Abstract and Introduction
Abstract
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.
Introduction
Ulcerative colitis (UC) is a chronic inflammatory disease primarily affecting the colonic mucosa. UC is characterised by a relapsing and remitting course; treatments are aimed at inducing and maintaining disease remission. UC disease activity can result in reduced quality of life, social and occupational disability, and increased health care utilisation. Direct costs of this condition are estimated at US $3.4–8.6 billion and could be as high as US $8.1–14.9 billion when accounting for the total economic impact of UC. Medication use contributes to 25% of the direct costs of UC. However, considering that hospitalisation represents nearly 50% of direct costs and flares of disease activity nearly double the mean economic impact on the individual, improved disease control is likely to reduce the net economic burden of UC.
Antibodies against tumour necrosis factor-alpha (anti-TNF) are effective therapies in the armamentarium used to treat UC. Infliximab is a chimeric monoclonal antibody against soluble and membrane-bound TNF with a murine Fc region. Adalimumab is fully humanised, but has similar action against TNF. A third anti-TNF, golimumab was recently approved in 2013 for moderate-to-severe UC. When assessed in individual randomised controlled trials (RCT), these anti-TNF therapies are approximately twice or more effective than placebo for inducing and maintaining clinical response and remission in UC.
The comparative efficacy of individual anti-TNF therapies in UC has not been well studied. In Crohn's disease, the SWITCH randomised clinical trial suggested that at approved standard dosing, adalimumab may be less effective at inducing and maintaining remission than infliximab, although the data are inconclusive. Head-to-head clinical trials among individual anti-TNF therapies have not been performed. Network meta-analysis (NMA) uses the results of direct comparisons to a common comparator (anti-TNF vs. placebo) to simulate comparisons between individual anti-TNF agents, yielding an estimate of comparative efficacy. In the absence of head-to-head RCTs, we employed both traditional and network meta-analyses of infliximab, adalimumab and golimumab clinical trials to assess comparative efficacy between anti-TNF therapies for UC.