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

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).