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

Josef S. Smolen; Robert B. M. Landewe; Johannes W. J. Bijlsma; Gerd R. Burmester; Maxime Dougados; Andreas Kerschbaumer; Iain B. McInnes; Alexandre Sepriano; Ronald F. van Vollenhoven; Maarten de Wit; Daniel Aletaha; Martin Aringer; John Askling; Alejandro Balsa; Maarten Boers; Alfons A. den Broeder; Maya H. Buch; Frank Buttgereit; Roberto Caporali; Mario Humberto Cardiel; Diederik De Cock; Catalin Codreanu; Maurizio Cutolo; Christopher John Edwards; Yvonne van Eijk-Hustings; Paul Emery; Axel Finckh; Laure Gossec; Jacques-Eric Gottenberg; Merete Lund Hetland; Tom W. J. Huizinga; Marios Koloumas; Zhanguo Li; Xavier Mariette; Ulf Mueller-Ladner; Eduardo F. Mysler; Jose A. P. da Silva; Gyula Poor; Janet E. Pope; Andrea Rubbert-Roth; Adeline Ruyssen-Witrand; Kenneth G. Saag; Anja Strangfeld; Tsutomu Takeuchi; Marieke Voshaar; Rene Westhovens; Desiree van der Heijde

doi:10.1136/annrheumdis-2019-216655

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

Josef S. Smolen^*, Robert B. M. Landewe, Johannes W. J. Bijlsma, Gerd R. Burmester, Maxime Dougados, Andreas Kerschbaumer, Iain B. McInnes, Alexandre Sepriano, Ronald F. van Vollenhoven, Maarten de Wit, Daniel Aletaha, Martin Aringer, John Askling, Alejandro Balsa, Maarten Boers, Alfons A. den Broeder, Maya H. Buch, Frank Buttgereit, Roberto Caporali, Mario Humberto CardielDiederik De Cock, Catalin Codreanu, Maurizio Cutolo, Christopher John Edwards, Yvonne van Eijk-Hustings, Paul Emery, Axel Finckh, Laure Gossec, Jacques-Eric Gottenberg, Merete Lund Hetland, Tom W. J. Huizinga, Marios Koloumas, Zhanguo Li, Xavier Mariette, Ulf Mueller-Ladner, Eduardo F. Mysler, Jose A. P. da Silva, Gyula Poor, Janet E. Pope, Andrea Rubbert-Roth, Adeline Ruyssen-Witrand, Kenneth G. Saag, Anja Strangfeld, Tsutomu Takeuchi, Marieke Voshaar, Rene Westhovens, Desiree van der Heijde

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	S685-S699
Number of pages	15
Journal	Annals of the Rheumatic Diseases
Volume	79
Issue number	6
DOIs	https://doi.org/10.1136/annrheumdis-2019-216655
Publication status	Published - Jun 2020

Keywords

TREAT-TO-TARGET
INTERLEUKIN-6 RECEPTOR INHIBITION
CONSENSUS-BASED RECOMMENDATIONS
RAPID RADIOGRAPHIC PROGRESSION
DOSE GLUCOCORTICOID THERAPY
TREATMENT STRATEGIES
REMISSION INDUCTION
CERTOLIZUMAB PEGOL
RHEUMATOLOGY/EUROPEAN LEAGUE
AMERICAN-COLLEGE

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Cite this

Smolen, J. S., Landewe, R. B. M., Bijlsma, J. W. J., Burmester, G. R., Dougados, M., Kerschbaumer, A., McInnes, I. B., Sepriano, A., van Vollenhoven, R. F., de Wit, M., Aletaha, D., Aringer, M., Askling, J., Balsa, A., Boers, M., den Broeder, A. A., Buch, M. H., Buttgereit, F., Caporali, R., ... van der Heijde, D. (2020). EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Annals of the Rheumatic Diseases, 79(6), S685-S699. https://doi.org/10.1136/annrheumdis-2019-216655

@article{c6be64da641940ecb28ef131a72ab61a,

title = "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 = "TREAT-TO-TARGET, INTERLEUKIN-6 RECEPTOR INHIBITION, CONSENSUS-BASED RECOMMENDATIONS, RAPID RADIOGRAPHIC PROGRESSION, DOSE GLUCOCORTICOID THERAPY, TREATMENT STRATEGIES, REMISSION INDUCTION, CERTOLIZUMAB PEGOL, RHEUMATOLOGY/EUROPEAN LEAGUE, AMERICAN-COLLEGE",

author = "Smolen, {Josef S.} and Landewe, {Robert B. M.} and Bijlsma, {Johannes W. J.} and Burmester, {Gerd R.} and Maxime Dougados and Andreas Kerschbaumer and McInnes, {Iain B.} and Alexandre Sepriano and {van Vollenhoven}, {Ronald F.} and {de Wit}, Maarten and Daniel Aletaha and Martin Aringer and John Askling and Alejandro Balsa and Maarten Boers and {den Broeder}, {Alfons A.} and Buch, {Maya H.} and Frank Buttgereit and Roberto Caporali and Cardiel, {Mario Humberto} and {De Cock}, Diederik and Catalin Codreanu and Maurizio Cutolo and Edwards, {Christopher John} and {van Eijk-Hustings}, Yvonne and Paul Emery and Axel Finckh and Laure Gossec and Jacques-Eric Gottenberg and Hetland, {Merete Lund} and Huizinga, {Tom W. J.} and Marios Koloumas and Zhanguo Li and Xavier Mariette and Ulf Mueller-Ladner and Mysler, {Eduardo F.} and {da Silva}, {Jose A. P.} and Gyula Poor and Pope, {Janet E.} and Andrea Rubbert-Roth and Adeline Ruyssen-Witrand and Saag, {Kenneth G.} and Anja Strangfeld and Tsutomu Takeuchi and Marieke Voshaar and Rene Westhovens and {van der Heijde}, Desiree",

