Concomitant Use of Etrasimod With Opioids or Antidepressants in Patients With Ulcerative Colitis-A Safety Analysis.

Abstract

Background: Etrasimod is an oral, once-daily (q.d.), selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the S1P receptor modulator ozanimod, etrasimod does not have a molecular structure to inhibit monoamine oxidase (MAO). Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs).

Aims: This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials.

Methods: Safety data pooled from both trials were analysed in subgroups of patients receiving etrasimod 2 mg q.d. (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥ 1 concurrent AE potentially associated with serotonin syndrome, including hypertension-related events.

Results: Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) were taking concomitant opioids or antidepressants, respectively. The incidence of AEs potentially related to serotonin syndrome, including hypertension-related AEs, was low (≤ 8.6%) and generally comparable in all subgroups. No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications.

Conclusions: The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis further supports the low likelihood of clinically relevant drug-drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants. (ClinicalTrials.gov: NCT03945188; NCT03996369).