Skip to content

Rheumatoid arthritis — guidelines

TL;DR — Major RA guidelines agree on early DMARD treatment, methotrexate as the anchor for most active disease, repeated treat-to-target assessment, escalation after inadequate response, steroid minimization and shared decision-making. They diverge where evidence is weak or values/costs differ: initial combination conventional therapy, glucocorticoid bridging, preference for triple therapy versus biologic/targeted escalation, JAK-inhibitor placement and tapering sequence. EULAR 2025 now supersedes EULAR 2022 and retains explicit MACE, malignancy and thromboembolism risk consideration for JAK inhibitors; ACR 2021 predates the final ORAL Surveillance report (Smolen 2026, PMID 41826212; Fraenkel 2021, PMID 34101376). Regional guidance must be read in its publication and access context. The registry in the literature layer records current and superseded documents; this page synthesizes recommendations.

Core convergence

Principle EULAR 2025 ACR 2021 Cross-guideline synthesis
Start a DMARD early Yes Yes Do not wait for erosions
Initial anchor MTX for most MTX monotherapy favored for moderate/high activity Optimize before declaring failure
Target Remission/LDA Treat to target Measure repeatedly
Reassess Improvement by 3 months, target by 6 Rapid titration and reassessment Avoid therapeutic inertia
Glucocorticoids Short-term bridge may accompany initial csDMARD Prefer initiation without longer-term steroids Minimize cumulative exposure
Escalation bDMARD or risk-assessed JAK after inadequate response MTX optimization then add/switch Comorbidity and access shape choice
Tapering Only sustained remission; reduce cautiously Continue at least one DMARD; gradual reduction Withdrawal flares are common

EULAR 2025 update and the 2022 foundation

EULAR 2025 reduced the document to five overarching principles and nine recommendations. It recommends methotrexate, ideally with short-term glucocorticoids, then addition of a biologic after insufficient response at three to six months; a JAK inhibitor may be considered only after careful MACE, malignancy and thromboembolic risk assessment. After first advanced-therapy failure, another biologic from the same or another class or a risk-assessed JAK inhibitor is acceptable; sustained-remission tapering is allowed, but stopping frequently causes flare (Smolen 2026, PMID 41826212). Its efficacy review included 72 studies and explicitly identified only two antifibrotic RCT reports for RA-ILD and seven prevention studies through January 2025, quantifying why these branches remain conditional (Konzett 2026, PMID 41997804).

The 2022 algorithm remains important as the immediately superseded evidentiary foundation:

EULAR begins methotrexate plus short-term glucocorticoids for most, uses prognostic factors and target response to guide escalation, and places biologics and JAK inhibitors after inadequate response with explicit consideration of MACE, malignancy and thromboembolic risk (Smolen 2023, PMID 36357155). The supporting review screened 8,969 records and included 169 articles (Kerschbaumer 2023, PMID 36368906).

ACR 2021 algorithm

ACR strongly favors methotrexate monotherapy over hydroxychloroquine/sulfasalazine or biologic/targeted monotherapy for DMARD-naive moderate-to-high disease activity, conditionally favors MTX monotherapy over initial dual/triple therapy, and emphasizes avoiding longer-term glucocorticoids (Fraenkel 2021, PMID 34101376). Patient representatives participated in GRADE-based voting.

Meaningful disagreements

Topic Difference Why it exists
Initial glucocorticoid bridge EULAR more accepting; ACR more steroid-averse Different weighting of rapid benefit and cumulative harm
Triple therapy before biologic ACR conditionally favors adding b/tsDMARD after maximally tolerated MTX in target failure, while cost contexts may favor triple therapy Speed, preferences, access and toxicity burden
JAK placement EULAR 2022 incorporates ORAL Surveillance Publication timing and regulatory change
Hydroxychloroquine More acceptable in low activity under ACR Disease severity and structural-risk weighting
Taper sequence No universal sequence Sparse head-to-head evidence; TARA found similar strategies

Non-pharmacological guidance

The 2022 ACR integrative guideline strongly recommends consistent exercise and conditionally addresses rehabilitation, diet and other interventions as adjuncts to DMARDs (England 2023, PMID 37227116). Physical-therapy guidance supports individualized exercise, education and self-management (Peter 2021, PMID 34003240).

