Background/Purpose: Methotrexate (MTX) is the first line standard of care for the management of rheumatoid arthritis (RA). In the event of an inadequate response to MTX and the presence of a poor RA prognosis factor, recommendations include initiation of biological (bDMARD) or synthetic (tsDMARD) targeted therapy in combination with MTX.
STRATEGE2 aims to establish the maintenance of MTX within two years after initiating a first targeted therapy.

Methods: STRATEGE2 is a non-interventional study including RA patients treated with MTX for at least 3 months (M) and requiring initiation of a first b/tsDMARD due to disease activity. MTX maintenance was evaluated 12M (primary endpoint) and 24M after initiation of targeted therapy. Non-maintenance is defined as: permanent discontinuation of MTX and/or dose reduction and/or transition from the subcutaneous (SC) to oral (PO) route.

Results: Between Feb. 2019 and Dec. 2020, 53 French sites enrolled 180 RA patients, with 173 patients being followed up at 12M and 157 at 24M. At baseline: 75.1% women, mean age 56.1±13.7 years, average duration of diagnosis 5.6±7.3 years, MTX treatment for an average duration of 4.3±5.4 years. The majority (72.3%) received MTX via SC with an average dose of 18.8±4.2 mg/week. And 50.0% of patients received associated corticosteroid therapy (CS) at a mean dose of 9.6±6.0 mg/day.
MTX treatment characteristics (dose in mg/week±SD and SC administration in %) changed from 17.8±4.5 – SC: 66.3% at baseline to 15.9±4.5 – SC: 54.9% at 12M, then 15.8±4.6 – SC: 55.9% at 24M. Based on the composite endpoint, MTX maintenance remained unchanged for 39.9% of patients at 12M and 34.4% at 24M. MTX was discontinued at 12M and 24M in 16.8% and 24.8% of patients respectively (cumulative).
MTX modifications at 12M and 24M were: dose reduction 2.9% and 2.5%, change of route (SC to PO) 26.0% and 23.6% or both strategies 14.4% and 14.6%.
Therapeutic adaptations were noted for b/tsDMARDs from inclusion to 12M and 24M: For anti-TNF, the changes were 57.6%, 46.5%, and 40.9%. For anti-IL6 or IL17, the changes were 12.8%, 17.0%, and 20.5%. Other b/DMARDs exhibited changes of 19.2%, 19.5%, and 21.2%. For tsDMARDs, changes were observed at 10.5%, 17.0%, and 17.4%.
Use of CS (% and dose in mg/day±SD) remains high with 47.1% ; 9.3±7.5 at inclusion, 39.0% ; 8.9±9.0 at 12M, then 37.8% ; 9.3±9.3 at 24M. Finally, RA activity measured by DAS28 (mean±SD). DAS28 improved from 4.3±1.2 at baseline to 2.6±1.1 at 12M and stabilized to 2.4±1.1 at 24M.
Uni- and multivariate analysis indicated that age (OR=1.04, 95% CI [1.01 ; 1.07], p < 0.020) and disease activity’s patients assessment (VAS) (OR=1.02 95% CI [1.00 ; 1.04], p < 0.047) are parameters associated with MTX maintenance.

Conclusion: Many therapeutic adaptations were observed in the two years following the initiation of b/tsDMARD. Twenty-four months after the introduction of b/tsDMARD, MTX was adjusted (reduction in dosage and/or return to the PO route) for almost 41% of patients. More than 3 out of 4 patients continued to use MTX as a combination therapy and more than 1 out of 3 did not require any adaptation. These practices are in line with the latest EULAR guidelines which recommend the combination of b/tsDMARDs with MTX.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/methotrexate-maintenance-in-rheumatoid-arthritis-two-years-after-initiation-of-a-first-targeted-therapy-results-from-the-prospective-stratege2-study/