POS1015 SAFETY OF GUSELKUMAB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS WHO ARE BIO-NAÏVE OR TNFi-EXPERIENCED: POOLED RESULTS FROM 4 RANDOMIZED CLINICAL TRIALS THROUGH 2 YEARS

Abstract

BackgroundGuselkumab (GUS), a selective IL-23p19 subunit inhibitor, demonstrated efficacy and a favorable safety profile in active psoriatic arthritis (PsA) in the Phase (Ph)21, Ph3 (DISCOVER [D]-1&2)2,3, and Ph3b COSMOS4 randomized controlled trials (RCTs).ObjectivesAssess GUS safety through 2 years (Y) in biologic (bio)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced (exp) active PsA patients (pts) pooled across 4 RCTs (Week [W] 56: Ph2 and COSMOS; W60: D1; W112: D2).MethodsEligible pts in COSMOS had inadequate response to 1 or 2 prior TNFi; 9% of Ph2 pts and 30% of D1 pts had 1 or 2 prior TNFi; D2 pts were bio-naïve. Incidence rates of adverse events (AEs) are summarized among all treated pts for the placebo (PBO)-controlled (W0-24) and active treatment periods through 2Y (max duration of exposure 100 W) according to actual treatment received, calculated as the number of events per 100 pt-Y of follow-up (PY), along with 95% confidence intervals (CI). Gastrointestinal (GI)-related serious AEs (SAEs) were identified using the Medical Dictionary for Regulatory Activities (MedDRA) system-organ class; major adverse cardiovascular events (MACE; predefined as MI, Stroke, or CV death) and opportunistic infections (OIs) were identified through medical review.ResultsAcross the 4 RCTs, 1508 pts with active PsA received GUS 100 mg every 4 weeks (Q4W) or Q8W and were followed for a median of 1.2 Y, representing 2125 PY. In the overall population (N=1554), which includes PBO-treated pts that discontinued study agent prior to W24, 1138 pts were bio-naïve and 416 pts were TNFi-exp. Among all treated pts, the overall GUS safety profile was generally consistent with that of PBO through W24; rates remained low through 2Y of GUS (Table 1). The GUS safety profile was similar to that observed with PBO within the bio-naïve and TNFi-exp cohorts through W24. Incidence rates of AEs were generally consistent between cohorts in GUS-treated pts; whereas, TNFi-exp PBO-treated pts had more SAEs, study agent d/c due to AEs, and serious infections than bio-naïve PBO pts (Figure).Table 1.Overall Treatment-emergent AEsPBO-controlled (W0-24)aThrough up to 2YPBOb(N=517)GUS Q8W (N=664)GUS Q4W (N=373)Combined GUS (N=1037)GUS Q8W (N=664)GUS Q4W (N=373)Combined GUSc(N=1508)Total (median) PY230 (0.5)305 (0.5)172 (0.5)478 (0.5)941 (1.1)645 (2.1)2125 (1.2)Events/100 PY (95% CI)AEs223 (204, 243)233 (216, 250)223 (201, 246)229 (216, 243)164 (156, 172)139 (130, 148)146 (141, 151)SAEs8.7 (5.3, 13)4.9 (2.8, 8.1)5.2 (2.4, 9.9)5.0 (3.2, 7.5)6.4 (4.9, 8.2)4.7 (3.1, 6.6)5.7 (4.7, 6.8)AEs leading to study agent d/c4.4 (2.1, 8.0)3.6 (1.8, 6.5)7.0 (3.6, 12.2)4.8 (3.1, 7.2)2.6 (1.6, 3.8)2.9 (1.8, 4.6)2.7 (2.1, 3.5)Infections59 (50, 70)56 (48, 65)57 (47, 70)57 (50, 64)43 (38, 47)37 (33, 42)39 (36, 42)Serious Infections2.2 (0.71, 5.1)0.33 (0.01, 1.8)1.7 (0.36, 5.1)0.84 (0.23, 2.1)1.7 (0.97, 2.8)0.77 (0.25, 1.8)1.5 (1.0, 2.1)Malignancy0.44 (0.01, 2.4)0.98 (0.20, 2.9)0.00 (0.00, 1.7)0.63 (0.13, 1.8)0.42 (0.12, 1.1)0.00 (0.00, 0.46)0.28 (0.10, 0.61)MACE0.44 (0.01, 2.4)0.33 (0.01, 1.8)0.58 (0.01, 3.2)0.42 (0.05, 1.5)0.21 (0.03, 0.77)0.46 (0.10, 1.4)0.24 (0.08, 0.55)GI-related SAEs1.3 (0.27, 3.8)0.33 (0.01, 1.8)0.00 (0.00, 1.7)0.21 (0.01, 1.2)0.32 (0.07, 0.93)0.46 (0.10, 1.4)0.28 (0.10, 0.61)OIs0.00 (0.00, 1.3)0.00 (0.00, 0.98)0.00 (0.00, 1.7)0.00 (0.00, 0.63)0.21 (0.03, 0.77)0.00 (0.00, 0.46)0.14 (0.03, 0.41)MedDRA Version 23.1.a Includes safety follow-up data through 2Y for pts who d/c study agent prior to W24 and did not receive any study agent at or after W24.b Includes data prior to GUS in PBO pts who switched from PBO to GUS.c Includes PBO to GUS cross-over at W24.ConclusionThe favorable GUS safety profile demonstrated through W24 persisted through 2Y across bio-naïve and TNFi-exp pts.