Difficult-to-treat RA

EULAR points to consider emphasize reconfirming diagnosis, assessing inflammation, adherence and comorbidity, and selecting another mechanism when objective inflammatory activity persists (Nagy 2022, PMID 34407926). This prevents the D2T label from becoming a license for indefinite mechanism cycling.

RA-ILD

The 2023 ACR/CHEST ILD framework is conditional because disease-specific randomized evidence is sparse. An appraisal summarizes mycophenolate, azathioprine and rituximab as first-line options and adds antifibrotic/immunomodulatory choices after progression (Saavedra 2025, PMID 39822854).

Regional updates

Body Update Distinct context Source
EULAR 2025 European/global, DMARD strategy; published 2026 Smolen 2026, PMID 41826212
EULAR 2022 Superseded foundation Smolen 2023, PMID 36357155
ACR 2021 US, GRADE and patient panel Fraenkel 2021, PMID 34101376
French Society of Rheumatology 2024 Adds at-risk RA and RA-ILD topics Fautrel 2024, PMID 39389412
Mexican College of Rheumatology 2023 Mexican access and practice context Abud-Mendoza 2024, PMID 38796394
Japan College of Rheumatology 2024 Japanese regulatory/practice setting Harigai 2025, PMID 39820350
ACR integrative 2022 Exercise, rehabilitation, diet England 2023, PMID 37227116
APLAR 2024 Asia-Pacific; 14 consensus statements spanning measurement, DMARDs, infection and pregnancy Yamaoka 2026, PMID 42362943
ALAT 2025 Latin American RA-ILD recognition and treatment Alberti 2026, PMID 42034552
DGRh 2026 German S3 DMARD guideline; rapid treat-to-target adjustment, three-month glucocorticoid discontinuation goal, cautious de-escalation and a new RA-ILD section DGRh — “Neue Leitlinie zur rheumatoiden Arthritis,” https://www.dgrh.de/pressemitteilung/neue-leitlinie-zur-rheumatoiden-arthritis/, accessed 2026-08-31
SARAA 2024 South African RA management and access context South African Medical Journal guideline, https://www.scielo.org.za/scielo.php?pid=S0256-95742024001000006&script=sci_arttext, accessed 2026-08-30

A systematic review of guidelines found broad agreement on core care and variable methodological quality; recommendation convergence does not mean evidence certainty is high for every branch (Conley 2023, PMID 37291382).

Applying recommendations without false precision

Guidelines address populations and require adaptation for infection history, pregnancy, lung disease, kidney/liver function, malignancy, cardiovascular/VTE risk, frailty, cost and patient preference. “Conditional” means choices should vary, not that the recommendation is unimportant.

Reading rules for recommendations

  • Check publication date against major safety evidence.
  • Distinguish strong from conditional recommendations.
  • Preserve regional access and regulatory context.
  • Do not convert consensus into high-certainty evidence.

