POS1028 GUSELKUMAB MAINTAINS RESOLUTION OF DACTYLITIS AND ENTHESITIS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS THROUGH 2 YEARS FROM A PHASE 3 STUDY

Abstract

BackgroundGuselkumab (GUS), a selective inhibitor of IL-23, significantly improved the diverse manifestations of active psoriatic arthritis (PsA), including dactylitis and enthesitis, in DISCOVER (D)-1 & 2 trials of patients (pts) with active PsA1,2, with maintenance of response rates through 1 year (yr).3,4 Dactylitis and enthesitis, extra-articular manifestations of PsA, can be difficult to treat and cause significant disease burden.5,6ObjectivesTo evaluate the ability of GUS to provide long-term resolution of dactylitis and enthesitis in pts with PsA through 2 yrs of D-2.MethodsD-2 biologic naïve pts with active PsA were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS Q4W. Independent assessors evaluated dactylitis (total score: 0-60) and enthesitis (Leeds Enthesitis Index [LEI]; total score 0-6). These post hoc analyses assessed baseline (BL) frequency and severity of enthesitis in pts with dactylitis and dactylitis frequency in pts with enthesitis. Post BL, changes in dactylitis and LEI scores over time (least squares [LS] mean changes; analysis of covariance [ANCOVA]) and rates of resolution of dactylitis and enthesitis (Chi square correlation test) were determined in pts with these manifestations at BL (missing data imputed as no change/response).ResultsAt BL, more D-2 pts had enthesitis (68%) than dactylitis (45%). At BL, 78% of pts with dactylitis vs 61% without (w/o) dactylitis had enthesitis and 51% of pts with enthesitis vs 32% w/o enthesitis had dactylitis. Among pts with enthesitis at BL, a higher percentage of pts with dactylitis (52%) had severe enthesitis (LEI score ≥3) vs pts w/o dactylitis (44%). Among those with the condition at BL, resolution rates of dactylitis (57%, Q4W; 64%, Q8W) and enthesitis (44%, Q4W; 54%, Q8W) at W24 increased through W52 (dactylitis: 74%, Q4W; 78%, Q8W; enthesitis: 57%, Q4W; 61%, Q8W) and were maintained at W100 (dactylitis: 72%, Q4W; 83%, Q8W; enthesitis: 62%, Q4W; 70%, Q8W). Consistent results were observed when evaluating mean changes in dactylitis and LEI scores and in pts who crossed over from PBO to GUS Q4W at W24 (Table 1). In pts with dactylitis and enthesitis at BL, GUS-treated pts showed significant correlations between resolution of enthesitis and dactylitis at W24 (p=0.004), W52 (p<0.001) and W100 (p=0.039), with nearly 90% of pts with enthesitis resolution also achieving dactylitis resolution at W52 and W100 (Figure).Table 1.LS mean change from baseline over time in dactylitis and LEI scores in pts with manifestation at baselineGUS 100 mg Q4WGUS 100 mg Q8WPBO → GUS 100 mg Q4WDactylitis score (0-60)Pts, N12111199W24a-5.9 (-6.7, -5.0)-6.0 (-6.8, -5.1)-4.0 (-5.0, -3.1)W52a-6.5 (-7.2, -5.8)-7.2 (-7.9, -6.5)-6.9 (-7.6, -6.2)W100a-6.5 (-7.1, -5.8)-7.5 (-8.1, -6.8)-6.9 (-7.6, -6.2)LEI score (1-6)Pts, N170158178W24a-1.5 (-1.8, -1.3)-1.6 (-1.8, -1.4)-1.0 (-1.3, -0.8)W52a-1.8 (-2.0, -1.6)-1.9 (-2.1, -1.7)-2.0 (-2.2, -1.8)W100a-1.9 (-2.1, -1.7)-2.1 (-2.3, -1.8)-2.1 (-2.3, -1.9)aResults are LS mean change (95% confidence interval [CI]); LS mean change determined by ANCOVA; missing data was imputed as no change for pts who discontinued treatment and using multiple imputation for remaining missing dataGUS, guselkumab; LEI, Leeds Enthesitis Index; LS, least squares; PBO, placebo; pts, patients; Q4W, every 4 weeks; Q8W, every 8 weeks; W, weekConclusionPts with PsA often present with concurrent enthesitis and dactylitis, both of which can be recalcitrant to treatment. GUS resolved enthesitis and dactylitis in substantial proportions of pts through W100. GUS-treated pts who achieved enthesitis resolution were more likely to achieve dactylitis resolution and vice versa.