Safety of sequential biological therapy in inflammatory bowel disease: results from a tertiary referral centre.

BACKGROUND: Biologicals represent the cornerstone of treatment for moderate-to-severe inflammatory bowel diseases (IBD). Many patients cycle between biologicals when encountering loss of response or adverse events. AIM: To assess the occurrence of serious infections and malignancies with exposure to several (classes of) biologicals. METHODS: We performed a retrospective cohort study in a tertiary referral centre including consecutive IBD patients exposed to adalimumab, infliximab, ustekinumab or vedolizumab between 1996 and 2019. All serious infections and malignancies, as well as potential confounders, were accounted for. RESULTS: In total, 1575 patients were included with a median (interquartile range) follow-up of 10 (6-16) years and a duration of biological therapy of 71 (39-112) months. Incidence rates of serious infections were 3.4 per 100 patients' years (PY) in the post-biological setting. Serious infections after biological exposure were associated with systemic steroids in monotherapy (hazard ratio 2.96 [95% confidence interval 1.78-4.93], p < 0.0001), combination therapy of systemic steroids and a biological (2.44 [1.37-4.34], p = 0.002), female gender (1.25 [1.04-1.51], p = 0.02), and prior serious infections in the pre-biological setting (1.42 [1.03-1.96], p = 0.03). Malignancy rates were 1.06 per 100PY in the post-biological setting and increased with older age at biological initiation (1.04 [1.02-1.05], p < 0.0001). The risk for serious infections or malignancies was independent of type and number of biologicals to which the patient was exposed. CONCLUSION: This study shows that the sequential use of biological therapy in IBD does not seem to convey an overall higher risk of serious infections or malignancies, but that underlying more refractory disease seems to increase this risk.

Review article: how the intestinal microbiota may reflect disease activity and influence therapeutic outcome in inflammatory bowel disease.

BACKGROUND: Intestinal bacteria produce metabolites and by-products necessary for homeostasis. Imbalance in this equilibrium is linked to multiple pathologies including inflammatory bowel disease (IBD). The role of the gut microbiota in determining treatment response is becoming apparent, and may act as biomarker for efficacy. AIM: To describe knowledge about the intestinal microbiota on disease severity and treatment outcomes in IBD METHODS: Descriptive review using PubMed to identify literature on the intestinal microbiota in IBD RESULTS: Severe IBD has a less diverse microbiota with fewer commensal microbiota communities and more opportunistic pathogenic bacteria originating from the oral cavity or respiratory tract. IBD treatments can alter gut microbiota composition, but in vitro/in vivo studies are needed to prove causation. A diversification of the microbiota is observed during remission. Patients with a more diverse baseline microbiome and higher microbial diversity show better response to anti-tumour necrosis factor-α, vedolizumab and ustekinumab therapy. Higher abundance of short chain fatty acid-producing bacteria, fewer mucus-colonising bacteria and lower abundance of pro-inflammatory bacteria have also been associated with a favourable outcome. Predictive models, based on a combination of microbiota, clinical data and serological markers, have good accuracy for treatment outcome and disease severity. CONCLUSION: The intestinal microbiota in IBD carries a set of promising biomarkers of disease activity and prediction of therapeutic outcome. Current insights may also help in designing microbiota modulation strategies to improve outcomes in IBD.