THE INCIDENCE OF ACTIVE TUBERCULOSIS AND IMPACT OF PROPHYLACTIC TREATMENT AMONG PATIENTS WITH LATENT TUBERCULOSIS, IN THE PHASE 3 ELEVATE UC 52 AND ELEVATE UC 12 TRIALS

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Introduction

Most clinical trials of systemic ulcerative colitis (UC) therapies exclude patients (pts) with isolated proctitis, who are considered a more treatment-refractory population, creating a need for clinical evidence. Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active UC. The phase 3 etrasimod ELEVATE UC trials included pts with isolated proctitis (< 10 cm rectal involvement), provided they met all other eligibility criteria.¹

Aims & Methods

This post hoc analysis assessed predefined efficacy and safety outcomes in subgroups of pts with isolated proctitis and more extensive colitis (proctosigmoiditis/left-sided colitis/pancolitis). In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts (aged 16–80 years) with moderately to severely active UC were randomised 2:1 to etrasimod 2 mg once daily or placebo. ELEVATE UC 52 comprised a 12-week (wk) induction period followed by a 40-wk maintenance period with a treat-through design. ELEVATE UC 12 comprised a 12-wk induction period. Clinical endpoints were assessed in pts with isolated proctitis (data pooled from both trials) and in pts with more extensive colitis (individual trial data). Sustained and corticosteroid-free clinical remission were assessed at Wk 52 (ELEVATE UC 52 only). Bowel urgency Numeric Rating Scale (NRS) was assessed at Wks 12 and 52. Safety was assessed up to Wk 52.

Results

This analysis included 64 (pooled; Wk 12) and 36 (ELEVATE UC 52; Wk 52) pts with isolated proctitis, and 397 (ELEVATE UC 52; Wks 12 and 52) and 326 (ELEVATE UC 12; Wk 12) pts with more extensive colitis. Similar proportions of pts with isolated proctitis achieved the predefined efficacy endpoints vs those with more extensive colitis (Table). Pts with isolated proctitis receiving etrasimod had similar improvements in urgency NRS scores vs those with more extensive colitis (mean change from baseline: Wk 12, -2.8 vs -2.9 [both trials]; Wk 52, -5.0 vs -4.1). Safety in pts with isolated proctitis was generally similar to that in the overall trial population.¹

Table. Achievement of prespecified efficacy endpoints among pts with isolated proctitis^a and those with more extensive colitis in the etrasimod ELEVATE UC trials (full analysis set)
Endpoint	Pts with isolated proctitis			Pts with more extensive colitis
Endpoint	ELEVATE UC 12 + ELEVATE UC 52			ELEVATE UC 52			ELEVATE UC 12
Wk 12	PBO, n (%) [N=22]	Etrasimod 2 mg QD, n (%) [N=42]	Percentage difference from PBO^b	PBO, n (%) [N=135]	Etrasimod 2 mg QD, n (%) [N=262]	Percentage difference from PBO^b	PBO, n (%) [N=103]	Etrasimod 2 mg QD, n (%) [N=223]	Percentage difference from PBO^b
Clinical remission^c Clinical response^d Symptomatic remission^e Endoscopic improvement^f Endoscopic improvement-histological remission^g	3 (13.6) 9 (40.9) 5 (22.7) 5 (22.7) 3 (13.6)	18 (42.9) 30 (71.4) 22 (52.4) 22 (52.4) 16 (38.1)	45.5*** 35.2* 44.2* 41.3 40.7**	10 (7.4) 48 (35.6) 30 (22.2) 20 (14.8) 7 (5.2)	68 (26.0) 162 (61.8) 118 (45.0) 93 (35.5) 55 (21.0)	18.5* 26.0* 22.7* 20.6* 16.0***	16 (15.5) 43 (41.7) 31 (30.1) 21 (20.4) 9 (8.7)	57 (25.6) 141 (63.2) 108 (48.4) 71 (31.8) 36 (16.1)	9.9* 21.0* 18.0 11.4* 7.4*
Wk 52, ELEVATE UC 52	PBO, n (%) [N=9]	Etrasimod 2 mg QD, n (%) [N=27]	Percentage difference from PBO^b	PBO, n (%) [N=135]	Etrasimod 2 mg QD, n (%) [N=262]	Percentage difference from PBO^b	N/A
Clinical remission^c Clinical response^d Symptomatic remission^e Endoscopic improvement^f Endoscopic improvement-histological remission^g Sustained clinical remission^h Corticosteroid-free clinical remissionⁱ	1 (11.1) 3 (33.3) 1 (11.1) 3 (33.3) 3 (33.3) 1 (11.1) 1 (11.1)	12 (44.4) 15 (55.6) 15 (55.6) 14 (51.9) 8 (29.6) 8 (29.6) 12 (44.4)	44.4* 32.3 53.6* 29.5 -2.3 35.7* 44.4*	10 (7.4) 32 (23.7) 27 (20.0) 16 (11.9) 12 (8.9) 3 (2.2) 9 (6.7)	82 (31.3) 128 (48.9) 112 (42.7) 99 (37.8) 71 (27.1) 46 (17.6) 82 (31.3)	24.0* 25.2* 22.8* 26.0* 18.4* 15.5* 24.8***	N/A
p<0.05; p<0.01; **p<0.001 (nominal p values are reported without adjustment for multiple comparisons) ^aPts with isolated proctitis at baseline (defined as < 10 cm of rectal involvement) met all other eligibility criteria for inclusion (MMS 4–9, ES ≥ 2 [centrally read] and RBS ≥1) ^bTreatment comparisons and 2-sided p values were obtained using the Cochran–Mantel–Haenszel method within each subgroup, adjusting to study stratification (for pooled data only), naïvety to prior biologic/Janus kinase inhibitor therapy, baseline corticosteroid use and baseline disease activity (MMS 4–6 or 7–9). Difference (%) is for etrasimod minus PBO and is based on estimated common risk difference using Mantel–Haenszel weights ^cClinical remission was defined as an SFS=0 (or =1 with a ≥ 1-point decrease from baseline), RBS=0 and ES ≤ 1 (excluding friability) ^dClinical 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 ^eSymptomatic remission was defined as an SFS=0 (or =1 with a ≥ 1-point decrease from baseline) and an RBS=0 ^fEndoscopic improvement was defined as a score of ≤ 1 (excluding friability) ^gEndoscopic improvement-histologic remission was defined as an ES ≤ 1 (excluding friability) with histologic remission as measured by a Geboes Index score < 2.0 ^hSustained clinical remission was defined as clinical remission at both Wks 12 and 52 ⁱCorticosteroid-free remission was defined as remission at Wk 52 with no use of corticosteroids for at least the last 12 study wks immediately before Wk 52 ES, endoscopic subscore; MMS, modified Mayo score; N, total number of patients; n, number of patients with evaluable data within each category; N/A, not applicable; PBO, placebo; pt, patient; RBS, rectal bleeding subscore; SFS, stool frequency subscore; QD, once daily; UC, ulcerative colitis; wk, week

Conclusion

Etrasimod treatment had similar efficacy in pts with isolated proctitis and in those with more extensive colitis. Prospective confirmation in larger pt cohorts with isolated proctitis is necessary. Safety was consistent with the overall population.¹

