EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

Abstract

Objectives: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.

Methods: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.

Results: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.

Conclusions: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Keywords: DMARDs (biologic); DMARDs (synthetic); economic evaluations; rheumatoid arthritis; treatment.

Conflict of interest statement

Competing interests: DA: grants from Abbvie, Novartis, Roche and honoraria from Abbvie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi/Genzyme; MA: honoraria from AbbVie, Astra Zeneca, BMS, Boehringer Ingelheim, Chugai, HEXAL, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB; JA: grants from Abbvie, BMS, Lilly, Merck, Pfizer, Roche, Samsung Bioepis, UCB; AB: grants from Pfizer, Bristol-Myers Squibb and honoraria from Pfizer, Roche, AbbVie, Bristol-Myers Squibb, UCB, MSD, Novartis, Sanofi, Biogen, Sandoz, Celltrion, Nordic, Gilead; JWJB: honoraria from Lilly, Roche, Sanofi; MB: honoraria from BMS, Teva, Novartis, Pfizer, GSK; AdB: grants from Abbvie, Biogen, Celltrion and honoraria from Abbvie, Biogen, Boehringer-Ingelheim, Celgene, Fresenius, MSD, Roche.MHB has received grants from Pfizer, Roche and UCB and consulting fees from Abbvie, Eli-Lilly, Merck.Serono, Pfizer, Sandoz, Sanofi; GB: grants from Abbvie, Pfizer, Sanofi, UCB and honoraria from Abbvie, Celgene, Gilead, Lilly, MSD, Novartis, Pfizer, Sanofi, Roche. FB: grants from Abbvie, BMS, Horizon, Medac, Pfizer, Roche, Lilly, Sanofi and honoraria from Abbvie, Galapagos, Horizon, Medac, Pfizer, Roche, Sanofi, Janssen, BMS, MSD, Lilly; RC: honoraria from Abbvie, BMS, Celgene, Celltrion, Gilead, Janssen, Lilly MSD, Mundipharma, Novartis-Sandoz, Pfizer, Roche, Sanofi and UCB; MC; honoraria from Abbvie, Astellas, BMS, Lilly, Pfizer and Roche; DDC: no conflict; CC: honoraria from AbbVie, Accord Healthcare, Alfasigma, Berlin Chemie, Egis, Eli Lilly, Ewopharma, Genesis, MSD, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB; MD: grants from Pfizer, Abbvie, UCB, Janssen, Novartis and honoraria from Pfizer, Abbvie, UCB, Janssen, MSD, Novartis, BMS, Celgene, Biogen, Sandoz; CJE: grants from Abbvie, Biogen and honoraria from Abbvie, BMS, Biogen, Celgene, Fresenius, Gilead, Janssen, Lilly, Mundipharma, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB; PE: grants from AbbVie, Novartis, Samsung, Lilly and honoraria from AbbVie, Novartis, BMS, Gilead, Samsung, Lilly; AF: grants from BMS, Pfizer and honoraria from AB2 BIO, Abbvie, BMS, Lilly, MSD, Pfizer, Roche, Sanofi; LG: grants from Abbvie, BMS, Lilly, UCB and honoraria from Abbvie, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sanofi-Aventis, UCB; J-EG: grants from BMS, Pfizer and honoraria from Abbvie, BMS, Lilly, Sanofi-Genzyme, Roche, UCB; MLH: grants from Abbvie, Biogen, BMS, Celltrion, MSD, Novartis, Orion, Pfizer, Samsung, UCB; TH: grants from Lilly, Merck, UCB, BMS, Janssen, Pfizer, Sanofi-Aventis, Galapagos, Boeringher and honoraria from Abblynx, BMS, Janssen, Pfizer, Sanofi-Aventis, Crescendo Bioscience, Galapagos, Lilly; AK: honoraria from BMS, Pfizer, Celgene, MSD; MK: no conflicts of interest; RBML: honoraria from AbbVie, BMS, Celgene, Eli-Lilly, Jansen Pharmaceuticals, Galapagos, Novartis, MSD, Pfizer, UCB and Director of Rheumatology Consultancy BV; XM: honoraria from BMS, Gilead, Pfizer, Samsung, UCB; IBM: 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; EM: grants from Pfizer, Lilly, BMS, AbbVie, GSK, Astra and honoraria from Pfizer, BMS, Roche, Lilly, AbbVie, Gemma, Sanofi; TWJH: grants from Eli Lilly, Merck, UCB, BMS, Janssen, Pfizer, Sanofi-Aventis, Galapagos, Boehringer and honoraria from Abblynx, Abbvie, BMS, Boehringer, Crescendo-Bioscience, Epirus, Galapagos, Janssen, Lilly, Merck, Novartis, Nycomed, Pfizer, Roche, Sanofi-Aventis, Takeda, UCB; ZL: no conflicts of interest; UM-L: honoraria from Abbvie, BMS, MSD, Chugai, Roche, Pfizer, Sanofi, Boehringer, Actelion, Medac, Lilly; GP: no conflicts of interest; JP: grants from BMS, Merck, UCB and honoraria from AbbVie, Actelion, Amgen, BMS, Bayer, GSK, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB; AR-R: honoraria from Abbvie, Chugai, BMS, Sanofi, Roche, Lilly, Janssen, Novartis, Celgene, MSD, UCB; AR-W: grants from Pfizer, Abbvie and honoraria from Abbvie, Amgen, BMS, Janssen, Lilly, Medac, Nordic Pharma, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB; KS: grants from Amgen, Ironwood/AstraZeneca, Horizon, SOBI, Takeda and honoraria from AbbVie, Amgen, Ironwood/AstraZeneca, Bayer, Gilead, Horizon, Kowa, Radius, Roche/Genentech, SOBI, Takeda, Teijin; MSV: no conflicts of interest. AS: honoraria from Novartis; JSS: grants from Abbvie, AstraZeneca, Janssen, Lilly, Novartis, Roche and honoraria from Abbvie, Amgen, AstraZeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB; AS: grants from AbbVie, Bristol-Myers Squibb, Celltrion, Hexal AG Lilly, MSD Sharp & Dome, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, UCB and honoraria from AbbVie, BMS, MSD, Pfizer, Roche; TT: grants from AbbVie, Asahikasei, Astellas, AYUMI, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nipponkayaku, Novartis, Pfizer, Takeda and honoraria from AbbVie, Astellas, Astra Zeneca, BMS, Chugai, Diaichi Sankyo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nipponkayaku, Novartis, Pfizer, Sanofi, Teijin, Taiho Pharmaceutical, Taisho Pharmaceutical, Takeda, UCB; DvdH: grants from UCB and honoraria from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB and Director Imaging Rheumatology BV; YvE-H: honoraria from Celgene; RFvV: grants from BMS, GSK, Lilly, UCB and honoraria from AbbVie, AstraZeneca, Biotest, BMS, Celgene, GSK, Janssen, Lilly, Novartis, Pfizer, Roche, UCB; RW: grants from Roche, BMS and honoraria from Celltrion, Galapagos-Gilead; MdW: honoraria from 'Stichting Tools', Janssen-Cilag.

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.