In moderately to severely active UC, etrasimod increased remission at 12 and 52 wk but increased adverse events
Given their overall safety and convenience, etrasimod and other oral sphingosine-1-phosphate receptor modulators can be considered as first-line therapy in clinically appropriate patients with ulcerative colitis (UC) who do not respond to 5-aminosalicylic acid medications, an ACP Journal Club commentary said.
Two industry-funded, phase 3 randomized controlled trials (ELEVATE UC 52 and ELEVATE UC 12) assessed etrasimod as induction and maintenance therapy for ulcerative colitis (UC) at more than 300 clinical centers in up to 40 countries. They found that in patients with moderately to severely active UC, the drug increased remission at 12 and 52 weeks. Adverse events were reported in 206 (71%) of 289 patients in the etrasimod group and 81 (56%) of 144 patients in the placebo group in ELEVATE UC 52 and in 112 (47%) of 238 patients in the etrasimod group and 54 (47%) of 116 patients in the placebo group in ELEVATE UC 12. The small proportion of patients who had serious adverse events was similar between groups.
The study was published March 2 by The Lancet. The following commentary by Reem Al-Jabri, MD, and Waqqas Afif, MD, MSc, was published in the ACP Journal Club section of the July Annals of Internal Medicine.
The trials by Sandborn and colleagues report on the efficacy and safety of etrasimod vs. placebo in patients with moderately to severely active UC. Etrasimod is the second oral sphingosine-1-phosphate (S1P) receptor modulator, after ozanimod, that has shown efficacy in patients with UC. Etrasimod has a substantially shorter half-life than ozanimod (30 h vs. 11 d) and does not require dose titration at initiation.
In these treat-through trials (patients continued the therapy to which they were randomly assigned through the induction and maintenance phases), etrasimod induced and maintained remission in patients with moderately to severely active UC. Although this trial design mimics clinical practice and offers an extended placebo-controlled follow-up, it is difficult to compare its results to those of other placebo-controlled phase 3 UC studies that used a responder re-randomization design. Another unique feature of these trials was the inclusion of patients with isolated proctitis (<10 cm), who are usually excluded from UC studies. Etrasimod was also shown to be effective in these occasionally difficult-to-treat patients.
In the absence of head-to-head trials, the role of S1P receptor modulators in the treatment of UC is unclear. Etrasimod was effective in both biologic agent– and JAK inhibitor–naive and –experienced patients, but as is the case with other available treatment options, the treatment effect was more pronounced in patients naive to biologic agent therapy.
Given their overall safety profile (no increased risk for severe adverse events or infectious complications) and convenient oral administration, S1P receptor modulators can be considered as first-line therapy after failure of 5-aminosalicylic acid medications in clinically appropriate patients.