Introduction
Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate receptor modulator for the treatment of ulcerative colitis (UC). Cumulative safety data of up to 5 years of etrasimod exposure in the global UC clinical programme have been reported.1
Aims & Methods
We present the long-term efficacy of etrasimod 2 mg QD through 2 years in the ongoing ELEVATE UC open‑label extension (OLE) study (NCT03950232), stratified by prior biologic/Janus kinase inhibitor (bio/JAKi) exposure. The OLE enrolled patients from five parent studies. Efficacy endpoints were evaluated at Weeks 52 and 104 of the OLE, and included clinical remission, clinical response, endoscopic improvement, symptomatic response and symptomatic remission. Endpoints were assessed among bio/JAKi-naïve and -experienced patients (as defined at parent study baseline) who entered the OLE as clinical responders (data cut-off: 20 June 2024). Data are reported using observed cases with corresponding modified nonresponder imputation (NRI) rates.
Results
Data from 390 etrasimod-treated patients were included (bio/JAKi naïve: N=287; bio/JAKi experienced: N=103). Among bio/JAKi-naïve patients, at Weeks 52 and 104 of the OLE, respectively, clinical response rates were 90.4% (NRI: 76.7%) and 87.1% (63.9%), clinical remission rates were 55.8% (47.3%) and 52.7% (38.7%), endoscopic improvement rates were 63.9% (53.7%) and 63.3% (45.3%), symptomatic response rates were 96.6% (79.9%) and 95.4% (68.2%) and symptomatic remission rates were 82.5% (68.2%) and 76.0% (54.4%). Results were similar among bio/JAKi-experienced patients (Table); at Weeks 52 and 104 of the OLE, respectively, clinical remission rates were 57.7% (43.7%) and 55.0% (33.0%) and endoscopic improvement rates were 67.6% (46.6%) and 64.8% (35.0%).
| Table. Efficacy of etrasimod 2 mg QD at Weeks 52 and 104 of ELEVATE UC OLE among clinical responders in parent studies (N=390)a |
Efficacy endpoints % (n/N)
| Bio/JAKi naïve (N=287)
| Bio/JAKi experienced (N=103)
|
OLE Week 52
| OLE Week 104
| OLE Week 52
| OLE Week 104
|
Observed
| NRIb
| Observed
| NRIb
| Observed
| NRIb
| Observed
| NRIb
|
Clinical responsec
| 90.4 (217/240)
| 76.7 (217/283)
| 87.1 (175/201)
| 63.9 (175/274)
| 83.3 (65/78)
| 63.1 (65/103)
| 83.3 (50/60)
| 50.0 (50/100)
|
Clinical remissiond
| 55.8 (134/240)
| 47.3 (134/283)
| 52.7 (106/201)
| 38.7 (106/274)
| 57.7 (45/78)
| 43.7 (45/103)
| 55.0 (33/60)
| 33.0 (33/100)
|
Endoscopic improvemente
| 63.9 (152/238)
| 53.7 (152/283)
| 63.3 (124/196)
| 45.3 (124/274)
| 67.6 (48/71)
| 46.6 (48/103)
| 64.8 (35/54)
| 35.0 (35/100)
|
Symptomatic responsef
| 96.6 (226/234)
| 79.9 (226/283)
| 95.4 (187/196)
| 68.2 (187/274)
| 92.3 (72/78)
| 69.9 (72/103)
| 94.9 (56/59)
| 56.0 (56/100)
|
Symptomatic remissiong
| 82.5 (193/234)
| 68.2 (193/283)
| 76.0 (149/196)
| 54.4 (149/274)
| 82.1 (64/78)
| 62.1 (64/103)
| 84.7 (50/59)
| 50.0 (50/100)
|
aEfficacy was assessed among clinical responders to etrasimod 1 mg, 2 mg or placebo QD at the last visit of the parent study prior to OLE entry. bNRI includes in the denominator those patients who had reached the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed. Patients with missing data were treated as nonresponders. cClinical response was defined as a ≥2-point and ≥30% decrease from parent study baseline in MMS and a ≥1-point decrease from parent study baseline in RBS or absolute RBS ≤1. dClinical remission was defined as SFS=0 (or =1 with a ≥1-point decrease from parent study baseline), RBS=0 and ES ≤1 (excluding friability). eEndoscopic improvement was defined as ES ≤1. fSymptomatic response was defined as a ≥30% decrease from parent study baseline in composite RBS and SFS. gSymptomatic remission was defined as SFS=0 (or =1 with a ≥1-point decrease from parent study baseline) and RBS=0. bio/JAKi, biologic/Janus kinase inhibitor; ES, endoscopic subscore; MMS, modified Mayo score; N, number of patients in subgroup; n, number of patients; NRI, modified nonresponder imputation; OLE, open-label extension; QD, once daily; RBS, rectal bleeding subscore; SFS, stool frequency subscore; UC, ulcerative colitis. |
Conclusion
Etrasimod demonstrated durable efficacy through 2 years of treatment in the OLE across clinical, endoscopic and symptomatic outcomes in patients with active UC with and without prior bio/JAKi exposure. This study is ongoing with future data readouts expected.
References
1. Rubin DT et al. J Crohns Colitis 2026; 20: i2593–i2595.
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
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AAf consulting fees: AbbVie, Bristol Myers Squibb, Lilly, Janssen, Pfizer Inc, Sanofi, Takeda; speaker fees: AbbVie, Bristol Myers Squibb, Lilly, Janssen, Pfizer Inc, Takeda; grant/research support: AbbVie, Janssen, Lilly, Pfizer Inc, Takeda; co-founder/board member of Scrubs & Heels Foundation.
PS consulting fees: Janssen, PRO.MED.CS Praha a.s and URGO; speaker fees: Polpharma and PRO.MED.CS Praha a.s.
MG, KL employees of Pfizer AG and shareholders of Pfizer Inc.
MKe employee at time of analysis and shareholder of Pfizer Inc.
MKu, CZ, DB, JCW employees and shareholders of Pfizer Inc.
MS employee of Pfizer Inc.
SD lecture/speaker fees\: AbbVie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer Inc, Takeda; consultancy/advisory fees: AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Gilead Sciences, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Pfizer Inc, Roche, Sandoz, Takeda, TiGenix, UCB, Vifor; directorship/ownership: Gastroenterology and Endoscopy.
DTR grant support: Takeda, Pfizer Inc; consulting fees: AbbVie, Abivax SA, Altrubio, Athos Therapeutics Inc, Bristol Myers Squibb, Celltrion, Connect BioPharma, Lilly, Genentech (Roche) Inc., Iterative Health, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer Inc, Sanofi, Spyre, Takeda, Vedanta Biosciences, Ventyx.