title: Efficacy of conventional synthetic disease-modifying antirheumatic drugs, glucocorticoids and tofacitinib: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis.
abstract: OBJECTIVE
  To update a previous systematic review assessing the efficacy of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis (RA).
  
  
  METHODS
  Two systematic reviews of the literature using PubMed, Embase and the Cochrane library were performed from 2009 until January 2013 to assess the efficacy of csDMARDs (as monotherapy or combination therapy) in adults with RA, and the efficacy of glucocorticoids in early RA. A third systematic review was performed until March 2013 to assess the efficacy of tofacitinib by meta-analysis.
  
  
  RESULTS
  For glucocorticoids, of 222 hits, five publications relating to four new trials were analysed for efficacy, confirming that initial treatment of RA with low-dose prednisone plus methotrexate (MTX) results in better clinical and structural outcomes at 1 and 2 years than treatment with MTX alone. For csDMARDs, of 498 studies, only two new studies were randomised controlled trials comparing MTX monotherapy with MTX in combination with another csDMARD without differences in glucocorticoid usage. Using tight control principles, clinical outcomes were no better with immediate triple therapy than with 'step-up' therapy. For tofacitinib, the pooled analysis of 10 trials showed that tofacitinib was more efficacious on signs and symptoms, disability and appeared to be more efficacious on structural damage than control treatment with placebo (OR (95% CI)--American College of Rheumatology 20% (ACR20) response: 2.44 (1.97 to 3.02)) or treatment with MTX (ACR20 response: 2.38 (1.66 to 3.43)).
  
  
  CONCLUSIONS
  Addition of low-dose glucocorticoids to csDMARD therapy produces benefits in early RA. Under tight control conditions, combination therapy with csDMARDs is no better than MTX monotherapy. Tofacitinib is a new DMARD with proven efficacy.
authors.affiliation: Department of Rheumatology, Nîmes University Hospital; EA 2415, Montpellier I University, , Nîmes, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Gaujoux-Viala
authors.forename: Jackie
authors.initials: J
authors.lastname: Nam
authors.forename: Sofia
authors.initials: S
authors.lastname: Ramiro
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.forename: Maya H
authors.initials: MH
authors.lastname: Buch
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Laure
authors.initials: L
authors.lastname: Gossec
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine / Q000379:methods; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D008727:Methotrexate
keywords: Corticosteroids; DMARDs (synthetic); Rheumatoid Arthritis; Treatment