title: Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: a meta-analysis.
abstract: BACKGROUND
  Concerns exist regarding the potential development of malignancies in patients with rheumatoid arthritis (RA) who are receiving biologic response modifiers (BRMs).
  
  
  OBJECTIVE
  To assess the risk of malignancy in patients with RA enrolled in randomized controlled trials (RCTs) of BRMs.
  
  
  METHODS
  Electronic databases, conference proceedings, and websites of regulatory agencies were searched for RCTs evaluating abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab in RA from inception through July 9, 2012.
  
  
  METHODS
  Independent selection of studies included RCTs that compared the safety of any BRMs used in RA patients with placebo and/or any traditional disease-modifying antirheumatic drugs with a minimum of 24 weeks of follow-up.
  
  
  METHODS
  Independent reviewers selected studies and extracted data on quality and outcomes. Pooled estimates and 95% confidence intervals were calculated for each BRM.
  
  
  RESULTS
  Sixty-three RCTs with 29,423 patients were analyzed. No statistically significant increased risk of developing malignancy was observed. Of the 29,423 patients, 211 developed a malignancy during the trial (118 solid tumors, 48 skin cancers, 14 lymphomas, 5 hematologic nonlymphomas, and 26 not specified). The incidence rate for any malignancy during the first year of therapy was very low in the BRM plus methotrexate group (0.77%; 95% CI, 0.65%-0.92%), the BRM monotherapy group (0.64%; 95% CI, 0.42%-0.95%), and the controls (0.66%; 95% CI, 0.52%-0.84%). Anakinra plus methotrexate showed lower odds compared with methotrexate alone (Peto odds ratio, 0.11; 95% CI, 0.03-0.45). No statistically significant risk was observed for specific cancer sites, although the Peto odds ratio for lymphoma was 2.1 (95% CI, 0.55-8.4) in patients receiving tumor necrosis factor inhibitors compared with controls.
  
  
  CONCLUSIONS
  The use of BRMs among patients with RA included in RCTs of at least 6 months' duration was not significantly associated with an increased risk of malignancy compared with other disease-modifying antirheumatic drugs or with placebo.
authors.affiliation: University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lopez-Olivo
authors.forename: Jean H
authors.initials: JH
authors.lastname: Tayar
authors.forename: Juan A
authors.initials: JA
authors.lastname: Martinez-Lopez
authors.forename: Eduardo N
authors.initials: EN
authors.lastname: Pollono
authors.forename: Jose Polo
authors.initials: JP
authors.lastname: Cueto
authors.forename: M Rosa
authors.initials: MR
authors.lastname: Gonzales-Crespo
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fulton
authors.forename: Maria E
authors.initials: ME
authors.lastname: Suarez-Almazor
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D007155:Immunologic Factors