In the Journals

Methotrexate alone yields similar outcomes to combined therapy for initial RA treatment

Initial methotrexate monotherapy, adding a TNF inhibitor at 26 weeks, produced long-term results similar to initial combined therapy among patients with early rheumatoid arthritis, according to findings published in the Annals of the Rheumatic Diseases.

“The European League Against Rheumatism and American College of Rheumatology recommend clinical remission or low disease activity if remission is unlikely to be obtained, as the treatment goal for rheumatoid arthritis,” Arthur Kavanaugh, MD, of the University of California San Diego School of Medicine, and colleagues wrote. “Conventional synthetic disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, are recommended as part of an initial treatment strategy.”

According to the researchers, a biological DMARD, such as a TNF inhibitor, is further recommended if the patient’s condition has not improved within 3 months, or if the clinical target has not been met within 6 months.

To test the treat-to-target strategy, the researchers compared the responses of patients with early RA who received an initial treatment of methotrexate alone — followed by the TNF inhibitor adalimumab (Humira, AbbVie) after an inadequate response to methotrexate — with those treated with methotrexate and adalimumab at the outset. They conducted a post-hoc analysis of OPTIMA, a 78-week, randomized, double-blind, phase 4 study.

In the first of the study’s two periods, patients received either weekly doses of methotrexate alone, or methotrexate weekly plus 40 mg of adalimumab every other week, for 26 weeks. In period 2, those with stable low disease activity continued methotrexate monotherapy or were randomly assigned to either continue with adalimumab plus methotrexate, or to withdraw from adalimumab treatment and continue on methotrexate monotherapy. Those who failed to achieve low disease activity in period 1 maintained treatments of methotrexate plus adalimumab, or received adalimumab newly added to their methotrexate monotherapy.

According to the researchers, 53% of the 466 patients treated with adalimumab plus methotrexate achieved good clinical results at week 26, compared with 30% of the 460 treated with methotrexate monotherapy. In addition, 45% of those treated with adalimumab plus methotrexate had good functional results, compared with 33% of those with methotrexate alone. Lastly, 87% of those with adalimumab plus methotrexate reported good radiographic outcomes, compared with 72% of those with methotrexate monotherapy.

From week 26 to week 78, patients who received adalimumab following methotrexate failure reported clinical and functional results similar to those who were initially treated with adalimumab plus methotrexate. However, fewer patients initially treated with adalimumab plus methotrexate experienced radiographic progression at weeks 52 and 78, the researchers found.

“Consistent with current treatment recommendations, starting with methotrexate monotherapy and optimizing treatment by adding adalimumab after treatment failure at 26 weeks allowed patients with early RA to achieve comparable long-term clinical, functional and disease activity outcomes with patients who started with initial adalimumab plus methotrexate combination therapy,” Kavanaugh and colleagues wrote. “This strategy also prevented potential overtreatment of approximately 25% of patients with early RA.” – by Jason Laday

Disclosure: Kavanaugh reports providing expert advice to, and receiving grants and support from, AbbVie. See the full study for additional authors’ disclosures.

Initial methotrexate monotherapy, adding a TNF inhibitor at 26 weeks, produced long-term results similar to initial combined therapy among patients with early rheumatoid arthritis, according to findings published in the Annals of the Rheumatic Diseases.

“The European League Against Rheumatism and American College of Rheumatology recommend clinical remission or low disease activity if remission is unlikely to be obtained, as the treatment goal for rheumatoid arthritis,” Arthur Kavanaugh, MD, of the University of California San Diego School of Medicine, and colleagues wrote. “Conventional synthetic disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, are recommended as part of an initial treatment strategy.”

According to the researchers, a biological DMARD, such as a TNF inhibitor, is further recommended if the patient’s condition has not improved within 3 months, or if the clinical target has not been met within 6 months.

To test the treat-to-target strategy, the researchers compared the responses of patients with early RA who received an initial treatment of methotrexate alone — followed by the TNF inhibitor adalimumab (Humira, AbbVie) after an inadequate response to methotrexate — with those treated with methotrexate and adalimumab at the outset. They conducted a post-hoc analysis of OPTIMA, a 78-week, randomized, double-blind, phase 4 study.

In the first of the study’s two periods, patients received either weekly doses of methotrexate alone, or methotrexate weekly plus 40 mg of adalimumab every other week, for 26 weeks. In period 2, those with stable low disease activity continued methotrexate monotherapy or were randomly assigned to either continue with adalimumab plus methotrexate, or to withdraw from adalimumab treatment and continue on methotrexate monotherapy. Those who failed to achieve low disease activity in period 1 maintained treatments of methotrexate plus adalimumab, or received adalimumab newly added to their methotrexate monotherapy.

According to the researchers, 53% of the 466 patients treated with adalimumab plus methotrexate achieved good clinical results at week 26, compared with 30% of the 460 treated with methotrexate monotherapy. In addition, 45% of those treated with adalimumab plus methotrexate had good functional results, compared with 33% of those with methotrexate alone. Lastly, 87% of those with adalimumab plus methotrexate reported good radiographic outcomes, compared with 72% of those with methotrexate monotherapy.

From week 26 to week 78, patients who received adalimumab following methotrexate failure reported clinical and functional results similar to those who were initially treated with adalimumab plus methotrexate. However, fewer patients initially treated with adalimumab plus methotrexate experienced radiographic progression at weeks 52 and 78, the researchers found.

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“Consistent with current treatment recommendations, starting with methotrexate monotherapy and optimizing treatment by adding adalimumab after treatment failure at 26 weeks allowed patients with early RA to achieve comparable long-term clinical, functional and disease activity outcomes with patients who started with initial adalimumab plus methotrexate combination therapy,” Kavanaugh and colleagues wrote. “This strategy also prevented potential overtreatment of approximately 25% of patients with early RA.” – by Jason Laday

Disclosure: Kavanaugh reports providing expert advice to, and receiving grants and support from, AbbVie. See the full study for additional authors’ disclosures.