Systematic review with meta-analysis: malignancies with anti-tumour necrosis factor-α therapy in inflammatory bowel disease

Aliment Pharmacol Ther. 2014 Mar;39(5):447-58. doi: 10.1111/apt.12624. Epub 2014 Jan 20.

Abstract

Background: Anti-tumour necrosis factor-α (TNFα) antibodies are efficacious in inflammatory bowel disease (IBD). These drugs carry the theoretical risk of malignancy, particularly lymphoma, but no systematic review and meta-analysis has examined this issue.

Aim: To pool data from all available placebo-controlled studies to estimate risk of malignancy with anti-TNFα therapy in IBD.

Methods: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to November 2013. Randomised controlled trials (RCTs) comparing anti-TNFα therapy with placebo in adults with Crohn's disease (CD) or ulcerative colitis (UC) were eligible. Data were pooled to obtain a relative risk (RR) of malignancy with a 95% confidence interval (CI).

Results: The search strategy identified 25,338 citations, of which 22 RCTs were eligible (11 infliximab, six adalimumab, four certolizumab and one golimumab) involving 7054 patients (4566 CD and 2488 UC). In total, there were 16 (0.39%) malignancies in 4135 IBD patients allocated to anti-TNFα, compared with 13 (0.45%) in 2919 patients randomised to placebo. There were no cases of lymphoma in the active treatment group, compared with three (0.1%) in the control group. The RR of malignancy for patients receiving anti-TNFα therapy compared with placebo was 0.77 (95% CI 0.37-1.59). When seven individuals with nonmelanoma skin cancer were excluded from the analysis, the RR was 0.90 (95% CI 0.40-2.02).

Conclusions: Anti-TNFα therapy was not associated with an increased risk of malignancy in patients with IBD. However, no trials provided data for risk of malignancy beyond 1 year of treatment, meaning that an increased risk in the longer term cannot be excluded.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adalimumab
  • Anti-Inflammatory Agents / adverse effects*
  • Anti-Inflammatory Agents / therapeutic use
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Certolizumab Pegol
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / epidemiology
  • Crohn Disease / drug therapy*
  • Crohn Disease / epidemiology
  • Humans
  • Immunoglobulin Fab Fragments / adverse effects
  • Immunoglobulin Fab Fragments / therapeutic use
  • Infliximab
  • Neoplasms / chemically induced
  • Neoplasms / epidemiology*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Randomized Controlled Trials as Topic
  • Risk
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin Fab Fragments
  • Tumor Necrosis Factor-alpha
  • Polyethylene Glycols
  • golimumab
  • Infliximab
  • Adalimumab
  • Certolizumab Pegol