Safety of extended treatment with anakinra in patients with rheumatoid arthritis

Objective: To determine the safety profile of anakinra after extended exposure in a diverse clinical trial population of patients with rheumatoid arthritis. Methods: A six month, randomised, double blind phase comparing anakinra ( 100 mg/day) with placebo was followed by open label anakinra treatment for up to three years in patients with rheumatoid arthritis. Concomitant non-steroidal anti-inflammatory drugs, corticosteroids, and other disease modifying antirheumatic drugs were permitted. Results: In all 1346 patients with rheumatoid arthritis received anakinra for up to three years. Patients had varying levels of disease severity, concomitant drug use, and comorbid conditions. Cumulative, exposure adjusted event ( EAE) rates for all adverse events ( AEs), serious AEs, and deaths were similar during each year of anakinra treatment; the overall rate ( 0 to 3 years) was similar to that observed for controls during the blinded phase. The most frequent AEs were injection site reactions ( 122.26 events/100 patient-years), rheumatoid arthritis progression ( 67.80 events/100 patient-years), and upper respiratory infections ( 26.09 events/100 patient-years). The EAE rate of serious infections was higher for patients treated with anakinra for 0 to 3 years ( 5.37 events/100 patient-years) than for controls during the blinded phase ( 1.65 events/100 patient-years). However, if the patient was not receiving corticosteroid treatment at baseline, the serious infection rate was substantially lower ( 2.87 event/100 patient-years). The overall incidence of malignancies was consistent with expected rates reported by SEER. Neutralising antibodies developed in 25 patients, but appeared to be transient in 12; neutralising antibody status did not appear related to occurrence of malignancies or serious infections. There were no clinically significant trends in laboratory data related to anakinra. Conclusion: Anakinra is safe and well tolerated for up to three years of continuous use in a diverse population of patients with rheumatoid arthritis.