Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies

Sandborn, William J.; Vermeire, Séverine; Peyrin–Biroulet, Laurent; Dubinsky, Marla C.; Panés, Julián; Yarur, Andrés; Ritter, Timothy E.; Baert, Filip; Schreiber, Stefan; Sloan, Sheldon; Cataldi, Fabio; Shan, Kevin; Rabbat, Christopher J.; Chiorean, Michael; Wolf, Douglas C.; Sands, Bruce E.; D’Haens, Geert R.; Danese, Silvio; Goetsch, Martina; Feagan, Brian G.

doi:10.1016/s0140-6736(23)00061-2

Cited by 141 publications

(68 citation statements)

References 27 publications

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“…Across both trials, a total of nine bradycardia events were observed, all of them among patients receiving etrasimod. 120 All but one event (8/9) was first reported on day 1 of treatment with the remaining first reported on day 2, and none reported after day 2. Seven were asymptomatic, and none required pharmacological treatment to reverse bradycardia.…”

Section: Evidence From Ibd Clinical Trialsmentioning

confidence: 96%

“…Follow‐up time was 52 and 12 weeks respectively. Across both trials, a total of nine bradycardia events were observed, all of them among patients receiving etrasimod 120 . All but one event (8/9) was first reported on day 1 of treatment with the remaining first reported on day 2, and none reported after day 2.…”

Section: Risk Of Cardiac Conduction Abnormalities With Smdsmentioning

confidence: 99%

“…No patient discontinued treatment for cardiac conduction abnormalities; only one patient who received placebo during OASIS experienced heart rate lowering with a nadir of 48 beats/minute. 119 ELEVATE UC 52 and ELEVATE UC 12 were two phase 3, placebocontrolled trials which comprised 289 and 238 UC patients who received treatment with etrasimod 2 mg. 120 Follow-up time was 52 and 12 weeks respectively. Across both trials, a total of nine bradycardia events were observed, all of them among patients receiving etrasimod.…”

Section: Evidence From Ibd Clinical Trialsmentioning

confidence: 99%

“…ELEVATE UC 52 and ELEVATE UC 12 were two phase 3, placebo‐controlled trials which comprised 289 and 238 UC patients who received treatment with etrasimod 2 mg 120 . Follow‐up time was 52 and 12 weeks respectively.…”

Section: Risk Of Cardiac Conduction Abnormalities With Smdsmentioning

confidence: 99%

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Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs

Olivera

Lasa

Peretto

et al. 2023

Aliment Pharmacol Ther

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Background:In the context of an ageing inflammatory bowel disease (IBD) population, cardiovascular comorbidities become particularly relevant. Novel small molecule drugs (SMDs) for the treatment of moderate-to-severe IBD have been recently approved, including Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P) modulators. Data from rheumatoid arthritis population have raised concerns about the risk of cardiovascular events with the use of tofacitinib, which was extrapolated to other immune-mediated diseases and other JAK inhibitors. S1P receptor modulation has been associated with potential cardiovascular events, especially bradycardia and cardiac conduction abnormalities. Aim:To review the incidence of cardiovascular events with the use of SMDs in patients with IBD and to provide practical recommendations on mitigation strategies.

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Section: Evidence From Ibd Clinical Trialsmentioning

confidence: 96%

Section: Risk Of Cardiac Conduction Abnormalities With Smdsmentioning

confidence: 99%

Section: Evidence From Ibd Clinical Trialsmentioning

confidence: 99%

Section: Risk Of Cardiac Conduction Abnormalities With Smdsmentioning

confidence: 99%

See 2 more Smart Citations

Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs

Olivera

Lasa

Peretto

et al. 2023

Aliment Pharmacol Ther

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“…The conducted phase 3 trial also included patients with isolated ulcerative proctitis, where efficacy of etrasimod could also be shown. There were 9 etrasimod-associated events of bradycardia, and two patients discontinued the study due to symptomatic bradycardia [32].…”

Section: S1pr Modulatorsmentioning

confidence: 99%

Current and Emerging Targeted Therapies for Ulcerative Colitis

Pietschner¹,

Räth²,

Atreya³

2023

Visc Med

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Background: Ulcerative colitis is one of the main entities of inflammatory bowel diseases. The clinical course of this immune-mediated disorder is marked by unpredictable exacerbations and asymptomatic remission, causing lifelong morbidity. Optimized anti-inflammatory treatment is a prerequisite to not only restore the quality of life of the affected patients but also halt progressive bowel damage and reduce the risk for colitis-associated neoplasia. Advances in understanding the underlying immunopathogenesis of ulcerative colitis have led to the advent of targeted therapies that selectively inhibit crucial molecular structures or signaling pathways that perpetuate the inflammatory reaction. Summary: We will delineate the mode of action and summarize efficacy and safety data of current and emerging targeted therapies in ulcerative colitis, which encompasses representatives of the drug classes of antibodies, small molecules, and oligonucleotides. These substances have already been approved for induction and maintenance treatment or are being tested in late-stage clinical trials in moderately-to-severely active ulcerative colitis patients. These advanced therapies have enabled us to define and achieve novel therapeutic outcomes, such as clinical and endoscopic remission, histological remission, mucosal healing, and recently, also barrier healing as an emerging outcome measure. Key Messages: Established and emerging targeted therapies and monitoring modalities broaden our therapeutic armamentarium and have enabled us to define novel therapeutic outcomes that have the potential to modify the individual disease course of patients with ulcerative colitis.

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Risankizumab for Ulcerative Colitis

Louis,

Schreiber,

Panaccione

et al. 2024

JAMA

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ImportanceThe clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown.ObjectiveTo evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis.Design, Setting, and ParticipantsTwo phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab.InterventionsFor the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks.Main Outcomes and MeasuresThe primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial.ResultsAmong the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P &lt; .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P &lt; .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No adverse event signals were detected in the treatment groups.Conclusion and RelevanceCompared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up.Trial RegistrationClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135

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Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies

Cited by 141 publications

References 27 publications

Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs

Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs

Current and Emerging Targeted Therapies for Ulcerative Colitis

Risankizumab for Ulcerative Colitis

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