Treatment Strategies in Early Rheumatoid Arthritis Methotrexate Management: Results from a Prospective Cohort


To assess “real-word” practice patterns surrounding treatment initiation and treatment adjustments over time for methotrexate (MTX) and non-MTX-based treatments strategies in early rheumatoid arthritis (ERA).


We studied an incident multicenter ERA cohort (enrolled 2007-2017 within one year of symptoms) fulfilling ACR/EULAR criteria. Adult RA patients were eligible if they initiated MTX (+/-other DMARDs) within 90 days of cohort entry. We compared time until treatment change for four initial MTX-based therapy and time to second treatment change after the first change. Treatment change definition included: change of route for MTX monotherapy, adding or stopping a DMARD/biologic, and changing dose/frequency of a DMARD or biologic.


There was great variability of treatment at initiation and during therapy adjustment. In 1,484 ERA patients, the majority initiated MTX monotherapy (oral or subcutaneous, SC). Patients on SC MTX mono changed less (45% vs 79%) and remained longer (hazard ratio, HR: 0.52, 95% CI: 0.41-0.67) on therapy than those on oral MTX. Most therapy adjustments involved adding a DMARD or changing to a non-MTX DMARD. Those on biologics and on triple therapy had a longer time without treatment change (HR: 0.26, 95% CI: 0.16-0.42 and HR: 0.57, 95% CI: 0.38-0.85).


We found large variability in the way MTX-based therapies are prescribed in clinical practice. Our findings support use of subcutaneous MTX monotherapy or MTX combination as initial therapy. For subsequent treatment after initial MTX-based therapy, those initiating either biologics or triple therapy had a longer time to treatment change than oral MTX monotherapy.