Sphingosine 1 phosphate receptor (S1PR) modulators are the latest drug class to have received approval for the treatment of ulcerative colitis, and have brought a new mechanism of action to this landscape. They target immune cell trafficking, specifically the egress of lymphocytes from lymph nodes to the bloodstream, and have proven to be an efficacious and safe anti-inflammatory mechanism. This narrative review aims to distil the key trial data on the efficacy and safety of ozanimod and etrasimod, the two S1PR modulators currently licensed for use in UC. We discuss the higher response rates in the advanced therapy naive versus exposed subgroups. We summarise their safety profiles, taking into consideration open label extension data. Finally, we consider where this class of drugs may be best placed in the treatment landscape and also provide a practical guide for their use in clinical practice.

Hyperparathyroidism may be a precipitating factor to the development of myelofibrosis; however, this is extremely rare with only a few documented case reports of myelofibrosis caused by secondary hyperparathyroidism. We describe a case of a 24-year-old female who had a failed live donor renal transplant and secondary hyperparathyroidism. While on haemodialysis she became increasingly pancytopenic despite erythropoietin injections and adequate iron, vitamin B12 and folate replacement. Her secondary hyperparathyroidism evolved to tertiary hyperparathyroidism despite vitamin D supplementation and phosphate binders. In order to determine the cause of her pancytopenia, a bone marrow biopsy was performed that confirmed myelofibrosis due to her secondary hyperparathyroidism. Following a successful parathyroidectomy in a tertiary hospital, her pancytopenia resolved and she is now awaiting a second transplant.

Objective: Risankizumab is an interleukin-23 p19 subunit inhibitor which received approval for Crohn’s disease (CD) by UK licensing authorities in May 2023. Our aim was to evaluate the real-world outcomes of risankizumab in the UK. Design: We conducted a retrospective, multicentre, cohort study of patients with CD treated with risankizumab across 25 health boards in the UK between 1 January 2021 and 1 November 2024. Our primary outcome was treatment persistence at 6 months. Our secondary endpoints were steroid-free clinical remission (Harvey-Bradshaw index <5), C-reactive protein (CRP) remission (CRP ≤5 mg) and faecal calprotectin (FCAL) remission (FCAL <250 µg/g). Results: We included 763 patients with a median follow-up time of 27 weeks (IQR 18–41 weeks) with a total of 432 and 110 patients having 6-month and 12-month data available. The median number of advanced therapy exposures was 3 (2–4), with 92% (704/763) having failed anti-tumour necrosis factor therapy and 72% (548/763) having failed ustekinumab. Treatment persistence at 6 and 12 months was 95.4% and 89.2%, respectively. Unadjusted persistence rates for ustekinumab-naive versus ustekinumab-exposed patients were 92.7% vs 95.3% and 89.0% vs 74.2% at 6 and 12 months, respectively (p=0.62). Rates of clinical, CRP and FCAL remission were 52% (123/236), 53% (169/319) and 44% (69/156) at 6 months. Rates of clinical remission for ustekinumab naive versus exposed were 57% (29/51) vs 51% (94/185) (p=0.54) 6 months. Adverse events occurred in 17% (n=127) of the cohort, of which 12% (n=92) were serious. Conclusion: Risankizumab was effective in a large, real-world, medically refractory CD cohort with excellent persistence and good clinical and biochemical remission rates.

Objective Inflammatory bowel disease (IBD) can have an impact on maternal and neonatal outcomes. This study reports the pregnancy outcomes, rates of gestational diabetes (GDM) and hypertensive disorders of pregnancy (HOP) in women with IBD cared for in a dedicated IBD-maternal fetal medicine (IBD-MFM) clinic compared with a group of age-matched controls. Design/methods A retrospective cohort study comparing the outcomes of 146 patients with IBD cared for in a dedicated IBD-MFM clinic and 292 consecutive, age-matched controls without IBD. We analysed the associations between IBD and maternal/neonatal outcomes. ORs were calculated and a multivariate logistic regression model was used to correct for confounding variables. Results A diagnosis of IBD was significantly associated with the development of GDM compared with controls (OR 1.86, CI 1.05 to 3.29, p=0.033). This was independent of confounding variables such as corticosteroid exposure. A diagnosis of IBD was associated with a significantly lower rate of HOP compared with controls (OR 0.04, CI 0.01 to 0.37, p=0.004). 45.2% of patients with IBD had active disease during pregnancy which significantly increased the risk of small for gestational age (SGA) (OR 5.16, CI 1.35 to 19.68, p=0.02) but not low birth weight (LBW), preterm birth or risk of neonatal intensive care admissions (NICU). Biologic use was not associated with adverse maternal or neonatal outcomes. Conclusions A diagnosis of IBD is associated with a significant increase in the risk of GDM and is independent of confounding variables. Active disease in pregnancy was significantly associated with SGA but not LBW, preterm birth or NICU admissions.

