Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial

• Published in: Annals of the rheumatic diseases Vol. 68; no. 6; pp. 797 - 804
• Main Authors: Smolen, J, Landewé, R B, Mease, P, Brzezicki, J, Mason, D, Luijtens, K, van Vollenhoven, R F, Kavanaugh, A, Schiff, M, Burmester, G R, Strand, V, Vencovský, J, van der Heijde, D
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2009; BMJ Publishing Group; BMJ Publishing Group LTD
• Series: Extended report
• Subjects: Adult; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Arthrography; Biological and medical sciences; Blood Coagulation - drug effects; Bones, joints and connective tissue. Antiinflammatory agents; Certolizumab Pegol; Clinical and Epidemiological Research; Diseases of the osteoarticular system; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunoglobulin Fab Fragments - administration & dosage; Immunoglobulin Fab Fragments - adverse effects; Immunoglobulin Fab Fragments - therapeutic use; Immunoglobulins; Immunomodulators; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Inflammatory joint diseases; Male; Medical sciences; Medicin och hälsovetenskap; Methotrexate; Methotrexate - administration & dosage; Methotrexate - therapeutic use; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - adverse effects; Polyethylene Glycols - therapeutic use; Quality of life; Rheumatoid arthritis; TNF inhibitors; Treatment Outcome; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-TNF; Antineoplastic agent; Immunopathology; Toxicity; Certolizumab pegol; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease; Immunomodulator; Chronic; Rheumatoid arthritis; Antirheumatic agent; Methotrexate
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/ard.2008.101659

Background:Certolizumab pegol is a PEGylated tumour necrosis factor inhibitor.Objective:To evaluate the efficacy and safety of certolizumab pegol versus placebo, plus methotrexate (MTX), in patients with active rheumatoid arthritis (RA).Methods:An international, multicentre, phase 3, randomised, double-blind, placebo-controlled study in active adult-onset RA. Patients (n = 619) were randomised 2:2:1 to subcutaneous certolizumab pegol (liquid formulation) 400 mg at weeks 0, 2 and 4 followed by 200 mg or 400 mg plus MTX, or placebo plus MTX, every 2 weeks for 24 weeks. The primary end point was ACR20 response at week 24. Secondary end points included ACR50 and ACR70 responses, change from baseline in modified Total Sharp Score, ACR core set variables and physical function.Results:Significantly more patients in the certolizumab pegol 200 mg and 400 mg groups achieved an ACR20 response versus placebo (p⩽0.001); rates were 57.3%, 57.6% and 8.7%, respectively. Certolizumab pegol 200 and 400 mg also significantly inhibited radiographic progression; mean changes from baseline in mTSS at week 24 were 0.2 and −0.4, respectively, versus 1.2 for placebo (rank analysis p⩽0.01). Certolizumab pegol-treated patients reported rapid and significant improvements in physical function versus placebo; mean changes from baseline in HAQ-DI at week 24 were −0.50 and −0.50, respectively, versus −0.14 for placebo (p⩽0.001). Most adverse events were mild or moderate, with low incidence of withdrawals due to adverse events. Five patients developed tuberculosis.Conclusion:Certolizumab pegol plus MTX was more efficacious than placebo plus MTX, rapidly and significantly improving signs and symptoms of RA and physical function and inhibiting radiographic progression.Trial registration number:NCT00175877