References

Sandborn WJ et al. Lancet 2023: Epub ahead of print

Disclosure

LPB: research: Takeda, Fresenius Kabi, Celltrion; consultancy: AbbVie, Alimentiv, Alma, Amgen, Applied MolecularTransport, Arena, Biogen, BMS, Celltrion, CONNECTBiopharm, Cytoki, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer, GSK, HAC, IAG ImageAnalysis, Index, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM, ONO, OSE, Pandion, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia, Abivax; speaker: Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Eli Lilly, Gilead, Viatris, Medac, Sanofi; stock: CTMA.
MCD: research: Janssen; consultancy: AbbVie, Arena, BMS, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; shares/royalties: Trellus; directorship/ownership interests: Trellus.
BES: research/grants: Arena, Janssen. Lecture/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda. Consultancy: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Revolo, Takeda, Theravance, Wassermann; grants: AbbVie, Pfizer.
SS: speaker: AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Dr. Falk, Fresenius, Janssen, MSD, Pfizer, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Dr. Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention, Takeda, Theravance.
WR: speaker: AbbVie, Celltrion, Dr. Falk, Ferring, Janssen, Galapagos, MSD, Roche, Pfizer, Pharmacosmos, Shire, Takeda, Therakos; consultant: AbbVie, Amgen, AOP Orphan, Arena, Astellas, AstraZeneca, Bioclinica, Boehringer Ingelheim, BMS, Calyx, Celgene, Celltrion, Eli Lilly, Dr. Falk, Ferring, Galapagos, Gatehouse, Genentech, Gilead, Grünenthal, ICON, Index, Inova, Janssen, Landos Biopharma, Medahead, MedImmune, Microbiotica, Mitsubishi Tanabe, MSD, Novartis, OMass, Otsuka, Parexel, Periconsulting, Pharmacosmos, Pfizer, Protagonist, Provention, Quell, Sandoz, Seres, Setpointmedical, Sigmoid, Sublimity, Takeda, Teva, Therakos, Theravance, Zealand; advisory board: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Celltrion, Galapagos, Janssen, Mitsubishi Tanabe, MSD, Pharmacosmos, Pfizer, Sandoz, Takeda; research: AbbVie, Janssen, MSD, Sandoz, Sanofi, Takeda.
BGF: consultant/advisory: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, BMS, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared, Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.
SD: consultancy/advisory: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, J&J, MSD, Mundipharma, Pfizer, Roche, Sandoz, Takeda, TiGenix, UCB Vifor; speaker: AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda; directorship/ownership interests: Gastroenterology and Endoscopy.
AJY: consultancy: Pfizer, Arena, Takeda, BMS; speaker: BMS.
GD’H: advisor: AbbVie, AstraZeneca, Alimentiv, BMS, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, J&J, Takeda, Pfizer, Polpharma, Prometheus, Tillotts, Ventyx; speaker: AbbVie, Boehringer Ingelheim, Celltrion, J&J, Takeda, Pfizer, Tillotts.
MG, KW, JCW, IM, AMcD, LB, CJR: Pfizer employees & shareholders.
SV: research: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, J&J, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.

EFFICACY AND SAFETY OF ETRASIMOD IN PATIENTS WITH MODERATE TO SEVERE ISOLATED PROCTITIS RELATIVE TO THOSE WITH MORE EXTENSIVE COLITIS: RESULTS FROM THE PHASE 3 ELEVATE UC 52 AND ELEVATE UC 12 TRIALS

Laurent Peyrin-Biroulet 1, Marla C. Dubinsky 2, Bruce E. Sands 2, Julian Panés 3, Stefan Schreiber 4, Walter Reinisch 5, Brian G. Feagan 6, Silvio Danese 7, Andres Yarur 8, Geert R. D'Haens 9, Martina Goetsch 10, Karolina Wosik 11, Joseph Wu 12, Irene Modesto 13, Aoibhinn McDonnell 14, Lauren Bartolome 15, Christopher J. Rabbat 15, Severine Vermeire 16

1 University of Lorraine, CHRU-Nancy, Nancy, France|||University of Lorraine, Inserm, NGERE, Nancy, France

2 Icahn School of Medicine at Mount Sinai, New York, United States

3 Formerly Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain

4 University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany

5 Medical University of Vienna, Vienna, Austria

6 Western University, London, Canada|||Alimentiv Inc, London, Canada

7 IRCCS San Raffaele Hospital and Vita Salute San Raffaele University, Milan, Italy

8 Inflammatory Bowel Disease Center and Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, United States

9 Amsterdam University Medical Centers, Amsterdam, Netherlands

10 Pfizer AG, Zürich, Switzerland

11 Pfizer Canada, Kirkland, Canada

12 Pfizer Inc, Groton, United States

13 Pfizer Inc, Madrid, Spain

14 Pfizer Ltd, Sandwich, United Kingdom

15 Pfizer Inc, New York, United States

16 University Hospitals Leuven, Leuven, Belgium

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

Targeting immune cell trafficking in IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

Etrasimod is an investigational, oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC).

Aims & Methods

We report efficacy and safety of etrasimod in patients (pts) with/without concomitant corticosteroid (CS) use at baseline (BL) of the ELEVATE UC phase 3 trials. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts with moderately to severely active UC were randomised 2:1 to once‑daily etrasimod 2 mg or placebo (PBO). ELEVATE UC 52 used a treat-through design with a 12-week (wk) induction period followed by a 40-wk maintenance period. ELEVATE UC 12 had a 12‑wk induction period. At entry, pts were permitted to receive oral concomitant CS (prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day], or equivalent]) if on a stable dose for ≥ 4 wks prior to screening endoscopy; from Wk 12 CS tapering was recommended. Primary and secondary efficacy endpoints (defined in Table) and safety were assessed by BL concomitant CS status.

Results

In ELEVATE UC 52, 32.2% (93/289) and 29.2% (42/144) of etrasimod- and PBO-treated pts, respectively, were receiving CS at BL. In ELEVATE UC 12, 27.3% (65/238) and 29.3% (34/116) of etrasimod- and PBO-treated pts were receiving CS at BL. Among pts receiving CS at BL in ELEVATE UC 52, a higher proportion of etrasimod- vs PBO-treated pts achieved the endpoint of clinical remission (CR) at Wk 12 (p<0.05) and Wk 52 (p<0.001); this was also observed in pts not receiving CS at BL (p<0.001 at Wks 12 and 52; Table). In ELEVATE UC 12, a higher observed proportion of etrasimod- vs PBO-treated pts receiving CS at BL achieved CR at Wk 12 (p>0.05); a significant difference was observed in pts not receiving CS at BL (p<0.01). In both studies, similar results were observed across all secondary endpoints, with greater differences between etrasimod and PBO seen in pts not receiving CS at BL (Table). Across both ELEVATE trials, there were fewer serious adverse events and serious infections in the etrasimod arm in pts with CS at BL, than in those without CS at BL. In the PBO arms, the opposite was true.

Table. Efficacy at Wk 12 and Wk 52 in patients with and without CS use at baseline in the ELEVATE UC 52 and UC 12 phase 3 trials
	ELEVATE UC 52 Week 12		ELEVATE UC 52 Week 52		ELEVATE UC 12 Week 12
	CS at BL	no-CS at BL	CS at BL	no-CS at BL	CS at BL	no-CS at BL
Clinical remission,^a n/N (%)^b PBO Etrasimod Diff. % (95% CI)^c p^c	7/42 (16.7) 30/93 (32.3) 16.03 (1.08, 30.98) 0.036	5/102 (4.9) 51/196 (26.0) 22.70 (15.27, 30.13) <0.001	4/42 (9.5) 29/93 (31.2) 21.72 (8.82, 34.62) <0.001	7/102 (6.9) 65/196 (33.2) 26.72 (18.53, 34.92) <0.001	7/34 (20.6) 19/65 (29.2) 8.53 (-8.64, 25.71) 0.330	10/82 (12.2) 43/173 (24.9) 13.19 (3.78, 22.60) 0.006
Endoscopic improvement,^d n/N (%)^b PBO Etrasimod Diff. % (95% CI)^c p^c	12/42 (28.6) 38/93 (40.9) 12.25 (-4.73, 29.23) 0.157	12/102 (11.8) 70/196 (35.7) 25.52 (16.25, 34.80) <0.001	9/42 (21.4) 36/93 (38.7) 17.15 (1.55, 32.74) 0.031	10/102 (9.8) 77/196 (39.3) 29.96 (21.04, 38.88) <0.001	11/34 (32.4) 22/65 (33.8) 1.40 (-17.69, 20.49) 0.886	11/82 (13.4) 56/173 (32.4) 19.43 (9.41, 29.46) <0.001
Symptomatic remission,^en/N (%)^b PBO Etrasimod Diff. % (95% CI)^c p^c	13/42 (31.0) 42/93 (45.2) 14.47 (-2.68, 31.62) 0.098	19/102 (18.6) 92/196 (46.9) 28.68 (18.22, 39.14) <0.001	9/42 (21.4) 37/93 (39.8) 18.01 (2.28, 33.74) 0.025	19/102 (18.6) 90/196 (45.9) 28.15 (17.92, 38.38) <0.001	14/34 (41.2) 29/65 (44.6) 3.23 (-16.61, 23.08) 0.750	20/82 (24.4) 85/173 (49.1) 25.58 (13.73, 37.42) <0.001
Endoscopic improvement, histological remission,^fn/N (%)^b PBO Etrasimod Diff. % (95% CI)^c p^c	5/42 (11.9) 20/93 (21.5) 10.28 (-2.99, 23.55) 0.129	4/102 (3.9) 46/196 (23.5) 20.11 (12.77, 27.45) <0.001	7/42 (16.7) 24/93 (25.8) 8.15 (-6.32, 22.61) 0.270	8/102 (7.8) 55/196 (28.1) 21.10 (12.97, 29.23) <0.001	5/34 (14.7) 10/65 (15.4) 0.68 (-13.53, 14.89) 0.926	5/82 (6.1) 31/173 (17.9) 12.17 (4.48, 19.86) 0.002
Clinical response,^g n/N (%)^b PBO Etrasimod Diff. % (95% CI)^c p^c	19/42 (45.2) 63/93 (67.7) 22.86 (5.21, 40.51) 0.011	33/102 (32.4) 119/196 (60.7) 28.56 (17.03, 40.10) <0.001	13/42 (31.0) 43/93 (46.2) 15.25 (-1.74, 32.23) 0.079	22/102 (21.6) 100/196 (51.0) 30.17 (19.62, 40.71) <0.001	18/34 (52.9) 38/65 (58.5) 5.32 (-15.06, 25.70) 0.609	30/82 (36.6) 113/173 (65.3) 29.85 (17.40, 42.29) <0.001
Data in bold indicate significant p values. All data shown refer to the full analysis set (MMS 4–9) with CS at baseline (CS at BL) or no CS at baseline (no-CS at BL) ^aClinical remission, the primary efficacy endpoint, was defined as SFS=0 (or =1 with a ≥ 1-point decrease from baseline), RBS=0, and ES ≤ 1 (excluding friability) ^bPercentages are based on N, the number of patients in the subgroup in the analysis set by treatment, patients missing an assessment at the specified analysis visit are considered non-responders ^cDifference is for etrasimod minus placebo and is based on estimated common risk difference using the Mantel-Haenszel weights; p-value is 2-sided to test the hypothesis of the risk difference being 0 ^dEndoscopic improvement (key secondary efficacy endpoint) was defined as an ES ≤ 1 (excluding friability) ^eSymptomatic remission (key secondary efficacy endpoint) was defined as SFS=0 (or =1 with a ≥ 1-point decrease from baseline) and RBS=0 ^fEndoscopic improvement , histological remission (key secondary efficacy endpoint) was defined as ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0 ^gClinical response (other secondary efficacy endpoint) 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 BL, baseline; CI, confidence interval; CS, corticosteroid; ES, endoscopic subscore; Etra, etrasimod; MMS, modified Mayo score; N, the number of patients in the subgroup in the analysis set by treatment; n, number of responding patients; PBO, placebo; RBS, rectal-bleeding subscore; SFS, stool-frequency subscore; UC ulcerative colitis