Competing guideline positions by decision

Decision Position A Position B / tension
Initial glucocorticoid bridge EULAR 2022 supports short-term glucocorticoids with initial conventional DMARDs and rapid discontinuation (Smolen 2023, PMID 36357155). ACR 2021 conditionally prefers initiation without even short-term glucocorticoids and strongly opposes longer-term use, reflecting greater weighting of cumulative harm (Fraenkel 2021, PMID 34101376).
Methotrexate inadequate response EULAR escalates according to prognostic factors, with a biologic or JAK inhibitor after insufficient response in poor-prognosis disease (Smolen 2023, PMID 36357155). ACR 2021 conditionally prefers adding a biologic/targeted synthetic drug over conventional triple therapy, while RACAT supports clinical noninferiority of triple therapy; access and cost alter the preferred sequence (Fraenkel 2021, PMID 34101376; O'Dell 2013, PMID 23755969).
JAK positioning EULAR retains JAK inhibitors as effective options but requires explicit MACE, malignancy and thrombosis risk consideration (Smolen 2023, PMID 36357155). ACR 2021 predates final ORAL Surveillance publication; its positioning should not be read as a post-signal safety judgment.
Vaccination and methotrexate ACR 2022 gives medication-specific holding guidance, including around influenza vaccination (Bass 2023, PMID 36597813). EULAR 2019 emphasizes preferably vaccinating before immunosuppression and avoiding live vaccines in many immunosuppressed states; schedules and products are region-specific (Furer 2020, PMID 31413005).
Reproductive health ACR reproductive guidance separates paternal and maternal exposure, preconception, pregnancy and lactation rather than assigning a single drug label (Sammaritano 2020, PMID 32090466). Product labels and national teratology services may be more conservative; shared decisions should use indication-specific evidence.
RA-ILD screening/treatment ACR/CHEST conditionally supports PFT/HRCT screening in at-risk patients and supplies a separate treatment framework (Johnson 2024, PMID 38973714; PMID 38973731). Articular RA algorithms were not designed to optimize lung outcomes; evidence for most RA-ILD drugs is low certainty.
Lifestyle and work EULAR treats physical activity, smoking cessation, healthy weight and work participation as core longitudinal care (Gwinnutt 2023, PMID 35260387). Lifestyle intervention complements, rather than substitutes for, DMARD suppression of synovitis.

Cardiovascular guidance emphasizes systematic risk assessment and management, but RA-specific multiplication factors and screening intervals are not uniformly adopted (Drosos 2022, PMID 35110331). Most disagreements arise from evidence weighting rather than factual conflict: population risk, drug price, health-system capacity, and tolerance for glucocorticoid or JAK harms differ. A recommendation’s year is therefore part of its meaning; documents predating ORAL Surveillance, current vaccination products, or RA-ILD guidance should not be silently treated as current on those questions.

The 2024 APLAR update adds an Asia-Pacific framework with 14 consensus statements and explicit infection-reactivation, vaccination and pregnancy context (Yamaoka 2026, PMID 42362943). The official 2025 ALAT RA-ILD guideline adds a Latin American respiratory-society perspective on screening, joint control, DMARDs and antifibrotics (Alberti 2026, PMID 42034552). South African guidance emphasizes early diagnosis, shared decisions, infection/TB vigilance and local access constraints; unlike a global algorithm, it is designed for the South African health-system context (South African Medical Journal — “South African Rheumatism and Arthritis Association 2024 updated guidelines for the management of rheumatoid arthritis,” https://www.scielo.org.za/scielo.php?pid=S0256-95742024001000006&script=sci_arttext, accessed 2026-08-30).

The 2026 German DGRh S3 update replaces its 2018 predecessor. Its official release specifies assessment every one to three months in active disease, treatment adjustment when improvement is insufficient at three months or target is missed at six months, glucocorticoid reduction with discontinuation generally within three months, gradual DMARD reduction—but not complete withdrawal—in sustained remission, and its first dedicated RA-ILD recommendation (DGRh — “Neue Leitlinie zur rheumatoiden Arthritis,” https://www.dgrh.de/pressemitteilung/neue-leitlinie-zur-rheumatoiden-arthritis/, accessed 2026-08-31). These are national S3 recommendations; their new RA-ILD and de-escalation positions should be compared with EULAR and ACR/CHEST rather than silently merged into them.

Evidence map

This map adds directly adjacent evidence used to bound interpretation. Inclusion means the record informs this topic or a tightly linked decision; it does not imply that every study supports every conclusion on the page.

