title: Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis.
abstract: OBJECTIVE
  To update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) recommendations for the management of RA.
  
  
  METHODS
  Systematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included.
  
  
  RESULTS
  Forty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1-1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found.
  
  
  CONCLUSIONS
  The findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA.
authors.affiliation: Department of Clinical Immunology & Rheumatology, Academic Medical Center, University of Amsterdam, , Amsterdam, The Netherlands.
authors.forename: Sofia
authors.initials: S
authors.lastname: Ramiro
authors.forename: Cécile
authors.initials: C
authors.lastname: Gaujoux-Viala
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Nam
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Maya
authors.initials: M
authors.lastname: Buch
authors.forename: Laure
authors.initials: L
authors.lastname: Gossec
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Kevin
authors.initials: K
authors.lastname: Winthrop
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000139:chemically induced; D009894:Opportunistic Infections / Q000139:chemically induced; D017410:Practice Guidelines as Topic; D018570:Risk Assessment / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha
keywords: DMARDs (biologic); DMARDs (synthetic); Rheumatoid arthritis; anti-TNF; outcomes research