Conclusion

Regardless of concomitant CS use at BL, etrasimod generally demonstrated efficacy at Wks 12 and 52, with greater treatment effect seen in pts without CS use at BL. No additional safety signal was apparent when etrasimod was initiated in combination with CS compared to without CS.

Disclosure

BES: financial support for research/grants, e.g. Grant/Research Support: Arena, Janssen. Lecture fees/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda. Consultancy, Advisory Committee/Board Member: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
KBG: research support: Celltrion, Galapagos, Pfizer Inc; speaker honoraria and/or consulting fees: AbbVie, Celltrion, Ferring Pharmaceuticals, Immunic Therapeutics, Janssen, Novartis, Pfizer Inc, Samsung Bioepis, Takeda, Tillotts.
DTR: grant support: Takeda, Helmsley Charitable Trust, GastroIntestinal Research Foundation; consultancy fees/is a member of advisory boards: AbbVie, AltruBio, ASLAN Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chronicles, Syneos, ClostraBio, Connect Biopharma, EcoR1, Genentech/Roche, Gilead Sciences, Iterative Health, Janssen Pharmaceuticals, Kaleido Biosciences, Eli Lilly, Pfizer Inc, Prometheus, Reistone, Seres Therapeutics, Takeda, Target RWE, Trellus Health; is on the Board of Trustees for Crohn’s & Colitis Foundation and Cornerstones Health, Inc; holds stock options in Alike Health, AltruBio, Datos Health and Iterative Health.
YL: speaker: Pfizer, Takeda, Abbvie, Jannsen; Consultancy, Advisory Committee/Board Member: Pfizer, BMS, Takeda, Abbvie, Amgen BioJamp, Lilly
JP: personal: AbbVie, Arena Pharmaceuticals, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Revolo, Takeda, Theravance and Wassermann; grant support: AbbVie, Pfizer.
MG: employee & shareholder of Pfizer AG.
WW, KS, JCW, CCS: employees & shareholders of Pfizer Inc.
KW: employee & shareholder of Pfizer Canada Inc.
SS: speaker: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Janssen, MSD, Pfizer, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Dr. Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer Inc, Protagonist, Provention, Takeda, Theravance.

EFFICACY AND SAFETY OF ETRASIMOD IN PATIENTS WITH AND WITHOUT CONCOMITANT CORTICOSTEROID TREATMENT IN THE PHASE 3 ELEVATE UC 52 AND ELEVATE UC 12 TRIALS

Bruce E. Sands 1, Krisztina Barbara Gecse 2, David T. Rubin 3, Yvette Leung 4, Julian Panés 5, Martina Goetsch 6, Wenjin Wang 7, Kevin Shan 8, John C. Woolcott 7, Christina Smith 7, Karolina Wosik 9, Stefan Schreiber 10

1 Icahn School of Medicine at Mount Sinai, New York, United States

2 Amsterdam University Medical Center, Amsterdam, Netherlands

3 University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, United States

4 University of British Columbia, Vancouver, Canada

5 Formerly of Hospital Clínic Barcelona, IDIBAPS, CIBRehd, Barcelona, Spain

6 Pfizer AG, Zürich, Switzerland

7 Pfizer Inc, Collegeville, United States

8 Pfizer Inc, New York, United States

9 Pfizer Inc, Kirkland, Canada

10 University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Presentation

IMPACT OF PRIOR BIOLOGIC/JANUS KINASE INHIBITOR THERAPY ON THE EFFICACY OF ETRASIMOD: SUBGROUP ANALYSIS FROM THE PHASE 3 ELEVATE UC 52 AND ELEVATE UC 12 TRIALS

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Introduction

Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC).

Aims & Methods

The study design for phase 3 ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials has been described previously.¹ ELEVATE UC 52 comprised a 12‑week (wk) induction period followed by a 40‑wk maintenance period with a treat-through design. ELEVATE UC 12 comprised a 12‑wk induction period. Patients (pts) had a documented history of inadequate response/loss of response/intolerance to ≥ 1 treatment for UC. This subgroup analysis evaluated the efficacy and safety of etrasimod 2 mg once daily vs placebo (PBO) in adults with UC by prior exposure to advanced (biologic/Janus kinase inhibitor [bio/JAKi]) therapy. We present subgroup efficacy analyses of the primary and select secondary endpoints at Wk 12 and Wk 52 in ELEVATE UC 52 and Wk 12 in ELEVATE UC 12 in pts naïve to, or with prior exposure to, ≥ 1 bio/JAKi therapy. Additional symptomatic endpoints were analysed by study visit to Wk 12 (pooled ELEVATE UC 52 and ELEVATE UC 12).

Results

In ELEVATE UC 52 and ELEVATE UC 12, respectively, 274 and 222 pts with a baseline modified Mayo score 5–9 were treated with etrasimod, and 135 and 112 pts with PBO. Pts treated with etrasimod vs PBO, in both bio/JAKi‑naïve and -exposed subgroups, achieved statistically significant improvements in clinical remission, clinical response and endoscopic improvement at Wks 12 and 52 in ELEVATE UC 52 (Table). In ELEVATE UC 12, bio/JAKi-naïve pts achieved statistically significant improvements in all endpoints, while pts in both subgroups achieved statistically significant improvements in clinical response (Table). In bio/JAKi‑naïve and -exposed pts, respectively, pooled data showed the earliest significant improvements were during Wks 2 and 12 for symptomatic response and Wks 4 and 2 for symptomatic remission (Table).