Adjacent evidence Relevance to this page
Grigor C, et al. TICORA tight-control trial. Lancet. 2004. (PMID 15262104) Adjacent evidence from classification-and-diagnosis.md, clinical-trials-landscape.md, conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, epidemiology-and-burden.md, genetics-environment-and-mucosal-origins.md, overview.md, preclinical-autoimmunity-and-prevention.md, treat-to-target-and-remission.md
Korpela M, et al. FIN-RACo five-year outcomes. Arthritis Rheum. 2004. (PMID 15248204) Adjacent evidence from classification-and-diagnosis.md, clinical-trials-landscape.md, conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, epidemiology-and-burden.md, genetics-environment-and-mucosal-origins.md, overview.md, preclinical-autoimmunity-and-prevention.md, treat-to-target-and-remission.md
Studenic P, et al. 2022 ACR/EULAR RA remission criteria revision. Arthritis Rheumatol. 2023. (PMID 36274193) Adjacent evidence from classification-and-diagnosis.md, conventional-dmards.md, epidemiology-and-burden.md, overview.md, treat-to-target-and-remission.md
Messelink MA, et al. Best target in a treat-to-target strategy in RA. Ann Rheum Dis. 2023. (PMID 37116986) Adjacent evidence from conventional-dmards.md, treat-to-target-and-remission.md
Mandl P, et al. Imaging for treat to target in RA. Rheumatology. 2019. (PMID 31518423) Adjacent evidence from biomarkers-and-tissue-precision.md, classification-and-diagnosis.md, conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, epidemiology-and-burden.md, genetics-environment-and-mucosal-origins.md, overview.md, preclinical-autoimmunity-and-prevention.md, synovial-immunobiology.md, treat-to-target-and-remission.md
Michaud K, et al. Systematic literature review of residual symptoms and unmet need in RA. Arthritis Care Res. 2021. (PMID 32619340) Adjacent evidence from conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, epidemiology-and-burden.md, patient-experience-and-advocacy.md, treat-to-target-and-remission.md
Tascilar K, et al. RETRO tapering and stopping trial. Lancet Rheumatol. 2021. (PMID 38297524) Adjacent evidence from clinical-trials-landscape.md, conventional-dmards.md, treat-to-target-and-remission.md
Haschka J, et al. Relapse rates tapering or stopping antirheumatic therapy. Ann Rheum Dis. 2016. (PMID 25660991) Adjacent evidence from conventional-dmards.md, treat-to-target-and-remission.md
van Mulligen E, et al. TARA two-year tapering trial. Ann Rheum Dis. 2020. (PMID 32482645) Adjacent evidence from clinical-trials-landscape.md, conventional-dmards.md, treat-to-target-and-remission.md
Rivellese F, et al. Synovial biopsy biomarker analysis of R4RA. Nat Med. 2022. (PMID 35589854) Adjacent evidence from biologic-dmards.md, biomarkers-and-tissue-precision.md, clinical-trials-landscape.md, conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, genetics-environment-and-mucosal-origins.md, jak-inhibitors-and-targeted-therapy.md, preclinical-autoimmunity-and-prevention.md, synovial-immunobiology.md, treat-to-target-and-remission.md
Wang W, et al. Side effects of methotrexate therapy for rheumatoid arthritis: systematic review. Eur J Med Chem. 2018. (PMID 30243154) Adjacent evidence from classification-and-diagnosis.md, conventional-dmards.md, epidemiology-and-burden.md, overview.md, treat-to-target-and-remission.md
Hazlewood GS, et al. Methotrexate monotherapy and combination therapy: Cochrane network meta-analysis. BMJ. 2016. (PMID 27102806) Adjacent evidence from conventional-dmards.md, treat-to-target-and-remission.md
Katchamart W, et al. Methotrexate monotherapy versus non-biological DMARD combinations. Ann Rheum Dis. 2009. (PMID 19054823) Adjacent evidence from conventional-dmards.md, treat-to-target-and-remission.md
van Vollenhoven RF, et al. SWEFOT one-year randomized trial. Lancet. 2009. (PMID 19665644) Adjacent evidence from clinical-trials-landscape.md, conventional-dmards.md, treat-to-target-and-remission.md
Bijlsma JW, et al. Glucocorticoids in treatment of RA. Clin Exp Rheumatol. 2015;33:S34-S36. (PMID 26457916) Adjacent evidence from conventional-dmards.md, treat-to-target-and-remission.md
Ling SF, et al. Pharmacogenetics of methotrexate response in RA. 2020. (PMID 31849277) Adjacent evidence from biomarkers-and-tissue-precision.md, conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, genetics-environment-and-mucosal-origins.md, preclinical-autoimmunity-and-prevention.md, synovial-immunobiology.md, treat-to-target-and-remission.md
Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021. (PMID 33004335) Adjacent evidence from classification-and-diagnosis.md, conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, epidemiology-and-burden.md, overview.md, treat-to-target-and-remission.md
Buch MH, et al. Persistent inflammatory and non-inflammatory mechanisms in refractory RA. Nat Rev Rheumatol. 2021. (PMID 33293696) Adjacent evidence from classification-and-diagnosis.md, conventional-dmards.md, difficult-to-treat-and-refractory-ra.md, treat-to-target-and-remission.md
Evidence-map records are listed in full below and were live-retrieved from PubMed in this build session.

