The Efficacy and Safety of Biological and Immunosuppressive Combination Therapy are Equal to Biological Monotherapy for Inflammatory Bowel Disease: A Systemic Review and Meta-Analysis

Abstract

Background: The current concern exists regarding the efficacy and safety of biological agent monotherapy versus combination therapy with an immunomodulator (IM) in patients with inflammatory bowel disease (IBD). We performed a meta-analysis of results from randomized controlled trials (RCTs) to compare the efficacy and safety of biological and immunosuppressive combination therapy with biological monotherapy in IBD. Methods: We comprehensively and systematically identified eligible studies from Embase, PubMed, and Cochrane library comparing the biological and immunomodulator treatment with biological monotherapy. Raw data from RCTs meeting inclusion criteria were extracted for meta-analysis. Sensitivity analysis was applied for all results. Funnel plots were performed for publication bias. Findings: Of 3574 identified studies, 12 were eligibly included in our meta-analysis. Overall, there was no statistically significant benefit for combination treatment over anti-TNF monotherapy in inducing clinical remission and preventing relapse in both CD and UC (RR = 1.04; 95% CI = 0.94-1.16). There were no benefits for combination treatment over monotherapy in further subgroup analysis of quiescent CD (RR = 1.01, 95% CI = 0.84-1.22), active CD (RR = 1.06; 95% CI = 0.92-1.23), quiescent UC (RR = 0.61; 95% CI = 0.12-3.00), and active UC (RR = 1.09; 95% CI = 0.79-1.52). Similarly, there were no statistically significant benefits for combination therapy in subgroup of infliximab treatment (RR = 1.05; 95% CI = 0.89-1.24) and adalimumab treatment (RR = 1.04; 95% CI = 0.90-1.20) in both UC and CD. For safety analysis, no significant differences were observed in the overall pooled summary for adverse events (RR = 1.05; 95% CI = 0.89-1.23), opportunistic infections (RR = 1.13; 95% CI = 0.94-1.36), and serious infections (RR = 1.20; 95% CI = 0.83-1.73) of combination therapy versus monotherapy. However, an increase of risk of liver enzyme abnormality (RR = 3.47; 95% CI = 1.67-7.21) and a decrease of infusion reactions (RR = 0.43; 95% CI = 0.23-0.80) were seen in combination therapy. Interpretation: The use of combination therapy among patients with IBD is not significantly associated with an increase of efficacy and safety in preventing relapse and inducing remission compared with anti-TNF monotherapy, but increases liver function damage. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (81630017, 91740117). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The PRISMA guidelines were applied for systematic reviews.