Table. Subgroup analysis of the proportion of patients achieving the primary and select secondary efficacy and symptomatic endpoints in the ELEVATE UC 52 and ELEVATE UC 12 trials stratified by prior bio/JAKi exposure^a
	ELEVATE UC 52, Wk 12			ELEVATE UC 52, Wk 52			ELEVATE UC 12, Wk 12
Endpoint, n/N (%)^b by prior bio/JAKi exposure	PBO (N=135)	Etrasimod 2 mg once daily (N=274)	% difference (95% CI) p value^c	PBO (N=135)	Etrasimod 2 mg once daily (N=274)	% difference (95% CI) p value^c	PBO (N=112)	Etrasimod 2 mg once daily (N=222)	% difference (95% CI) p value^c
Clinical remission^{d, e} Naïve Exposed	9/93 (9.7) 1/42 (2.4)	60/194 (30.9) 14/80 (17.5)	21.5 (12.67, 30.30) <0.001 14.7 (4.82, 24.62) 0.004	7/93 (7.5) 2/42 (4.8)	71/194 (36.6) 17/80 (21.3)	28.8 (19.89, 37.67) <0.001 14.6 (3.36, 25.82) 0.011	12/74 (16.2) 5/38 (13.2)	41/148 (27.7) 14/74 (18.9)	11.9 (0.98, 22.73) 0.033 6.6 (-7.18, 20.29) 0.349
Clinical response^f Naïve Exposed	35/93 (37.6) 11/42 (26.2)	132/194 (68.0) 39/80 (48.8)	29.6 (17.77, 41.45) <0.001 19.9 (2.95, 36.92) 0.021	25/93 (26.9) 6/42 (14.3)	103/194 (53.1) 29/80 (36.3)	26.1 (14.65, 37.58) <0.001 19.7 (5.32, 34.07) 0.007	32/74 (43.2) 14/38 (36.8)	97/148 (65.5) 41/74 (55.4)	22.3 (8.63, 35.89) 0.001 20.1 (1.14, 39.12) 0.038
Endoscopic improvement^g Naïve Exposed	17/93 (18.3) 2/42 (4.8)	76/194 (39.2) 20/80 (25.0)	21.2 (11.07, 31.36) <0.001 19.1 (7.20, 30.95) 0.002	12/93 (12.9) 2/42 (4.8)	78/194 (40.2) 24/80 (30.0)	28.1 (18.60, 37.60) <0.001 23.1 (10.77, 35.32) <0.001	14/74 (18.9) 7/38 (18.4)	51/148 (34.5) 17/74 (23.0)	16.2 (4.90, 27.40) 0.005 5.5 (-10.00, 20.97) 0.487
Endpoint, n/N (%)^b by prior bio/JAKi exposure	Pooled ELEVATE UC 52 and ELEVATE UC 12, up to Wk 12 PBO			Pooled ELEVATE UC 52 and ELEVATE UC 12, up to Wk 12 Etrasimod 2 mg once daily			Pooled ELEVATE UC 52 and ELEVATE UC 12, up to Wk 12 % difference (95% CI) p value^c
Symptomatic response^h at the earliest visit with significant difference Naïve (Wk 2) Exposed (Wk 12)	49/167 (29.3) 31/80 (38.8)			141/342 (41.2) 85/154 (55.2)			12.1 (3.47, 20.69) 0.0060 16.0 (2.79, 29.19) 0.0176
Symptomatic remissionⁱ at the earliest visit with significant difference Naïve (Wk 4) Exposed (Wk 2)	24/167 (14.4) 7/80 (8.8)			105/342 (30.7) 28/154 (18.2)			16.7 (9.67, 23.79) <0.0001 9.0 (0.54, 17.54) 0.0371
^aThis is a subgroup analysis of the full analysis set; therefore, only patients with a baseline MMS score between 5 and 9 were included. Patients with a baseline MMS of 4 were excluded ^bPatients missing an assessment at the specified analysis visit were considered nonresponders ^cDifference (%) is for etrasimod minus PBO and is based on estimated common risk difference using Mantel–Haenszel weights, stratified by baseline corticosteroid use (Yes/No) and baseline disease activity (MMS: ≤ 6 or ≥ 7). The 2-sided nominal p value is to test the hypothesis of the common risk difference being 0; p<0.05 is considered statistically significant ^dSFS = 0 (or = 1 with ≥ 1-point decrease from baseline), RBS = 0 and ES ≤ 1 (excluding friability) ^ePatients in clinical remission at Wk 52 were also in clinical remission without corticosteroids if they had not been receiving corticosteroids for at least 12 wks immediately prior to Wk 52 ^fA ≥ 2-point and ≥ 30% decrease from baseline in MMS, and a ≥ 1-point decrease from baseline in RBS or an absolute RBS of ≤ 1 ^gES of ≤ 1 (excluding friability) ^hDecrease from baseline ≥ 30% in composite RBS and SFS ⁱSFS = 0 (or = 1 with ≥ 1-point decrease from baseline), RBS = 0 bio, biologic; CI, confidence interval; ES, endoscopic subscore; JAKi, Janus kinase inhibitor; MMS, modified Mayo score; PBO, placebo; n, the number of unique patients achieving each endpoint; N, the number of patients in the subgroup in the analysis set by treatment; RBS, rectal bleeding subscore; SFS, stool frequency subscore; UC, ulcerative colitis; Wk, week

Conclusion

In ELEVATE UC 52, both bio/JAKi-naïve and -exposed pts treated with etrasimod showed statistically significant improvements in induction and maintenance efficacy endpoints vs PBO. In ELEVATE UC 12, etrasimod demonstrated statistically significant improvements vs PBO in induction in bio/JAKi-naïve pts. For symptomatic response in the pooled analysis, a significant treatment difference occurred later for bio/JAKi-exposed than -naïve pts.

References

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171

Disclosure

SV: research: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy/advisory: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, J&J, MateriaPrima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.
BES: research: Arena, Janssen. Speaker: BMS, Janssen, Lilly, Pfizer, Takeda. consultancy/advisory: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus, Sun, Takeda, Teva. Stock: Ventyx. Non-financial: Janssen, Lilly, Pfizer, Takeda.
LPB: research: Takeda, Fresenius Kabi, Celltrion; consultancy: AbbVie, Alimentiv, Alma Bio, Amgen, AppliedMolecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer, GSK, HAC, IAG Image Analysis, Index, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM, ONO, OSE, Pandion, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia, Abivax; speaker: Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena, Eli Lilly, Gilead, Viatris, Medac, Sanofi; stock: CTMA.
GD’H: advisor: AbbVie, AstraZeneca, Alimentiv, BMS, Boehringer Ingelheim, Celltrion, Cosmo, Eli Lilly, Galapagos, GSK, J&J, Takeda, Pfizer, Polpharma, Prometheus, Tillotts, Ventyx; speaker: AbbVie, Boehringer Ingelheim, Celltrion, J&J, Takeda, Pfizer, Tillotts.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Revolo, Takeda, Theravance, Wassermann; grants: AbbVie, Pfizer.
AJY: consultancy: Pfizer, Arena, Takeda, BMS; speaker: BMS.
DW: research grants: AbbVie, Arena, BMS, Janssen, Pfizer, Takeda, Ventyx; speaker: AbbVie, BMS, Janssen, Pfizer, Takeda; consultant: AbbVie, Arena, BMS, Janssen, Pfizer, Takeda.
TR: speaker: Takeda, Janssen, Pfizer, BMS, AbbVie, Lilly; Data Adjudication: Ferring/Rebiotix; Advisory boards: AbbVie, Ardelyx, Arena, Boehringer Ingelheim, BMS/Celgene, Ferring, Genentech/Roche, Gilead, Intercept, Iterative Scopes (shareholder), Janssen, Lilly, Pfizer, Prometheus, Sanofi, Takeda, Nestle/Seres
SS: speaker: AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Dr. Falk, Fresenius, Janssen, MSD, Pfizer, Takeda; consultancy/advisory: AbbVie, Arena, Biogen, BMS, Celgene, Celltrion, Dr. Falk, Fresenius, Gilead, IMAB, Janssen, MSD, Mylan, Pfizer, Protagonist, Provention, Takeda, Theravance.
KS, CJR: employees & shareholders of Pfizer.
MVC: grants: Pfizer, Janssen, Novartis, BMS; consultancy: AbbVie, Arena, BMS, Medtronic, Pfizer, Prometheus, Eli Lilly, Janssen, Takeda; speaker: AbbVie, Janssen, Medtronic, Pfizer, BMS, Takeda.
FB: research: AbbVie, Amgen, Janssen, Takeda; speaker: AbbVie, Arena, Celltrion, Ferring, Galapagos, Janssen, MSD, Pfizer, Takeda; consultancy: AbbVie, Amgen, Arena, Celgene, Celltrion, Ferring, Fresenius Kabi, Janssen, MSD, Pfizer, Sandoz.
MCD: research: Janssen; consultancy: AbbVie, Arena, BMS, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; stock: Trellus; directorship/ownership interests: Trellus.
MG: employee & shareholder of Pfizer AG.
SD: consultancy/advisory: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead, Hospira, Janssen, J&J, MSD, Mundipharma, Pfizer, Roche, Sandoz, Takeda, TiGenix, UCB, Vifor; speaker: AbbVie, Amgen, Ferring, Gilead, Janssen, Mylan, Pfizer, Takeda; directorship/ownership interests: Gastroenterology and Endoscopy.
BGF: consultant/advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, AppliedMolecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/BMS, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared, Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director (central reading services; not a company employee, no equity); shareholder: Gossamer

