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Rheumatoid arthritis
Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis
  1. Andreas Kerschbaumer1,
  2. Alexandre Sepriano2,3,
  3. Sytske Anne Bergstra3,
  4. Josef S Smolen1,
  5. Désirée van der Heijde3,
  6. Roberto Caporali4,
  7. Christopher John Edwards5,
  8. Patrick Verschueren6,
  9. Savia de Souza7,
  10. Janet E Pope8,
  11. Tsutomu Takeuchi9,
  12. Kimme L Hyrich10,
  13. Kevin L Winthrop11,
  14. Daniel Aletaha1,
  15. Tanja A Stamm12,13,
  16. Jan W Schoones14,
  17. Robert B M Landewé15,16
  1. 1 Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria
  2. 2 CHRC Campus Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal
  3. 3 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  4. 4 Department of Rheumatology, University of Milan, Milan, Italy
  5. 5 NIHR Southampton Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  6. 6 Department of Rheumatology, University Hospitals Leuven and Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium
  7. 7 Patient Research Partner Network, European Alliance of Associations for Rheumatology, Zurich, Switzerland
  8. 8 Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada
  9. 9 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Japan
  10. 10 Centre for Epidemiology Versus Arthritis, The University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University NHS Trust, Manchester, UK
  11. 11 School of Public Health, Oregon Health & Science University, Portland, Oregon, USA
  12. 12 Section for Outcomes Research, Centre for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
  13. 13 Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria
  14. 14 Walaeus Library, Leiden University Medical Center, Leiden, The Netherlands
  15. 15 Amsterdam Rheumatology Center, AMC, Amsterdam, The Netherlands
  16. 16 Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
  1. Correspondence to Dr Andreas Kerschbaumer, Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria; andreas.kerschbaumer{at}meduniwien.ac.at

Abstract

Objectives To update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).

Methods This systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.

Results Of 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.

Conclusion The results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

  • rheumatoid arthritis
  • DMARDs (synthetic)
  • anti-TNF
  • outcomes research

Data availability statement

Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as online supplemental information. Detailed data of all included studies are also available in the public domain.

https://doi.org/10.1136/ard-2022-223365

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    Data availability statement

    Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as online supplemental information. Detailed data of all included studies are also available in the public domain.

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    Footnotes

    • Handling editor David S Pisetsky

    • Twitter @AlexSepriano, @Janetbirdope

    • Contributors All authors contributed and finally approved the current manuscript. AK accepts full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish together with the senior author (RL) and the convenor of the taskforce (JSS).

    • Funding The European Alliance of Associations for Rheumatology.

    • Competing interests AK: Speakers bureau, Consultancy: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, Janssen, Merck Sharp and Dohme, Novartis, UCB and Pfizer. AS: received speaker/consulting fees from UCB, Novartis and Lilly. SAB: received an ASPIRE grant from Pfizer. JSS received 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. RC received consulting fees from Abbvie, BMS, Amgen, Celltrion, Eli-Lilly, Fresenius-Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, UCB Pharma. CJE has received fees from Abbvie, Astra Zeneca, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Galapagos, GSK, Janssen, Eli Lilly, Pfizer, Roche, Sanofi for advisory boards, speakers bureau and research support. PV received consulting fees from Abbvie, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer, Sidekick Health, UCB and speaker's fees from Eli Lilly, Galapagos, MSD and Roularta and holds the Pfizer Chair Early RA Management at KU Leuven. JEP received research grants from AbbVie, Frensenius Kabi, Mallinckrodt Pharmaceuticals, Pfizer, Seattle Genetics and consulting fees from AbbVie, Amgen, Astra Zeneca, BI, BMS, Celltrion, EMERALD, Frensenius Kabi, Galapagos, GSK, Janssen, Lilly, Mallinckrodt Pharmaceuticals, Medexus, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Roche, Sandoz, Samsung, Sobi, Viatris. TT received grants from AbbVie, Asahikasei, AYUMI, Chugai, Eli Lilly Japan, Mitsubishi-Tanabe, Ono, and honoraria from AbbVie, Asahikasei, Astellas, Bristol-Myers Squibb, Chugai., Daiichi Sankyo., Eisai, Eli Lilly Japan, Gilead Sciences, Janssen K.K., Mitsubishi-Tanabe, Pfizer Japan. KLH received speaker’s fees from Abbvie and research grants from Pfizer and BMS. KLW received research grants from Pfizer, BMS, and GSK, and scientific consulting fees from UCB, Abbvie, BMS, Galapagos, Gilead, Lilly, GSK, Roche, and Novartis. DA received grants, speaker fees, or consultancy fees from Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, and Sobi. TAS has received grant/research support from AbbVie and Roche, has been a consultant for AbbVie and Sanofi Genzyme, and has been a paid speaker for AbbVie, Novartis, Roche, Sanofi, and Takeda. RBML: 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 Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

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

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.