Being able to accurately predict which patients with RA may remain in remission would help clinicians to facilitate shared decision-making.

After switching from combination therapy to monotherapy, patients with RA with overall lower disease activity (LDA) are more likely to achieve and remain in remission, according to findings from Jeffrey R. Curtis, MD, MS, MPH, and colleagues.

Once achieving remission, the study authors observed, patients may forego continuing with dual therapies of methotrexate plus etanercept, adding that reducing therapy may be preferable for patients, due to medication burden, cost, and tolerability. The findings were published in The Journal of Rheumatology.

While some patients who persist in remission may choose to discontinue their therapy, others may consider tapering their therapy, provided that a therapeutic dose of at least one DMARD is maintained, the study authors point out. They note that patients achieve remission more often through combination therapy with biologics and conventional disease-modifying antirheumatic drugs (cDMARDs) than by using either treatment alone. “Dose reduction is recommended over discontinuation, but if a DMARD is discontinued, it is recommended that patients do so gradually,” Dr. Curtis and colleagues wrote. They added that while some patients persist in remission after withdrawing therapy, others may experience a worsening of their condition. (Figure)

Baseline Characteristics of Patients in Remission

Dr. Curtis and colleagues conducted the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects With Rheumatoid Arthritis (SEAM-RA), a phase 3, multicenter, randomized withdrawal, double-blind, controlled study consisting of patients with RA on methotrexate plus etanercept.

Among 371 adult patients enrolled in the study, 253 were in remission and were able to participate in the double-blind period. Covariates linked with achieving remission according to a Simplified Disease Activity Index (SDAI) of 3.3 or less at the end of the run-in period included less severe clinical disease parameters, younger age, and longer duration of methotrexate treatment, after adjusting for other factors. To identify baseline factors linked with remission or LDA, multivariate logistic regression analysis was performed.

“If remission SDAI was sustained through a 24-week run-in period, patients then entered a 48-week double-blind period and were randomized 2:2:1 to receive methotrexate monotherapy, etanercept monotherapy, or continue combination therapy,” the study authors wrote. At the end of the 48-week double-blind period, covariates linked with sustaining remission/LDA included lower C-reactive protein, lower Patient Global Assessment of Disease Activity (PtGA), longer RA duration in the methotrexate arm, shorter duration of etanercept treatment rheumatoid factor (RF) negativity, and lower magnesium.

The Role of Magnesium Demands Further Investigation

The study team observed that patients taking methotrexate and etanercept who had higher magnesium concentrations at baseline had lower odds of maintaining remission/LDA; there was an especially strong correlation with patients on etanercept as monotherapy. Therefore, magnesium’s role in controlling RA demands further investigation, they said.

“Patients with overall LDA are more likely to achieve and remain in SDAI remission/LDA after switching from combination therapy to monotherapy,” Dr. Curtis and colleagues wrote, adding that RF-negative status and lower PtGA scores were strongly linked with remaining in remission/LDA with etanercept monotherapy or methotrexate.

These findings, the study team noted, may help assist clinicians in “deciding whether to discontinue methotrexate or etanercept in a patient with RA in sustained remission.” Identifying clinical markers linked with patients remaining in remission or LDA after tapering would enable informed decisions about whether to taper therapy. In addition, “being able to accurately predict which patients may remain in remission would be helpful for clinicians and to facilitate shared decision making,” the study authors wrote.