Briakinumab More Effective Than Methotrexate in Psoriasis

Laura Newman 

October 26, 2011

October 26, 2011 — Briakinumab (Abbott) has been proven to be a far more effective drug than methotrexate for improving moderate to severe psoriasis, according to a 52-week, head-to-head-trial published in the October 27 issue of the New England Journal of Medicine. But an outside expert criticized the trial for including too few patients and criticized Abbott for hiring a ghost writer to prepare the first draft of the article.

"There have been no head-to-head trials in the short term and intermediate term," Kim A. Papp, MD, told Medscape Medical News. "From that aspect alone, this is an important and useful piece of work, and it will be instrumental in supplying effectiveness and tolerability information" on both drugs.

Dr. Papp, a dermatologist at Probity Medical Research, Inc, in Windsor, Ontario, Canada, is one of the co-investigators on the trial, which involved 7 researchers from Canada and Europe. Abbott withdrew its US Food and Drug Administration application for the drug in January 2011 after the agency requested additional safety information.

A total of 317 patients with moderate to severe psoriasis were randomly assigned to 2 treatment groups in the multicenter trial. The briakinumab group included 154 patients who received 200 mg of the biologic at weeks 0 and 4 and 100 mg at week 8 and every 4 weeks thereafter. The methotrexate group included 163 patients who received 5 to 25 mg weekly.

Results from the study reveal that at 24 weeks, a total of 81.8% briakinumab-treated patients showed improvement of at least 75% in the Psoriasis Area and Severity Index (PASI) score, and 80.5% scored 0 (no evidence of disease, or clear) or 1 (minimal disease) in the physician's global assessment compared with 39.9% and 34.4%, respectively, in patients receiving methotrexate (P < .001 for both comparisons).

At week 52, 66.2% briakinumab-treated patients vs 23.9% of the patients in the methotrexate group demonstrated at least a 75% improvement in the PASI score (P < .0001 for comparison at both 24 and 52 weeks). The median time to a 75% improvement in PASI score was significantly shorter in patients treated with briakinumab, at 56 days vs 140 days (P < .001). Mean improvements in the Dermatology Life Quality Index were significantly better for the briakinumab group vs the methotrexate group at all points (P < .001).

Adverse events in the briakinumab-treated patients were not significantly worse than those in patients treated with methotrexate. Specifically, 12 patients in the briakinumab group (7.8%) stopped the study because of adverse events vs 10 patients in the methotrexate group (6.1%). Adverse events in the briakinumab group were serious for 5 patients (gastrointestinal hypomotility coincident with legionaella infection, breast cancer, breast neoplasm [intraductal carcinoma], prostate cancer, and herpes zoster).

Of the 10 methotrexate-treated patients who withdrew, the adverse events were serious in 5 patients (increased hepatic enzyme levels and hepatitis, sacroiliitis, diverticulitis, erythrodermic psoriasis, and angioedema and urticaria). No major cardiovascular events or cardiovascular-related deaths occurred in the study. When adverse events were counted, including the open-label continuation study, serious adverse events rose to 13.6% for briakinumab-treated patients, or 11.3 events per 100 patient-years; serious infections in 3.2% (2.8 events/100 person-years); and cancers in 3.2% (2.0 events/100 person-years).

Major adverse cardiac events (MACEs) have been raised as a problem in previous studies of biologics. Dr. Papp called MACEs "a nonissue." A meta-analysis of randomized controlled trials of ustinekumab and briakinumab and MACEs found no significant increase in MACEs; however, the authors write: "This study may have been underpowered to identify a significant difference."

Dr. Papp sees the issue as "more emotionally driven" and urged a "less reactive approach." He said that if this latest trial were to be put into the meta-analysis, the meta-analysis would likely have the power it needed. "Not all patients respond to any one treatment, so that we are constantly searching for new treatments," he said, adding that he considers the newer therapies to be "very well characterized" and "well-tolerated, whereas with methotrexate, we don't know optimal dosing, [and] tolerability and hepatic concerns are an issue."

However, Dr. Papp acknowledged, "Methotrexate has been a mainstay of treatment for decades," but "biologics have easier-to-use risk profiles and are much safer than methotrexate."

As for Abbott's involvement with the study, Dr. Papp was emphatic, stating: "There is no influence within companies. Sponsors do not step in and impose any sort of influence in any way." Abbott Laboratories provided support for the study, and the first draft of the manuscript was written by a medical writer employed by Abbott, with input from the authors.

Steven Feldman, MD, professor of dermatology, pathology, and public health sciences, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, who was not involved with the study, told Medscape Medical News:"It's really unfortunate for patients that we don't have the option of this drug.... The drug is twice as effective as methotrexate, and is at least as safe."

On the other hand, Sheldon Greenfield, MD, Donald Bren professor of medicine and executive director of the Health Policy Research Institute, University of California, Irvine, questioned the study. "Abbott should not have hired the writer," he said. "It's a slant — it's called ghostwriting, and it is a red flag." He also went on to say that the trial was too short and included too few patients to detect harm.

Dr. Kapp is a consultant, speaker, and investigator for Abbott Laboratories and sits on advisory boards for briakinumab and Humira. The lead author of the study is an Abbott employee. Other authors also indicated that they have consulted for Abbott. Dr. Feldman has received research, consulting, and/or speaking support from Abbott, Amgen, Janssen, Galderma, GSK/Stiefel, Novartis, the National Biological Corporation, and the National Psoriasis Foundation. Dr. Greenfield has disclosed no relevant financial relationships.

N Engl J Med. 2011;365:1586-1596. Abstract

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