IMPACT OF PRIOR BIOLOGIC/JANUS KINASE INHIBITOR THERAPY ON THE EFFICACY OF ETRASIMOD: SUBGROUP ANALYSIS FROM THE PHASE 3 ELEVATE UC 52 AND ELEVATE UC 12 TRIALS

Severine Vermeire 1, Bruce E. Sands 2, Laurent Peyrin-Biroulet 3, Geert R. D'Haens 4, Julian Panés 5, Andres Yarur 6, Doug Wolf 7, Timothy Ritter 8, Stefan Schreiber 9, Kevin Shan 10, Chris Rabbat 11, Michael Chiorean 12, Filip Baert 13, Marla C. Dubinsky 2, Martina Goetsch 14, Silvio Danese 15, Brian G. Feagan 16

1 University Hospital Leuven, Leuven, Belgium

2 Icahn School of Medicine at Mount Sinai, New York, United States

3 University of Lorraine, CHRU-Nancy, Nancy, France|||University of Lorraine, Inserm, NGERE, Nancy, France

4 Amsterdam University Medical Centers, Amsterdam, Netherlands

5 Formerly of Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain

6 Cedars-Sinai Medical Center, Los Angeles, United States

7 Atlanta Gastroenterology Associates, Atlanta, United States

8 GI Alliance, Southlake, United States

9 University Hospital Schleswig-Holstein, Kiel University, Kiel, Germany

10 Pfizer Inc, San Diego, United States

11 Pfizer Inc, New York, United States

12 Swedish Medical Center, Seattle, United States

13 AZ Delta Deltalaan 2, Roeselare, Belgium

14 Pfizer AG, Zürich, Switzerland

15 IRCCS San Raffaele Hospital and Vita Salute San Raffaele University, Milan, Italy

16 Western University, London, Canada|||Alimentiv Inc, London, Canada

Event

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

Sequential therapies in IBD: Raising the bar

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Poster

Standard Poster

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Introduction

Etrasimod is an investigational, once-daily, oral, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC). In the ELEVATE UC 52 trial, primary and key secondary efficacy endpoints at Week 52 were evaluated among all patients randomised at baseline. The efficacy of etrasimod can be further characterised by evaluating efficacy endpoints at Week 52 among the subset of patients who met each efficacy endpoint at the end of the induction period (Week 12).

Aims & Methods

Here, we report proportions of patients receiving etrasimod that sustained induction efficacy endpoints at Week 52. In ELEVATE UC 52 (NCT03945188), patients (16–80 years) with moderately to severely active UC (defined as modified Mayo Score 4–9, endoscopic subscore ≥2 and rectal bleeding subscore [RBS] ≥1) were randomised 2:1 to once-daily etrasimod 2 mg or placebo. The ELEVATE UC 52 clinical trial comprised a 12-week induction period followed by a 40-week maintenance period with a treat-through design. This post hoc analysis assessed efficacy endpoints at Week 52 among the subset of patients who met the following efficacy endpoints at Week 12: clinical remission, endoscopic improvement, endoscopic improvement-histologic remission, symptomatic remission and RBS of 0.

Results

In ELEVATE UC 52, 81/289 (28.0%) patients treated with etrasimod achieved clinical remission at Week 12; of these, 66.7% (54/81) sustained clinical remission at Week 52 (Table). Among the 108/289 (37.4%) patients who achieved endoscopic improvement at Week 12, 72.2% (78/108) sustained the endpoint at Week 52; of 66/289 (22.8%) who achieved endoscopic improvement-histologic remission at Week 12, 63.6% (42/66) sustained the endpoint at Week 52; of 134/289 (46.4%) patients who achieved symptomatic remission at Week 12, 74.6% (100/134) sustained the endpoint at Week 52; of 166/289 (57.4%) patients who achieved an RBS of 0 at Week 12, 75.3% (125/166) sustained the endpoint at Week 52.

Table. Proportions of patients receiving etrasimod who sustained Week 12 induction efficacy endpoints at Week 52 (full analysis set)
	Maintained response at Week 52	Loss of response/discontinued treatment
Clinical remission^a n/N (%)	54/81 (66.7)	27/81 (33.3)
Endoscopic improvement^b n/N (%)	78/108 (72.2)	30/108 (27.8)
Endoscopic improvement-histologic remission^c n/N (%)	42/66 (63.6)	24/66 (36.4)
Symptomatic remission^d n/N (%)	100/134 (74.6)	34/134 (25.4)
RBS=0 n/N (%)	125/166 (75.3)	41/166 (24.7)
^aClinical remission is defined as an SFS=0 (or =1 with a ≥1-point decrease from baseline), RBS=0 and ES ≤1 (excluding friability) ^bEndoscopic improvement is defined as an ES ≤1 (excluding friability) ^cEndoscopic improvement-histologic remission is defined as an ES ≤1 (excluding friability) with histologic remission measured by a Geboes Index score <2 ^dSymptomatic remission is defined as an SFS=0 (or =1 with a ≥1-point decrease from baseline) and RBS=0 ES, endoscopic subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore.

Conclusion

These findings suggest efficacy endpoints achieved at Week 12 were sustained by large proportions of etrasimod-treated patients at Week 52 based on both subjective and objective measures including clinical, endoscopic and histologic efficacy responses. Further analyses of larger samples sizes with longer follow-up are needed to evaluate long-term efficacy of etrasimod in patients with moderately to severely active UC.

Disclosure

BES: research/grants, e.g. Grant/Research Support: Arena, Janssen. Lecture fees/Speakers Bureau: BMS, Janssen, Lilly, Pfizer, Takeda. Consultancy, Advisory Committee/Board Member: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, BMS, Celltrion, Fresenius Kabi, Genentech, GSK, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
SV: grant/research support: AbbVie, MSD, Pfizer, Galapagos, Takeda; consultancy/advisory: AbbVie, AbolerIS, Alimentiv, Arena, AstraZeneca, Avaxia, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr. Falk, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson & Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillotts, Zealand; lecture/speaker: AbbVie, Dr. Falk, Ferring, Hospira, MSD, Takeda, Tillotts.
MCD: grant/research support: Janssen; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, Janssen, Pfizer, Prometheus, Takeda, Trellus Health, UCB; shares/royalties: Trellus; directorship/ownership interests: Trellus.
BGF: consultant/on advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco., Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus, Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen., Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared Ltd., Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.
RP: research support: AbbVie, Janssen, Takeda, Pfizer; consultancy: Abbott, AbbVie, Abivax, Alimentiv, Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan, Organon, Pandion, Pendopharm, Pfizer, Progenity, Prometheus, Protagonist, Roche, Sandoz, Satisfai, Shire, Sublimity, Takeda, Theravance, Trellus, Viatris, Ventyx, UCB; speaker: AbbVie, Amgen, Arena, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Gilead, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda; member of advisory boards: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead, GSK, BIOJAMP, Janssen, Merck, Mylan, Novartis, Oppilan, Organon, Pandion, Pfizer, Progenity, Protagonist, Roche, SandozShire, Sublimity, Takeda, Ventyx.
VJ: financial support: Celgene/Bristol-Myers Squibb, Pfizer, AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead and TiGenix; consultancy: AbbVie, Alimentiv, Amgen, Anokion, Applied Strategic, Arena, Asahi Kasei, Asieris, AstraZeneca, BIOJAMP, Celgene/Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, F Hoffmann La Roche, Flagship Pioneering, Fresenius Kabi, Fusion MD, Galapagos, Genentech, Gilead, GSK, Janssen, Knightslab, Organon, Landos, McKesson, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Prometheus, Protagonist, Reistone, Roche, Sandoz, Second Genome, Sorriso, Takeda, Teva, Topivert, Ventyx, Viatris, Vividion; lecture: AbbVie, Ferring, Galapagos, Janssen, Pfizer, Takeda, Bristol-Myers Squibb.
AJY: consultancy: Pfizer, Arena, Takeda, Bristol-Myers Squibb; lecture/speaker: Bristol-Myers Squibb.
MVC: grant support: Pfizer, Janssen, Novartis, Bristol-Myers Squibb; consultancy: AbbVie, Arena, Bristol-Myers Squibb, Medtronic, Pfizer, Prometheus, Eli Lilly, Janssen and Takeda; speaker: AbbVie, Janssen, Medtronic, Pfizer, Bristol-Myers Squibb, Takeda.
JP: personal: AbbVie, Arena, Athos, Atomwise, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Galapagos, Genentech/Roche, GSK, Immunic, Janssen, Mirum, Morphic, Nestlé, Origo, Pandion, Pfizer, Progenity, Revolo, Takeda, Theravance and Wassermann; grant support: AbbVie, Pfizer.
MG: employee & shareholder of Pfizer AG.
CJR, PS, JW: employees & shareholders of Pfizer.
SG: financial support/grants: GSK; speaker: Janssen, AbbVie, Pfizer, Takeda, Eli Lilly, Celltrion; advisory board: Janssen, AbbVie, Takeda, Pfizer, Bristol-Myers Squibb, Gilead, Galapagos, Ferring; Steering Committee member: Janssen, Bristol-Myers Squibb, AbbVie; Drug Monitoring Committee member: Janssen.

