Study results show treatment with certolizumab pegol and methotrexate produced significant symptom improvement in patients with rheumatoid arthritis.
Because joint damage progression in rheumatoid arthritis (RA) is rarely reversible, early and effective treatment is essential. Current treatment guidelines agreed upon by European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) recommend that RA patients be treated with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) from the point of diagnosis, with the possible addition of methotrexate (MTX) unless contraindicated. Early diagnosis and intervention increases the chance of preventing joint damage progression, which can make a huge difference in a patient’s quality of life.
The recent trend in RA treatment and research is the use of biological agents that target inflammatory cytokines such as tumor necrosis factor (TNF), which play key roles in the pathogenesis of rheumatoid arthritis. These treatments have been shown to inhibit the progression of joint damage. A new study from Japan published in The Annals of Rheumatic Diseases further posits that certolizumab pegol (CZP), a humanized anti-TNF antibody fragment conjugated to polyethylene glycol, showed significant radiographic progression relative to placebo plus MTX.
Named C-OPERA, the study was double-blind for 1 year, with either CZP or placebo administered concomitantly with MTX. It was designed to include MTX-naïve, early RA patients with poor prognostic factors. Eligible patients were 20—64 years old with RA who had less than 12 months of persistent arthritic symptoms, and who were MTX-naïve. Patients with high risk of infection or history of/active tuberculosis or malignancy, and patients previously exposed to MTX, leflunomide or biological DMARDs were excluded. Co-administration of any DMARD except MTX was prohibited during the study.There was no study arm that measured CZP monotherapy.
Efficacy of the treatment was measured by inhibition joint damage progression, and secondary efficacy endpoints included clinical remission rates, assessed by ACR/EULAR criteria (Simple Disease Activity Index (SDAI)-based and Boolean-based) and DAS28 (ESR) at weeks 24 and 52. Higher ACR/EULAR remission rates were observed with CZP+MTX compared with placebo + MTX. Similarly, DAS28 (ESR) remission rates at week 24 were approximately 20% higher with CZP+MTX than placebo +MTX (52.8% vs. 30.6%; p<.001).
Adverse events in the C-OPERA study—including organ infections, gastrointestinal disorders, and hepatobiliary disorders—were more frequently observedthan in a similar Japanese trial, perhaps due to the increased dosage of MTX over what was used in the previous study. But overall, the authors note, safety results in both the CZP + MTX group and the placebo + MTX groups were similar, with no new safety signals observed with addition of CZP.“These efficacy and safety findings from C-OPERA in MTX-naive early RA suggest that CZP could be used as possible first-line treatment concomitantly with MTX in patients with poor prognostic factors,” noted the study authors.