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Clinical Trial
. 2024 Oct 15;18(10):1596-1605.
doi: 10.1093/ecco-jcc/jjae060.

Etrasimod for the Treatment of Ulcerative Colitis: Analysis of Infection Events from the ELEVATE UC Clinical Programme

Miguel Regueiro  1 , Britta Siegmund  2 , Andres J Yarur  3 , Flavio Steinwurz  4 , Krisztina B Gecse  5 , Martina Goetsch  6 , Abhishek Bhattacharjee  7 , Joseph Wu  8 , Jesse Green  9 , Aoibhinn McDonnell  10 , Catherine Crosby  11 , Krisztina Lazin  6 , Diogo Branquinho  12 , Irene Modesto  12 , Maria T Abreu  13
Affiliations
Clinical Trial

Etrasimod for the Treatment of Ulcerative Colitis: Analysis of Infection Events from the ELEVATE UC Clinical Programme

Miguel Regueiro et al. J Crohns Colitis. .

Abstract

Background and aims: Infections are a safety concern in patients with ulcerative colitis [UC]. Etrasimod is an oral, once daily [QD], selective sphingosine 1-phosphate [S1P]1,4,5 receptor modulator for the treatment of moderately to severely active UC. It leads to selective and reversible lymphocyte sequestration and partial peripheral lymphocyte count decrease. We report infection events from the phase 3 ELEVATE programme.

Methods: Proportions, incidence rates [IRs; per 100 patient-years], and descriptive analyses of all serious, severe, herpes zoster and opportunistic infections are reported in the Pivotal UC cohort [ELEVATE UC 52 and ELEVATE UC 12]. Cox regression models evaluated potential baseline risk factors.

Results: In this analysis [n = 787], proportions [IRs] of all infection events were similar for patients receiving etrasimod 2 mg QD (18.8% [41.1]) or placebo (17.7% [49.0]). Serious infections occurred in three [0.6%] and five [1.9%] patients receiving etrasimod and placebo, respectively. Two herpes zoster events were reported in each group [etrasimod: 0.4%; placebo: 0.8%], all localised and non-serious. One opportunistic infection event was reported in each group. No patient with an absolute lymphocyte count [ALC] < 0.2 × 109/L reported serious/severe or opportunistic infections; no baseline risk factors were identified for such events. No deaths occurred.

Conclusions: Patients receiving etrasimod demonstrated no increased risk of infection. The incidence of serious infections and herpes zoster was similar in each group. Among patients receiving etrasimod, no association between ALC < 0.5 × 109/L and infection events was observed. Longer-term follow-up will further characterise the etrasimod safety profile. Clinicaltrials.gov: NCT03945188; NCT03996369.

Keywords: Etrasimod; infections; ulcerative colitis.

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Conflict of interest statement

MR reports grants and research support from AbbVie, Bristol Myers Squibb, Celgene, Genentech, Gilead, Janssen, Pfizer, Takeda, and UCB; consultancy fees from AbbVie, ALFASIGMA, S.p.A., Allergan, Amgen, Bristol Myers Squibb, Celgene, Genentech, Gilead, Janssen, Lilly, Miraca Labs, Pfizer, Prometheus, Salix, Seres, Takeda, TARGET Pharma Solutions, and UCB; and holds stock in Wolters Kluwer Health as an Author/Editor of UpToDate. BS reports research support from Pfizer; lecture fees from AbbVie, CED Service GmbH, Chiesi, Falk, Ferring, Gilead, Janssen, Lilly, Materia Prima, Pfizer, and Takeda; and consultancy fees from AbbVie, Abivax, Arena Pharma, Bristol Myers Squibb, Boehringer, CED Service GmbH, Celgene, CT-Scout, Endpoint Health, Falk, Forga Software, Galapagos, Gilead, Janssen, Lilly, Materia Prima, Pfizer, Pharma Insight, PredictImmune, PsiCro, and Takeda. AJY reports consultancy fees from Arena, Bristol Myers Squibb, Pfizer, and Takeda; and lecture/speaker fees from Bristol Myers Squibb. FS reports consultancy/speaker fees from AbbVie, Amgen, Celltrion, Eurofarma, Ferring, Janssen, Pfizer, Sandoz, and Takeda. KBG reports research support from Celltrion, Galapagos, and Pfizer; and speakers’ honoraria and/or consultancy fees from AbbVie, Celltrion, Ferring Pharmaceuticals, Immunic Therapeutics, Janssen, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, and Tillotts. MG is an employee and shareholder of Pfizer AG. AB is an employee of Pfizer Healthcare India Pvt; and shareholder of Pfizer Inc. JW, JG, CC, DB, and IM are employees and shareholders of Pfizer Inc. AM is an employee of Pfizer Ltd, and a shareholder of Pfizer. KL is an employee of Pfizer AG, and a shareholder of Pfizer. MTA reports consulting fees from AbbVie, Bristol Myers Squibb, Celsius, Eli Lilly, Gilead, Janssen, Janssen Biotech, Pfizer, Prometheus, Prometheus Bioscience, Takeda, and UCB Biopharma.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Patient demographics and baseline disease characteristics in the pooled phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials. 5-ASA, 5-aminosalicylates; BMI, body mass index; hsCRP, high-sensitivity C-reactive protein; JAKi, Janus kinase inhibitor; MMS, modified Mayo score; QD, once daily; UC, ulcerative colitis.
Figure 2
Figure 2
Incidence rates per 100 PY for infection events [Pivotal UC cohort]. N, number of patients in the analysis set; n, number of patients with infection events; PY, patient-years; QD, once daily; UC, ulcerative colitis.
Figure 3
Figure 3
Multivariable Cox regression model of risk factors predicting all infection events [including non-serious] among patients receiving etrasimod 2 mg QD and placebo in the ELEVATE UC clinical programme. HRs [95% CI] are plotted on a logarithmic scale. A backward model selection algorithm was used on a multivariable Cox model that included effects for study [ELEVATE UC 52 and ELEVATE UC 12], treatment group [etrasimod 2 mg QD and placebo] and a set of candidate baseline risk factors selected from the corresponding simple Cox table [at least one comparison p-value < 0.1; Supplementary Table 3]. This candidate set of baseline risk factors was subject to backward model selection, except the study and treatment group which was mandatorily included in the model. No potential risk factors for serious, severe, opportunistic infections, or infection events leading to study treatment discontinuation were retained in the multivariable Cox model. BMI, body mass index; CI, confidence interval; HR, hazard ratio; IR, incidence rate; PY, patient-years; QD, once daily; UC, ulcerative colitis.
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