MAINTENANCE OF WEEK 12 RESPONSES THROUGH WEEK 52 WITH ETRASIMOD IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: POST HOC ANALYSIS OF THE PHASE 3 ELEVATE UC 52 TRIAL

Bruce E. Sands 1, Severine Vermeire 2, Marla C. Dubinsky 1, Brian G. Feagan 3, Remo Panaccione 4, Vipul Jairath 5, Andres Yarur 6, Michael Chiorean 7, Julian Panés 8, Martina Goetsch 9, Christopher J. Rabbat 10, Pooja Shah 11, Joseph Wu 12, Subrata Ghosh 13

1 Icahn School of Medicine at Mount Sinai, New York, United States

2 University Hospitals Leuven, Leuven, Belgium

3 Western University, London, Canada|||Alimentiv Inc, London, Canada

4 University of Calgary, Calgary, Canada

5 Western University, London, Canada

6 Cedars-Sinai Medical Center, Los Angeles, United States

7 Swedish Medical Center, Seattle, United States

8 Formerly Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain

9 Pfizer AG, Zürich, Switzerland

10 Pfizer Inc, New York, United States

11 Pfizer Inc, Collegeville, United States

12 Pfizer Inc, Groton, United States

13 APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

Targeting immune cell trafficking in IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

UEG Presentation

EARLY DISEASE CLEARANCE WITH ETRASIMOD AND CORRELATION WITH WEEK 52 OUTCOMES AND BIOMARKERS: A POST HOC ANALYSIS OF THE PHASE 3 ELEVATE UC TRIALS

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Introduction

The concept of disease clearance (DC), which includes symptomatic, endoscopic and histologic remission, has been proposed as the ultimate goal in ulcerative colitis (UC) treatment. However, the prognostic value of this endpoint remains uncertain.¹Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active UC.

Aims & Methods

We report a post hoc analysis from the ELEVATE UC trials to assess relationships between histological/composite endpoints, biomarkers and efficacy outcomes in etrasimod-treated patients (pts). In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts with moderately to severely active UC were randomised 2:1 to once‑daily etrasimod 2 mg or placebo (PBO). DC was defined as Nancy Histological Index=0, Mayo endoscopic subscore [ES]=0, rectal bleeding subscore=0, stool frequency subscore=0 or 1 (if 1, must have ≥ 1 point decrease from baseline). Other endpoints are defined in the Table. Kappa correlation coefficients² were estimated between histological endpoints at Wk 12 and efficacy outcomes at Wk 52, and between histological endpoints and biomarkers at Wks 12 and 52.

Results

At Wk 12 in both trials, DC was achieved by more etrasimod- than PBO-treated pts (8.4% [23/274] vs 1.5% [2/135] and 9.9% [22/222] vs 4.5% [5/112], p<0.001 and p=0.042, respectively). The proportion of pts with clinical remission at Wk 52 was higher among pts who achieved DC at Wk 12 (17/23; 74%) vs pts who did not (71/251; 28%). Histologic-endoscopic mucosal improvement at Wk 12 had the highest correlation with efficacy outcomes at Wk 52 (κ 0.357–0.438; Table). Faecal calprotectin and C‑reactive protein normalisation showed slight/fair to substantial agreement with histologic endpoints (κ 0.223–0.630; 0.075–0.6, respectively; Table). Absolute lymphocyte count < 0.5x10⁹/L showed no agreement (κ -0.100–0.216; Table).

Table. Correlations between histological and efficacy endpoints in ELEVATE UC 52, and histological endpoints and biomarker status in ELEVATE UC 52 and 12 among patients (with baseline modified Mayo score of 5 to 9) receiving etrasimod 2 mg QD
Correlations with Wk 12 histological endpoints and efficacy endpoints at Wk 52 of ELEVATE UC 52
ELEVATE UC 52: Wk 12 endpoint (N=274)	Definition	Clinical remission^d at Wk 52		CS-free clinical remission^e at Wk 52		Symptomatic remission^f at Wk 52	Endoscopic improvement^g at Wk 52	Endoscopic improvement- histologic remission^h at Wk 52
Histologic remission^a Histologic-endoscopic mucosal improvement^a Endoscopic improvement-histologic remission^b Endoscopic normalisation-histologic remission^c Disease clearance^c	Geboes < 2.0 Geboes ≤ 3.1 + ES 0–1 Geboes < 2.0 + ES 0–1 Geboes < 2.0 + ES 0 NHI=0, ES=0, RBS=0, SFS=0 or 1 (if 1, must have ≥ 1-point decrease from baseline)	0.266 0.392 0.338 0.217 0.200		0.266 0.392 0.338 0.217 0.200		0.299 0.357 0.297 0.169 0.164	0.292 0.423 0.367 0.223 0.194	0.365 0.438 0.431 0.307 0.260
Correlations with biomarker status at the same visit (Wk 12 and Wk 52)
ELEVATE UC 12: Wk 12 endpoint (N=222) ELEVATE UC 52: Wk 12 or Wk 52 endpoints (N=274)	Absolute lymphocyte count (< 0.5 x 10⁹/L)			Faecal calprotectin normalisation (< 150 mg/kg)			hsCRP normalisation (< 5 mg/L)
Histologic remission^a Histologic-endoscopic mucosal improvement^a Endoscopic improvement-histologic remission^b Endoscopic normalisation-histologic remission^c Disease clearance^c	ELEVATE UC 12 (Wk 12) 0.060 0.124 0.041 0.004 -0.022	ELEVATE UC 52 (Wk 12) -0.006 -0.100 -0.055 0.036 0.014	ELEVATE UC 52 (Wk 52) 0.216 0.132 0.160 0.098 0.067	ELEVATE UC 12 (Wk 12) 0.370 0.535 0.290 0.227 0.236	ELEVATE UC 52 (Wk 12) 0.268 0.497 0.298 0.257 0.223	ELEVATE UC 52 (Wk 52) 0.571 0.630 0.538 0.458 0.431	ELEVATE UC 12 (Wk 12) 0.199 0.180 0.386 0.075 0.084	ELEVATE UC 52 (W12) 0.193 0.267 0.287 0.089 0.094	ELEVATE UC 52 (Wk 52) 0.497 0.533 0.600 0.373 0.365
Kappa correlation coefficients are shown, ≤ 0 indicate no agreement, 0.01–0.20 indicate none to slight agreement, 0.21–0.40 indicate in fair agreement, 0.41–0.60 indicate in moderate agreement, 0.61–0.80 indicate substantial agreement, and coefficients 0.81–1.00 indicate an almost perfect agreement ^aPre-specified exploratory endpoint; ^bPre-specified key secondary endpoint subject to type I error control; ^cPost hoc endpoint; ^dClinical remission was defined as SFS=0 (or =1 with a ≥ 1-point decrease from baseline), RBS=0, and ES ≤ 1 (excluding friability); ^eCS-free clinical remission was defined as the proportion of patients in clinical remission at Wk 52 and who had not been receiving CS for ≥ 12 wks prior to Wk 52; ^fSymptomatic remission was defined as SFS=0 (or =1 with a ≥ 1-point decrease from baseline) and RBS=0; ^gEndoscopic improvement was defined as an ES ≤ 1 (excluding friability); ^hEndoscopic improvement-histologic remission was defined as ES ≤ 1 (excluding friability) with histologic remission measured by a Geboes Index score < 2.0 CS, corticosteroid; ES, endoscopic subscore; hsCRP, high-sensitivity C-reactive protein; NHI, Nancy Histological Index; RBS, rectal bleeding subscore; SFS, stool frequency subscore; QD, once daily; Wk, week

Conclusion

Early achievement of DC showed only fair correlation with Wk 52 efficacy outcomes. Correlation of faecal calprotectin < 150 mg/kg with histological endpoints was most often moderate and improved from Wks 12 to 52. A different approach is needed for development of robust predictive models.

