Introduction

Abdominal pain is a common but often overlooked symptom in patients with ulcerative colitis (UC). The causes of pain during deep remission remain incompletely known, although factors in the brain-gut axis may play a role.

Aims & Methods

The aim of this study was to determine factors associated with abdominal pain in UC patients. Three existing study cohorts of adults with UC were used. Cohort I included 133 patients (49 active), cohort II 287 patients (155 active) and cohort III 92 patients (20 active). The abdominal pain domain of the Gastrointestinal Symptom Rating Scale was used to assess the severity of pain, identifying subjects with at least mild severity of abdominal pain. The Hospital Anxiety and Depression Scale was used to identify subjects with anxiety and or depression (scores ≥8) Patients also completed questionnaires to assess severity of fatigue (Fatigue Impact Scale (FIS, cohort I)), and quality of life (QoL, the IBD questionnaire (IBDQ, cohort II)).

Results

In the three cohorts 39%, 24% and 20% of the patients with active disease and 20%, 7% and 15% of the patients in remission reported at least mild severity of abdominal pain. A higher proportion of UC patients with at least mild abdominal pain had anxiety (83%, 44%, and 40% vs 42%, 18% and 7%; p<0.01) and depression (40%, 33% and 40% vs 13%, 9% and 13% p<0.05). Disease-specific QoL was lower in patients with at least mild abdominal pain, both in patients with active disease (median [IQR] IBDQ score 182 [150-198] vs 144 [115-160], p<0.001) and in remission (IBDQ score 203 [190-213] vs 171 [141-181], p<0.001). In UC patients in remission, having at least mild abdominal pain was associated with more severe impact of fatigue on daily life, (FIS 81 [67-100] versus 29 [14-58], p<0.001).

Conclusion

Abdominal pain is relatively common in patients with UC with active disease as well as in remission. This is associated with anxiety, depression and more severe fatigue and a lower QoL. Hence, paying attention to abdominal pain and associated factors seems important to optimize clinical management of these patients.

Disclosure

Tom van Gils: None
Hans Törnblom: Consultant/Advisory Board member: Cinclus Pharma, Dr Falk Pharma Gmbh, VIPUN Medical.
Speakers’ bureau: Tillotts, Takeda, Galapagos
Börje Jonefjäll: Consultant/advisory board member: Tillots. Speaker for MSD, AbbVie, Tillotts, MEDA, and Takeda.
Hans Strid: Consultant/Advisory Board member: Tillotts, Takeda, Abbvie, Pharmacosmos, BMS
Magnus Simrén: Unrestricted research grants: Glycom/DSM, Genetic Analysis AS
Consultant/Advisory Board member: Danone Nutricia Research, Ironwood, Biocodex, Genetic Analysis AS, Tillotts, Takeda, Arena, Kyowa Kirin, Abbvie, BioGaia, Cinclus Pharma and Pharmanovia.
Speakers’ bureau: Tillotts, Kyowa Kirin, Takeda, Biocodex, Sanofi, Janssen Immunology, Pfizer, Ferrer, BioGaia and Falk Foundation.

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

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.