SAN DIEGO, CA—Based on the final 10-year results of the PREMIER trial, adalimumab with or without methotrexate maintained effective disease control for up to 10 years in patients with early, aggressive rheumatoid arthritis (RA), reported study investigators at the 2013 ACR/ARHP Annual Meeting.
The PREMIER trial demonstrated the superiority of initial adalimumab plus methotrexate vs. the individual monotherapies in MTX-naïve patients with early, aggressive RA.
Edward C. Keystone, MD, of the University of Toronto, Toronto, Ontario, Canada, and his team conducted a post hoc analysis to assess long-term outcomes in patients treated with adalimumab, with or without methotrexate, for up to 10 years.
Patients who completed the 2-year blinded study were eligible to receive open-label adalimumab for up to an additional 8 years, with methotrexate added at the investigator’s discretion. The 28-joint disease activity score (DAS28) was used to determine the percentages of patients in clinical low disease activity (DAS28[CRP] <3.2) or remission (DAS28[CRP] <2.6) over the course of the trial. Physical function was determined through the disability index of the health assessment questionnaire (HAQ-DI). Radiographic progression (change from baseline in modified Total Sharp Score [mTSS]) was assessed in 10-year completers with radiographic data available at baseline and at Year 10.
Of the 799 patients randomized, 497 patients (62%) entered the open-label extension and 250 (31%) maintained the open-label adalimumab ± methotrexate through Year 10. Methotrexate co-therapy was reinitiated in 261 patients (53%) during the open-label extension.
Researchers found that patients completing 10 years of therapy continued to demonstrate effective disease control (mean DAS28=2.4; mean HAQ-DI=0.6; mean ∆mTSS=7.8). Although the addition of open-label adalimumab ± methotrexate to the initial methotrexate and adalimumab arms at Year 2 led to increases in the proportions achieving DAS28(CRP) <2.6 and HAQ-DI <0.5 over time, differences between initial treatment arms persisted through Year 10.
Further, ΔmTSS remained significantly lower over time in the initial adalimumab + methotrexate arm compared with the 2 monotherapy arms (ΔmTSS =4.0, 11.0, and 8.8 at Year 10 for the initial adalimumab + methotrexate, methotrexate, and adalimumab arms, respectively; both P<0.05), despite open-label adalimumab ± methotrexate slowing progression similarly in each of the arms.
“Patients initially randomized to adalimumab + methotrexate during the 2-year double-blind period demonstrated better radiographic outcomes that persisted in 10-year completers,” Dr. Keystone concluded. No new safety findings were observed.