Introduction

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

Aims & Methods

This post hoc analysis of ELEVATE UC 52 and ELEVATE UC 12 describes etrasimod efficacy and safety in patients stratified according to baseline disease activity. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients aged 16–80 years with moderately to severely active UC were randomised 2:1 to etrasimod 2 mg once daily or placebo.¹ ELEVATE UC 52 had a treat-through design comprising a 12-week (wk) induction period followed by a 40-wk maintenance period. ELEVATE UC 12 comprised a 12-wk induction period. In this analysis, data were pooled from both trials and patients’ baseline UC activity was stratified as moderately or severely active based on a Modified Mayo score (MMS) of 5–7 or 8–9, respectively. Efficacy endpoints were measured at Wk 12 and included mean percentage change from baseline in MMS and clinical response/remission according to MMS category. Efficacy data were analysed descriptively, and 95% confidence intervals (CIs) were calculated for all means or proportions using normal approximation or simultaneous estimation method, respectively. Safety was assessed up to Wk 52 in the pooled safety analysis set.

Results

Of the 743 patients in this analysis, 525 (70.7%) had a baseline MMS 5–7 and 218 (29.3%) had a baseline MMS 8–9. Baseline characteristics were broadly similar between subgroups, with the exception of lower rates of proctitis in patients with MMS 8–9 vs 5–7 (3.3% and 3.0% vs 9.3% and 9.4% in etrasimod and placebo groups, respectively). At Wk 12, patients treated with etrasimod showed larger mean percentage reductions (95% CI) in MMS, vs placebo, regardless of baseline disease activity (48.4% [52.3, 44.4] vs 27.0% [32.2, 21.7] for baseline MMS 5–7, and 46.4% [51.2, 41.5] vs 29.8% [37.2, 22.3] for baseline MMS 8–9). At Wk 12, more patients treated with etrasimod achieved clinical response, vs placebo, regardless of baseline disease activity, with an overall reduction from baseline disease activity as measured by MMS categorisation in both baseline MMS subgroups (Table). Generally, rates of treatment-emergent adverse events (TEAEs) were similar across treatment and baseline disease activity subgroups (proportion of patients with any TEAE: 59.0% vs 50.8% and 65.1% vs 56.1% for etrasimod vs placebo, in baseline MMS 5–7 and 8–9 groups, respectively).

Conclusion

Etrasimod showed greater reductions in disease severity and higher rates of clinical response, vs placebo, regardless of baseline disease activity. The safety profile of etrasimod was consistent with the overall trial population¹ and was not impacted by baseline disease activity.

References

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

Disclosure

BES has received consulting fees from AbbVie, Abivax, Alimentiv, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Boston Pharmaceuticals, 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 Therapeutics, MRM Health, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Sun Pharma, Surrozen, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, Ventyx Biosciences; speaker fees from Abivax, Bristol Myers Squibb, Janssen, Lilly, Pfizer, Takeda; research grants from Bristol Myers Squibb, Janssen, Pfizer, Takeda, Theravance Biopharma; stock options from Ventyx Biopharma; and other support from Bristol Myers Squibb, Lilly, Janssen, Pfizer and Takeda. MCD is a consultant for AbbVie, Abivax, AstraZeneca, Bristol Myers Squibb, Janssen, Lilly, Merck, Pfizer Inc, Prometheus Labs, Spyre and Takeda. PGK has received consulting and speaker fees from AbbVie, Janssen, Pfizer Inc, and Takeda and has received scientific grants from Pfizer Inc and Takeda. SV has received 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, Lilly, Ferring, Galapagos, Genentech/Roche, Gilead, Hospira, Imidomics, Janssen, Johnson and Johnson, Materia Prima, MiroBio, Morphic, MrMHealth, MSD, Mundipharma, Pfizer Inc, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance Biopharma, Tillots Pharma AG and Zealand Pharma; and grant/research support from AbbVie, MSD, Pfizer Inc, Galapagos, Janssen and Takeda. RP has received consulting fees from Abbott, AbbVie, Abbivax, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, Trellus, Viatris, Ventyx, UCB; speaker fees from AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Lilly, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, Takeda; an advisory board member for AbbVie, Alimentiv (formerly Robarts), Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ferring, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Shire, Sublimity Therapeutics, Takeda, Ventyx; and received research support from AbbVie, Janssen, Takeda and Pfizer. MDL is a consultant for AbbVie, Janssen, Pfizer Inc, Takeda, BMS, Target PharmaSolutions, Prometheus, Lilly, Salix, Valeant, Genentech, Roche, Calibr, Theravance; and has received research support from Pfizer Inc and Takeda. JCW, JW and EB are employees and shareholders of Pfizer Inc. AM is an employee of Pfizer Ltd and shareholder of Pfizer Inc. MG is an employee and shareholder of Pfizer AG. AJY has received consultancy fees from AbbVie, Pfizer Inc, Arena, Takeda, Bristol Myers Squibb; and speaker fees from Bristol Myers Squibb.

