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

Abstract

SummaryBackgroundAnti‐tumour necrosis factor‐alpha agents (anti‐TNF) are effective therapies for the treatment of Crohn's disease (CD), but their comparative efficacy is unknown.AimTo perform a network meta‐analysis comparing the efficacy of anti‐TNF therapies in CD.MethodsAfter screening 506 studies, reviewers extracted information on 10 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.ResultsCompared to placebo, TMA revealed that anti‐TNF agents result in a higher likelihood of induction of remission and response (RR: 1.66, 95% CI: 1.17–2.36 and RR: 1.43, 95% CI: 1.17–1.73, respectively) as well as maintenance of remission and response (RR: 1.78, 95% CI: 1.51–2.09 and RR: 1.68, 95% CI: 1.46–1.93, respectively). NMA found nonsignificant trends between infliximab and adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated superiority of adalimumab to certolizumab pegol for induction of remission (RR: 2.93, 95% CrI: 1.21–7.75). Sample size calculations suggest that adequately powered head‐to‐head comparative efficacy trials would require greater than 3000 patients.ConclusionsAll anti‐TNF agents are effective for induction and maintenance of response and remission in the treatment of CD. Although adalimumab is superior to certolizumab pegol for induction of remission, there is no evidence of clinical superiority among anti‐TNF agents. Head‐to‐head trials among the anti‐TNF agents are impractical in terms of size and cost.

Indian Society of Gastroenterology consensus statements on Crohn’s disease in India

“…The meta-analyses also confirm that, in CD patients who initially responded to biologics, these agents are useful in maintaining remission in these patients up to 56 weeks [104][105][106]. Typically, the likelihood of maintenance of remission compared to placebo was in the range of relative response rate of 1.78 (95 % CI 1.51-2.09).…”

“…Infliximab and other anti-tumor necrosis factor antibodies are useful in induction of remission in moderate to severe CD Voting: A68, B26, C6 Level of evidence: I Grade of recommendation: A A number of meta-analyses of clinical trials evaluating anti-tumor necrosis factor (TNF) antibodies in induction of remission at week 4 in CD have all concluded that these agents are useful in inducing remission in these patients [104][105][106]. Typically, the likelihood of induction of remission compared to placebo was in the range of relative response rate of 1.66 (95 % CI 1.17-2.36).…”

Cost-minimization and budget impact analysis of certolizumab pegol for patients with Crohn’s disease, moderate or severe, with relapse after conventional treatment from the perspective of the Brazilian private payer

“…Its efficacy and safety, according to various systematic reviews and meta-analyses using its clinical trials as the basis, as well as trials of its alternatives adalimumab and infliximab, are considered equivalent, thus justifying its use in moderate to severe Crohn's disease patients who are unresponsive or with poor response to synthetic disease-modifying drugs (Shao et al, 2009;Singh et al, 2014;Stidham et al, 2014). The drug is currently approved by the Brazilian Health Surveillance Agency (ANVISA) for the treatment of moderate to severe CD not responding to conventional treatment, among other indications (ANVISA, 2016).…”

“…The study by Stidham et al (2014) has indirectly evaluated adalimumab, infliximab and certolizumab pegol in a systematic review and demonstrated that there is no statistical difference in terms of efficacy superiority between them. Additionally, Nikfar et al (Nikfar et al, 2013) demonstrated that there are no statistically significant differences between the probabilities for placebo's and certolizumab pegol's adverse events occurring.…”

“…Further taking into consideration scientific literature showing that drug efficacy and safety do not have statistically significant differences (Shao et al, 2009;Nikfar et al, 2013;Singh et al, 2014;Stidham et al 2014), a cost-minimization analysis was chosen. Moreover, we carried out a budget impact analysis.…”