To further characterize the effect of guselkumab, a selective interleukin-23p19-subunit inhibitor approved for psoriatic arthritis (PsA), on enthesitis and assess relationships between enthesitis resolution and patient status/outcomes.Adults with active PsA despite standard therapies in the Phase-3 DISCOVER-1 and DISCOVER-2 studies were randomized 1:1:1 to guselkumab 100 mg every-4-weeks (Q4W); guselkumab 100 mg at Week0, Week4, Q8W; or placebo through Week20 followed by guselkumab 100 mg Q4W (Placebo→Q4W). Independent assessors evaluated enthesitis using the Leeds Enthesitis Index (LEI; total score 0-6). Enthesitis findings through Week24 were prespecified to be pooled across studies; post hoc and Week52 analyses also employed pooled data.Among 1,118 randomized, treated patients in DISCOVER-1 and 2 who had ≥1LEI site evaluated, 65% had enthesitis at baseline. These patients exhibited numerically more swollen and tender joints, systemic inflammation, and impaired physical function than patients without enthesitis. Guselkumab Q4W and Q8W were superior to placebo in resolving pre-existing enthesitis at Week24 (45% and 50% vs 29%; both adjusted p= 0.0301). Enthesitis resolution rates continued to rise; 58% of guselkumab-randomized patients achieved resolution at Week52, including patients with mild (LEI = 1; 70-75%), moderate (LEI = 2; 69-73%), or severe (LEI = 3-6; 42-44%) enthesitis at baseline. Among guselkumab-randomized patients with resolved enthesitis at Week24, 42% achieved minimal disease activity at Week52, vs 17% of patients with unresolved enthesitis.Guselkumab resulted in higher proportions of PsA patients with resolved enthesitis by Week24, with maintenance of resolution rates through 1 year. As enthesitis confers greater disease burden, sustained resolution could portend better patient outcomes.DISCOVER 1 (NCT03162796) and DISCOVER 2 (NCT03158285).
Dennis McGonagle, Iain B McInnes, Atul Deodhar, Georg Schett, May Shawi, Shelly Kafka, Chetan S Karyekar, Alexa P Kollmeier, Elizabeth C Hsia, Xie L Xu, Shihong Sheng, Prasheen Agarwal, Bei Zhou, Christopher T Ritchlin, Proton Rahman, Philip J Mease