title: 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.
abstract: 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.
  
  
  OBJECTIVE
  To investigate the efficacy and safety of a second anti-TNF agent after primary/secondary failure or intolerance to a first drug.
  
  
  METHODS
  
  
  
  METHODS
  studies evaluating the efficacy of infliximab (IFX), adalimumab (ADA) and certolizumab-pegol (CZP) as the second anti-TNF in CD or UC.
  
  
  METHODS
  Bibliographical searches (PubMed/Embase).
  
  
  RESULTS
  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.
authors: Gastroenterology Unit, Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
authors: J P
authors: JP
authors: Gisbert
authors: A C
authors: AC
authors: Marín
authors: A G
authors: AG
authors: McNicholl
authors: M
authors: M
authors: Chaparro
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000068582:Certolizumab Pegol; D002986:Clinical Trials as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003424:Crohn Disease / Q000188:drug therapy; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068879:Adalimumab; D000068582:Certolizumab Pegol