GOTHENBURG, SWEDEN – Phase III clinical trial results for briakinumab show high treatment response levels with the passage of time.
In the 52-week M10-255 trial, for example, 317 psoriasis patients were randomized to an investigational interleukin-12 and interleukin-23 inhibitor or to oral methotrexate for a year. The PASI 75 rate (the proportion of patients who showed at least a 75% improvement in scores on the Psoriasis Area and Severity Index), compared with baseline, was 82% at week 24 and 66% at week 52 in the briakinumab arm.
More interestingly, the PASI 90 rate was 64% at week 24 and 60% at week 52. That means that almost everyone who achieved a PASI 75 also had a PASI 90 response. And the PASI 100 rate was also impressive, at 42% by week 24 and 45.5% by week 52, Dr. Kristian Reich reported at a satellite symposium sponsored by Abbott at the congress.
"It appears we have a new pattern of clinical response here. If you are a responding patient, with time there is a tendency to achieve a very high level of response. For me personally, these PASI 90 and 100 rates are a different level of efficacy that I have not seen ... with any other therapy in psoriasis," said Dr. Reich, professor of dermatology at Georg-August University in Göttingen, Germany.
No head-to-head comparative studies have been done pitting briakinumab against other biologic agents for psoriasis. Nevertheless, the 42% PASI 100 rate seen with briakinumab in the M10-255 trial exceeds the week-24 or -28 PASI 100s reported in published trials involving other biologics: a high of 29% with ustekinumab at 90 mg, 26% with infliximab, 22% with adalimumab, and a low of 19% with ustekinumab at 45 mg, Dr. Reich said.
Psoriasis patients in the M10-255 trial had a mean baseline PASI score of 18, and a 19-year history of the disease. They were randomized to briakinumab at 200 mg at weeks 0 and 4, then 100 mg once every 4 weeks, or to oral methotrexate with folic acid.
In all, 72% of patients in the methotrexate arm discontinued the drug by week 52, with lack of efficacy the reason for 80% of dropouts. Only 6% of subjects discontinued methotrexate because of adverse events. This was the same percentage of patients who dropped out of briakinumab therapy because of adverse events; another 14% did so because of lack of efficacy.
NAPSI (Nail Psoriasis Severity Index) scores decreased by 58% and 78% at 24 and 52 weeks, respectively, in the briakinumab group, compared with 37% and 39% with methotrexate.
Through 1 year of follow-up, the safety profile was quite similar in the two study arms, with the exception of a higher rate of diarrhea with briakinumab – 9.7% compared with 3.7% with methotrexate – and a twofold higher rate of nausea in the methotrexate arm, he noted.
An interim safety analysis from the open-label extensions of all phase III trials in the briakinumab development program, involving 2,298 treated patients, indicated that the incidence of malignancy was 1.4 cases per 100 patient-years, whereas any serious infection occurred at a rate of 1.0 per 100 patient-years. The rates of these and other adverse events are what one would expect from an anti-interleukin-12/23 drug, and are on balance quite acceptable, said Dr. Reich.
He disclosed that he has served as a consultant and speaker for and/or participated in clinical trials sponsored by Abbott (which funded the M10-255 trial), Biogen Idec, Bristol-Myers Squibb Co., Centocor, Merck Serono, Schering-Plough, UCB, and Wyeth.