note = "Funding Information: Acknowledgements The task force is grateful to EULAR for funding this activity under project number CLI111. Funding Information: Contributors The paper was drafted by JSS and RBML and all authors contributed with specific comments and revisions to the paper. Funding This study was funded by European League Against Rheumatism (grant number:CLI111). 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 {\textquoteright}Stichting Tools{\textquoteright}, Janssen-Cilag. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2020",

month = jun,

doi = "10.1136/annrheumdis-2019-216655",

language = "English",

volume = "79",

pages = "S685--S699",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "Elsevier BV",

number = "6",

}

Smolen, JS, Landewe, RBM, Bijlsma, JWJ, Burmester, GR, Dougados, M, Kerschbaumer, A, McInnes, IB, Sepriano, A, van Vollenhoven, RF, de Wit, M, Aletaha, D, Aringer, M, Askling, J, Balsa, A, Boers, M, den Broeder, AA, Buch, MH, Buttgereit, F, Caporali, R, Cardiel, MH, De Cock, D, Codreanu, C, Cutolo, M, Edwards, CJ, van Eijk-Hustings, Y, Emery, P, Finckh, A, Gossec, L, Gottenberg, J-E, Hetland, ML, Huizinga, TWJ, Koloumas, M, Li, Z, Mariette, X, Mueller-Ladner, U, Mysler, EF, da Silva, JAP, Poor, G, Pope, JE, Rubbert-Roth, A, Ruyssen-Witrand, A, Saag, KG, Strangfeld, A, Takeuchi, T, Voshaar, M, Westhovens, R & van der Heijde, D 2020, 'EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update', Annals of the Rheumatic Diseases, vol. 79, no. 6, pp. S685-S699. https://doi.org/10.1136/annrheumdis-2019-216655

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. / Smolen, Josef S.; Landewe, Robert B. M.; Bijlsma, Johannes W. J. et al.
In: Annals of the Rheumatic Diseases, Vol. 79, No. 6, 06.2020, p. S685-S699.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

T2 - 2019 update

AU - Smolen, Josef S.

AU - Landewe, Robert B. M.

AU - Bijlsma, Johannes W. J.

AU - Burmester, Gerd R.

AU - Dougados, Maxime

AU - Kerschbaumer, Andreas

AU - McInnes, Iain B.

AU - Sepriano, Alexandre

AU - van Vollenhoven, Ronald F.

AU - de Wit, Maarten

AU - Aletaha, Daniel

AU - Aringer, Martin

AU - Askling, John

AU - Balsa, Alejandro

AU - Boers, Maarten

AU - den Broeder, Alfons A.

AU - Buch, Maya H.

AU - Buttgereit, Frank

AU - Caporali, Roberto

AU - Cardiel, Mario Humberto

AU - De Cock, Diederik

AU - Codreanu, Catalin

AU - Cutolo, Maurizio

AU - Edwards, Christopher John

AU - van Eijk-Hustings, Yvonne

AU - Emery, Paul

AU - Finckh, Axel

AU - Gossec, Laure

AU - Gottenberg, Jacques-Eric

AU - Hetland, Merete Lund

AU - Huizinga, Tom W. J.

AU - Koloumas, Marios

AU - Li, Zhanguo

AU - Mariette, Xavier

AU - Mueller-Ladner, Ulf

AU - Mysler, Eduardo F.

AU - da Silva, Jose A. P.

AU - Poor, Gyula

AU - Pope, Janet E.

AU - Rubbert-Roth, Andrea

AU - Ruyssen-Witrand, Adeline

AU - Saag, Kenneth G.

AU - Strangfeld, Anja

AU - Takeuchi, Tsutomu

AU - Voshaar, Marieke

AU - Westhovens, Rene

AU - van der Heijde, Desiree

N1 - Funding Information: Acknowledgements The task force is grateful to EULAR for funding this activity under project number CLI111. Funding Information: Contributors The paper was drafted by JSS and RBML and all authors contributed with specific comments and revisions to the paper. Funding This study was funded by European League Against Rheumatism (grant number:CLI111). 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. Publisher Copyright: © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

KW - TREAT-TO-TARGET

KW - INTERLEUKIN-6 RECEPTOR INHIBITION

KW - CONSENSUS-BASED RECOMMENDATIONS

KW - RAPID RADIOGRAPHIC PROGRESSION

KW - DOSE GLUCOCORTICOID THERAPY

KW - TREATMENT STRATEGIES

KW - REMISSION INDUCTION

KW - CERTOLIZUMAB PEGOL

KW - RHEUMATOLOGY/EUROPEAN LEAGUE

KW - AMERICAN-COLLEGE

U2 - 10.1136/annrheumdis-2019-216655

DO - 10.1136/annrheumdis-2019-216655

M3 - Article

C2 - 31969328

SN - 0003-4967

VL - 79

SP - S685-S699

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 6

ER -

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

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