title: Adverse symptoms with anti-TNF-alpha therapy in inflammatory bowel disease: systematic review and duration-response meta-analysis.
abstract: BACKGROUND
  Anti-tumor necrosis factor-alpha (TNF-α) agents have considerable advances in treating inflammatory bowel disease (IBD). These drugs carry possible risk of adverse symptoms, and no meta-analysis has examined this issue and the potential duration-response relationship.
  
  
  OBJECTIVE
  The purpose of this study was to assess duration-response relationship between anti-TNF-α agents and risk of adverse symptoms from all available randomized control trials (RCTs) with placebo arms in IBD.
  
  
  METHODS
  PubMed, OVID, and Cochrane Library were searched to January 2015. The RCTs comparing anti-TNF-α therapy with placebo in adults with IBD were eligible. We estimated pooled relative risks (RRs) of adverse symptoms for anti-TNF-α therapy and examined both non-linear and linear duration-response relations between therapy duration and significant related adverse symptoms.
  
  
  RESULTS
  Twenty-three RCTs with 7325 patients were included. Adverse symptoms of headache, nausea/vomit, abdominal pain, fever, and arthralgia showed no significant relationship with anti-TNF-α therapy, respectively. Fatigue was significantly associated with anti-TNF-α therapy (RR 1.35, 95% confidence interval (CI) 1.01-1.81), and subgroup analysis indicated that long therapy duration (>30 weeks) and combination without azathioprine (AZA) were two risk factors for the occurrence of fatigue (RR 1.74, 95% CI 1.03-2.93; RR 1.65, 95% CI 1.13-2.40). In the trials without AZA combination, there was a linear duration-response relationship between therapy duration and risk of fatigue (P = 0.0217), and duration of 35 weeks increased the risk of fatigue by 50%.
  
  
  CONCLUSIONS
  This meta-analysis suggested a promotive effect of anti-TNF-α therapy to the occurrence of fatigue, and for the anti-TNF-α therapy without AZA combination, a linear duration-response relationship existed between therapy duration and risk of fatigue.
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University, No. 169, Donghu Road, Wuchang District, Wuhan, 430071, Hubei Province, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Xue
authors.initials: X
authors.lastname: Lin
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhao
authors.forename: Jin
authors.initials: J
authors.lastname: Li
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha