Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Andreas Kerschbaumer¹, Alexandre Sepriano^{2

3}, Sytske Anne Bergstra³, Josef S Smolen⁴, Désirée van der Heijde³, Roberto Caporali⁵, Christopher John Edwards⁶, Patrick Verschueren⁷, Savia de Souza⁸, Janet E Pope⁹, Tsutomu Takeuchi¹⁰, Kimme L Hyrich¹¹, Kevin L Winthrop¹², Daniel Aletaha⁴, Tanja A Stamm^{13

14}, Jan W Schoones¹⁵, Robert B M Landewé^{16

17}

Affiliations

¹ Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria andreas.kerschbaumer@meduniwien.ac.at.
² CHRC Campus Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
³ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
⁵ Department of Rheumatology, University of Milan, Milan, Italy.
⁶ NIHR Southampton Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ Department of Rheumatology, University Hospitals Leuven and Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium.
⁸ Patient Research Partner Network, European Alliance of Associations for Rheumatology, Zurich, Switzerland.
⁹ Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada.
¹⁰ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Japan.
¹¹ Centre for Epidemiology Versus Arthritis, The University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University NHS Trust, Manchester, UK.
¹² School of Public Health, Oregon Health & Science University, Portland, Oregon, USA.
¹³ Section for Outcomes Research, Centre for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
¹⁴ Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria.
¹⁵ Walaeus Library, Leiden University Medical Center, Leiden, The Netherlands.
¹⁶ Amsterdam Rheumatology Center, AMC, Amsterdam, The Netherlands.
¹⁷ Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands.

PMID: 36368906
DOI: 10.1136/ard-2022-223365

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Andreas Kerschbaumer et al. Ann Rheum Dis. 2023 Jan.

. 2023 Jan;82(1):95-106.

doi: 10.1136/ard-2022-223365. Epub 2022 Nov 11.

Authors

Affiliations

¹ Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria andreas.kerschbaumer@meduniwien.ac.at.
² CHRC Campus Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
³ Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Medicine III, Division of Rheumatology, Medical University of Vienna, Vienna, Austria.
⁵ Department of Rheumatology, University of Milan, Milan, Italy.
⁶ NIHR Southampton Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
⁷ Department of Rheumatology, University Hospitals Leuven and Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium.
⁸ Patient Research Partner Network, European Alliance of Associations for Rheumatology, Zurich, Switzerland.
⁹ Schulich School of Medicine, University of Western Ontario, London, Ontario, Canada.
¹⁰ Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Japan.
¹¹ Centre for Epidemiology Versus Arthritis, The University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University NHS Trust, Manchester, UK.
¹² School of Public Health, Oregon Health & Science University, Portland, Oregon, USA.
¹³ Section for Outcomes Research, Centre for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
¹⁴ Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Vienna, Austria.
¹⁵ Walaeus Library, Leiden University Medical Center, Leiden, The Netherlands.
¹⁶ Amsterdam Rheumatology Center, AMC, Amsterdam, The Netherlands.
¹⁷ Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands.

PMID: 36368906
DOI: 10.1136/ard-2022-223365

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.

Keywords: DMARDs (synthetic); anti-TNF; outcomes research; rheumatoid arthritis.

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Conflict of interest statement

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

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Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Affiliations

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Authors

Affiliations

Abstract

Conflict of interest statement

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Medical