Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Nov 4;18(11):1780-1794.
doi: 10.1093/ecco-jcc/jjae079.

Impact of Prior Biologic or Janus Kinase Inhibitor Therapy on Efficacy and Safety of Etrasimod in the ELEVATE UC 52 and ELEVATE UC 12 Trials

Séverine Vermeire  1 , Bruce E Sands  2 , Laurent Peyrin-Biroulet  3   4   5   6   7   8 , Geert R D'Haens  9 , Julian Panés  10 , Andres J Yarur  11 , Douglas C Wolf  12 , Timothy Ritter  13 , Stefan Schreiber  14 , John C Woolcott  15 , Irene Modesto  16 , Michael Keating  16 , Kevin Shan  16 , Joseph Wu  17 , Michael V Chiorean  18 , Filip Baert  19 , Marla C Dubinsky  20 , Martina Goetsch  21 , Silvio Danese  22 , Brian G Feagan  23   24
Affiliations
Clinical Trial

Impact of Prior Biologic or Janus Kinase Inhibitor Therapy on Efficacy and Safety of Etrasimod in the ELEVATE UC 52 and ELEVATE UC 12 Trials

Séverine Vermeire et al. J Crohns Colitis. .

Erratum in

Abstract

Background and aims: 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]. This subgroup analysis evaluated the efficacy and safety of etrasimod 2 mg once daily vs placebo by prior biologic/Janus kinase inhibitor [bio/JAKi] exposure in ELEVATE UC 52 and ELEVATE UC 12.

Methods: Pre-defined efficacy endpoints were assessed at Weeks 12 and 52 in ELEVATE UC 52 and Week 12 in ELEVATE UC 12 in bio/JAKi-naïve and -experienced patients, and at Week 12 [pooled] based on prior advanced therapy exposure mechanism.

Results: In the ELEVATE UC 52 and ELEVATE UC 12 analysis populations, 80/274 [29.2%] and 74/222 [33.3%] patients receiving etrasimod and 42/135 [31.1%] and 38/112 [33.9%] patients receiving placebo, respectively, were bio/JAKi-experienced. In both bio/JAKi-naïve and -experienced patients, a significantly greater proportion receiving etrasimod vs placebo achieved clinical remission [p < 0.05] in ELEVATE UC 52 at Weeks 12 [naïve: 30.9% vs 9.7%; experienced: 17.5% vs 2.4%] and 52 [naïve: 36.6% vs 7.5%; experienced: 21.3% vs 4.8%]; in ELEVATE UC 12, this was observed only for bio/JAKi-naïve patients [naïve: 27.7% vs 16.2%, p = 0.033; experienced: 18.9% vs 13.2%, p = 0.349]. Similar patterns were observed for most efficacy endpoints. Among patients with prior anti-integrin exposure [N = 90], a significantly greater proportion achieved clinical response [54.1% vs 27.6%, p = 0.030], but not clinical remission [9.8% vs 3.4%, p = 0.248], with etrasimod vs placebo.

Conclusions: Bio/JAKi-naïve and -experienced patients had clinically meaningful induction and maintenance treatment benefits with etrasimod vs placebo.

Clinicaltrials.gov: NCT03945188; NCT03996369.

Keywords: Ulcerative colitis; advanced therapies; etrasimod.

