McDonnell, Aoibhinn

Abstract Background Patient age can impact the safety and efficacy of ulcerative colitis (UC) treatments. Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. Here, we evaluate the impact of age on etrasimod safety and efficacy in patients with UC in the phase 3 ELEVATE UC clinical program. Methods Data were pooled from ELEVATE UC 52 and ELEVATE UC 12 in patients receiving etrasimod 2 mg QD or placebo. Proportions and incidence rates (IRs) per 100 patient-years of treatment-emergent adverse events (AEs) were stratified by age (<40, 40-59, and ≥60 years). With the same age stratifications, efficacy was evaluated in patients with baseline Modified Mayo scores of 5-9 and 4-9 for the primary efficacy endpoint (clinical remission) and secondary efficacy endpoints. Results Overall, 787 patients were enrolled (<40 years, n = 420 [53.4%]; 40-59 years, n = 276 [35.1%]; and ≥60 years, n = 91 [11.6%]). Arthralgia, fatigue, and hypertension IRs were higher in older patients, irrespective of treatment. Serious AEs and AEs leading to treatment discontinuation were low and consistent across age groups. Significantly more patients receiving etrasimod 2 mg QD vs placebo achieved efficacy endpoints, regardless of age. Conclusions The safety profile of etrasimod 2 mg QD in the ELEVATE UC population was consistent across age groups, with no change in the incidence of AEs. Patients receiving etrasimod vs placebo showed significant clinical benefit, regardless of age. ClinicalTrials.gov NCT03945188; NCT03996369.

Abstract Background Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We assessed the benefit of etrasimod monotherapy and the impact of concomitant corticosteroids (CS) and/or 5-aminosalicylates (5-ASA) therapy. Methods In ELEVATE UC 52 and ELEVATE UC 12, patients with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg QD or placebo for 52 and 12 weeks, respectively. Oral CS or 5-ASA were allowed at baseline. Patients in the monotherapy subgroup received etrasimod or placebo without concomitant CS and/or 5-ASA at baseline. Predefined primary (clinical remission) and key secondary efficacy endpoints aligned with those from both trials and were assessed at Week 12 and Week 52. Safety was assessed up to Week 52. Results Clinical remission rates at Weeks 12 and 52 were significantly higher for etrasimod compared with placebo in patients receiving monotherapy (Week 12: 26.2% vs 4.8%; Week 52: 35.7% vs 4.0%). Differences vs placebo were statistically significant for all predefined endpoints at both time points in patients receiving monotherapy or etrasimod with concomitant 5-ASA only (all P < .05); numerical differences, due to small sample sizes, vs placebo were observed for all endpoints in the CS only and CS + 5-ASA subgroups. Safety was consistent with the overall population. Conclusions Etrasimod monotherapy showed consistent efficacy and safety vs placebo; no apparent benefit was observed with concomitant CS and/or 5-ASA in patients receiving etrasimod. Clinical trial registration NCT03945188; NCT03996369.

Background: Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). It is known that non-serious treatment-emergent adverse events (TEAEs) may not lead to UC drug discontinuation but can affect treatment tolerability. Objectives: This post hoc analysis evaluated the incidence of specific, common, non-serious TEAEs reported in the etrasimod UC clinical programme and the characteristics of affected patients. Design: Data included patients from the Placebo-controlled UC cohort (phase II OASIS, and phase III ELEVATE UC 52 and ELEVATE UC 12 trials) receiving QD etrasimod (2 or 1 mg) or placebo. Methods: Proportions and incidence rates (IRs; the number of patients with a TEAE divided by the total exposure in patient-years (PYs), per 100 PY) of Headache, Pyrexia, Nausea and Dizziness TEAEs were reported. Changes in heart rate among patients with Dizziness TEAEs were also evaluated. Results: Among 943 patients (etrasimod 2 mg, N = 577 (276.7 PY); etrasimod 1 mg, N = 52 (11.4 PY); placebo, N = 314 (115.1 PY)), 48, 34, 27 and 21 patients experienced events of Headache, Pyrexia, Nausea and Dizziness, respectively. All events were non-serious; one patient treated with etrasimod was discontinued due to a Pyrexia TEAE. Numerically, IRs of Headache and Dizziness TEAEs were higher, and Nausea slightly higher, with etrasimod versus placebo (13.45 vs 8.63 per 100 PY, 6.52 vs 1.69 and 7.18 vs 5.13 per 100 PY, respectively); IRs were similar for Pyrexia. The duration of most TEAEs was 1–10 days. Conclusion: In the etrasimod UC clinical programme, all Headache, Pyrexia, Nausea and Dizziness events were non-serious. Headache and Dizziness were more frequent, and Nausea slightly more frequent, among patients receiving etrasimod versus placebo. The post hoc nature of this analysis is a limitation. These results reiterate the favourable safety profile and tolerability of etrasimod. Trial registration: ClinicalTrials.gov: NCT02447302; NCT03945188; NCT03996369.