Meta-analysis/Systematic review Tumor necrosis factor-α antibodies (infliximab, adalimumab and certolizumab) in Crohn's disease: systematic review and meta-analysis

Abstract

IntroductionThis meta-analysis compares the effectiveness and safety of tumor necrosis factor α (TNF-α) antibodies (infliximab, adalimumab and certolizumab) with either a placebo or each of them in the treatment of Crohn's disease (CD).Material and methodsA systematic review of literature published up to November 2012 was performed and a meta-analysis of identified studies was carried out. We searched the following databases: PubMed, EMBASE, The Cochrane Library and others. Only randomized or clinical controlled trials were included.ResultsNineteen clinical trials fulfilled the established criteria (5 studies for infliximab vs. placebo, 6 for each adalimumab or certolizumab vs. placebo and 2 comparing infliximab with adalimumab). The results of meta-analysis showed that anti-TNF therapy in patients with CD is safe and statistically significantly more effective when compared with the placebo for induction of remission at week 4 (RB = 1.90, 95% CI: 1.55–2.33, p < 0.00001), maintenance of remission at weeks 20–30 (RB = 1.86, 95% CI: 1.61–2.15, p < 0.00001) and at weeks 48–56 (RB = 2.75, 95% CI: 2.13–3.54, p < 0.00001) in patients who responded to the induction therapy and patients randomized before the induction. Anti-TNF agents were also superior to the placebo in fistula healing (during short-term induction, as well as long-term maintenance) and inducing CR-70 but not CR-100 at week 4. Moreover, the anti-TNF therapy had a significant effect on achieving both CR-70 and CR-100 during long-term maintenance.ConclusionsInfliximab, adalimumab and certolizumab are effective as both induction and maintenance therapy in moderate to severe Crohn's disease in adults, including patients with fistulas. The safety profile was acceptable.

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).…”

“…In short-term treatment, anti-TNF antibodies were significantly better than placebo in healing and closure of fistulae with a relative response rate of 2.44 (95 % CI 1.13-5.28) [105]. Recent studies with longer-term follow up indicate that one third of enterocutaneous fistulae and up to two thirds of perianal fistulae heal with infliximab, with closure being associated with longer-term treatment [108,109].…”

“…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).…”

Biosimilars in rheumatology: current perspectives and lessons learnt

“…This position is supported by the observa tion that the TNF inhibitors certolizumab pegol (which is licensed in Canada and Europe for the treatment of AS, PsA and RA, but not inflammatory bowel diseases) and etanercept, neither of which induces ADCC, are less effective as induction therapy for patients with Crohn disease compared with monoclonal antiTNF anti bodies with a functionally active Fc region. 22,23 By contrast, other TNF inhibitors, such as adalimumab, golimumab, and reference inflixi mab, have proven efficacy in patients with inflammatory bowel diseases. Nevertheless, the observed differences in FcγRIIIa binding and induction of ADCC by CTP13 did not preclude Health Canada from extra polating data from studies in patients with RA and AS to the indications of PsA and plaque psoriasis.…”

Intravenous Versus Subcutaneous Anti-TNF-Alpha Agents for Crohn’s Disease: A Comparison of Effectiveness and Safety

“…[22][23][24][25] However, randomized clinical trials found rates of serious adverse events to be similar between biologic agents and placebo, and a study of adalimumab in clinical practice found rates of adverse events consistent with clinical trials. 22,[28][29][30][31][32][33] The results of this real-world analysis found …”