Symptomatic Improvement Observed Within 2 Days of Etrasimod Induction Therapy: Results From ELEVATE UC 52 and ELEVATE UC 12 Studies in Patients With Ulcerative Colitis

The time from treatment initiation to symptom relief is a key outcome for patients with UC, which can be used to guide therapeutic decisions.¹ Patient-reported outcomes of interest to assess symptom relief include rectal bleeding and stool frequency, both of which can be informed by the daily use of patient e-diaries.² Dubinsky and colleagues presented results from a study to evaluate the speed of onset of symptomatic improvement as measured by RBS and SFS, using these e-diaries from the ELEVATE UC program.³ The ELEVATE UC program was designed to evaluate etrasimod, an oral, once-daily, selective sphingosine 1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active UC.^1,4,⁵ The efficacy and safety of etrasimod have been shown in the ELEVATE UC 52 and ELEVATE UC 12 studies, which demonstrated that higher rates of clinical remission and response during the 12-week induction periods were achieved with etrasimod vs placebo.⁴

For this daily diary analysis, data from patients in both ELEVATE studies were pooled and used to calculate daily Mayo RBS and SFS, partial modified Mayo score (RBS + SFS), and change from baseline during the first 28 days of therapy. At baseline, each of these measures were found to be balanced across patients receiving etrasimod or placebo.

Symptomatic response was defined as 30% or greater change from baseline (decrease in partial modified Mayo score), and symptomatic remission was defined as an RBS of 0 and an SFS of 0 or 1 with at least 1-point improvement from baseline.³ The proportions of patients achieving symptomatic response and symptomatic remission were greater among patients receiving etrasimod compared with placebo (Figure 4). Differences were based on estimated common risk difference using the Mantel-Haenszel weights and stratified by actual naive to biologic/JAK inhibitor therapy at trial entry, actual baseline corticosteroid use, and actual baseline disease activity. The differences between the 2 treatment groups became significant from day 2 for symptomatic response (difference, 5.56; 95% CI, 0.79-10.33; P=.022) and day 11 for symptomatic remission (difference, 4.69; 95% CI, 0.36-9.03; P=.034).

Figure 4.

The proportion of patients with ulcerative colitis achieving symptomatic response and symptomatic remission from the ELEVATE UC 52 and ELEVATE UC 12 studies.

^*P<.05; **P<.01; ***P<.001

^aFirst day of a significant difference from PBO. PBO, placebo; QD, once daily.

Adapted from Dubinsky et al. Abstract 33. Presented at: ACG 2023; October 20-25, 2023; Vancouver, Canada.³

Rectal bleeding remission was defined as an RBS of 0, and stool frequency normalization was an SFS of 0. The proportion of patients achieving rectal bleeding remission and stool frequency normalization was increased in patients treated with etrasimod vs placebo. The differences between treatment groups became significant from day 15 for rectal bleeding remission (difference, 6.33; 95% CI, 0.14-12.51; P=.045) and day 3 for stool frequency normalization (difference, 3.51; 95% CI, 0.87-6.14; P=.009).

The study investigators concluded that the phase 3 ELEVATE UC trials demonstrated clinically relevant symptomatic improvements that were apparent in etrasimod-treated patients as early as day 2 of induction therapy. These findings suggested that etrasimod has a rapid treatment effect with early symptomatic response, although these results are noted to be limited owing to the nature of the post hoc analysis.