Biological therapy for inflammatory bowel disease: cyclical rather than lifelong treatment?

Inflammatory bowel disease (IBD) treatment was revolutionised with the arrival of biological therapy two decades ago. There are now multiple biologics and increasingly novel small molecules licensed for the treatment of IBD. Treatment guidelines highlight the need for effective control of inflammation and early escalation to advanced therapies to avoid long-term complications. Consequently, a large proportion of patients with IBD receive advanced therapies for a long time. Despite their beneficial risk-benefit profile, these treatments are not without risk of side effects, are costly to healthcare providers and pose a burden to the patient. It is, therefore, paramount to examine in which circumstances a temporary cessation of therapy can be attempted without undue clinical risk. Some patients may benefit from cyclical rather than continuous treatment. This review examines the risk of relapse after discontinuation of advanced therapies, how to identify patients at the lowest risk of relapse and the chance of recapturing response when flaring after discontinuation.

Antenatal thiopurine exposure in women with IBD is associated with intrahepatic cholestasis of pregnancy.

BACKGROUND: Pregnant women with inflammatory bowel disease (IBD) continue thiopurines to maintain remission. Other studies have reported intrahepatic cholestasis of pregnancy (ICP) in IBD pregnancies exposed to thiopurines. We aimed to investigate whether thiopurines are associated with an increased risk of ICP. RESEARCH DESIGN AND METHODS: Single-center retrospective cohort study comparing incidence of ICP in thiopurine-exposed versus non-exposed patients with IBD compared with age-matched pregnant controls. RESULTS: The IBD cohort consisted of 386 pregnancies in 243 patients with IBD, with 386 age-matched controls. In patients with IBD, ICP was significantly more common among thiopurine-exposed pregnancies (9.0% vs 1.8%; odds ratio [95% confidence interval] = 5.34 [1.78-16.02]; p = 0.021). IBD patients with thiopurine exposure were significantly more likely to experience ICP compared to non-IBD controls (9.0% vs 1.3%; p < 0.001). Patients with IBD not exposed to thiopurines had a comparable ICP incidence with controls (1.8% vs 1.3%; p = 0.75). Severe ICP occurred in 80% of thiopurine-exposed ICP cases versus 40% in non-exposed (p = 0.25), versus 20% in controls (p = 0.09). CONCLUSION: Thiopurine exposure was associated with a significantly increased risk of ICP among patients with IBD compared to non-exposed IBD patients and age-matched general population controls. The course of ICP was not significantly different in thiopurine-exposed cases.

Obstetric Considerations in Pregnant Women with Crohn's Disease.

Crohn's disease affects many women of childbearing age. Fecundity rates are often lower than in the general population due to reduced fertility during active inflammation, effects of pelvic surgery or voluntary childlessness. Many women have concerns regarding the effects of pregnancy on their Crohn's, any potential effect of medication on the fetus, and passing on Crohn's disease to the offspring. International guidelines on reproduction for women with Crohn's disease provide evidence-based advice to patients and health care professionals. There is an increasing literature on the safety of advanced medication for Crohn's disease during pregnancy. This review article therefore focuses on obstetric considerations beyond medication safety. We provide information on fertility, factors affecting pregnancy and fetal outcomes, obstetric complications, factors influencing mode of delivery, management of intestinal stomas during pregnancy and general considerations around breast feeding.

Sources of excess steroid prescriptions and clinical adverse outcomes associated with steroid excess in patients with inflammatory bowel disease: The Leeds IBD Steroids study.

BACKGROUND: Corticosteroids remain important for managing inflammatory bowel disease (IBD) flares. Steroid excess, however, may be a marker of poor care. Patients access steroid prescriptions from primary (General Practitioners [GP]) or secondary care (hospital-based). Sources of prescriptions and associated outcomes are not well described. METHODS: Patients attending IBD clinics with linked primary care information were included. We examined appropriateness and timeliness of treatment escalation and avoidability of steroid excess in relation to prescription sources. RESULTS: Of 2246 patients, 33% were exposed to steroids over 2 years. Primary care issued 28% of prescriptions. Secondary care prescriptions were more often of appropriate dose and duration (85% vs 41%, p < 0.001). Further flares occurred in 50% of patients prescribed steroids from primary care (vs 39%; p = 0.003). Steroid excess was observed in 15%. Patients with steroid excess who received prescriptions from primary care that were not communicated to secondary care less often received timely treatment escalation (49% vs 66%, p = 0.042) and steroid excess was more often avoidable (73% vs 56%, p = 0.022). Patients with steroid excess had higher risks of hospitalisation for IBD (OR = 12.33, 95% CI [8.89-17.11]), hospitalisation for infections (OR = 2.89, 95% CI [1.82-4.61]) and GP prescribed antibiotics (OR = 1.41, 95% CI [1.07-1.86]). CONCLUSION: Patients commonly access steroids through primary care, but doses and durations are frequently inappropriate with patients more likely to flare. Steroid excess was associated with IBD admissions, admissions for infections and antibiotic prescriptions. Improved liaison between primary and secondary care is required to reduce steroid excess.

Comparative Outcomes of Budesonide MMX versus Prednisolone for Ulcerative Colitis: Results from a British Retrospective Multi-Centre Real-World Study.

During the COVID-19 pandemic many IBD units chose Budesonide MMX (Cortiment) as the first-line treatment for flares of ulcerative colitis (UC) in outpatients for its favourable side effect profile. This retrospective study of all UC patients treated with oral steroids between 1 March 2019-30 June 2019 and 1 March 2020-30 June 2020 aimed to compare Cortiment with Prednisolone in routine clinical practice. Outcomes included the need for hospitalisation for acute severe ulcerative colitis, symptoms at four weeks and end of treatment, and the need for rescue Prednisolone. The 2019 and 2020 cohorts did not differ at the baseline. Cortiment prescriptions rose from 24.5% in 2019 to 70.1% in 2020 (p < 0.001). At week four there were significant differences between 2019 and 2020 in mean bowel frequency (3.49 vs. 5.85, p = 0.001), rectal bleeding <50% (89.7% vs. 73.1% of patients, p = 0.039), and physician global assessment (PGA) (39.2% vs. 19.8% in remission, p = 0.045). There was no significant difference in hospital admissions, rectal bleeding, and PGA at week eight. Rescue Prednisolone was required in 10% of Cortiment patients in 2019 vs. 31.3% in 2020 (p = 0.058). Active IBD is associated with worse COVID-19 outcomes prompting the careful evaluation of the choice of first-line steroid for UC, as Cortiment was associated with worse outcomes at four weeks.

Acute severe ulcerative colitis: management advice for internal medicine and emergency physicians.

Acute severe ulcerative colitis is a medical emergency that warrants in-patient management. This is best served within a multidisciplinary team setting in specialised centres or with expert consultation. Intravenous corticosteroids remain the cornerstone in the management of ASUC and should be initiated promptly, along with general management measures and close monitoring of patients. Unfortunately, one-third of patients will fail to respond to steroids. Response to intravenous corticosteroid therapy needs to be assessed on the third day and rescue therapies, including cyclosporine and infliximab, should be offered to patients not responding. Choice of rescue therapy depends on experience, drug availability and factors associated with each individual patient, such as comorbidities, previous medications or contra-indications to therapy. Patients who have not responded within 7 days to rescue therapy must be considered for surgery. Surgery is a treatment option in ASUC and should not be delayed in cases of failure of medical therapy, because such delays increase surgical morbidity and mortality. This review summarises the current management of acute severe ulcerative colitis and discusses potential future developments.