As Dr. Paul Emery of the University of Leeds, UK, explains in an email to Reuters Health, “This study used a unique endpoint of sustained low disease activity . . . and compared background methotrexate with either certolizumab or placebo.”
For the study, online May 26 in the BMJ, Dr. Emery and colleagues randomized 660 patients to the combination and 219 to methotrexate and placebo; 500 in the certolizumab group and 143 in the placebo group completed the study.
All patients were naive to disease-modifying anti-rheumatic drugs (DMARDs) and had had active RA for no more than a year. Oral methotrexate was initiated at 10 mg per week and was escalated, if tolerated, to a maximum of 25 mg per week by Week 8.
The mean maximum-tolerated dose of methotrexate achieved by Week 8 was 21 mg per week for the certolizumab group and 22 mg per week for the placebo and methotrexate group.
At Week 52, significantly more patients in the certolizumab group achieved sustained remission (28.9% vs. 15.0%) and sustained low disease activity (43.8% vs. 28.6%).
Inhibition of radiographic progression and improvements in physical functioning by a variety of measures were also significantly greater in the certolizumab group.
The incidence of adverse events was similar for both treatment arms.
The greatest response to the combination “for almost all endpoints,” say the researchers, was seen in the 75.9% of patients in whom four months or less had passed since RA diagnosis.
The study, Dr. Emery continued, “showed that there was a 50% increase in sustained low-disease activity in the certolizumab group, and this resulted in improved function and better inhibition of structural damage compared to placebo.”
In light of these findings, the researchers conclude that “an aggressive combination of certolizumab with a ‘treat-to-tolerance’ strategy for methotrexate at an early stage of disease may contribute to overcome the currently perceived ‘efficacy ceiling.'”
Commenting on the findings by email, rheumatologist Dr. Glen Hazlewood of Calgary, Canada, tells Reuters Health, “The study adds data for methotrexate plus certolizumab being superior to methotrexate alone for initial treatment. The size of the effects for clinical response (symptom improvement) are similar to what we see in other DMARD-naive trials with other biologics (this study was included in our recent BMJ network meta-analysis).”