Long-term Safety of Ozanimod in Relapsing Multiple Sclerosis and Moderately to Severely Active Ulcerative Colitis

Introduction: Ozanimod (OZA), an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved for the treatment (tx) of moderately to severely active ulcerative colitis (UC) and for the tx of relapsing multiple sclerosis (RMS). OZA is a first-in-class S1P receptor modulator approved for UC, and one of several S1P receptor modulators used for the tx of RMS. OZA has been extensively studied in RMS with large patient (pt) populations and long exposure times, which can provide more insight into the safety profile of OZA in UC. Methods: This analysis evaluated the tolerability and safety of long-term OZA 0.92 mg/d tx from clinical trial data in adults with moderately to severely active UC and from clinical trial data in adults with RMS. The UC population included pts pooled from phase 2 (NCT01647516), phase 3 (NCT02435992), and respective open-label extension (OLE; NCT02531126) trials through January 10, 2022. The RMS population included pts treated with OZA 0.92 mg in DAYBREAK (NCT02576717; October 16, 2015–February 1, 2022), an ongoing OLE trial of pts from phase 1‒3 OZA studies. Safety outcomes included tx-emergent adverse events (TEAEs) and TEAEs of special interest based on association with S1P modulation. Exposure-adjusted incidence rates (EAIRs) per 100 pt-years (PY) were calculated to adjust for time on study. Results: Mean (SD) OZA exposure in 1158 pts with UC was 28.4 (23.3) mo (2714.9 total PY exposure); OZA exposure in 2494 pts with RMS was 56.4 (15.9) mo (11,732.2 PY; UC and MS combined: 14,447.1 PY). TEAEs occurred in 74.6% of UC and 88.2% of RMS pts. Serious TEAEs were reported in 17.3% of UC and 14.1% of RMS pts, and TEAEs leading to OZA discontinuation in 9.3% and 3.6%, respectively. The most common TEAEs were lymphopenia (12.3%; EAIR 5.6/100 PY), anemia (8.4%; EAIR 3.7/100 PY), lymphocyte count decreased (7.9%; EAIR 3.5/100 PY), and nasopharyngitis (7.9%; EAIR 3.5/100 PY) in pts with UC, and nasopharyngitis (20.6%; EAIR 5.1/100 PY), headache (16.9%; EAIR 4.0/100 PY), and upper respiratory infection (11.9%; EAIR 2.7/100 PY) in pts with RMS. In UC and MS, respectively, EAIR/100 PY were 20.2 and 22.9 for any infection, 1.6 and 0.8 for serious infection, 1.2 and 1.4 for opportunistic infection, and 0.6 and 0.3 for malignancy. Alanine aminotransferase levels ≥5 times the upper limit of normal occurred in 2.3% and 0.8% of UC and RMS pts, respectively. Conclusion: Long-term OZA 0.92 mg/d was generally well tolerated and safe for most pts with moderately to severely active UC or RMS.