Systematic review with network meta‐analysis: the efficacy of anti‐tumour necrosis factor‐alpha agents for the treatment of ulcerative colitis

Abstract

Summary Background Antibodies against tumour necrosis factor‐alpha (anti‐TNF) are effective therapies in the treatment of ulcerative colitis (UC), but their comparative efficacy is unknown. Aim To perform a network meta‐analysis comparing the efficacy of anti‐TNF agents in UC. Methods After screening 506 studies, reviewers extracted information on seven studies. Traditional meta‐analysis (TMA) was used to compare each anti‐TNF agent to placebo. Bayesian network meta‐analysis (NMA) was performed to compare the effects of anti‐TNF agents to placebo. In addition, sample sizes for comparative efficacy trials were calculated. Results Compared to placebo, TMA revealed that anti‐TNF agents result in a higher likelihood of induction of remission and response (RR: 2.45, 95% CI: 1.72–3.47 and RR: 1.65, 95% CI: 1.37–1.99 respectively) as well as maintenance of remission and response (RR: 2.00, 95% CI: 1.52–2.62 and RR: 1.76, 95% CI: 1.46–2.14 respectively). Individually, infliximab, adalimumab and goliumumab resulted in a higher likelihood of induction and maintenance for both remission and response. NMA found nonsignificant trends in comparisons of the individual agents. The required sample sizes for direct head‐to‐head trials between infliximab and adalimumab for induction and maintenance are 174 and 204 subjects respectively. Conclusions This study demonstrates that, compared to placebo, infliximab, adalimumab and golimumab are all effective for the induction and maintenance of remission in ulcerative colitis. However, network meta‐analysis demonstrates that no single agent is clinically superior to the others and therefore, other factors such as cost, safety, route of administration and patient preference should dictate our choice of anti‐TNF agents. A randomised comparative efficacy trial between infliximab and adalimumab in UC is of practical size and should be performed.

Systematic review with network meta‐analysis: the efficacy of anti‐TNF agents for the treatment of Crohn's disease

“…41 Our group recently published a comparative effectiveness study for anti-TNF agents in ulcerative colitis showing a trend of IFX superiority over ADA for induction (RR = 0.46, 95% CrI: 0.10-3.05). 42 Thorlund and colleagues also performed NMA yielding a comparable point estimate of IFX superiority over ADA, but using informative priors they reported statistical significance (OR = 0.42, 95% CrI: 0.17-0.97). 43 Deciding on whether to use informative priors remains controversial.…”

Initial experience with golimumab in clinical practice for ulcerative colitis

“…Its treatment depends on the course or behavior of the disease, and although therapy with corticosteroids, 5-aminosalicylates, and immunomodulators is effective in most cases, biological agents as anti-tumor necrosis factors (TNF) are necessary in cases where the disease is refractory or intolerant to therapeutic agents (1). The consequence of treatment failure in UC patients is a greater number of colectomies, and a possible alternative therapy in UC patients is a TNF-blocking agent, which has been shown to be effective, inducing clinical response and remission, and reducing the need for colectomy (2,3).…”

The Importance of Considering Differences in Study Design in Network Meta-analysis: An Application Using Anti-Tumor Necrosis Factor Drugs for Ulcerative Colitis

“…12 Only the ACT-1, ULTRA-2, and PURSUIT trials were included in the replicated NMAs, given that these were larger trials and were consistently included in the 3 NMAs of interest ( Figure 3). 2,4,5 Because outcomes were dichotomous and were captured in multi-arm trials, a binomial likelihood model 13 was used for all analyses. Both fixed-and random-effects NMAs were conducted; although, the fixed-effects model was chosen for the reference case analysis, as the evidence network largely comprised single-study connections.…”