Introduction

There is an ongoing paradigm shift toward serology-based diagnosis of celiac disease (CeD). It is essential to target potential endoscopies for those most likely to benefit. Anemia is a common symptom of CeD that may warrant further investigations, but the prevalence and clinical relevance of endoscopic findings in anemic CeD patients remain unclear.

Aims & Methods

The aim of this study was to compare the prevalence of upper and lower endoscopic findings between anemic patients and non-CeD controls, and to identify predictors of significant findings in CeD patients. Medical data, including upper and lower endoscopy findings, were collected from 162 CeD patients and 350 controls. Binary logistic regression analysis was used to identify predictors of findings.

Results

CeD patients were younger (median 49 vs 66 years, p<0.001) and had fewer risk factors such as smoking (14% vs 25%, p<0.001), alcohol abuse (4% vs 14%, p<0.001), chronic comorbidities (55% vs 83%, p<0.001), and previous malignancies (1% vs 8%, p=0.002).
In comparison of upper endoscopy findings, CeD patients had fewer significant findings (21% vs 53%, p<0.001), H. Pylori positive gastritis (6% vs 19%, p<0.001), gastric ulcers (0% vs 5%, p=0.006), and atrophic gastritis (3% vs 9%, p=0.005) compared to the controls.
Twenty-four patients and 208 controls had undergone lower endoscopy with celiac patients more frequently demonstrating significant findings (54% vs 28%, p=0.008), non-specific inflammation (21% vs 1%, p<0.001) and colorectal cancer (25% vs 9%, p=0.018).
Predictors of significant upper endoscopy findings in CeD patients were older age (OR 1.03, 95% CI 1.01-1.05), age >50 (2.44, 1.18-5.06), co-existing chronic conditions (3.45, 1.53-7.78), gastrointestinal symptoms (2.31, 1.07-4.98), and use of acetylsalicylic acid (2.38, 1.01-5.06), and of colonoscopy findings older age (1.01, 0.99-1.04), co-existing conditions (3.48, 1.12-10.8), and gastrointestinal symptoms (4.73, 1.34-16.7).

Conclusion

CeD patients had fewer findings on upper endoscopy but, despite being younger and having fewer risk factors, showed more findings on lower endoscopy compared to controls. In older CeD patients presenting with anemia, lower endoscopy should be strongly considered.

Introduction

Upadacitinib, a selective JAK inhibitor, is approved for moderate-to-severe Crohn’s disease (CD). However, real-world data on its effectiveness and safety, particularly in highly refractory populations, remain scarce. The UPITA-Crohn registry was established to evaluate the outcomes of upadacitinib in clinical practice across multiple centers in Andalusia, Spain.

Aims & Methods

This ambispective, multicenter registry included 142 patients with refractory CD treated with upadacitinib in 12 Andalusian hospitals. Clinical and biochemical data were collected at baseline, weeks 12 and 16, and at 6 months. Clinical remission (CR) was defined as a Harvey-Bradshaw Index (HBI) <5; clinical-biochemical remission (CBR) as HBI <5, CRP <5 mg/L, and fecal calprotectin <250 μg/g; and steroid-free remission (SFR) as HBI <5 without corticosteroids from week 12. Outcomes were also analyzed overall and according to prior exposure to advanced therapies.

Results

The UPITA-Crohn registry cohort included 142 patients with refractory Crohn’s disease. The mean age was 40.8 years (range 18–76), with 40% male. The mean disease duration at the time of upadacitinib initiation was 13.3 years (range 1–42), with a mean of 2.7 failed advanced therapies, highlighting a population with longstanding and complex disease. Most patients had ileocolonic involvement (50%), 22% had perianal disease, and 32% had previously undergone resective surgery.
The majority (74.4%) received induction with upadacitinib 45 mg for 12 weeks. At week 12, clinical remission was achieved by 54% of patients, with 15% reaching clinical-biochemical remission. At 6 months, among those still on treatment, 48.3% maintained clinical remission, 16.1% achieved clinical-biochemical remission, and 18.4% achieved steroid-free remission (Table 1).
When stratified by prior therapy, 6-month clinical remission was similar between patients with ≥2 prior advanced therapies (48.5%) and those with only 1 prior therapy (47.4%), with no significant difference. Steroid-free and clinical-biochemical remission rates were also slightly higher among less refractory patients, but differences were modest.
A total of 31 patients (21.8%) discontinued upadacitinib before 6 months, mainly due to primary non-response (70.9%). Adverse events were reported in 21.1% of patients, most commonly infections (9 cases), acne (7), transient transaminase elevation (5), and herpes zoster (2). Seven discontinuations were due to serious adverse events, including thrombosis, stroke, myocardial infarction, fever, and severe infections.

Table 1: Effectiveness Outcomes

Conclusion

Upadacitinib demonstrated meaningful effectiveness and a manageable safety profile in a real-world cohort of refractory Crohn’s disease patients. Notably, clinical remission rates remained stable even in those with multiple prior advanced therapies, suggesting upadacitinib may be a valuable option for patients with limited alternatives.