Systematic review with meta-analysis: the efficacy of a second anti-TNF in patients with inflammatory bowel disease whose previous anti-TNF treatment has failed

Aliment Pharmacol Ther. 2015 Apr;41(7):613-23. doi: 10.1111/apt.13083. Epub 2015 Feb 4.


Background: One-third of patients with Crohn's disease (CD) or ulcerative colitis (UC) receiving anti-TNFs do not respond to treatment, and a relevant proportion experience loss of response or intolerance.

Aim: To investigate the efficacy and safety of a second anti-TNF agent after primary/secondary failure or intolerance to a first drug.

Inclusion criteria: studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab-pegol (CZP) as the second anti-TNF in CD or UC.

Search strategy: Bibliographical searches (PubMed/Embase).

Data synthesis: percentage of response/remission; the meta-analysis was performed using the inverse variance method.

Results: We included 46 studies (37 CD, 8 UC, 1 pouchitis). The CD studies comprised 32 switching IFX→ADA, 4 IFX→CZP and 1 ADA→IFX. Overall, the second anti-TNF after the failure of IFX in CD induced remission in 43% and response in 63% of patients. The remission rate was higher when the reason to withdraw the first anti-TNF was intolerance (61%) than after secondary (45%) or primary failure (30%); response rates were, respectively, 72%, 62% and 53%. All UC studies switched IFX→ADA, six of them reporting remission rates ranging from 0% to 50%. Adverse events rate ranged from 0% to 81% in CD, most of them mild (serious adverse event 0-21%, discontinuation rate <20%).

Conclusions: The efficacy of a second anti-TNF in CD patients largely depends on the cause for switching. The remission rate is higher when the reason to withdraw the first anti-TNF is intolerance (61%), compared with secondary (45%) or primary failure (30%). Further studies of switch ADA→IFX are needed to evaluate this strategy. PROSPERO-registry-number: CRD42014012943.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adalimumab
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Certolizumab Pegol
  • Clinical Trials as Topic
  • Colitis, Ulcerative / drug therapy
  • Crohn Disease / drug therapy
  • Humans
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use*
  • Inflammatory Bowel Diseases / drug therapy*
  • Infliximab
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / therapeutic use*
  • Remission Induction
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


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