Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up

• Published in: JAMA : the journal of the American Medical Association 2011-04, Vol.305 (14), p.1460-1468
• Main Authors: Bartelds, Geertje M, Krieckaert, Charlotte L. M, Nurmohamed, Michael T, van Schouwenburg, Pauline A, Lems, Willem F, Twisk, Jos W. R, Dijkmans, Ben A. C, Aarden, Lucien, Wolbink, Gerrit Jan
• Format: Article
• Language: English
• Subjects: Adalimumab; Adult; Aged; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibody Formation; Antirheumatic Agents - immunology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Clinical outcomes; Female; General aspects; Humans; Immunology; Male; Medical sciences; Middle Aged; Monoclonal antibodies; Prospective Studies; Remission Induction; Rheumatoid arthritis; Treatment Failure
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2011.406

CONTEXT Short-term data on the immunogenicity of monoclonal antibodies showed associations between the development of antidrug antibodies and diminished serum drug levels, and a diminished treatment response. Little is known about the clinical relevance of antidrug antibodies against these drugs during long-term follow-up. OBJECTIVE To examine the course of antidrug antibody formation against fully human monoclonal antibody adalimumab and its clinical relevance during long-term (3-year) follow-up of patients with rheumatoid arthritis (RA). DESIGN, SETTING, AND PATIENTS Prospective cohort study February 2004-September 2008; end of follow-up was September 2010. All 272 patients were diagnosed with RA and started treatment with adalimumab in an outpatient clinic. MAIN OUTCOME MEASURES Disease activity was monitored and trough serum samples were obtained at baseline and 8 time points to 156 weeks. Serum adalimumab concentrations and antiadalimumab antibody titers were determined after follow-up. Treatment discontinuation, minimal disease activity, and clinical remission were compared for patients with and without antiadalimumab antibodies. RESULTS After 3 years, 76 of 272 patients (28%) developed antiadalimumab antibodies—51 of these (67%) during the first 28 weeks of treatment. Patients without antiadalimumab antibodies had much higher adalimumab concentrations (median, 12 mg/L; IQR, 9-16 mg/L) compared with patients with antibody titers from 13 to 100 AU/mL (median, 5 mg/L; IQR, 3-9 mg/L; regression coefficient, −4.5; 95% CI, −6.0 to −2.9; P