title: Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review.
abstract: To systematically compare the risk of adverse events (AEs) for 13 targeted immunomodulators (TIMs) indicated for ankylosing spondylitis (AS), inflammatory bowel diseases, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis (PsA), or rheumatoid arthritis (RA).
  
  
  
  We searched electronic databases through July 2015 to retrieve randomized controlled trials (RCTs) and observational studies comparing AEs between 2 or more TIMs head-to-head. We reported on the following outcomes: number of AEs, discontinuation due to AEs, serious AEs, mortality, serious infections, tuberculosis, herpes zoster, and malignancies. We qualitatively synthesized the literature and conducted random-effects meta-analyses if 3 or more studies provided data for an outcome.
  
  
  
  Ten head-to-head RCTs and 51 observational studies were included in this systematic review. A majority of the studies (70%) were conducted in RA patients. Risk of treatment discontinuation due to AEs was higher with infliximab than with adalimumab or etanercept in RA, PsA, and AS. A higher risk for serious infections was noted with infliximab than with abatacept, adalimumab, or etanercept in RA. Risk for treatment discontinuation due to AEs, serious infections, and tuberculosis was lower with etanercept than with adalimumab in RA. Limited evidence suggested no comparative differences in risk for mortality, malignancies, and herpes zoster for adalimumab, etanercept, and infliximab in RA.
  
  
  
  Important differences were noted in the safety profile of TIMs in RA, generally favoring abatacept, adalimumab, and etanercept over infliximab. Head-to-head comparative evidence for other TIMs and non-RA populations was insufficient to draw conclusions for most of the safety outcomes.
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Rishi J
authors.initials: RJ
authors.lastname: Desai
authors.affiliation: Danube University, Krems, Austria.
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: Thaler
authors.affiliation: Danube University, Krems, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Mahlknecht
authors.affiliation: Danube University, Krems, Austria, and RTI International, Research Triangle Park, North Carolina.
authors.forename: Gerald
authors.initials: G
authors.lastname: Gartlehner
authors.affiliation: Pacific Northwest Evidence-Based Practice Center, Oregon Health & Science University, Portland, Oregon.
authors.forename: Marian S
authors.initials: MS
authors.lastname: McDonagh
authors.affiliation: Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Mesgarpour
authors.affiliation: Danube University, Krems, Austria.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mazinanian
authors.affiliation: Danube University, Krems, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Glechner
authors.affiliation: Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Chandrasekar
authors.initials: C
authors.lastname: Gopalakrishnan
authors.affiliation: Harrison School of Pharmacy, Auburn University, Auburn, Alabama.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hansen
mesh_terms: D001171:Arthritis, Juvenile / Q000188:drug therapy; D015535:Arthritis, Psoriatic / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy*; D007155:Immunologic Factors / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D064887:Observational Studies as Topic; D011565:Psoriasis / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D013167:Spondylitis, Ankylosing / Q000188:drug therapy
chemical_list: D007155:Immunologic Factors