Open questions

  • How should 2021 ACR pharmacologic guidance be updated after ORAL Surveillance? (Ytterberg 2022, PMID 35081280)
  • Which regional differences reflect evidence versus drug access and pricing?
  • Does a short glucocorticoid bridge improve net outcomes in modern rapid-escalation systems?
  • Can guideline adherence be linked to mortality and disability rather than process measures?
  • Which RA-ILD recommendations will survive disease-specific randomized trials?

References

  1. Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update. Ann Rheum Dis. 2026;85:991-1009. PMID 41826212
  2. Fraenkel L, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2021;73:1108-1123. PMID 34101376
  3. Konzett V, et al. Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2026;85:1039-1054. PMID 41997804
  4. Smolen JS, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82:3-18. PMID 36357155
  5. Kerschbaumer A, et al. Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2023;82:95-106. PMID 36368906
  6. England BR, et al. 2022 American College of Rheumatology Guideline for Exercise, Rehabilitation, Diet, and Additional Integrative Interventions for Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2023;75:1603-1615. PMID 37227116
  7. Peter WF, et al. Clinical Practice Guideline for Physical Therapist Management of People With Rheumatoid Arthritis. Phys Ther. 2021;101:pzab127. PMID 34003240
  8. Nagy G, et al. EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2022;81:20-33. PMID 34407926
  9. Saavedra AA, et al. Treatment of rheumatoid arthritis-associated interstitial lung disease: An appraisal of the 2023 ACR/CHEST guideline. Curr Treatm Opt Rheumatol. 2024;10:43-60. PMID 39822854
  10. Fautrel B, et al. 2024 update of the recommendations of the French Society of Rheumatology for the diagnosis and management of patients with rheumatoid arthritis. Joint Bone Spine. 2024;91:105790. PMID 39389412
  11. Abud-Mendoza C, et al. Update of the guidelines for the pharmacological treatment of rheumatoid arthritis by the Mexican College of Rheumatology 2023. Reumatol Clin (Engl Ed). 2024;20:263-280. PMID 38796394
  12. Harigai M, et al. 2024 Update of the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis: Secondary publication. Mod Rheumatol. 2025;35:387-401. PMID 39820350
  13. Yamaoka K, et al. 2024 Update of the Asia-Pacific League of Associations for Rheumatology (APLAR) Recommendations for Rheumatoid Arthritis Management. Int J Rheum Dis. 2026;29:e70752. PMID 42362943
  14. Alberti ML, et al. Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD): An Official 2025 ALAT Clinical Practice Guideline. Arch Bronconeumol. 2026:S0300-2896(26)00122-5. PMID 42034552
  15. Conley B, et al. What are the core recommendations for rheumatoid arthritis care? Systematic review of clinical practice guidelines. Clin Rheumatol. 2023;42:2267-2278. PMID 37291382
  16. O'Dell JR, et al. Therapies for active rheumatoid arthritis after methotrexate failure. N Engl J Med. 2013;369:307-18. PMID 23755969
  17. Bass AR, et al. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken). 2023;75:449-464. PMID 36597813
  18. Furer V, et al. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020;79:39-52. PMID 31413005
  19. Sammaritano LR, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken). 2020;72:461-488. PMID 32090466