References

1. D’Amico F et al. United Eur Gastroenterol J 2022;10:777–784
2. Cohen JA et al. Educ Psychol Meas 1960;20:37–46

Disclosure

FM: grant support: GEDII and National Science Foundation; personal fees: AbbVie, Amgen, Biogen, Celgene, Celltrion, Dr. Falk Pharma, Ferring Pharmaceuticals, Hospira, Janssen, Laboratórios Vitória, MSD, Pfizer, Sandoz, Takeda, UCB, Vifor.
LPB: grant/research support: Takeda, Fresenius Kabi and Celltrion; consultancy fees: AbbVie, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Biogen, Bristol-Myers Squibb, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Eli Lilly, Medac, Mopac, Morphic, MSD, Norgine, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par'Immune, Pfizer Inc, Prometheus, Protagonist, Roche, Sandoz, Takeda, Theravance, Thermo Fisher, TiGenix, Tillotts, Viatris, Vifor, Ysopia and Abivax; lecture/speaker fees: Galapagos, AbbVie, Janssen, Genentech, Ferring Pharmaceuticals, Tillotts, Celltrion, Takeda, Pfizer, Sandoz, Biogen, MSD, Amgen, Vifor, Arena Pharmaceuticals, Eli Lilly, Gilead Sciences, Viatris, Medac, Sanofi; holds stock in CTMA.
BES: research grants: Arena, Janssen. Lecture fees/Speakers Bureau: Bristol-Myers Squibb, Janssen, Lilly, Pfizer, Takeda. Consultancy, Advisory Committee/Board Member: AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Genentech, Glaxo SmithKline, Janssen, Lilly, Merck, Pfizer, Prometheus Biosciences, Sun Pharma Global, Takeda Pharmaceuticals International, Teva Branded Pharmaceutical Products R&D. Shareholder/Stock Options: Ventyx Biosciences. Other non-financial support: Janssen, Lilly, Pfizer, Takeda.
SD: consultancy/advisory fees: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB and Vifor; lecture/speaker fees: AbbVie, Amgen, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Mylan, Pfizer Inc, Takeda; has directorship/ownership interests in Gastroenterology and Endoscopy.
VJ: financial support: Celgene/Bristol-Myers Squibb, Pfizer, AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Takeda, Gilead and TiGenix; consultancy: AbbVie, Alimentiv, Amgen, Anokion, Applied Strategic, Arena, Asahi Kasei, Asieris, AstraZeneca, BIOJAMP, Celgene/Bristol-Myers Squibb, Celltrion, Eli Lilly, Ferring, F Hoffmann La Roche, Flagship Pioneering, Fresenius Kabi, Fusion MD, Galapagos, Genentech, Gilead, GSK, Janssen, Knightslab, Organon, Landos, McKesson, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Prometheus, Protagonist, Reistone, Roche, Sandoz, Second Genome, Sorriso, Takeda, Teva, Topivert, Ventyx, Viatris, Vividion; lecture: AbbVie, Ferring, Galapagos, Janssen, Pfizer, Takeda, Bristol-Myers Squibb.
MG: employee & shareholder of Pfizer AG.
AB: employee of Pfizer Healthcare India & shareholder of Pfizer.
JW, DB & IM: employees & shareholders of Pfizer.
BGF: consultant/on advisory board: AbbVie, AbolerIS, AgomAB, AllianThera, Amgen, AnaptysBio, Applied Molecular Transport, Arena, Avoro Capital, Atomwise, BIOJAMP, Biora, Boehringer Ingelheim, Boxer, Celsius, Celgene/Bristol-Myers Squibb, Connect, Cytoki, Disc Medicine, Duality, EcoR1, Eli Lilly, Equillium, Ermium, First Wave, FirstWord, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer, GSK, Hinge, HotSpot, InDex, Imhotex, Immunic, JAK, Janssen, Japan Tobacco, Kaleido, Landos, Leadiant, L.E.K., Lenczner Slaght, LifeSci, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic, Mylan, OM, Origo, Orphagen, Pandion, Pendopharm, Pfizer, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM, Q32, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres, Silverback, Surrozen, Takeda, Teva, Thelium, TiGenix, Tillotts, Ventyx, VHSquared Ltd., Viatris, Ysios, YSOPIA, Zealand; speaker: AbbVie, Janssen, Takeda; Alimentiv Senior Scientific Director, provides central reading services; not a company employee, no equity stake; shareholder: Gossamer.

EARLY DISEASE CLEARANCE WITH ETRASIMOD AND CORRELATION WITH WEEK 52 OUTCOMES AND BIOMARKERS: A POST HOC ANALYSIS OF THE PHASE 3 ELEVATE UC TRIALS

Fernando Magro 1, Laurent Peyrin-Biroulet 2, Bruce E. Sands 3, Silvio Danese 4, Vipul Jairath 5, Martina Goestch 6, Abhishek Bhattacharjee 7, Joseph Wu 8, Diogo Branquinho 9, Irene Modesto 10, Brian G. Feagan 11

1 University of Porto and Centro Hospitalar São João, Porto, Portugal

2 University of Lorraine, CHRU-Nancy, Nancy, France|||University of Lorraine, Inserm, NGERE, Nancy, France

3 Icahn School of Medicine at Mount Sinai, New York, United States

4 IRCCS San Raffaele Hospital and Vita Salute San Raffaele University, Milan, Italy

5 Western University, London, Canada

6 Pfizer AG, Zürich, Switzerland

7 Pfizer Healthcare India Pvt. Ltd, Chennai, India

8 Pfizer Inc, Groton, United States

9 Pfizer Inc, New York, United States

10 Pfizer Inc, Madrid, Spain

11 Western University, London, Canada|||Alimentiv Inc, London, Canada

Event

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

Traffic control in IBD

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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Introduction

When conventional ulcerative colitis (UC) therapy fails to achieve or maintain remission, advanced UC therapies should be considered to improve patient outcomes. The responder re-randomisation trial (efficacy reported at the end of the maintenance phase for patients who achieved induction clinical response) is a common design used in UC drug development. 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. The etrasimod ELEVATE UC 52 trial utilised a treat-through design, where efficacy at the end of the maintenance phase was reported for the total baseline population.

Aims & Methods

This post hoc analysis evaluated the efficacy of etrasimod vs placebo at Week 52 among biologic/Janus kinase inhibitor (bio/JAKi)-naïve patients with moderately to severely active UC who achieved clinical response at Week 12. ELEVATE UC 52 (NCT03945188) comprised a 12-week induction phase followed by a 40-week maintenance phase with a treat-through design. Patients were randomised 2:1 to receive etrasimod 2 mg or placebo QD. Week 12 clinical response was defined as a ≥2-point and ≥30% decrease from baseline in modified Mayo score (MMS), and a ≥1-point decrease or absolute value ≤1 in rectal bleeding subscore. Efficacy outcomes evaluated in Week 12 bio/JAKi-naïve responders (baseline MMS 5–9) were the achievement of clinical remission, clinical response, symptomatic remission, endoscopic improvement, endoscopic improvement-histologic remission and corticosteroid-free clinical remission at Week 52.

Results

Among bio/JAKi-naïve patients, Week 12 clinical response was achieved by 132/194 (68.0%) receiving etrasimod and 35/93 (37.6%) receiving placebo. Among Week 12 responders, significantly greater proportions receiving etrasimod vs placebo achieved clinical remission (51.5% vs 17.1%; p<0.001) and all secondary endpoints at Week 52 (all p<0.05; Table).

Table. Efficacy endpoints at Week 52 among bio/JAKi-naïve patients who met clinical response criteria at Week 12 (baseline MMS 5–9)
	Placebo QD (N=35)	Etrasimod 2 mg QD (N=132)	Adjusted % difference (95% CI) [p value]
Clinical remission, n (%)^a	6 (17.1)	68 (51.5)	34.6 (19.41, 49.83) [p<0.001]
Clinical response, n (%)^b	19 (54.3)	99 (75.0)	20.5 (2.50, 38.53) [p=0.026]
Symptomatic remission, n (%)^c	16 (45.7)	93 (70.5)	24.4 (6.07, 42.63) [p=0.009]
Endoscopic improvement, n (%)^d	8 (22.9)	75 (56.8)	34.4 (17.83, 50.99) [p<0.001]
EIHR, n (%)^e	7 (20.0)	53 (40.2)	20.6 (4.55, 36.58) [p=0.012]
CS-free clinical remission, n (%)^f	6 (17.1)	68 (51.5)	34.6 (19.41, 49.83) [p<0.001]
p<0.05 are highlighted in bold. Treatment comparisons within each subgroup (adjusted percentage difference and 95% CI) and 2-sided p values were obtained using the Cochran–Mantel–Haenszel method, adjusting to reported randomisation stratification of baseline CS use and baseline disease activity (MMS of 4–6 or 7–9). Missing response was considered as nonresponse. ^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. ^cSymptomatic remission was defined as an SFS=0 (or =1 with a ≥1-point decrease from baseline) and an RBS=0. ^dEndoscopic improvement defined as an ES of ≤1. ^eEIHR was defined as an ES ≤1 with histological remission (Geboes Index score <2.0). ^fCS-free clinical remission was defined as the proportion of patients with clinical remission at Week 52 who had not been receiving CS for ≥12 weeks immediately prior to Week 52. bio, biologic; CI, confidence interval; CS, corticosteroid; EIHR, endoscopic improvement-histologic remission; ES, endoscopic subscore; JAKi, Janus kinase inhibitor; MMS, modified Mayo score; QD, once daily; RBS, rectal bleeding subscore; SFS, stool frequency subscore.

