番茄社区

Etrasimod, an investigational selective sphingosine 1-phosphate (S1P) receptor modulator, led to clinically meaningful improvements in patients with moderately to severely active ulcerative colitis (UC), according to an analysis of two randomized trials.

In , the clinical remission rate was over three times higher for those who received etrasimod compared with placebo at 12 weeks (27% vs 7.4%) and over four times higher at 52 weeks (32.1% vs 6.7%; P˂0.001 for both). In , the clinical remission rate was also higher (24.8% vs 15.2%, respectively, P=0.026), reported William J. Sandborn, MD, of the University of California San Diego.

In both trials, etrasimod also met all secondary efficacy endpoints, including endoscopic improvement, symptomatic remission, clinical response, and mucosal healing, among others, according to findings presented at a late-breaking presentation at the Digestive Disease Week annual meeting.

Similar treatment-emergent adverse events and serious adverse events occurred among both treatment groups, without any new safety findings for up to 52 weeks in ELEVATE UC 52.

A previous phase II trial from Sandborn and colleagues that evaluated etrasimod also showed efficacy in adults with moderate to severe UC.

For their current study, Sandborn and team examined data from ELEVATE UC 52 (n=433) and ELEVATE UC 12 (n=354), two global phase III double-blind trials that enrolled adults with moderate to severe UC from June 2019 to February 2022 and September 2020 to December 2021, respectively.

Both trials randomized patients 2:1 to receive oral etrasimod 2 mg once daily or placebo. Moderate or severe disease activity were defined by a modified Mayo Score (MMS) of 4 to 9 with a centrally read endoscopic subscore ≥2 and a rectal bleeding subscore ≥1, as well as documented history of inadequate response, loss of response, or an intolerance to at least one UC treatment. Patients were stratified according to their baseline corticosteroid use and disease activity (MMS 4-6 or 7-9), in addition to prior exposure to biologics or Janus kinase (JAK) inhibitors.

In ELEVATE UC 52, 433 patients were randomized, and 207 completed treatment through week 52. This study consisted of a 12-week induction period, followed by 40 weeks of treatment; if patients did not experience disease improvement at 12 weeks, they were able to discontinue and enroll in the ongoing open-label extension study, , which currently has about 912 patients enrolled and is expected to be completed in August 2027. ELEVATE UC 12 consisted only of a 12-week induction period; 354 patients were randomized and 316 completed treatment through week 12.

Of those treated with etrasimod, 62.6% in both trials were naive to biologics and JAK inhibitors, as were 61.8% and 62.9% of placebo-treated patients, respectively.

Among both groups, treatment-emergent adverse events included COVID-19 infection, headache, worsening of UC, pyrexia, dizziness, arthralgia, nausea, and abdominal pain. No serious adverse events of atrioventricular block or bradycardia occurred.

Comment