Tocilizumab was effective both on its own and when combined with methotrexate, Dr. Gerd R. Burmester of Charite Medical University of Berlin and his colleagues found.
Tocilizumab, an interleukin-6 (IL-6) blocker, has been tested as a monotherapy and in combination with disease-modifying antirheumatic drugs (DMARDs) in RA patients, Dr. Burmester and colleagues note in their report, published online Oct. 28 in the Annals of the Rheumatic Diseases.
To investigate whether the drug might be effective in patients with early-stage, progressive RA, the researchers randomly assigned 1,162 methotrexate-naive patients to 4 mg/kg tocilizumab-methotrexate, 8 mg/kg tocilizumab-methotrexate, 8 mg/kg tocilizumab-placebo or placebo-methotrexate.
At Week 24, 45% of the 8 mg/kg tocilizumab-methotrexate group, 39% of the 8 mg/kg tocilizumab-placebo group, and 15% of the placebo-methotrexate had achieved remission (p<0.0001), defined as Disease Activity Score 28-erythrocyte sedimentation rate below 2.6.
By Week 52, patients on 8 mg/kg tocilizumab-methotrexate also had greater improvement in disease progression and function than patients who took placebo only.
Clinical efficacy with 8 mg/kg tocilizumab only and with 4 mg tocilizumab-methotrexate was at least equivalent to that of methotrexate for improving functions and symptoms and slowing joint damage.
“Our findings suggest that synergy between IL-6 inhibition and methotrexate action, rather than higher serum drug levels, drives the higher clinical response observed with (tocilizumab-methotrexate),” the researchers write.
“Although 8 mg/kg (tocilizumab-methotrexate) is the most effective treatment, both 4 mg/kg (tocilizumab-methotrexate) and 8 mg/kg (tocilizumab) monotherapy represent good alternative treatments for subsets of patients, such as those unable to tolerate (methotrexate) or the higher 8 mg/kg dose because of contraindications or adverse reactions,” they add.
The researchers plan to observe the patients for up to two years of blinded treatment to investigate outcomes and long-term safety in early RA patients.
Dr. Burmester was not available for an interview by press time.
Roche funded this research. Five coauthors reported relevant relationships.