatol. 2011;165:652-660). Briakinumab is not yet available for use.

Alan Ehrlich, MD, is a deputy editor for DynaMed, a database that provides evidence-based information on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals. He is also an assistant clinical professor in Family Medicine at the University of Massachusetts Medical School in Worcester.