PubMed Disclaimer

Conflict of interest statement

SV received lecture/speaker fees from AbbVie, Dr. Falk Pharma, Ferring, Galapagos, Hospira, Janssen, MSD, Takeda, and Tillotts; consultancy/advisory fees from AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk Pharma, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead Sciences, Hospira, IMIDomics, Janssen, Johnson and Johnson, Materia Prima, MiroBio, Morphic, MRM Health, MSD, Mundipharma, Pfizer Inc, ProDigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts, and Zealand Pharma; grants/research support from AbbVie, Pfizer Inc, Galapagos, Janssen, and Takeda. BES: received consulting fees from AbbVie, Abivax, Alimentiv, Amgen, Arena, Artugen Therapeutics, AstraZeneca, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Fresenius Kabi, Galapagos, Genentech [Roche], Gilead Sciences, GlaxoSmithKline, Gossamer Bio, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Morphic, MRM Health, Pfizer Inc, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, Ventyx Biosciences; speaking fees from Abivax, Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda; research grants from Bristol Myers Squibb, Janssen, Pfizer, Takeda, Theravance Biopharma; other support from Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda; shareholder/stock options for Ventyx Biosciences. LP-B received fees from Adacyte, AbbVie, Abivax, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, Connect Biopharma, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC Pharma, IAG Image Analysis, InDex Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharmaceutical Co, Ose Immunotherapeutics, Pandion Therapeutics, Par’Immune, Pfizer Inc, Prometheus, Protagonist Therapeutics, Roche, Roivant Sciences, Samsung, Sandoz, Sanofi, Takeda, Theravance Biopharma, Thermo Fisher, TiGenix, Tillotts, Viatris, VectivBio, Ventyx, Vifor, and Ysopia. GRD’H served as an adviser for AbbVie, AstraZeneca, Alimentiv, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, Johnson and Johnson, Takeda, Pfizer Inc, Polpharma, Prometheus Biosciences, Tillotts, and Ventyx; received speaker fees from AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly, Johnson and Johnson, Takeda, Pfizer Inc, and Tillotts. JP received personal fees from AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celsius, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Janssen, Mirum, Morphic, Pandion Therapeutics, Pfizer Inc, Progenity, Prometheus, Protagonist Therapeutics, Revolo Biotherapeutics, Sanofi, Takeda, Theravance Biopharma, and Wassermann; grant support from AbbVie and Pfizer Inc. AJY received consultancy fees from Pfizer Inc, Arena, Takeda, and Bristol Myers Squibb; lecture and speaking fees from Bristol Myers Squibb. DCW received research grant support from AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer Inc, Takeda, and Ventyx; lecture fees from AbbVie, Bristol Myers Squibb, Janssen, Pfizer Inc, and Takeda; consultancy fees from AbbVie, Arena, Bristol Myers Squibb, Janssen, Pfizer Inc, and Takeda. TR served on speaker panels for Takeda, Janssen, Pfizer Inc, Bristol Myers Squibb, AbbVie, and Lilly; served on a data adjudication committee for Ferring/Rebiotix; served on advisory boards for AbbVie, Ardelyx, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Ferring, Genentech/Roche, Gilead Sciences, and Intercept Pharma; shareholder for Iterative Scopes. SS received lecture/speaker fees from AbbVie, Arena, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Fresenius Kabi, Janssen, MSD, Pfizer Inc, and Takeda; consultancy/advisory fees from AbbVie, Arena, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Fresenius Kabi, Gilead Sciences, I-Mab, Janssen, MSD, Mylan, Pfizer Inc, Protagonist Therapeutics, Provention Bio, Takeda, and Theravance Biopharma. JW, IM, MK, KS, JW, and MG are employees and shareholders of Pfizer Inc. MVC received grant support from Pfizer Inc, Janssen, Novartis, and BMS; consulting fees from AbbVie, Arena, BMS, Medtronic, Pfizer Inc, Prometheus, Lilly, Janssen, and Takeda; speaker fees from AbbVie, Janssen, Medtronic, Pfizer Inc, BMS, Takeda, and Fresenius Kabi. FB received financial support for research/grants from AbbVie, Amgen, Janssen, and Takeda; received lecture fees and served on a speaker’s bureau for AbbVie, Arena, Celltrion, Ferring, Galapagos, Janssen, Merck Sharp & Dohme, Pfizer Inc, and Takeda; consultancy fees from AbbVie, Amgen, Arena, Celgene, Celltrion, Ferring, Fresenius Kabi, Janssen, Merck Sharp & Dohme, Pfizer Inc, and Sandoz. MCD received consulting fees from AbbVie, Abivax, Arena, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Takeda, and