Certolizumab pegol used with methotrexate is beneficial for treating patients with early active rheumatoid arthritis and poor prognostic factors who have not previously been treated with disease-modifying anti-rheumatic drugs, according to the C-EARLY trial. This finding was presented at the American College of Rheumatology Annual Meeting, San Francisco, CA, November 7-11.
Furthermore, a post hoc analysis of the C-EARLY data shows patients who fail to experience improvements by week 12 are unlikely to achieve remission at week 52.
“In line with treat-to-target recommendations, these data show that week 12 is an appropriate decision point at which to assess patient outcomes,” stated the investigators.
Certolizumab pegol (CZP), a Fab fragment humanized monoclonal antibody directed against tumor necrosis factor alpha (TNF-alpha), is currently recommended for moderate to severe active rheumatoid arthritis (RA) after failure of at least two conventional non-biological therapies, including methotrexate (MTX).
The C-EARLY trial, led by Michael Weinblatt from Brigham and Women’s Hospital in Boston, MA, set out to explore the effectiveness of CZP in MTX naïve patients.
In the phase 3 double-blind study, 879 patients, with active RA <1 year disease duration and poor prognostic factors were randomized 3:1 to CZP + MTX (n=655) or placebo + MTX (n=213). MTX was initiated at 10 mg/week and increased up to 25 mg/week by week 8. Patients who could not tolerate more than 15 mg/week MTX by week 8 were withdrawn.
Altogether, 500 patients completed the CZP + MTX arm and 143 completed the placebo + MTX arm.
The primary endpoint of sustained remission (defined as DAS28 (ESR) <2.6 at week 40 sustained to week 52) was achieved in 28.9% of CZP + MTX patients versus 15% of placebo + MTX patients (odds ratio (OR) 2.3; p<0.001).
Additionally, the secondary endpoint of sustained low disease activity [defined as DAS28 <3.2 at week 40 sustained to week 52] was achieved in 43.8% of CZP + MTX patients versus 28.6% of placebo + MTX patients (OR 2.0; p<0.001). Combination treatment also delivered greater improvements in physical function and radiographic outcomes at week 52 (P<0.001 for both).
The safety profile of CZP + MTX was similar to placebo + MTX, although the rate of infections was higher for CZP + MTX than placebo + MTX (71.8 versus 52.7/ 100 patient-years). The two arms were similar for serious infections (3.3 versus 3.7/ 100 patient years).
The C-EARLY trial, Weinblatt commented, is the first large randomized trial to explore sustained remission over 12 weeks. “It showed that a statistically significant and clinically relevant proportion of patients (in the CZP + MTX arm) achieved sustained remission,” he said.
In a post hoc analysis of the C Early data, also reported at the meeting, Weinblatt and colleagues found that patients receiving CZP + MTX who by week 12 had not achieved DAS28 improvements of >0.6 were 92% likely not to achieve remission by week 52. Patients who did not achieve DAS 28 improvements of >1.2 points were 93% likely not to be in remission by week 52.
In contrast, patients who did achieve an improvement from baseline in DAS28 (ESR) of >0.6 had a 45% chance of achieving remission at week 52, while those who achieved greater than 1.2 had a 49% chance of being in remission.
Dr. Weinblatt commented: “The response to treatment is not drug related; it is patient related. It is important to know if someone will obtain the disease hurdle. If no response is apparent by week 12, there is no shortage of other options.”
In the second dose withdrawal part of the C-EARLY trial (currently ongoing) patients who achieved sustained remission with CZP at 52 weeks are being re-randomized to varying reduced doses of CZP or being withdrawn altogether from CZP. The results will be available in 2016.