title: Meta-Regression of a Dose-Response Relationship of Methotrexate in Mono- and Combination Therapy in Disease-Modifying Antirheumatic Drug-Naive Early Rheumatoid Arthritis Patients.
abstract: To investigate a possible short-term dose-response relationship of initial treatment with methotrexate (MTX) in monotherapy and combination therapy in recent-onset rheumatoid arthritis (RA) patients.
  
  
  
  A systematic literature search was performed on trials and cohorts, including early, disease-modifying antirheumatic drug (DMARD)-naive RA patients treated with MTX, with data on clinical results within 6 months from treatment start. Cohen's effect sizes were calculated for the Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) level, and/or Disease Activity Score (DAS)/in 28 joints (DAS28) in 4 treatment groups: MTX monotherapy, or MTX in combination with synthetic (cs) DMARDs, biologic (b) DMARDs, or glucocorticoids. Random-effects meta-regression analyses were performed for each outcome, with treatment group as the predictor corrected for baseline HAQ or disease activity and assessment point.
  
  
  
  Thirty-one studies including 5,589 patients were included. The meta-regression did not support higher effectiveness of increasing MTX dose in monotherapy. The number of treatment groups using combination therapy with csDMARDs was too small to perform meta-regression analyses. In combination therapy with glucocorticoids, a higher MTX dose was associated with higher (worse) outcome HAQ, but not with DAS/DAS28 or ESR/CRP level. In combination therapy with bDMARDs, a higher MTX dose was associated with higher outcome HAQ and DAS/DAS28, but not with ESR/CRP level. All effect sizes were small.
  
  
  
  In DMARD-naive, early RA patients who start MTX, either as monotherapy or in combination with bDMARDs or glucocorticoids, a higher initial dose of MTX was not associated with better clinical outcomes. This finding suggests that there is little short-term gain from starting with high compared to low MTX doses.
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Bergstra
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C F
authors.initials: CF
authors.lastname: Allaart
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Stijnen
authors.affiliation: Amsterdam Rheumatology & Immunology Center, Zuyderland Medical Center Heerlen, The Netherlands.
authors.forename: R B M
authors.initials: RBM
authors.lastname: Landewé
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate