Objectives: This systematicliteraturereview(SLR)updatedevidenceontheefficacy ofdisease- modifying antirheumaticdrugs(DMARDs)andglucocorticoids(GCs)toinformthe2025update of theEuropeanAllianceofAssociationsforRheumatology(EULAR)managementrecommenda- tions forrheumatoidarthritis(RA). Methods: Medline (PubMed),Embase(OVID),CochraneCentralRegisterofControlledTrials, and WebofScienceweresearchedforrandomisedcontrolledtrials(RCTs)ofconventional-syn- thetic, biological,andtargeted-syntheticDMARDs(csDMARDs,bDMARDs,tsDMARDs),aswell as GCsandbiosimilars,publishedfrom14January2022to22January2025.Additional searches onDMARDs,GCs,andantifibrotics forRA-associatedinterstitiallungdisease(RAILD), and onDMARDsandGCsforpreventingRAinat-riskindividuals,wereconductedfromdatabase inception to22January2025. Results: A totalof12,567referenceswereidentified; 390full-textswerereviewed,and72studies were included.Phase3-4RCTsevaluatedcsDMARDs(hydroxychloroquine,iguratimod,leflunomide, andmethotrexate),bDMARDs(abatacept,otilimab,andozoralizumab),andtsDMARDs (ivarmacitinib, peficitinib, andtofacitinib).Twelvenovelcompoundswereassessedinphase2 RCTs, and3articlesinvestigatedGCs.Strategictrialscomparedconventionaltherapieswith bDMARD- ortsDMARD-basedstrategiesandexploredprecision-medicineapproachessuchas synovial biopsy-guidedtreatmentandtherapeuticdrugmonitoring.Additionalevidence addressed DMARDtapering.TwoRCTsassessedantifibrotics (nintedanibandpirfenidone)for RA ILD,and7studiesevaluatedDMARDsforRApreventioninat-riskpopulations. Conclusions: This SLR,togetherwiththesafetyreview,informedthe2025updateoftheEULAR RA managementrecommendations.Althoughfewphase3trialsonnovelagentswereavailable, strategic andhead-to-headstudiesprovidedimportantinsightsthatenabledfurtherrefinement of theestablishedtreatmentalgorithm.
Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis / V. Konzett, F. Laskou, J.S. Smolen, C.J. Edwards, D. Aletaha, D. Van Der Heijde, K.L. Winthrop, T. Takeuchi, R. Caporali, P. Verschueren, J.E. Pope, K.L. Hyrich, S. De Souza, T.A. Stamm Jette Primdahl, J.W. Schoones, R.B.M. Landewe, A. Kerschbaum. - In: ANNALS OF THE RHEUMATIC DISEASES. - ISSN 0003-4967. - (2026), pp. 1-16. [Epub ahead of print] [10.1016/j.ard.2026.03.020]
Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2025 update of the EULAR recommendations for the management of rheumatoid arthritis
R. Caporali;
2026
Abstract
Objectives: This systematicliteraturereview(SLR)updatedevidenceontheefficacy ofdisease- modifying antirheumaticdrugs(DMARDs)andglucocorticoids(GCs)toinformthe2025update of theEuropeanAllianceofAssociationsforRheumatology(EULAR)managementrecommenda- tions forrheumatoidarthritis(RA). Methods: Medline (PubMed),Embase(OVID),CochraneCentralRegisterofControlledTrials, and WebofScienceweresearchedforrandomisedcontrolledtrials(RCTs)ofconventional-syn- thetic, biological,andtargeted-syntheticDMARDs(csDMARDs,bDMARDs,tsDMARDs),aswell as GCsandbiosimilars,publishedfrom14January2022to22January2025.Additional searches onDMARDs,GCs,andantifibrotics forRA-associatedinterstitiallungdisease(RAILD), and onDMARDsandGCsforpreventingRAinat-riskindividuals,wereconductedfromdatabase inception to22January2025. Results: A totalof12,567referenceswereidentified; 390full-textswerereviewed,and72studies were included.Phase3-4RCTsevaluatedcsDMARDs(hydroxychloroquine,iguratimod,leflunomide, andmethotrexate),bDMARDs(abatacept,otilimab,andozoralizumab),andtsDMARDs (ivarmacitinib, peficitinib, andtofacitinib).Twelvenovelcompoundswereassessedinphase2 RCTs, and3articlesinvestigatedGCs.Strategictrialscomparedconventionaltherapieswith bDMARD- ortsDMARD-basedstrategiesandexploredprecision-medicineapproachessuchas synovial biopsy-guidedtreatmentandtherapeuticdrugmonitoring.Additionalevidence addressed DMARDtapering.TwoRCTsassessedantifibrotics (nintedanibandpirfenidone)for RA ILD,and7studiesevaluatedDMARDsforRApreventioninat-riskpopulations. Conclusions: This SLR,togetherwiththesafetyreview,informedthe2025updateoftheEULAR RA managementrecommendations.Althoughfewphase3trialsonnovelagentswereavailable, strategic andhead-to-headstudiesprovidedimportantinsightsthatenabledfurtherrefinement of theestablishedtreatmentalgorithm.
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