POS1017 GUSELKUMAB PROVIDES CONTINUED IMPROVEMENT IN KEY DOMAINS OF PSORIATIC ARTHRITIS THROUGH 2 YEARS

Abstract

BackgroundRecent guidelines from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recommend that psoriatic arthritis (PsA) therapy achieve lowest possible disease activity across 6 key domains and related conditions. 1 In the DISCOVER-1&2 trials, guselkumab (GUS) significantly improved signs and symptoms of PsA at Week (W) 24.ObjectivesEvaluate GUS efficacy through W100 of DISCOVER-2 by GRAPPA-recommended PsA domains (peripheral arthritis, skin, dactylitis, enthesitis, axial disease [nails not evaluated]) and related conditions of inflammatory bowel disease (IBD) and uveitis.MethodsEnrolled adults had active PsA, were naïve to biologics/JAK inhibitors, and had ≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dL. Randomized (1:1:1) patients (pts) received GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo (PBO) with crossover to GUS 100 mg Q4W at W24. Outcomes selected aligned with GRAPPA-recommended domains/conditions: overall disease activity (Psoriatic Arthritis Disease Activity Score [PASDAS], Minimal Disease Activity [MDA]), peripheral arthritis (changes in Disease Activity Index for Psoriatic Arthritis [DAPSA] and clinical DAPSA [cDAPSA]), skin (Psoriasis Area and Severity Index [PASI], Investigator’s Global Assessment of psoriasis [IGA]), dactylitis (Dactylitis Severity Score [DSS]), enthesitis (Leeds Enthesitis Index [LEI]), axial disease (spinal pain) and IBD/uveitis (adverse events [AEs]). Among 493 GUS-randomized pts, change from baseline (BL) through W100 in continuous outcomes were analyzed by Repeated Measures Generalized Linear Mixed Effects Models adjusting for respective BL score and GUS regimen. Achievement of therapeutic endpoints was summarized by descriptive statistics using nonresponder imputation (NRI) for missing categorical data.Results~90% of GUS-randomized pts completed treatment at W100. For continuous outcomes, improvements over time in key PsA domains extended through W100 of GUS (Figure 1). Therapeutic endpoint response rates also increased incrementally through W100 (Table 1). Mean improvements and response rates were consistent across key domains with no significant difference between GUS regimens. For related conditions, 1 GUS pt had IBD and 4 had uveitis at BL and none had AE of exacerbation through W100. No pt developed IBD through W100 (vs 1 PBO pt through W24); 1 GUS pt had AE of iridocyclitis through W100 (vs 1 PBO pt through W24).Table 1.Number (%) of GUS-randomized Pts (N=493) Achieving Therapeutic Endpoints Over Time (NRI)*WeekQ4WQ8W81624521008162452100MDA*8 (3)33 (14)47 (19)83 (34)93 (38)9 (4)42 (17)63 (25)77 (31)100 (40)DAPSA43 (18)61 (25)88 (36)125 (51)151 (62)43 (17)79 (32)97 (39)130 (52)147 (59) ≤14’; ≤45 (2)12 (5)21 (9)39 (16)52 (21)3 (1)15 (6)23 (9)46 (19)60 (24)cDAPSA41 (17)58 (24)89 (36)125 (51)150 (61)44 (18)75 (30)95 (38)131 (53)147 (60) ≤13* ≤35 (2)13 (5)29 (12)44 (18)59 (24)4 (2)19 (8)25 (10)53 (21)65 (26)PASDAS ≤3.225 (10)44 (18)58 (24)105 (43)126 (51)28 (11)56 (23)76 (31)106 (43)122 (49) ≤1.94 (2)11 (4)22 (9)36 (15)51 (21)2 (1)16 (6)23 (9)52 (21)58 (23)Skin PASI75†-137 (74)146 (79)160 (87)152 (83)-129 (73)139 (79)151 (86)144 (82) PASI90†-100 (54)114 (62)142 (77)136 (74)-97 (55)121 (69)131 (74)123 (70) PASI100†-62 (34)83 (45)106 (58)109 (59)-48 (27)80 (46)93 (53)94 (53) IGA 0/1 Response‡-122 (66)127 (69)147 (80)140 (76)-110 (62)124 (70)131 (74)126 (72)Enthesitis resolution§45 (27)66 (40)71 (43)93 (56)102 (61)50 (32)75 (48)87 (55)97 (62)110 (70)Dactylitis resolution§39 (32)64 (53)80 (66)90 (74)87 (72)34 (31)51 (46)66 (60)86 (77)92 (83)*Repeated Measures Generalized Linear Mixed Effects Models; excludes pts who achieved endpoint at BL.†Pts with BL IGA≥2 and BSA≥3%.‡IGA skin response = score of 0 or 1 and ≥2 grade improvement from BL.§Among pts with domain at BL.ConclusionIn DISCOVER-2 bio-naïve PsA pts, both GUS regimens provided continued improvements in key GRAPPA-recommended domains of PsA through up to 2 years of treatment.