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
- Cécile Gaujoux-Viala1,
- Jackie Nam2,3,
- Sofia Ramiro4,5,
- Robert Landewé6,
- Maya H Buch2,3,
- Josef S Smolen7,8,
- Laure Gossec9
- 1Department of Rheumatology, Nîmes University Hospital; EA 2415, Montpellier I University, Nîmes, France
- 2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
- 3NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
- 4Department of Clinical Immunology & Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- 5Department of Rheumatology, Hospital Garcia de Orta, Almada, Portugal
- 6Department of Clinical Immunology & Rheumatology, Academic Medical Center/University of Amsterdam & Atrium Medical Center, Heerlen, The Netherlands
- 7Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
- 82nd Department of Medicine, Hietzing Hospital Vienna, Vienna, Austria
- 9Department of Rheumatology, UPMC Univ Paris 06, GRC-UPMC 08 (EEMOIS); AP-HP, Pitié Salpêtrière Hospital, Paris, France
- Correspondence to Dr Cécile Gaujoux-Viala, Service de Rhumatologie, CHU de Nîmes Carémeau, Place du Professeur Robert Debré, 30029 Nîmes cedex 9, France;
- Received 9 September 2013
- Revised 2 November 2013
- Accepted 11 December 2013
- Published Online First 6 January 2014
Objectives 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.
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