Background/Purpose: Methotrexate (MTX) is recommended as the first DMARD in rheumatoid arthritis (RA) at a weekly dose of 20-25mg in combination with folic acid supplementation. Despite its widespread use and more than two decades of experience, considerable variations exist among rheumatologists in prescribing MTX.

Objective: To describe symptomatic and structural impact of the MTX optimization in early arthritis (EA) in daily clinical practice over 2 years.

Methods:

– Patients: from the French cohort of EA ESPOIR (at least 2 swollen joints for less than 6 months and suspicion of RA), fulfilling the new ACR-EULAR criteria for RA at baseline, and treated by MTX as first DMARD.

– Treatment group: optimized MTX was defined by at least 3 months of MTX during the first 6 months and dose of initiation at least 10 mg/week with escalation at 6 months at least at 20 mg/w or 0.3mg/kg/w if DAS28>2.6

– Outcomes: remissions (Boolean, SDAI and DAS28), functional stability (HAQ≤0.5 and deltaHAQ≤0.25), absence of radiographic progression (delta Sharp score<1) and absence of fast radiographic progression (delta Sharp score<1).

– Analyses:evaluation of the symptomatic and structural efficacy has been performed by generalized linear regression after adjustement on propensity score (by modelling the optimization of MTX by disease specific- and demographic variables obtained at baseline, using logistic regression analysis) in the group of patients receiving optimized MTX versus the ones receiving MTX without optimization.

Results: Within the first year of follow-up of 600 RA patients, 352 received MTX as first DMARD. The mean dose of MTX was 13.1 +/- 3.9 mg/week. In all, 76.1% of patients received at least 3 months of MTX during the first 6 months and 25.3% were treated initially at least by 10 mg/week with escalation at 6 months at least at 20 mg/w or 0.3mg/kg/w if DAS28>2.6; only 22.1% fulfilled the 2 criteria. MTX optimization was initiated in younger patients (45.2 years ± 12.6 vs 49.3 ± 11.3, p=0.009) with higher CRP (29.3±32.0 vs 24.4±36.7, p=0.006). After adjustment, optimized MTX was found to be more efficient in terms of remission and function than control (table).

Conclusion: Optimized MTX is more efficacious on remission and function than MTX without optimization in EA in daily practice but without impact on radiographic progression over 2 years.

Outcome	Optimized MTX N = 76 N (%) at m12	Non optimized MTX N=268 N (%)	Adjusted OR m0-m12 [95%CI]	Adjusted OR m12-m24 [95%CI]
Boolean remission	20 (27.4%)	25 (10.0%)	2.56 [1.22 – 5.37]	1.85 [0.98 – 3.52]
SDAI remission	23 (31.5%)	27 (10.8%)	2.35 [1.16 – 4.75]	2.30   [1.22 – 4.32]
DAS28 remission	40 (55.6%)	74 (29.6%)	2.81 [1.53 – 5.18]	2.72   [1.46 – 5.07]
Functional stability	54 (74.0%)	134 (52.6%)	3.01 [1.49 – 6.08]	1.93   [0.97 – 3.85]
Absence of radiographic progression	23 (34.9%)	81 (35.2%)	1.06 [0.56 – 2.01]	0.54   [0.26 – 1.10]
Absence of fast radiographic progression	23 (34.9%)	81 (35.2%)	0.76 [0.37 – 1.54]	0.44 [0.19 – 1.03]

*Ajusted on : SJC, CRP, ACPA or RF, Sharp score, Center, Age, Smoking, HAQ, ACR1987 criteria

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/methotrexate-optimization-ie-introduction-during-the-first-3-months-and-with-dose-escalation-at-6-months-at-least-at-20mgw-or-0-3mgkgw-is-associated-with-better-clinical-outcomes-in-daily-practic/