Introduction

Etrasimod is an oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). In patients with moderately to severely active UC, treatment guidelines recommend early use of advanced therapies rather than gradual step up after failure of 5-aminosalicylate (5-ASA).¹

Aims & Methods

This prespecified subgroup analysis assessed the efficacy of etrasimod vs placebo in patients in ELEVATE UC 52 (NCT03945188) with, and without, prior oral 5-ASA failure only (defined as inadequate response, loss of response or intolerance to previous treatment with oral 5-ASA but not to any other previous UC medication). Efficacy endpoints assessed at Weeks 12 and 52 included clinical remission, endoscopic improvement, symptomatic remission and composite histological endpoints.

Results

In total, 45 and 29 patients receiving etrasimod and placebo, respectively, had prior 5-ASA failure only and 244 and 115 patients did not. At Weeks 12 and 52, among those who had failed prior 5-ASA only, significantly more patients receiving etrasimod vs placebo achieved clinical remission (Week 12, % difference [Δ]: 38.3%, p < 0.001; Week 52, Δ: 45.0%, p < 0.001), endoscopic improvement (Week 12, Δ: 54.7%, p < 0.001; Week 52, Δ: 47.8%, p < 0.001), symptomatic remission (Week 12, Δ: 38.6%, p < 0.001; Week 52, Δ: 45.0%, p < 0.001) and endoscopic improvement-histologic remission (Week 12, Δ: 35.6%, p < 0.001; Week 52, Δ: 31.1%, p < 0.001; Table). Significantly more patients receiving etrasimod vs placebo in this subgroup achieved endoscopic normalisation-histologic remission (Week 12, Δ: 19.9%, p = 0.002; Week 52, Δ: 24.3%, p < 0.001) and disease clearance (Week 12, Δ: 15.6%, p = 0.008; Week 52, Δ: 27.8%, p < 0.001). Among those who had failed other therapies, significantly more patients receiving etrasimod vs placebo also achieved all endpoints at Weeks 12 and 52 (p < 0.01).

Conclusion

Etrasimod demonstrated robust efficacy as first-line advanced therapy in patients who had failed oral 5-ASA only, across all evaluated endpoints including stringent composite histological endpoints, consistent with the overall ELEVATE UC population. Etrasimod shows efficacy when used early in the UC treatment algorithm.

References

1. Singh S et al. Gastroenterology 2024; 167: 1307–1343.
Pfizer’s generative artificial intelligence tool MAIA was used to assist production of the abstract first draft. Authors reviewed/edited and take responsibility for the content.

Disclosure

DTR received grant support from Takeda; consultancy fees from AbbVie, Abivax SA, Altrubio, Avalo Therapeutics, Bausch Health, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celltrion, ClostraBio, Connect BioPharma, Douglas Pharmaceuticals, Eli Lilly & Co., Foresee, Genentech (Roche) Inc., Image Analysis Group, InDex Pharmaceuticals, Iterative Health, Janssen Pharmaceuticals, Odyssey Therapeutics, Pfizer Inc, Sanofi, Takeda Pharmaceuticals, Throne and Vedanta.
CWL received speaker fees from AbbVie, Dr Falk, Ferring, Hospira, Janssen, MSD, Pfizer Inc, Shire, Takeda and Warner-Chilcott; consultancy fees from AbbVie, Dr Falk, Gilead, GSK, Hospira, Iterative Scopes, Janssen, MSD, Oshi Health, Pfizer Inc, Pharmacosmos, Takeda, Topivert, Trellus Health and Vifor Pharma; research funding from AbbVie and Gilead.
FB received research/grant support from AbbVie, Amgen, Eurogenerics, Janssen and Takeda; lecture fees/speaker’s bureau from AbbVie, Arena Pharmaceuticals, Celltrion, Ferring, Galapagos, Janssen, Merck Sharp & Dohme, Pfizer Inc and Takeda; consultancy fees from AbbVie, Abivax, Amgen, Arena Pharmaceuticals, Celgene, Celltrion, Ferring, Fresenius Kabi, Janssen, Merck Sharp & Dohme, Pfizer Inc and Sandoz.
MK is an employee and shareholder of Pfizer Inc.
AB is an employee of Pfizer Healthcare India Private Ltd and shareholder of Pfizer Inc.
KL is an employee of Pfizer AG and shareholder of Pfizer Inc.
MG is an employee of Pfizer AG and shareholder of Pfizer Inc.
AMM is an employee and shareholder of Pfizer Inc.
KW is an employee of Pfizer Canada Inc and shareholder of Pfizer Inc.
JKM is an advisory committee/board member on AbbVie, Alimentiv, Amgen, AstraZeneca, Bausch Health, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, Lilly, Lupin, Organon, Paladin, Pfizer Inc, Pharmascience, Qu Biologics, Roche, Sandoz, SCOPE, Takeda, Teva and Viatris; receives lecture/speaker fees from AbbVie, Amgen, Bausch Health, Ferring, Fresenius Kabi, Janssen, Organon, Pfizer Inc, Pharmascience, Roche, Takeda and Viatris.

