Study Compares Methotrexate-Only Versus Combination Therapy in Early RA

Guidelines from the European League Against Rheumatism and the American College of Rheumatology recommend clinical remission (or low disease activity [LDA] if clinical remission is unlikely) as the treatment goal for a patient with rheumatoid arthritis (RA). While conventional disease-modifying antirheumatic drugs (DMARDs), including methotrexate, are recommended as part of an initial treatment strategy, if disease activity has not improved at 3 months, or a clinical target is not reached at 6 months, the addition of a biologic therapy, such as an anti—tumor necrosis factor (anti-TNF) is recommended.

A recent study published in Annals of the Rheumatic Diseases evaluated the treat-to-target strategy by assessing whether patients with early RA who start methotrexate as monotherapy, (followed by the anti-TNF agent adalimumab if they failed to achieve treatment goals with methotrexate alone), had similar or worse outcomes compared to patients who started with adalimumab plus methotrexate.

The 78-week, randomized, double-blind, phase 4 study included methotrexate-naïve patients who had active RA for more than 1 year. In the first study period, patients received methotrexate as monotherapy weekly (n = 460) or adalimumab at 40 mg every other week plus methotrexate weekly for 26 weeks (n = 466). In the second period, patients with stable LDA continued methotrexate as monotherapy or were re-randomized to adalimumab plus methotrexate for continuation or adalimumab withdrawal.

The researchers found the following:

• A significantly greater proportion of patients initially treated with adalimumab plus methotrexate (53%) compared with patients treated with methotrexate monotherapy (30%) achieved LDA (defined as a Disease Activity Score-28, with C-reactive protein, of less than 3.2).
• 45% of patients in the adalimumab plus methotrexate group, versus 33% of those in the methotrexate monotherapy group, achieved normal function (defined as a Health Assessment Questionnaire Disability Index score of less than 0.5).
• 87% of patients in the adalimumab plus methotrexate group, versus 72% of the methotrexate monotherapy group, demonstrated radiographic non-progression at week 26.
• From weeks 26 to 78, patients transitioned to adalimumab from methotrexate monotherapy achieved similar clinical and functional outcomes compared with patients initially treated with adalimumab plus methotrexate.
• Significantly more patients initially treated with adalimumab plus methotrexate had no radiographic progression at weeks 52 and 78 versus patients initially treated with methotrexate (86% versus 72% for both time points).

The researchers concluded that starting treatment with methotrexate as monotherapy and adding adalimumab if a patient fails to respond adequately at 26 weeks allowed patients with early RA to achieve comparable long-term clinical, functional, and disease-activity outcomes as those who began initial adalimumab plus methotrexate combination therapy, and that this strategy helped to prevent overtreatment of patients with early RA.