The efficacy of CZP in combination with methotrexate (MTX) has been proven in patients with established RA and insufficient response to MTX alone in the pivotal RAPID1 and RAPID2 studies (the mean disease duration was ∼6 years in both trials)
Data was collected from 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 Disease Modifying Antirheumatic Drugs (DMARD)-naïve Adults With Early Active Rheumatoid Arthritis (“C-early” trials, ClinicalTrials.Gov Identifier NCT01519791).
- Subjects must have a time since diagnosis of adult-onset Rheumatoid Arthritis (RA) less than 1 year as defined by the 2010 ACR/EULAR classification criteria from Screening Visit
- Positive Rheumatoid Factor (RF) and/or positive anticyclic Citrullinated Peptide Antibody (anti-CCP)
- Active RA disease
- Subject is naïve to RA related biologics
- A diagnosis of any other inflammatory Arthritis
- History of infected joint prosthesis, or other significant infection and other serious medical condition
- Known Tuberculosis (TB) disease or high risk of acquiring TB infection
njections will be given subcutaneously. CZP 400 mg at Baseline, Week 2 and Week 4, followed by a maintenance dose of 200 mg every 2 Weeks until Week 50. The MTX treatment is to be initiated at a dose of 10 mg per Week (oral tablets at the strength of 2.5 mg/tablet). The MTX dosage should be escalated by 5 mg every 2 Weeks such that the maximum dosage of 25 mg per Week is achieved by Week 6 to Week 8. Patients who could not tolerate ≥ 15 mg/week MTX by Week 8 were withdrawn while the maximum tolerated dose per patient (optimized dose) was maintained to Week 52.
Sustained remission, defined as a Disease Activity Score [Erythrocyte Sedimentation Rate] (DAS28[ESR]) < 2.6 at Weeks 40 and 52, was the measured primary outcome defined by the trial. Sustained low disease activity (LDA), defined as DAS28[ESR] ≤ 3.2 at both Weeks 40 and 52, was designated as secondary outcome in addition to changes from baseline in Modified Total Sharp Scores (mTSS), joint erosion scores, and joint narrowing scores at week 52.
At week 52, percentage of Subjects With DAS28 [ESR] < 2.6, 2011, those meeting American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) Remission Criteria Simplified for Clinical Practice, achieving Health Assessment Questionnaire- Disability Index (HAQ-DI) ≤ 0.5, Bristol Rheumatoid Arthritis Fatigue- Multidimensional Questionnaire (BRAF-MDQ), Simplified Disease Activity Index (SDAI), Work Productivity Survey – Rheumatoid Arthritis [WPS-RA]) Clinical Disease Activity Index (CDAI) Week 52
At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): −1.00 vs −0.82, p<0.001).
Limitations and Disclosures
This study was funded by UCB Pharma.
Summary and Clinical Applicability
Emery P, Bingham CO, Burmester GR, et al. Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study. Ann Rheum Dis. 2016;