P324 Tacrolimus for induction of remission in refractory ulcerative colitis: a Cochrane systematic review

Abstract

Abstract Background There is a limited number of treatment options for patients with corticosteroid refractory ulcerative colitis (UC). We aimed to evaluate tacrolimus for induction of remission in these patients. Methods MEDLINE, Embase, CENTRAL, Clinicaltrials.gov and ICTRP were searched up to October, 2021 to identify all relevant randomised contolled trials (RCTs). The authors independently reviewed potentially relevant studies to determine eligibility based on pre-specified criteria. A data extraction form was developed and used to extract data from included studies. Data were analysed using Review Manager. The primary outcomes were induction of remission and clinical improvement, as defined by the studies. Results Five RCTs were included with a total of, 347 participants with active UC. There is low certainty (oral and rectal) tacrolimus may be superior for clinical remission when compared to placebo (14/87 to, 1/61, RR, 3.76, 95% CI, 1.03 to, 13.73). There is low certainty (oral and rectal) tacrolimus may be superior for clinical improvement when compared to placebo (45/87 to, 7/61, RR, 4.47, 95% CI, 2.15 to, 9.29. The results on adverse events are of very low certainty and no conclusions can be drawn. There is low certainty there may be no difference in achievement of clinical remission when tacrolimus suppositories (16/44) were compared to beclomethasone (15/44) (RR, 1.07, 95% CI, 0.60 to, 1.88). There is low certainty there may be no difference in clinical improvement when tacrolimus suppositories (22/44) were compared to beclomethasone (22/44) (RR, 1.00, 95% CI, 0.66 to, 1.88). There is low cerainty there may be no difference in serious adverse events when tacrolimus suppositories (1/44) were compared to placebo suppositories (0/44) (RR, 1.00, 95% CI, 0.13 to, 71.70) and total adverse events (21/44 to, 14/44) (RR, 1.50, 95% CI, 0.88 to, 2.55). The evidence on the efficacy and safety of tacrolimus compared to cyclosporine is of very low quality and no conclusions can be drawn. Conclusion The cohorts studied are small, with missing data sets, short follow-up, and the clinical endpoints used are not in line with those suggested by regulatory bodies. No clinical practice conclusions can be made.This review highlights the need for further research that targets relevant clinical questions, uses appropriate trial methodology, and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration to capture the effectiveness of tacrolimus in the medium-to-long term. Well-structured efficacy studies need to be followed up by long-term phase, 4 extensions to provide key outputs and inform a real-world setting.