  20. Johnson SR, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases. Arthritis Rheumatol. 2024;76:1201-1213. PMID 38973714
  21. Johnson SR, et al. 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases. Arthritis Care Res (Hoboken). 2024;76:1051-1069. PMID 38973731
  22. Gwinnutt JM, et al. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases. Ann Rheum Dis. 2023;82:48-56. PMID 35260387
  23. Drosos GC, et al. EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases, including systemic lupus erythematosus and antiphospholipid syndrome. Ann Rheum Dis. 2022;81:768-779. PMID 35110331
  24. Grigor C, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364:263-9. PMID 15262104
  25. Korpela M, et al. Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study. Arthritis Rheum. 2004;50:2072-81. PMID 15248204
  26. Studenic P, et al. American College of Rheumatology/EULAR Remission Criteria for Rheumatoid Arthritis: 2022 Revision. Arthritis Rheumatol. 2023;75:15-22. PMID 36274193
  27. Messelink MA, et al. What is the best target in a treat-to-target strategy in rheumatoid arthritis? Results from a systematic review and meta-regression analysis. RMD Open. 2023;9:e003196. PMID 37116986
  28. Mandl P, et al. The role of ultrasound and magnetic resonance imaging for treat to target in rheumatoid arthritis and psoriatic arthritis. Rheumatology (Oxford). 2019;58:2091-2098. PMID 31518423
  29. Michaud K, et al. Systematic Literature Review of Residual Symptoms and an Unmet Need in Patients With Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021;73:1606-1616. PMID 32619340
  30. Tascilar K, et al. Treatment tapering and stopping in patients with rheumatoid arthritis in stable remission (RETRO): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Rheumatol. 2021;3:e767-e777. PMID 38297524
  31. Haschka J, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 2016;75:45-51. PMID 25660991
  32. van Mulligen E, et al. Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial. Ann Rheum Dis. 2020;79:1174-1181. PMID 32482645
  33. Rivellese F, et al. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. Nat Med. 2022;28:1256-1268. PMID 35589854
  34. Wang W, et al. Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review. Eur J Med Chem. 2018;158:502-516. PMID 30243154
  35. Hazlewood GS, et al. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis. BMJ. 2016;353:i1777. PMID 27102806
  36. Katchamart W, et al. Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2009;68:1105-12. PMID 19054823
  37. van Vollenhoven RF, et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet. 2009;374:459-66. PMID 19665644
  38. Bijlsma JW, et al. Glucocorticoids in the treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2015;33:S34-6. PMID 26457916
  39. Ling SF, et al. Pharmacogenetics of methotrexate response in rheumatoid arthritis: an update. Pharmacogenomics. 2020;21:3-6. PMID 31849277
  40. Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021;80:31-35. PMID 33004335
  41. Buch MH, et al. Persistent inflammatory and non-inflammatory mechanisms in refractory rheumatoid arthritis. Nat Rev Rheumatol. 2021;17:17-33. PMID 33293696
  42. Ytterberg SR, et al. Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis. N Engl J Med. 2022;386:316-326. PMID 35081280