Efficacy and safety of etrasimod in patients with moderate to severe isolated proctitis compared with patients with more extensive disease: a subgroup analysis of the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials

Introduction Etrasimod is an investigational, oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). Although approximately 30% of patients (pts) with UC present with isolated proctitis, [1] most phase 3 trials of systemic UC therapies exclude this subgroup.

Objectives This post hoc analysis of pts with UC enrolled in the ELEVATE UC trials assessed the efficacy and safety of etrasimod in pts with isolated proctitis vs those with more extensive disease (proctosigmoiditis/left-sided colitis/pancolitis).

Methodology In the phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials, pts (aged 16–80 years) with moderately to severely active UC were randomised 2:1 to etrasimod 2 mg once daily or placebo (PBO). ELEVATE UC 52 comprised a 12-week (wk) induction period followed by a 40-wk maintenance period with a treat-through design. ELEVATE UC 12 comprised a 12-wk induction period. Both trials allowed inclusion of pts with isolated proctitis (<10 cm rectal involvement; centrally read) provided they met all other eligibility criteria. Pre-defined clinical endpoints were assessed in pts with isolated proctitis in a pooled cohort from both studies and in a subgroup of pts with more extensive disease (data from individual studies). Safety was assessed up to Wk 52.

Result In ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 pts received etrasimod, and 144 and 116 pts received PBO, respectively. [2] This analysis included 64 pts (etrasimod, N=42; PBO, N=22) at Wk 12 and 36 pts (etrasimod, N=27; PBO, N=9) at Wk 52 with isolated proctitis. Proportions of pts with isolated proctitis achieving clinical remission and clinical response at Wks 12 and 52, and corticosteroid-free remission at Wk 52 were generally greater in pts receiving etrasimod vs PBO ([Fig. 1]). Efficacy findings were similar in pts with isolated proctitis vs those with more extensive disease ([Fig. 1]). Safety in pts with isolated proctitis was similar to the overall trial population. [2]

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Conclusion Etrasimod was effective for induction and maintenance of clinical remission in pts with UC and isolated proctitis. Efficacy and safety of etrasimod in pts with isolated proctitis were similar to those with more extensive disease in the ELEVATE UC trials. [2]

 

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• References

• 1 Katz et al. Inflamm Bowel Dis 2008; 14: S17
• 2 Sandborn et al. Lancet: Epub ahead of print 2023

Publikationsverlauf

Artikel online veröffentlicht:
28. August 2023