Date: 2016-03-24
Type of information: Results
phase: 4
Announcement: results
Company: UCB (Belgium)
Product: Cimzia® (certolizumab pegol)
Action mechanism:
Disease: rheumatoid arthritis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country: Australia, Austria, Bulgaria, Canada, Czech Republic, France, Germany, Greece, Hungary, Ireland, Italy, Mexico, Monaco, Poland, Portugal, Romania, Spain, Switzerland, UK, USA
Trial
details: Exxelerate was a Phase 4, 24-month (104-week) randomized, single-blind, parallel-group, head-to-head superiority study. The study was designed to evaluate the short- and long-term efficacy of certolizumab pegol (CZP) compared with adalimumab (ADA), both in combination with methotrexate (MTX), in the treatment of moderate to severe RA patients who have not responded adequately to MTX.
The primary endpoints of the study were the percentage of patients with an ACR20 response at Week 12 (i.e., 20% improvement in tender or swollen joint counts and a 20% improvement in at least three of the other five criteria: patient assessment, physician assessment, pain scale, disability/functional questionnaire, and acute phase reactant) and the percentage of patients who achieved low disease activity (DAS28[ESR] ?3.2) at Week 104.
Biologic-naïve patients (n=915) with moderate to severe RA and an inadequate response to MTX, were randomly assigned at baseline (Week 0) in a 1:1 ratio to receive either:
A standard loading dose regimen of CZP 400 mg at Weeks 0, 2 and 4 + MTX, followed by CZP 200 mg Q2W + MTX.
ADA 40 mg Q2W + MTX, with placebo also given at Weeks 0, 2 and 4 to maintain blinding
MTX dosing was maintained at 15–25 mg/week orally or subcutaneously, with one dose adjustment permitted between Week 12 and Week 52, and a one dose adjustment permitted between Week 52 and Week 104. For patients unable to tolerate MTX at these doses, MTX dose could be reduced to 10 mg/week after Week 12.
At Week 12, patients were categorized as responders, if they achieved low disease activity (LDA), defined as DAS28(ESR) ?3.2 or had a DAS28(ESR) change from baseline (CFB) reduction ?1.2.
Patient response at Week 12 determined what treatment they received from this point onwards. Week 12 responders continued with their initial treatment through to Week 104. Week 12 non-responders switched treatment, either from CZP to ADA or vice versa, depending on their initial randomised treatment. At Week 24, subjects achieving LDA defined as DAS28(ESR). (NCT01500278)
Latest
news: * On March, 24, 2016, UCB announced top-line results from EXXELERATE, the first head-to-head superiority study of two treatments in the anti-TNF class, comparing Cimzia® (certolizumab pegol) plus methotrexate (MTX) to Humira® (adalimumab) plus MTX in adult patients with moderate to severe rheumatoid arthritis (RA) who are inadequate responders to MTX. The primary endpoints for superiority were not met, as results between Cimzia® and Humira® were numerically comparable showing the percentage of patients achieving an ACR20 response at three months were 69.2 percent versus 71.4 percent, respectively, and percentage of patients achieving a state of low disease activity (LDA) at two years were 35.5 percent versus 33.5 percent, respectively.
For the study population (n=915), preliminary safety analysis across two years showed that overall safety, including serious adverse events and serious infections, was comparable between agents. Patients not responding to initial treatment at three months were switched to receive immediate treatment with the other agent without a wash-out period between treatments (patients switching from Humira® to Cimzia® received the loading dose of Cimzia®). No serious infectious events occurred in patients changing therapy during the period following the change when a patient is exposed, due to drug half-lives, to both agents (70 days). Reflective of stringent clinical trial processes and application of proper screening to prevent reactivation of tuberculosis (TB), a single case of TB infection occurred during the 2 year study. Data from this study will be submitted for presentation at upcoming congresses and in peer-reviewed medical journals.
