AMSTERDAM – Does pushing for a PASI 90 response instead of settling for a PASI 75 matter to patients being treated for moderate-to-severe chronic plaque psoriasis?
You bet it does, Dr. Mark G. Lebwohl asserted at the annual congress of the European Academy of Dermatology and Venereology.
Dr. Mark Lebwohl
He presented a pooled analysis of data from two large pivotal phase III randomized trials of secukinumab for psoriasis. The primary endpoints in the analysis were how often and how soon patients who achieved a PASI 75 or PASI 90 response at 12 weeks reported obtaining a Dermatology Life Quality Index (DLQI) response, defined as a score of 0 or 1.
The answer: More patients who had a PASI 90 response (meaning almost clear at 12 weeks) had a DLQI response, and it occurred a full 4 weeks faster than in PASI 75 responders – at a median of 8 weeks, compared with 12 weeks, reported Dr. Lebwohl, professor and chairman of the department of dermatology at Mt. Sinai Medical Center in New York.
Scores on the DLQI can range from 0, meaning no psoriasis-related impairment of the patient’s quality of life, up to 30. The average baseline score in this study population was 13.5, so a DLQI response dropping the score down to 0 or 1 represents a dramatic improvement in this patient-reported outcome.
Study participants completed the DLQI questionnaire at weeks 4, 8, 12, 24, 36, and again at week 52. The subjects’ mean baseline PASI score was 23.2.
The two double-blind, randomized, placebo-controlled clinical trials that formed the basis for this analysis were the recently published 52-week ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) studies (N. Engl. J. Med. 2014;371:326-38), in which patients were assigned to secukinumab at a dose of either 150 mg or 300 mg, placebo, or in the case of FIXTURE, to etanercept. The PASI 75 and 90 response rates at 12 weeks were markedly higher at both doses of secukinumab than with etanercept.
Dr. Lebwohl’s pooled analysis was restricted to the 1,470 study participants in the two studies who were randomized to active therapy. A total of 612 patients achieved a PASI 90 response by week 12. Another 365 had a PASI 75 response. Fully 89% of PASI 90 responders also had a DLQI response maintained out to week 52, as did 77% of PASI 75 responders.
The key finding: The median time to a DLQI response in the PASI 90 responders was 8 weeks, compared with 12 weeks in the PASI 75 responders. Thus, patients with a PASI 90 response obtained virtually total relief from what had previously been a debilitating disease a full month sooner than PASI 75 responders. And that, as reported by the patients themselves, constitutes a meaningful advantage, Dr. Lebwohl stated.
Secukinumab is a fully human monoclonal antibody directed against a novel target: interleukin-17A. Novartis has filed for marketing approval of the biologic agent with an indication for psoriasis both with the Food and Drug Administration and European regulators. Secukinumab is also being developed as a treatment for psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis.
Novartis funded the analysis. Dr. Lebwohl reported serving as a consultant to Novartis and more than a dozen other pharmaceutical companies.