AB0385 INTEGRATED SAFETY ANALYSIS ACROSS PHASE 3 CLINICAL STUDIES INCLUDING THE CONTROLLED AND UNCONTROLLED PERIODS FOR INTRAVENOUS GOLIMUMAB IN RHEUMATOID ARTHRITIS, PSORIATIC ARTHRITIS, AND ANKYLOSING SPONDYLITIS

Abstract

Background The GO-FURTHER, GO-VIBRANT, and GO-ALIVE randomized controlled trials evaluated the efficacy and safety of intravenous (IV) golimumab (GLM) in patients (pts) with active rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), respectively. Objectives This integrated analysis assessed safety events across indications in pts who received IV GLM. Methods Integrated safety data from 3 Phase 3, double-blind, placebo (PBO)-controlled trials were analyzed up to week (WK) 112 in RA pts and up to WK 60 in PsA and AS pts. Pts received either IV PBO or IV GLM (2 mg/kg) at 0, 4, 12, and 20 WKS. PBO pts crossed over to IV GLM at WK 24, except RA pts randomized to PBO who met early escape criteria crossed over at WK 16 and AS pts randomized to PBO who crossed over at WK 16. Cumulative adverse events (AEs) were reported by indication and pooled by treatment. Anti-drug antibodies (ADAs) were evaluated. Results Overall, 1248 pts were treated with IV GLM across indications. A numerically greater proportion (%) of IV GLM pts with RA reported safety events than pts with PsA or AS (Table 1): SAEs (18.2 vs 5.2 vs 3.4), infections (49.1 vs 22.8 vs 32.8), serious infections (6.2 vs 2.2 vs 1.5), and infusion reactions (4.6 vs 0.9 vs 1.5). Incidence (per 100 pt-years) of opportunistic infections, malignancy, active tuberculosis, and death with IV GLM was low (≤0.5) across indications (Table 2). Infections were the most commonly reported type of SAE among pooled IV GLM pts; the most frequent was pneumonia (10 [0.8%]). Incidence (per 100 pt-years) of serious infections was similar among IV GLM pts with and without corticosteroid use (3.35 vs 3.37, respectively). Overall, 1 IV GLM pt (PsA) experienced a demyelination event. A numerically greater proportion of IV GLM pts discontinued due to an AE than PBO pts (5.0% vs 0.9%, respectively). In IV GLM pts with baseline alanine aminotransferase (ALT) ≤ upper limit of normal (ULN), 1.2% had post-baseline ALT elevations ≥5X ULN. The proportion of IV GLM and PBO pts with post-baseline ALT elevations ≥5X ULN was 2.1% vs 0% with methotrexate and 0.7% vs 1.4% without methotrexate use at baseline, respectively. Using a drug-tolerant enzyme immunoassay, the incidence of ADAs was 22% through WK 52 across indications, which primarily consisted of low titer ADAs. Conclusion IV GLM demonstrated a consistent safety profile across indications in the PBO-controlled (up to WK 24) and uncontrolled study periods. Similar to WK 24 (1), more safety events occurred in RA pts, who represented the largest study population with older pts, longer disease duration, and more concomitant medication use.