Treatment of disease-modifying antirheumatic drug (DMARD)-naïve patients with early, active rheumatoid arthritis (RA) with certolizumab pegol (CZP) and dose-optimized methotrexate (MTX) resulted in higher rates of remission, sustained low disease activity, improved physical function, and inhibited structural damage, when compared to those treat with only MTX and placebo.
In the Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Certolizumab Pegol in Combination With Methotrexate in the Treatment of DMARD-naïve Adults With Early Active Rheumatoid Arthritis trial (“C-EARLY”, ClinicalTrials.gov Identifier NCT01519791) investigators evaluated the efficacy and safety of CZP+MTX compared with placebo and measure rates of remission and disease activity among patients with moderate-to-severe active, progressive RA.
“There is a positive benefit-risk ratio associated with CZP treatment in combination with MTX as initial therapy in DMARD-naïve patients within a year of diagnosis of severe, active RA,” the authors of the study wrote. “The beneficial effect of earlier treatment with biologics specifically in patients with poor prognostic factors may be an important consideration in determining the timing of treatment initiation in specific subgroups of patients.”
Patients were randomly assigned to receive CZP+MTX (n=660) or placebo with MTX (n=219). All patients were DMARD-naïve and had active RA for ≤1 year. The researchers measured sustained remission and sustained low disease activity at 40 weeks and 52 weeks.
After 52 weeks, more patients in the CZP+MTX group achieved sustained remission compared with placebo (28.9% vs 15.0%; P<.001). Patients in the CZP+MTX group also more frequently achieved sustained low disease activity (43.8% vs 28.6%; P<.001).
The results revealed significantly more inhibition of radiographic progression and improvements in physical functioning in CZP+MTX compared with placebo. Incidence of adverse events was similar between the 2 groups, although there was a higher rate of infection in the CZP+MTX group (71.8 per 100 patient-years vs 52.7 per 100 patient-years).
The rate of serious infection was also similar between CZP+MTX (3.3 per 100 patient-years) and placebo (3.7 per 100 patient-years).
“Overall, the results from C-EARLY suggest that it is possible to achieve [sustained remission] more frequently with combined CZP+MTX treatment than with MTX alone in DMARD-naïve patients with RA,” they wrote.
Summary and Clinical Applicability
DMARD-naive patients with early, active RA and poor disease prognostic factors who took CZP with dose-optimized MTX had higher rates of remission and low disease activity as compared to those taking only MTX.
The researchers concluded that there was a positive benefit-risk ratio associated with CZP+MTX as initial therapy for patients with acute RA. They also recommend that future studies consider the timing of treatment initiation when studying specific subgroups of patients.
“An aggressive combination of CZP with a ‘treat-to-tolerance’ strategy for MTX at an early stage of disease may contribute to overcome the currently perceived ‘efficacy ceiling’ for anti-TNFs,” the authors noted.
Limitations and Disclosures
The rates of sustained remission observed in the CZP+MTX arm (28.9%) were lower than those initially estimated from previous trials. However, the authors note that sustained remission is a more rigorous endpoint than clinical remission. The authors also note that one death occurred during the trial, caused by cardiorespiratory failure and acute respiratory distress syndrome. The patient was later diagnosed with a disseminated mycobacterium infection.
Emery P, Bingham CO, Burmester GR, et al. Certolizumab pegol in combination with dose-optimized methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomized, double-blind, placebo-controlled phase III study. Ann Rheum Dis. 2016; Published online ahead of print May 10, 2016. doi: 10.1136/annrheumdis-2015-209057.