Guselkumab Shows Week 24 Efficacy After TNF Inhibitor Failure in PsA

Key Takeaways

• Both guselkumab schedules were associated with higher week 24 responses than placebo across the reported efficacy endpoints.
• Week 24 efficacy appeared similar between the every-4-week and every-8-week guselkumab regimens.
• Adverse-event rates were broadly similar across groups through week 24, and one reported death was identified as myocardial infarction.

At week 24 in SOLSTICE, ACR20 responses reached 58.6% and 62.2% with guselkumab versus 34.8% with placebo. This phase 3b comparison enrolled adults with active psoriatic arthritis and inadequate response to one prior TNF inhibitor, testing guselkumab every 4 weeks and at weeks 0 and 4 then every 8 weeks against placebo through week 24. Published in Arthritis & Rheumatology, the trial also favored guselkumab across the prespecified endpoint set.

SOLSTICE was a phase 3b, randomized, multicenter, double-blind, placebo-controlled study evaluating guselkumab, an interleukin-23p19 subunit inhibitor, in adults with active psoriatic arthritis. Eligibility required at least three swollen joints, at least three tender joints, C-reactive protein of 0.3 mg/dL or higher, and inadequate response (inadequate efficacy and/or intolerance) to one prior TNF inhibitor. Among 451 randomized participants, 150 received guselkumab 100 mg every 4 weeks, 151 received doses at weeks 0 and 4 then every 8 weeks, and 150 received placebo. Placebo crossed over to guselkumab every 4 weeks at week 24. The primary endpoint was ACR20 at week 24, and secondary endpoints of ACR50, ACR70, IGA 0/1, PASI90, and minimal disease activity were analyzed by intention-to-treat.

Both guselkumab regimens outperformed placebo on all prespecified efficacy outcomes at week 24, spanning joint, skin, and composite disease measures. ACR50 responses were 31.4% and 32.1% with every-4-week and every-8-week dosing, versus 12.2% with placebo, while ACR70 responses were 17.5% and 17.3% versus 2.0%. IGA 0/1 response rates were 50.0% and 57.3% versus 17.4%, PASI90 rates were 49.4% and 45.5% versus 12.0%, and minimal disease activity rates were 18.8% and 23.9% versus 5.4%. All efficacy comparisons were reported as P < 0.001. Across these measures, efficacy appeared comparable between the every-4-week and every-8-week schedules at week 24.

Through week 24, at least one adverse event occurred in 46.7% of the every-4-week group, 53.6% of the every-8-week group, and 48.3% of placebo recipients. One death was reported and was identified as myocardial infarction. Safety data covered the blinded comparison period before placebo crossover at week 24. Week 24 safety findings were reported as consistent with the known guselkumab profile in psoriatic disease. Overall, guselkumab showed broader efficacy than placebo at week 24, with similar results between the two guselkumab regimens in this post-TNF inhibitor population.