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Background During the early COVID-19 pandemic, the British Society of Gastroenterology (BSG) developed a risk stratification grid to inform the United Kingdom (UK) government regarding strict social isolation, termed “shielding”. This advised inflammatory bowel disease (IBD) patients thought to be most clinically vulnerable to SARS-CoV-2 infection or severe COVID-19 outcomes, to stay at home and minimize face to face contact, even with household members. Those considered at highest risk included recent commencement of combination biologic and immunomodulator therapy, prednisolone ≥20mg/day, presence of comorbidities, age ≥70 years or clinically active disease in those receiving immunosuppression. Mesalazine was not considered to increase risk. An acknowledged limitation was an absence of COVID-19 risk data. This study sought to identify patient or IBD medication-related factors associated with severe outcomes from COVID-19. Methods PREPARE-IBD was a multi-centre observational United Kingdom (UK) cohort study including adult IBD patients (≥18 years) diagnosed with COVID-19 by PCR between 1st March 2020 and 31st August 2020. The primary outcome was severe COVID-19 defined as requirement for intensive care admission, invasive ventilation or death. We tested associations of severe outcomes with medications and other covariates using multiple logistic regression. Results 211 patients were included from 60 UK centres. 56 of 211 patients (26.5%) met the primary outcome. Severe COVID-19 was more common in ulcerative colitis relative to Crohn’s disease patients (33.9% [37/109] vs. 18.6% [16/86], p=0.018). Shortness of breath, nausea and vomiting were more common with severe COVID-19 (p<0.001 and p=0.023 respectively). Multivariable analysis identified co-morbidities and age as associated with severe COVID-19 outcomes; odds ratio (OR [95% CI]) 1.68 (1.23-2.35) for each co-morbidity, and an OR 1.03 (1.00-1.05) with each successive year of age. Neither clinically active IBD (OR 0.58 [0.26-1.26]), non-white ethnicity (OR 1.98 [0.92-4.28]), nor prednisolone use (OR 2.42 [0.47-11.26]) were associated with increased risk. On multivariable analysis, mesalazine was associated with severe COVID-19 outcomes (OR 2.03 [1.01-4.12]). Univariable analysis identified biologics and thiopurines as protective (OR 0.38 [0.15-0.87] and 0.32 [0.092-0.86] respectively). On multivariable analysis no association of severe COVID-19 outcomes with thiopurine or biologic exposure was seen. Conclusion Our data provide reassurance for the continued evidence-based use of corticosteroids, immunomodulators and biologic therapies in IBD during the ongoing COVID-19 pandemic, and is consistent with an as yet unexplained association between mesalazine use and severe COVID-19 outcomes.

Acute severe ulcerative colitis (ASUC) is a medical emergency which is associated with significant morbidity and a mortality rate of 1%. ASUC requires prompt recognition and treatment. Optimal management includes admission to a specialist gastrointestinal unit and joint management with colorectal surgeons. Patients need to be screened for concomitant infections and thromboprophylaxis should be administered to mitigate against the elevated risk of thromboembolism. Corticosteroids are still the preferred initial medical therapy but approximately 30%–40% of patients fail steroid therapy and require rescue medical therapy with either infliximab or cyclosporine. Emergency colectomy is required in a timely manner for patients who fail rescue medical therapy to minimise the risk of adverse post-operative outcomes. We discuss current and emerging evidence in the management of ASUC and outline management approaches for clinicians involved in managing ASUC.

Objective Anti-tumour necrosis factor (TNF) agents are associated with increased infection risk among elderly IBD patients, but little is known about non anti-TNF biologics in this cohort. We examined the safety and effectiveness of ustekinumab in elderly Crohn’s patients. Methods This retrospective multi-centre cohort study included Crohn’s patients ≥60-years old who commenced ustekinumab. We recorded Harvey-Bradshaw index (HBI), concomitant steroid therapy, treatment persistence and new infections or malignancies. Primary outcome was serious infections requiring hospitalisation. Results Seventy patients were included, with median age of 68 years. 43 (61.4%) had prior anti-TNF exposure, and 15 (21.4%) vedolizumab. Median treatment duration was 12 months, totalling 84 patient-years. Nine serious infections were reported, incidence 106.7/1000 patient-years. Systemic steroids were associated with increased risk of serious infections [odds ratio (OR) 7.83, 95% confidence interval (CI): 1.44–44.32, P = 0.02]. There were 27 “non-serious” infections; 321.4/1000 patient-years. Charlson co-morbidity index (OR 1.49, 95% CI: 1.05–2.12, P = 0.03) and steroid exposure (OR 44.10, 95% CI: 1.75–1112.10, P = 0.02) increased non-serious infection risk (P < 0.05). Mean HBI improved from 8.13 to 4.64 at 6 months and 4.10 at last follow up (P < 0.0001). 12-month treatment persistence was 55.7% (N = 39); 34 (48.6%) were steroid-free. Conclusion Ustekinumab was safe and effective in a cohort of elderly Crohn’s disease patients. Infections were mostly mild, not resulting in therapy discontinuation. Serious infection risk was comparable to previously reported rates with anti-TNF agents. Steroid exposure was associated with an increased serious infection risk.

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