UCB; grant/research support from Janssen; shareholder/royalties and directorship/ownership interest in Trellus Health. SD received lecture/speaker fees from AbbVie, Amgen, Ferring, Gilead Sciences, Janssen, Mylan, Pfizer Inc, and Takeda; consulting/advisory fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead Sciences, Hospira, Janssen, Johnson and Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB, and Vifor; holds directorship/ownership in Gastroenterology and Endoscopy. BGF serves as Senior Scientific Director for Alimentiv Inc, which provides central reading services; he is not a company employee and has no equity stake in the organisation which is owned by a medical trust; received speakers fees from AbbVie, Janssen, and Takeda; served as a consultant/advisory board member for AbbVie, AbolerIS Pharma, Agomab Therapeutics, AllianThera Biopharma, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital Advisors, Atomwise, BIOJAMP, Biora Therapeutics, Boehringer Ingelheim, Boxer, Celsius Therapeutics, Celgene/BMS, Connect Biopharma, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave BioPharma, FirstWord Group, Galapagos, Galen/Atlantica, Genentech/Roche, Gilead Sciences, Gossamer Bio, GSK, Hinge Bio, HotSpot Therapeutics, InDex Pharmaceuticals, Imhotex, Immunic Therapeutics, JAK Academy, Janssen, Japan Tobacco Inc., Kaleido Biosciences, Landos Biopharma, Leadiant Biosciences, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM Pharma, Origo Biopharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer Inc, Prometheus Therapeutics and Diagnostics, PlayToKnow AG, Progenity, Protagonist Therapeutics, PTM Therapeutics, Q32 Bio, Rebiotix, Redx, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen, Takeda, Teva, Thelium Therapeutics, TiGenix, Tillotts, Ventyx, VHSquared, Viatris, Ysios, Ysopia, and Zealand Pharma; shareholder for Gossamer Pharma.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
[A] Clinical remission,a [B] clinical response,b [C] endoscopic improvement,c and [D] CS-free clinical remissiond in ELEVATE UC 52 and ELEVATE UC 12, stratified by prior bio/JAKi exposure [baseline MMS 5–9]. Consistent with the statistical analysis plan and primary efficacy analyses, subgroup efficacy analyses were performed in patients with a baseline MMS of 5–9. Treatment comparisons [treatment differences and 95% CIs] and two-sided p-values were obtained using the CMH method assuming common proportion difference within each subgroup, adjusting to prior bio/JAKi therapy exposure [if applicable], baseline CS use, and baseline disease activity [MMS of 4–6 or 7–9]. Patients missing an assessment at the specified analysis visit were considered nonresponders; p < 0.05 are highlighted in bold. aClinical remission was defined as an SFS = 0 [or = 1 with a ≥ 1-point decrease from baseline], RBS = 0, and ES ≤ 1 [excluding friability]. bClinical response was defined as a ≥ 2-point and ≥ 30% decrease from baseline in MMS and a ≥ 1-point decrease from baseline in RBS or an absolute RBS ≤ 1. cEndoscopic improvement was defined as an ES ≤ 1. dCS-free clinical remission was defined as remission at Week 52 and had not been receiving CS for ≥ 12 study weeks before Week 52. Δ, adjusted percentage difference for etrasimod minus placebo; bio/JAKi, biologic/Janus kinase inhibitor; CI, confidence interval; CMH, Cochran–Mantel–Haenszel; CS, corticosteroid; ES, endoscopic subscore; MMS, modified Mayo score; RBS, rectal bleeding subscore; SFS, stool frequency subscore; QD, once daily; UC, ulcerative colitis.
Figure 2
Figure 2
Efficacy endpoints at Week 12 in ELEVATE UC 52 and ELEVATE UC 12 [pooled] in patients with prior exposure to anti-integrin therapy and prior exposure to bio/JAKi therapy excluding anti-integrins [baseline MMS 4–9]. This is a subgroup analysis of the pooled full analysis set of patients with a baseline MMS score of 4–9 in ELEVATE UC 52 and ELEVATE UC 12. Treatment comparisons [treatment differences and 95% CIs] and two-sided p-values were obtained using the CMH method assuming common proportion difference with the subgroup, adjusting to baseline CS use, baseline disease activity [MMS of 4–6 or 7–9], and study stratification [ELEVATE UC 52 or ELEVATE UC 12]. Patients missing an assessment at the specified analysis visit were considered nonresponders; p < 0.05 are highlighted in bold. The anti-integrin class included vedolizumab, etrolizumab, and other investigative anti-integrin therapies. Patients with prior anti-integrin exposure may also have had prior exposure to other bio/JAKi therapies. aClinical remission was defined as an SFS = 0 [or = 1 with a ≥ 1-point decrease from baseline], RBS = 0, and ES ≤ 1 [excluding friability]. bClinical response was defined as a ≥ 2-point and ≥ 30% decrease from baseline in MMS, and a ≥ 1-point decrease from baseline in RBS or an absolute RBS ≤ 1. cEndoscopic improvement was defined as an ES ≤ 1. dEIHR was defined as an ES ≤ 1 with histological remission as measured by a Geboes Index score < 2.0. eSymptomatic remission was defined as an SFS = 0 [or = 1 with a ≥ 1-point decrease from baseline] and an RBS = 0. fSymptomatic response was defined as ≥ 30% decrease from baseline in composite RB and SF subscores. bio/JAKi, biologic/Janus kinase inhibitor; CI, confidence interval; CMH; Cochran–Mantel–Haenszel; CS, corticosteroid; EIHR, endoscopic improvement–histological remission; ES, endoscopic subscore; MMS, modified Mayo score; QD, once daily; RBS, rectal bleeding subscore; SFS, stool frequency subscore; SD, standard deviation; UC, ulcerative colitis.
Figure 3
Figure 3
[A and B] Symptomatic responsea and [C and D] symptomatic remissionb over time in ELEVATE UC 52 and ELEVATE UC 12, stratified by prior bio/JAKi exposure [baseline MMS 5–9]; *p < 0.05. Consistent with the statistical analysis plan and the primary efficacy analyses, subgroup efficacy analyses were performed in patients with a baseline MMS of 5–9. Treatment comparisons [treatment difference and 95% CIs] and two-sided p-values were obtained using the CMH method assuming common proportion difference within each subgroup, adjusting to prior bio/JAKi therapy [if applicable], baseline CS use, and baseline disease activity [MMS of 4–6 or 7–9]. Patients missing an assessment at the specified analysis visit were considered nonresponders; p < 0.05 are highlighted in bold. aSymptomatic response was defined as a decrease from baseline ≥ 30% in composite RBS and SFS. bSymptomatic remission was defined as SFS = 0 [or = 1 with a ≥ 1-point decrease from baseline] and an RBS = 0. bio/JAKi, biologic/Janus kinase inhibitor; CI, confidence interval; CMH; Cochran–Mantel–Haenszel; CS, corticosteroid; MMS, modified Mayo score; N, total number of patients; n, number of patients with evaluable data within each category; RBS, rectal bleeding subscore; SFS, stool frequency subscore; QD, once daily; UC, ulcerative colitis.
Figure 3
Figure 3
[A and B] Symptomatic responsea and [C and D] symptomatic remissionb over time in ELEVATE UC 52 and ELEVATE UC 12, stratified by prior bio/JAKi exposure [baseline MMS 5–9]; *p < 0.05. Consistent with the statistical analysis plan and the primary efficacy analyses, subgroup efficacy analyses were performed in patients with a baseline MMS of 5–9. Treatment comparisons [treatment difference and 95% CIs] and two-sided p-values were obtained using the CMH method assuming common proportion difference within each subgroup, adjusting to prior bio/JAKi therapy [if applicable], baseline CS use, and baseline disease activity [MMS of 4–6 or 7–9]. Patients missing an assessment at the specified analysis visit were considered nonresponders; p < 0.05 are highlighted in bold. aSymptomatic response was defined as a decrease from baseline ≥ 30% in composite RBS and SFS. bSymptomatic remission was defined as SFS = 0 [or = 1 with a ≥ 1-point decrease from baseline] and an RBS = 0. bio/JAKi, biologic/Janus kinase inhibitor; CI, confidence interval; CMH; Cochran–Mantel–Haenszel; CS, corticosteroid; MMS, modified Mayo score; N, total number of patients; n, number of patients with evaluable data within each category; RBS, rectal bleeding subscore; SFS, stool frequency subscore; QD, once daily; UC, ulcerative colitis.
See this image and copyright information in PMC

References

    1. Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel J-F.. Ulcerative colitis. Lancet 2017;389:1756–70. - PMC - PubMed
    1. Magro F, Gionchetti P, Eliakim R, et al..; European Crohn’s and Colitis Organisation [ECCO]. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: definitions, diagnosis, extra-intestinal manifestations, pregnancy, cancer surveillance, surgery, and ileo-anal pouch disorders. J Crohns Colitis 2017;11:649–70. - PubMed
    1. Peyrin-Biroulet L, Sandborn W, Sands BE, et al.. Selecting therapeutic targets in inflammatory bowel disease [STRIDE]: determining therapeutic goals for treat-to-target. Am J Gastroenterol 2015;110:1324–38. - PubMed
    1. Raine T, Bonovas S, Burisch J, et al.. ECCO guidelines on therapeutics in ulcerative colitis: medical treatment. J Crohns Colitis 2022;16:2–17. - PubMed
    1. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD.. ACG Clinical Guideline: ulcerative colitis in adults. Am J Gastroenterol 2019;114:384–413. - PubMed

Publication types

Substances

Associated data

Grants and funding