Guselkumab (Tremfya) received Food and Drug Administration approval for the treatment of psoriatic arthritis (PsA) almost 2 years ago on the basis of a phase 3 trial, but a new substudy from that trial has now demonstrated long-term benefit in the subgroup of patients who entered the trial with axial involvement, according to data presented at the annual meeting of the Canadian Rheumatology Association.
“The symptom relief was clinically meaningful and durable through week 100,” reported Dafna D. Gladman, MD, professor of medicine and director of the psoriatic arthritis program at the University of Toronto.
Dr. Dafna D. Gladman
In the previously published double-blind, placebo-controlled DISCOVER-2 trial, two dosing regimens of the interleukin-23 (IL-23) inhibitor guselkumab were compared with placebo in biologic-naive patients. The active regimens were similarly effective relative to placebo for the primary endpoint of 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24.
In this new long-term subgroup analysis, outcomes at 2 years were evaluated in the 246 patients with axial involvement (33.3% of the total number of 739 evaluable patients). Baseline characteristics across treatment groups in this subset of the DISCOVER-2 trial were similar.
Guselkumab exhibits nearly twofold advantage
At 24 weeks relative to baseline, the improvement on multiple axial involvement outcome measures was approximately twofold greater with active therapy than with placebo. For example, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score fell 2.6 points in both active treatment arms versus 1.4 on placebo.
The same relative advantage was observed when the BASDAI spinal pain subscore was isolated. There were also comparable responses on a modified BASDAI that excluded the peripheral pain response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).
When evaluated at week 52 and again at week 100, all outcomes employed to evaluate change in axial involvement were sustained. Many were further improved. In patients who initiated therapy on placebo, all of whom were switched to guselkumab at the end of the 24-week double-blind period, at least the same degree of axial symptom control relative to baseline was achieved at both time periods.
Incremental improvement observed over time
“For most measures there was further improvement at 2 years, and there was generally consistent response across patient groups stratified by HLA [human leucocyte antigen] status,” Dr. Gladman reported.
Relative to the 2.6-point reduction in the BASDAI score in the two guselkumab arms at week 24, the reductions reached 3.0, 3.1, and 3.3 at 100 weeks in the every-4-week guselkumab group, every-8-week guselkumab group, and the crossed-over placebo group, respectively. For ASDAS, the reductions at week 24 were 1.4, 1.5, and 0.7 points and reached 1.6, 1.7, and 1.6 points at 100 weeks in the every-4-week, every-8-week, and placebo crossover groups, respectively.
The sustained improvement is consistent with a previous post hoc analysis in which data from the phase 3 DISCOVER-1 trial were pooled with those from DISCOVER-2. This analysis focused on the 312 patients in these studies with axial disease documented by imaging. Again, the study showed improvement at week 24 was sustained at week 52 independent of HLA-B27 status.