Dose-response relationship of methotrexate in mono- and combination therapy in rheumatoid arthritis

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Dose-response relationship of methotrexate in mono- and combination therapy in rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease affecting many joints of the body including joints of hands and the feet. The study mentioned here was performed to estimate the  possible short term dose-response relationship of initial treatment with methotrexate in monotherapy and combination therapy in patients with recent onset of RA.

A systematic literature search was executed on trials and cohorts comprising early, disease modifying antirheumatic drugs (DMARD) naive RA patients, treated with methotrexate, with data on clinical results within six months from treatment. Four treatment groups were made: methotrexate monotherapy, or methotrexate in combination with synthetic (cs)DMARDs, biologic (b)DMARDs or glucocorticoids. Cohen's effect sizes were calculated for the health assessment questionnaire (HAQ), C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR) and/or Disease Activity Score (DAS) 28 in  these groups. For each result obtained, random-effects meta-regression analyses were performed with the treatment group as predictor corrected for baseline HAQ or disease activity and assessment point.

A total of 31 studies comprising 5589 patients were considered. It was revealed that the meta regression did not support higher effectiveness of increasing methotrexate dose in monotherapy. However, the number of treatment groups using combination therapy with csDMARDs was too small to achieve meta-regression analyses. In combination therapy with glucocorticoids a higher methotrexate dose was related with higher (worse) outcome HAQ, but not with DAS/DAS28 or ESR/CRP. All the effect sizes were small.

It was concluded that in DMARD naive early RA patients who start methotrexate, either as monotherapy or in combination with bDMARDs or glucocorticoids, a higher initial dose of methotrexate was not associated with superior clinical outcomes. These results proposed that there is little short term gain from starting with high compared to low methotrexate doses.


Arthritis care and research

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Original title of article:

Meta-regression of a dose-response relationship of methotrexate in mono- and combination therapy in DMARD naive early rheumatoid arthritis patients


 SA Bergstra, CF Allaart, T Stijnen, RBM Landewé

Arthritis care and research
Therapeutic, Methotrexate, Rheumatoid Arthritis, Joints, Antimetabolites, Glucocorticoids, bDMARDs, Systematic Literature, Efficacy, HAQ, ESR/CRP Level, DAS/DAS28
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