Safety of extended treatment with anakinra in patients with rheumatoid arthritis

Abstract

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.

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

“…Infection rates in this study were low and generally consistent with other trials evaluating anakinra in adults with RA [27,30]. In a 6-month randomized, placebocontrolled, double-blind study followed by an open-label phase for up to 3 years, only 8% (n=105) of adult RA patients receiving anakinra (n=1346) experienced a serious infection, with pneumonia being the most frequent [27]. In adults, there were also three events of opportunistic infection (atypical mycobacterial infection, histoplasmosis, and candida esophagitis) occurring between 5 months to 2.5 years after initiating anakinra [27].…”

“…Infection rates in this study were low and generally consistent with other trials evaluating anakinra in adults with RA [27,30]. In a 6-month randomized, placebocontrolled, double-blind study followed by an open-label phase for up to 3 years, only 8% (n=105) of adult RA patients receiving anakinra (n=1346) experienced a serious infection, with pneumonia being the most frequent [27].…”

“…Similar to other subcutaneously administered biologics, ISRs appeared to be common with daily use of anakinra, occurred early in the trial, and resolved over time. The frequency of ISRs decreased in the double-blind period compared with the open-label phase, which is consistent with findings in adults in which ISRs were more common with the initial period of dosing and transient in duration [27]. In contrast, one patient (4%) receiving placebo experienced headache as compared with six patients (24%) who received anakinra.…”

“…In a 6-month randomized, placebocontrolled, double-blind study followed by an open-label phase for up to 3 years, only 8% (n=105) of adult RA patients receiving anakinra (n=1346) experienced a serious infection, with pneumonia being the most frequent [27]. In adults, there were also three events of opportunistic infection (atypical mycobacterial infection, histoplasmosis, and candida esophagitis) occurring between 5 months to 2.5 years after initiating anakinra [27]. In a prospective cohort study of RA patients (n=70) receiving anakinra for up to 1 year, 13% of the patients experienced an infection, two of which were considered serious [30].…”

Leukocyte Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction Treated with Anakinra

“…The unimpaired response to bacterial stimuli in leukocytes ex vivo is also consistent with the lack of opportunistic infections in patients treated with anakinra (17)(18)(19). This result is in contrast to the use of tumor necrosis factor (TNF)-α blockers, which resulted in a significant and worrisome increase in opportunistic infections, death due to overwhelming sepsis and worsening heart failure (20)(21)(22).…”