Corporal Michael J. Crescenz VA Medical Center Philadelphia, Pennsylvania
Introduction: Ozanimod (OZA), an oral S1P receptor modulator, is approved for the treatment (tx) of moderate/severe ulcerative colitis (UC) in the US and EU. Inflammatory bowel disease prevalence is increasing in older pts.
Methods: This post hoc analysis examined OZA efficacy and safety in pts < 60y and ≥60y in True North (TN). Pts were randomized to double-blind (DB) OZA 0.92 mg or placebo (PBO; Cohort 1 [C1]) or received open-label OZA (Cohort 2 [C2]) during the 10-week (W) TN induction period (IP). Pts with clinical response to OZA at W10 were rerandomized to DB OZA or PBO in the maintenance period (MP) through W52.
Results: This analysis included 562 pts < 60y (OZA, n=376; PBO, n=186) and 83 pts ≥60y (OZA, n=53; PBO, n=30) from C1 and 315 pts (< 60y) and 52 pts (≥60y) from C2. During MP, 196 pts (< 60y) and 34 pts (≥60y) continued on OZA; 196 pts (< 60y) and 31 pts (≥60y) were rerandomized to PBO. Demographics and baseline (BL) characteristics were generally well balanced across tx and age groups; older pts had less extensive disease, lower BL fecal calprotectin levels, and more polypharmacy. Adjusted tx differences favored OZA v PBO and were generally similar between age groups across all efficacy endpoints (clinical remission, clinical response, endoscopic improvement, mucosal healing) at W10 and W52. PBO response rates were higher in older v younger pts. During IP, tx-emergent adverse event (TEAE) incidence with OZA in C1 and C2 was lower in older pts; rates of serious TEAEs and TEAEs leading to tx discontinuation were similar in older v younger pts (Table). With continued OZA tx during MP, TEAEs occurred more often in older pts, serious TEAEs were less frequent in older pts, and TEAEs leading to tx discontinuation were similar in older v younger pts. Adverse events of special interest during MP were generally low overall, with the most common being infection (≥60y: 2 pts v < 60y: 3 pts), hepatic effects (≥60y: 0 pts v < 60y: 2 pts), macular edema (≥60y: 1pt v < 60y: 0 pts), malignancy (≥60y: 0 pts v < 60y: 2 pts), and pulmonary effects (≥60y: 0 pts v < 60y: 1 pt). One death from acute respiratory distress syndrome due to viral pneumonia occurred during IP in an older pt (64y) on OZA but was deemed unrelated to tx.
Discussion: OZA is a safe, tolerable, oral tx option for older UC pts with an absence of serious AEs of concern. OZA efficacy in older pts was comparable to younger pts. This study was limited by the small sample size, warranting larger future real-world studies.
