Brigida Barberio1, Christopher J Black2,3, Edoardo V Savarino1, Alexander C Ford2,3. 1. Department of Surgery, Oncology and Gastroenterology (DISCOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy. 2. Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK. 3. Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK.
Abstract
BACKGROUND: Despite randomized controlled trials [RCTs] and trial-based meta-analyses, the optimal rescue therapy for patients with acute glucorticosteroid-refractory ulcerative colitis [UC], to avoid colectomy and improve long-term outcomes, remains unclear. We conducted a network meta-analysis examining this issue. METHODS: We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register up to June 2020. We included RCTs comparing ciclosporin and infliximab, either with each other or with placebo, in patients with glucorticosteroid-refractory UC. RESULTS: We identified seven RCTs containing 534 patients [415 in head-to-head trials of ciclosporin vs infliximab]. Risk of colectomy at ≤ 1 month was reduced significantly with both treatments, compared with placebo (relative risk [RR] of colectomy with infliximab vs placebo = 0.37; 95% confidence interval [CI] 0.21-0.65, RR with ciclosporin vs placebo = 0.40; 95% CI 0.21-0.77). In terms of colectomy between > 1 month and < 1 year, both drugs ranked equally [P-score 0.75]. Neither treatment was more effective than placebo in reducing the risk of colectomy at ≥ 1 year. Both ciclosporin and infliximab were significantly more efficacious than placebo in achieving a response. Neither treatment was more effective than placebo in inducing remission, nor more likely to cause serious adverse events than placebo. CONCLUSIONS: Both ciclosporin and infliximab were superior to placebo in terms of response to therapy and avoiding colectomy up to 1 year, with no significant differences in efficacy or safety between the two. Ciclosporin remains a valid option to treat refractory UC patients, especially those who do not respond to previous treatment with infliximab, or as a bridge to other biological therapies.
BACKGROUND: Despite randomized controlled trials [RCTs] and trial-based meta-analyses, the optimal rescue therapy for patients with acute glucorticosteroid-refractory ulcerative colitis [UC], to avoid colectomy and improve long-term outcomes, remains unclear. We conducted a network meta-analysis examining this issue. METHODS: We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register up to June 2020. We included RCTs comparing ciclosporin and infliximab, either with each other or with placebo, in patients with glucorticosteroid-refractory UC. RESULTS: We identified seven RCTs containing 534 patients [415 in head-to-head trials of ciclosporin vs infliximab]. Risk of colectomy at ≤ 1 month was reduced significantly with both treatments, compared with placebo (relative risk [RR] of colectomy with infliximab vs placebo = 0.37; 95% confidence interval [CI] 0.21-0.65, RR with ciclosporin vs placebo = 0.40; 95% CI 0.21-0.77). In terms of colectomy between > 1 month and < 1 year, both drugs ranked equally [P-score 0.75]. Neither treatment was more effective than placebo in reducing the risk of colectomy at ≥ 1 year. Both ciclosporin and infliximab were significantly more efficacious than placebo in achieving a response. Neither treatment was more effective than placebo in inducing remission, nor more likely to cause serious adverse events than placebo. CONCLUSIONS: Both ciclosporin and infliximab were superior to placebo in terms of response to therapy and avoiding colectomy up to 1 year, with no significant differences in efficacy or safety between the two. Ciclosporin remains a valid option to treat refractory UC patients, especially those who do not respond to previous treatment with infliximab, or as a bridge to other biological therapies.