Systematic Review of therapies for refractory ulcerative proctitis.

BACKGROUND: Patients with ulcerative proctitis (UP) have favourable long-term outcomes but are typically excluded from ulcerative colitis clinical trials. Refractory proctitis presents a management conundrum for gastroenterologists and there remains a lack of clarity as to the best therapeutic strategy.

AIMS: To undertake a systematic review of studies assessing the clinical efficacy and safety of therapies for refractory proctitis METHODS: PubMed, Embase, Cochrane Library and Medline databases were searched without restriction through to 27th October 2022. Both interventional and non-interventional studies examining efficacy of therapeutic modalities for the induction and/or maintenance of remission in refractory proctitis were included. Included studies were grouped by therapeutic modalities as follows: a) immunomodulators b) monoclonal antibodies c) topical calcineurin inhibitors d) other topical therapies, and e) appendicectomy.

RESULTS: The search strategy identified 3301 studies, of which 13 met eligibility criteria for inclusion. Clinical remission rates for systemic therapies ranged from 20-26% for azathioprine, to 50-69% for TNF-alpha inhibitor therapies. The use of systemic therapies for proctitis raised safety concerns, with 22-37% of patients discontinuing therapies due to adverse effects across four retrospective cohort studies. Prospective clinical trials of topically applied tacrolimus demonstrated clinical remission rates of 42-46%, with a favourable safety profile. Substantial heterogeneity in study design precluded meta-analysis.

CONCLUSIONS: Refractory UP remains a neglected entity, with a dearth of prospective clinical trials to guide therapeutic decision-making. Current evidence supports a role for topically administered tacrolimus.