Introduction

Subcutaneous vedolizumab has become available for the treatment of inflammatory bowel diseases in 2021 after intravenous induction. The aim of this multicentre prospective study was to evaluate treatment persistence, efficacy and tolerance after switching from intravenous (IV) to subcutaneous (SC) vedolizumab (VDZ) in stable patients.

Aims & Methods

All consecutive patients with either ulcerative colitis (UC) or Crohn’s disease (CD), in clinical remission for at least 3 months and switching from IV to SC-VDZ, were included in this multicentre cohort study. Inclusion could take place prospectively or within 3 months after switch. Clinical remission was defined by partial Mayo score ≤2 for UC or Harvey Bradshaw index ≤4 for CD; concomitant 5-amonisalycilate or immunosuppressive treatment was allowed at stable doses. Concomitant biologic or JAK-inhibitor treatments were not permitted during the study period, which lasted for 12 months after switch. SC-VDZ was started at 108 mg every other week. Primary endpoint was SC-VDZ treatment persistence at 54 weeks (W54) after switch; need for surgery, prolonged corticosteroid courses (>14 days) and loss of follow-up were considered as treatment failure. This is an analysis based on early 6-months (M6) results, reporting rates of treatment persistence, need for optimisation, switch-back to IV-VDZ and adverse events.

Results

Overall, 337 patients were analysed of 348 included, after removal of 10 patients who had an active disease and one an active infection: 246 patients (73%) had UC, 91 (27%) had CD, with a median disease duration of 9 years [interquartile range: 4-17] in UC and 13 [8-19] years in CD. Patients with UC had been on IV-VDZ for a median time of 1.4 years [0.4-3.3] prior to switch, compared to 3.1 [1.3-6.1] for CD patients, with 205 patients overall (62%) on standard IV-VDZ regimen (300mg 8-weekly).
At M6, the SC-VDZ discontinuation-free survival rate was 93.9% [95% confidence interval: 91.3 - 96.5], with no significant difference between CD and UC (p=0.6). During follow-up, 33 patients (10%) had SC-optimisation, with similar rates in both diseases. Among them, 63% has an optimised IV-VDZ regimen prior to switch. In total, 13 (4%) patients switched-back to IV-VDZ: 3 due to loss of response despite SC-VDZ optimisation, 7 for injection site reaction and 3 for various non severe adverse-events. 181 (54%) patients declared adverse events, the most frequent being injection site reactions (20%) and infections (17%). Only one serious adverse event potentially related to treatment was reported (a digestive infection that led to hospitalisation with negative testing), though it did not lead to treatment discontinuation.

Conclusion

In this multicentre prospective cohort of patients with CD or UC in clinical remission who switched from IV to SC vedolizumab, drug persistence rate at 6 months was over 90%, with good safety results. 12-month results are pending.

Disclosure

Financial support: Takeda