UCB has announced data that may in the future offer alternative care options for rheumatoid arthritis (RA) patients who have not been treated with disease-modifying anti-rheumatic drugs (DMARD-naïve) and who are at risk for highly progressive disease. The Phase 3 C-EARLY™ study showed the benefits, at 52 weeks, of adding Cimzia® (certolizumab pegol) to optimized methotrexate treatment.

"The C-EARLY™ study found that adding Cimzia to optimized methotrexate achieved sustained remission and low disease activity in this at risk patient population. These findings demonstrate the importance of quickly identifying RA patients who will benefit from combination therapy following RA diagnosis. The study raises the bar for long-term treatment strategies for people living with RA," said lead study author Professor Paul Emery, Professor of Rheumatology, University of Leeds, UK.

The study was designed to evaluate the efficacy and safety of certolizumab pegol in combination with optimized methotrexate (MTX) for the treatment of DMARD-naïve adult patients with early, active RA.1,2 Optimized MTX was the highest dose the patient could tolerate up to a maximum of 25mg weekly. For all patients in the study, MTX therapy was initiated with 10mg weekly and increased to 25mg after 6-8 weeks, if well tolerated. At least 15mg weekly of MTX had to be taken to remain in the study.

The study showed that, after 52 weeks, treatment with certolizumab pegol plus optimized MTX resulted in more patients in sustained remission and low disease activity, greater improvements in the signs and symptoms of rheumatoid arthritis including physical function, and inhibition of structural damage compared with optimized MTX treatment alone. No new safety signals for certolizumab pegol were reported.1

Secondary results from the C-EARLY™ study were also presented at EULAR 2015 and showed that patients treated with certolizumab pegol plus MTX had greater improvements at one year in pain, disease activity, fatigue and health related quality of life, improved workplace and household productivity, and reduced need for assistance with regular activities compared to patients receiving placebo and MTX.2

Based on the results of this study, UCB has submitted a regulatory application to the European Medicines Agency for an extension of the certolizumab pegol indication in RA to include treatment in combination with MTX for adult patients with severe active and progressive RA not previously treated with MTX or other DMARDs.

A second phase of the study is ongoing for another year to evaluate the potential of reducing certolizumab pegol maintenance dosing frequency or withdrawing certolizumab pegol in subjects who achieve sustained low disease activity in period one of the study.

Key Primary and Key Secondary Outcomes

At Week 52, treatment with certolizumab pegol plus optimized MTX compared with placebo plus optimized MTX (full analysis set: n=655 CZP and 213 MTX; radiographic analysis set: n=528 CZP and 163 PBO) resulted in significantly more patients with:

  • sustained remission (28.9% vs. 15.0%; p<0.001)1
  • sustained low disease activity (43.8% vs. 28.6%; p<0.001) 1
  • inhibition of structural damage (change from baseline in van der Heijde modified total Sharp score [mTSS]: 0.2 vs. 1.9; p<0.001)1

Significant secondary endpoints for patients receiving certolizumab pegol with optimized MTX, compared to those taking placebo with optimized MTX, included improvements in:

  • patient-reported outcomes (certolizumab pegol plus MTX: n=655; placebo plus MTX: n=213; -1.0 vs. -0.8; p<0.001 for HAQ-DI) 2
  • household productivity (certolizumab pegol plus MTX: n=640; placebo plus MTX: n=206; 3.0 vs. 1.9; p<0.01 for household work days missed per month)2

Additionally, patients receiving certolizumab pegol plus optimized MTX reported a reduced need for assistance with their usual daily activities, and employed patients taking certolizumab pegol with optimized MTX (n=351) stated greater reductions in absenteeism and presenteeism after 52 weeks.2