Conclusion

Etrasimod demonstrated significant efficacy over placebo in all Week 52 efficacy outcomes in bio/JAKi-naïve induction treatment responders. These findings help contextualize data from the ELEVATE UC clinical programme for patients receiving their first advanced UC therapy within a treat-through trial design.

References

Disclaimer: 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

SV: Lecture/speaker/consultancy/advisory fees: AbbVie, AbolerIS Pharma, Alimentiv, Arena, AstraZeneca, Avaxia, Boehringer Ingelheim, BMS, Celgene, CVasThera, Dr Falk Pharma, Eli Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, J&J, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillotts, Zealand Pharma.
Grant/research support: AbbVie, MSD, Galapagos, Janssen, Pfizer Inc, Takeda.
BES: Consultant/speaker fees: AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, BMS, Calibr, Celgene, Celltrion, ClostraBio, Enthera, Equillium, Evommune, Ferring, Fresenius Kabi, Fzata, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Janssen, Kaleido, Kallyope, Lilly, Merck, Mobius Care, Morphic Therapeutics, MRM Health, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Palisade Bio, Pfizer Inc, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, TR1X, Union Therapeutics, Ventyx Biosciences.
Stock and stock options: Ventyx Biopharma.
Research grants/other support: Abivax, BMS, Janssen, Lilly, Pfizer Inc, Takeda.
MCD: Consultant: AbbVie, Abivax, Arena Pharmaceuticals, AstraZeneca, BMS, Eli Lilly, Galapagos, Genentech, Gilead Sciences, Janssen Pharmaceuticals, J&J, Merck, Pfizer Inc, Prometheus Laboratories, Prometheus Biosciences, Sanofi, Sphyre, Takeda, UCB.
Shareholder/royalties/directorship/ownership interest: Trellus Health.
BGF: Senior Scientific Director of Alimentiv Inc, which provides central reading services. He is not a company employee and has no equity stake in the organization, which is owned by a medical trust.
Consultant/speaker/advisory board: AbbVie, AbolerIS, AgomAB Therapeutics, Allianthera, Amgen, AnaptysBio, Applied Molecular Transport Inc, Arena Pharma, 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, First Word Group, Galapagos, Galen Atlantica, Genentech/Roche, Gilead, Gossamer Pharma, GlaxoSmithKline, Hinge Bio, Hot Spot Therapeutics, Index Pharma, Imhotex, Immunic Therapeutics, JAKAcademy, Janssen, Japan Tobacco Inc, Kaleido Biosciences, Landos Biopharma, Leadiant, L.E.K. Consulting, Lenczner Slaght, LifeSci Capital, Lument AB, Millennium, MiroBio, Morgan Lewis, Morphic Therapeutics, Mylan, OM Pharma, Origo BioPharma, Orphagen, Pandion Therapeutics, Pendopharm, Pfizer Inc, Prometheus Therapeutics and Diagnostics, Play to Know AG, Progenity, Protagonist, PTM Therapeutics, Q32 Bio, Rebiotix, REDX, Roche, Sandoz, Sanofi, Seres Therapeutics, Silverback Therapeutics, Surrozen Inc, Takeda, Teva, Thelium, Tigenix, Tillotts, Ventyx Biosciences, VHSquared Ltd, Viatris, Ysios, Ysopia, Zealand Pharma.
Shareholder: Gossamer Pharma.
RP: Consultant/speaker/advisory board: Abbott, AbbVie, Abivax, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, BMS, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer Inc, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, UCB.
Research support: AbbVie, Janssen, Takeda, Pfizer Inc.
VJ: Speaker/consultant/advisory board: AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, BMS, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer Inc, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Shire, Sorriso, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion.
AJY: Consultancy/lecture fees: AbbVie, Arena, BMS, Celltrion, Pfizer Inc, Takeda.
MVC: Grant support: BMS, J&J, Novartis, Pfizer Inc.
Consultant/speaker: AbbVie, Arena, BMS, Celltrion, Fresenius Kabi, J&J, Lilly, Medtronic, Pfizer Inc, Prometheus, Takeda.
AW: Grant/research support: AbbVie, Alfasigma, BMS, Buhlmann, Falk, Ferring, Galapagos, Janssen, Lilly, Pfizer Inc, Takeda.
MG: Employee: Pfizer AG; shareholder: Pfizer Inc.
JW/AMA/CC: Employees/shareholders: Pfizer Inc.
BS: Employee/shareholder: Pfizer Ltd.
SG: Steering/drug monitoring committee: AbbVie, BMS, Janssen.
Speaker/advisory board: AbbVie, BMS, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Janssen, Pfizer Inc, Takeda.
Financial support/grants: GlaxoSmithKline.

EFFICACY OF ETRASIMOD AT WEEK 52 AMONG BIOLOGIC/JANUS KINASE INHIBITOR-NAÏVE PATIENTS WITH ULCERATIVE COLITIS WHO REACHED CLINICAL RESPONSE AT WEEK 12: POST HOC ANALYSIS OF THE PHASE 3 ELEVATE UC 52 RANDOMISED TRIAL

Severine Vermeire 1, Bruce E. Sands 2, Marla C. Dubinsky 3, Brian G. Feagan 4, Remo Panaccione 5, Vipul Jairath 6, Andres Yarur 7, Michael Chiorean 8, Alissa Walsh 9, Martina Goestch 10, Joseph Wu 11, Burak Sahin 12, Arcangelo M. Abbatemarco 13, Christina Cognata 14, Subrata Ghosh 15

1 Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium

2 Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States

3 Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York City, NY, United States

4 Inflammatory Bowel Disease Unit, Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada|||Alimentiv Inc, London, ON, Canada

5 Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, AB, Canada

6 Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

7 Inflammatory Bowel Disease Center and Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, United States

8 Inflammatory Bowel Disease Center, Swedish Medical Center, Seattle, WA, United States

9 Translational Gastroenterology Unit, Oxford University Hospital, Oxford, United Kingdom

10 Pfizer AG, Zürich, Switzerland

11 Pfizer Inc, Cambridge, MA, United States

12 Pfizer Inc, Tadworth, United Kingdom

13 Pfizer Inc, New York, NY, United States

14 Pfizer Inc, Collegeville, PA, United States

15 APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland

Conference

UEG Week Berlin 2025

Topics

IBD

Submission format

Abstract

Session

IBD (Posters)

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

Table. Incidence of active TB in pts with a history of LTI receiving etrasimod and the proportion of pts receiving etrasimod with liver enzyme elevations (irrespective of TEAE classification) in ELEVATE UC 52 and ELEVATE UC 12 (pooled)
Pts, n	Pts receiving etrasimod 2 mg QD (N=527)
With a history of LTI With active TB	17 0
Liver enzyme elevations recorded any time post-baseline, n	Pts receiving concomitant etrasimod 2 mg QD + INH (N=9)
ALT >1 to ≤2 × ULN ALT >2 × ULN AST >1 to ≤2 × ULN AST >2 × ULN GGT >1 to ≤2 × ULN GGT >2 to ≤3 × ULN GGT >3 × ULN	3^a 0 3^a 0 3^b 1^b 0
^a_{One pt receiving etrasimod 2 mg QD was excluded in the count as elevated AST and ALT were experienced after the discontinuation of concomitant etrasimod + INH.}^b_{One pt had elevation of GGT >1 to ≤2 × ULN and GGT >2 to ≤3 × ULN. ALT, alanine transaminase; AST, aspartate transaminase; GGT, γ-glutamyl transferase; INH, isoniazid; LTI, latent tuberculosis; n, number of patients with event; N, number of patients in analysis set; pt, patient; QD, once daily; TB, tuberculosis; TEAE, treatment-emergent adverse event; UC, ulcerative colitis; ULN, upper limit of normal.}

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