P935 Remission rates of biologics and small molecules in extension studies of moderate to severe Ulcerative Colitis; A systematic review and Network Meta-analysis

Abstract

Abstract Background Ulcerative colitis is a relapsing and remitting inflammatory bowel disease characterised by symptoms of bloody diarrhoea and abdominal pain. In recent years, newer therapies have emerged such as biologics and small molecule therapies. However, these therapies have not been compared head-to-head in the longer term, and the choice in clinical practice is often at the discretion of the clinician. In this study we aim to compare these biologics and small molecule therapies across outcomes such as remission (as defined by the Mayo score) as well as histological, endoscopic and corticosteroid free remission in data beyond 52 weeks of medication administration. Methods Medical databases including MEDLINE, EMBASE and Cochrane were searched for phase III and IV randomised control trials examining efficacy of biologic and small molecule therapies in adults with moderate to severe ulcerative colitis beyond 52 weeks. A network meta-analysis was performed using the frequentist model to compare the aforementioned outcomes with pooled relative risk, heterogeneity and P values used to rank treatments. Results 13 randomised control trials (RCT) were included for analysis from a screen of 2516 abstracts. Of these 13 RCTs, there were 8 treatments directly compared to placebo beyond week 52. In terms of remission as defined by the Mayo score, Upadacitinib 30mg was found to be the best treatment for moderate-severe ulcerative colitis when compared to Upadacitnib 15mg, Vedolizumab and Etrolizumab in consecutive order. In achieving histological remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg) and Etrolizumab. For endoscopic remission, Upadacitinib 30mg was superior to Upadacitinib 15mg, Filgotinib (200mg and 100mg), Vedolizumab, Etrolizumab and Golimumab. For corticosteroid free remission, Filgotinib 200mg was superior to Golimumab, Upadacitinib (30mg and 15mg), Vedolizumab and Etrolizumab. Conclusion Large head-to-head trials of biologic and small molecule therapies in the treatment of moderate to severe ulcerative colitis beyond 52 weeks have not been performed. However, our results show Upadacitinib 30mg to be efficacious in terms of remission defined by the Mayo score as well as histologic, endoscopic and corticosteroid free remission when compared to other biologics and small molecule therapies. Whilst these newer therapies show promise, their overall performance over an extended period remains unclear and their use often precludes the efficacy of subsequent biologic or small molecule therapies. As such, the first choice of therapy must be made carefully to increase the probability of remission whilst also balancing the burden of adverse events.