Journal Article

The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression

Eguchi, Katsumi, Yasuda, Shinsuke, Kita, Yasuhiko, Takeuchi, Tsutomu, Yamanaka, Hisashi, Okada, Toshiyuki, Matsubara, Tsukasa, Tanaka, Yoshiya, Yamamoto, Kazuhiko, Shoji, Toshiharu, van der Heijde, Désirée, Ishiguro, Naoki, Origasa, Hideki, Watanabe, Akira, Iwamoto, Masahiro, Atsumi, Tatsuya, Miyasaka, Nobuyuki, Koike, Takao, Yamanishi, Yuji

2016

Overview

ObjectivesTo evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone.MethodsMTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52.Results316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX.ConclusionsIn MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients.Trial registration number(NCT01451203).

• Publisher: Elsevier Limited,BMJ Publishing Group
• Subject: Adult / Antibiotics / Antibodies - blood / Antirheumatic Agents - adverse effects / Antirheumatic Agents - therapeutic use / Arthritis, Rheumatoid - blood / Arthritis, Rheumatoid - diagnostic imaging / Arthritis, Rheumatoid - drug therapy / Blood Sedimentation / Boolean / Certolizumab Pegol - adverse effects / Certolizumab Pegol - therapeutic use / Clinical and Epidemiological Research / Clinical medicine / Disease / Double-Blind Method / Drug dosages / Drug Therapy, Combination - adverse effects / Female / Humans / Male / Methotrexate - adverse effects / Methotrexate - therapeutic use / Middle Aged / Patients / Peptides, Cyclic - immunology / Prognosis / Radiography / Remission (Medicine) / Remission Induction / Rheumatoid arthritis / Rheumatoid Factor - blood / Rheumatology / Severity of Illness Index / Treatment Outcome / Tumor necrosis factor-TNF