Guselkumab Improves Psoriatic Arthritis in Phase 2a Study

The anti-interleukin (IL)-23 monoclonal antibody guselkumab (Janssen) significantly improved joint symptoms, physical function, psoriasis, enthesitis, dactylitis and quality of life in patients with active psoriatic arthritis, researchers reported on Nov. 15 at the American College of Rheumatology annual meeting in Washington, D.C.

The phase 2a, randomized, double-blind, placebo-controlled multicenter study by Atul A. Deodhar, M.D., of Oregon Health and Science University, included 149 active psoriatic arthritis patients. Subjects had psoriasis plaques covering three percent or more of their body surface area, despite standard-of-care treatment, which in some patients included anti-TNFα agents.

In a 2:1 ratio, subjects received either 100 mg guselkumab, given subcutaneously, or placebo at baseline and week four; then, every eight weeks through week 44.

Patients in both arms who had less than a 5 percent improvement in swollen and tender joint counts by week 16 could opt out of this study and into an open-label ustekinumab study. All remaining placebo patients crossed over to the guselkumab arm at week 24.

The study met its primary and secondary endpoints, with significantly more patients in the active arm achieving American College of Rheumatology (ACR)20/50/70 responses and Psoriasis Area Severity Index (PASI) 75/90/100 responses at week 24. Nearly 40 percent of patients in the active group, versus 6.3 percent in the placebo arm, achieved PASI 100, or completely clear, at week 24.

As early as four weeks into treatment, 21 percent in the guselkumab group had an ACR20 response, compared to zero in the control group. ACR response in the active arm increased with time, with nearly 60 percent of subjects reaching a 20 percent improvement in joint symptoms at week 16, versus 16.3 percent of those on placebo. Fourteen percent of subjects on guselkumab achieved ACR70, versus 2 percent on placebo, at week 24.

Unresolved enthesitis remained in 71 percent of those in the placebo group at week 24, versus 43.4 percent in the active arm. The average percent change from baseline to week 24 for dactylitis was about a third of subjects on placebo, versus 100 percent on guselkumab. And the percent of patients achieving minimal disease activity at week 24 was 2 percent for placebo compared to 23 percent in the guselkumab group.

Subjects in the active arm also seemed to experience mental benefits, with higher scores on the SF-36 mental component summary (Physical Component Summary (PCS)) score.

The drug was well tolerated, according to the study. Subjects with one or more adverse events, including the most common infections, were similar in the two groups. The researchers reported no serious infections, cancer or death during the 24 weeks of the study.

Disclosures:

The study’s researchers report conflicts of interest with many of the companies that produce biologics, including Janssen.

References:

American College of Rheumatology annual meeting 2016. “Efficacy and Safety Results of Guselkumab, an Anti-IL23 Monoclonal Antibody, in Patients with Active Psoriatic Arthritis over 24 Weeks: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study,” Deodhar AA, Gottlieb AB, et al. Abstract Number 4L. Nov. 15, 2016.