An analysis of the DISCOVER-1 and DISCOVER-2 trials revealed that guselkumab led to a significant resolution of dactylitis and enthesitis in patients with active psoriatic arthritis. Resolution of these key symptoms was associated with ACR20/50/70 and PASI75/90 response.
The selective IL-23 blocker guselkumab demonstrated efficacy in patients with active psoriatic arthritis (PsA) in the two phase 3 trials DISCOVER-1 (NCT03162796) and DISCOVER‑2 (NCT03158285) . Dactylitis and enthesitis are both key PsA clinical manifestations that can be difficult to treat and increase the disease burden. In a pooled analysis of the DISCOVER-1 and -2 trials including 1,100 patients, relationships between improvements in dactylitis or enthesitis and other PsA domains in patients with dactylitis or enthesitis at baseline were assessed.
At baseline, 42% of the pooled patients had dactylitis (assessed in a total score 0-60) and 65% had enthesitis (assessed in the Leeds Enthesitis Index). At week 24, guselkumab in both doses significantly improved dactylitis (see Figure) and enthesitis scores compared with placebo. Rates of dactylitis or enthesitis resolution by week 24 were consistently significantly associated with ACR20/50/70 and PASI75/90 response (P<0.001). At week 24, significant correlations were observed between dactylitis change scores and PASI. As Prof. Dennis McGonagle (University of Leeds, UK) pointed out during the presentation, improvement in dactylitis by guselkumab was also associated with improved mental health. Likewise, improvements in enthesitis index score correlated with improved physical function.
Figure: Pooled DISCOVER-1 & 2: Improvement/resolution of dactylitis through week 24 among patients with dactylitis at baseline 
Unadjusted (nominal) *P<0.01, **P<0.001 versus placebo
- McGonagle D, et al. Effects of guselkumab, a monoclonal antibody that specifically binds to the p19-subunit of interleukin-23, on dactylitis and enthesitis in patients with active psoriatic arthritis: pooled results through week 24 from two phase 3 studies. 0895, ACR Convergence 2020, 5-9 Nov.
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