Background: Gastrointestinal (GI) bleeding is a common event that can be life-threatening. Mussetto et al demonstrated the feasibility of panenteric capsule endoscopy (PCE) in patients with melaena and a negative oesophagogastroduodenoscopy (OGD)—the bleeding source was identified in 80% of patients and colonoscopy was avoided in 50%. However, there are no large prospective trials and limited real-world data. At two tertiary centres in the UK, we retrospectively evaluated the outcomes of patients who underwent an inpatient PCE following a negative OGD for suspected upper GI bleeding. Methods: Capsule databases at each institution were reviewed from 2021 to 2024. The inclusion criteria were patients who had a suspected upper GI bleed (melaena and haemoglobin drop of >10 g/L) and underwent an inpatient PCE following a negative OGD. Data was extracted from the patient’s electronic health records. Results: 23 patients met the inclusion criteria. The mean age was 56 years. The median time from OGD to capsule ingestion was 4 days. The source of bleeding was identified by PCE in 70% of cases. A small bowel source was identified in 43%. PCE prevented unnecessary lower GI endoscopy in 70%. Capsule retention occurred in 1 patient and was managed conservatively. Rebleeding rates at 30 days, 6 months and 12 months were 9%, 4% and 0%. Conclusion: PCE is an option for patients presenting with melaena and has a negative upper GI endoscopy. The findings from this study are promising with a diagnostic yield of 70%. Large, multi-centre randomised studies are required to further investigate this strategy.

Background: Dye chromoendoscopy (DCE) is the recommended endoscopic modality for dysplasia detection in inflammatory bowel disease (IBD) surveillance, but randomised trials suggest comparable performance with virtual chromoendoscopy (VCE) and high-definition white light endoscopy (WLE). This multicentre UK study evaluated the association between modality and dysplasia detection in routine practice. Methods: We performed a multicentre study across six UK centres, identifying adults with ulcerative colitis (UC), colonic Crohn’s disease (CD), or primary sclerosing cholangitis associated IBD (PSC-IBD) undergoing surveillance colonoscopy between 2019-2024. Outcomes included dysplasia detection rate (DDR), neoplasia detection rate (NDR) and total lesion detection yield. Multivariable regression models and inverse probability weighting (IPW) analysis were used to evaluate detection rates taking into consideration recognised variables that associate with dysplasia risk. Findings: We included 3643 colonoscopies in 2831 patients (UC 54%, CD 22%, PSC-IBD 24%). The most frequently used modality was WLE (50%) followed by DCE (35%) and VCE (15%), with inter-centre variation in modality selection, dedicated surveillance lists, and withdrawal time. Raw DDR were higher with DCE (10%) and VCE (10%) vs. WLE (7%, p=0·012). On multivariable adjustment, modality was not independently associated with DDR. However, when variables were weighted with IPW, there was a numerically higher DDR with VCE (OR 1·60, 95% CI 1.00-2.58; p=0·051). VCE associated with higher NDR allowing the identification of more serrated and hyperplastic lesions. Longer withdrawal time, previous colorectal neoplasia, bowel preparation quality, and surveillance expertise were also associated with increased detection rates, whereas active inflammation had the opposite effect. Interpretation: In this large, multicentre study of clinical practice DCE was not superior to VCE or WLE for dysplasia detection. Identifying patients who will benefit most from surveillance and providing access to dedicated lists performed by experienced endoscopists with sufficient withdrawal time are key to increasing lesion detection in surveillance programmes.