Adalimumab and infliximab have been approved for the treatment of ulcerative colitis by several regulatory bodies across the globe. Both are viable treatment options when patients become refractory or intolerant to conventional therapy. Since placebo controlled randomized clinical trials for adalimumab were only published recently, the comparative effectiveness of adalimumab versus infliximab has not yet been established via accepted meta-analytic indirect comparison methods.
Method:
An exhaustive search strategy covered major medical databases and recent conventional meta-analyses to identify eligible randomized clinical trials (RCTs). A Bayesian random-effects indirect comparison meta-analysis was performed for five selected and patient-important clinical outcomes at 8 weeks and 52 weeks. Odds ratio (OR) estimates and associated 95% credible intervals (CrI) were produced.
Result:
Five eligible RCTs were identified from which data on clinical remission, clinical response, mucosal healing, response on the inflammatory bowel disease questionnaire (IBDQ), colectomy, serious adverse events, and discontinuation due to adverse events were extracted at 8 weeks and 52 weeks. For all efficacy outcomes at both time points, the indirect comparison meta-analysis of adalimumab versus infliximab favoured infliximab. At 8 weeks, clinical remission (OR=0.42, 95% CrI 0.17-0.97), clinical response (OR=0.45, 95% CrI 0.23-0.89) and mucosal healing (OR=0.46, 95% CrI 0.25-0.86) were all statistically significant, whereas IBDQ was not. At 52 weeks, OR estimates for all efficacy outcomes favoured infliximab, but since only two trials provided data for this time point, the results were not statistically significant. Sustained remission was also more likely with infliximab, and sustained response was statistically significantly more likely with infliximab (OR=0.53, 95% CrI 0.24-0.98). For serious adverse events and discontinuations due to adverse events, adalimumab and infliximab both trended towards smaller risk than placebo, but the findings were not statistically significant. Further, the indirect comparison of the adalimumab and infliximab yielded odds ratios close to 1.00 with wide credible intervals.
Conclusion:
Our findings suggest that infliximab is significantly more effective than adalimumab for the treatment of moderately to severe ulcerative colitis at 8 weeks, is numerically more effective at 52 weeks, and is more effective at sustaining 8 weeks outcomes till 52 weeks. Findings on safety outcomes were statistically inconclusive.