Article Text

Efficacy of pharmacological treatment in rheumatoid arthritis: a systematic literature research informing the 2019 update of the EULAR recommendations for management of rheumatoid arthritis
  1. Andreas Kerschbaumer1,
  2. Alexandre Sepriano2,3,
  3. Josef S Smolen1,
  4. Désirée van der Heijde2,
  5. Maxime Dougados4,
  6. Ronald van Vollenhoven5,
  7. Iain B McInnes6,
  8. Johannes W J Bijlsma7,
  9. Gerd R Burmester8,
  10. Maarten de Wit9,
  11. Louise Falzon10,
  12. Robert Landewé5
  1. 1 Medical University of Vienna, Vienna, Austria
  2. 2 Leiden University Medical Center, Leiden, The Netherlands
  3. 3 NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
  4. 4 Hospital Cochin, Paris, France
  5. 5 Amsterdam Rheumatology Center, Amsterdam, The Netherlands
  6. 6 University of Glasgow, Glasgow, UK
  7. 7 University Medical Center Utrecht, Utrecht, The Netherlands
  8. 8 Charité – University Medicine Berlin, Berlin, Germany
  9. 9 EULAR Standing Committee, Zurich, Switzerland
  10. 10 Northwell Health, New York, New York, USA
  1. Correspondence to Dr Andreas Kerschbaumer, Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria; andreas.kerschbaumer{at}


Objectives To inform the 2019 update of the European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA).

Methods A systematic literature research (SLR) to investigate the efficacy of any disease-modifying antirheumatic drug (DMARD) (conventional synthetic (cs)DMARD, biological (b) and biosimilar DMARD, targeted synthetic (ts)DMARD) or glucocorticoid (GC) therapy in patients with RA was done by searching MEDLINE, Embase and the Cochrane Library for articles published between 2016 and 8 March 2019.

Results 234 abstracts were selected for detailed assessment, with 136 finally included. They comprised the efficacy of bDMARDs versus placebo or other bDMARDs, efficacy of Janus kinase (JAK) inhibitors (JAKi) across different patient populations and head-to-head of different bDMARDs versus JAKi or other bDMARDs. Switching of bDMARDs to other bDMARDs or tsDMARDs, strategic trials and tapering studies of bDMARDs, csDMARDs and JAKi were assessed. The drugs evaluated included abatacept, adalimumab, ABT-122, baricitinib, certolizumab pegol, SBI-087, CNTO6785, decernotinib, etanercept, filgotinib, golimumab, GCs, GS-9876, guselkumab, hydroxychloroquine, infliximab, leflunomide, mavrilimumab, methotrexate, olokizumab, otilimab, peficitinib, rituximab, sarilumab, salazopyrine, secukinumab, sirukumab, tacrolimus, tocilizumab, tofacitinib, tregalizumab, upadacitinib, ustekinumab and vobarilizumab. The efficacy of many bDMARDs and tsDMARDs was shown. Switching to another tumour necrosis factor inhibitor (TNFi) or non-TNFi bDMARDs after TNFi treatment failure is efficacious. Tapering of DMARDs is possible in patients achieving long-standing stringent clinical remission; in patients with residual disease activity (including patients in LDA) the risk of flares is increased during the tapering. Biosimilars are non-inferior to their reference products.

Conclusion This SLR informed the task force regarding the evidence base of various therapeutic regimen for the development of the update of EULAR’s RA management recommendation.

  • rheumatoid arthritis
  • DMARDs (biologic)
  • DMARDs (synthetic)
  • anti-TNF

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  • Handling editor Dimitrios T Boumpas

  • Correction notice This article has been corrected since it published Online First. Table 5 formatting has been corrected and the MONARCH study line in table 3 transposed.

  • Contributors All authors contributed and finally approved the current manuscript.

  • Funding European League Against Rheumatism.

  • Competing interests AK: Honoraria from Bristol-Myers Squibb, Celgene, Gilead, Merck Sharp and Dohme, Novartis and Pfizer. AS: Honoraria as speaker: JSS: Grants from Abbvie, Astra-Zeneca, Janssen, Lilly, Novartis, Roche and honoraria from Abbvie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB. DvdH: Received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology bv. MD: Received research grants from and honorarium fees for his participation at advisory boards and/or symposium organised by PFIZER, UCB, ABBVIE, LILLY, NOVARTIS, BMS, ROCHE, UCB, MERCK. RvV: Research Support and Grants: BMS, GSK, Lilly, Pfizer, UCB Pharma. Consultancy, honoraria: AbbVie, AstraZeneca, Biotest, Celgene, GSK, Janssen, Lilly, Novartis, Pfizer, Servier, UCB. IM: grants from Astra Zeneca, UCB, BMS, Janssen, GSK, Compugen, Boehringer, Celgene and honoraria from Abbvie, BMS, Janssen, Novartis, UCB, Astra Zeneca, Celgene, Causeway, Lilly, Leo, Novimmune. JWB: Honoraria as speaker and for consulting: Abbvie, Lilly, MSD, Roche, Sanofi, SUNGB: Honoraria as speaker and for consulting: Abbvie, BMS, Gilead, Lilly, MSD, Pfizer, UCB, Roche, Sanofi. MdW: Over the last 2 years Stichting Tools has received fees for lectures or consultancy for contributions of Maarten de Wit from Abbvie, Celgene, Eli Lilly, Janssen-Cilag and Pfizer. LF: none. RL: Received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy bv.

  • Patient and public involvement statement The task force on this project involved a PPI representative (MdW), member of the EULAR Standing Committee of People with Arthritis/Rheumatism in Europe, who contributed during all task force meetings, especially to take patient perspectives into account and refine research questions.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information.

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