The safety of anakinra in high‐risk patients with active rheumatoid arthritis: Six‐month observations of patients with comorbid conditions

Abstract

Objective. To determine in a placebo-controlled, double-blind trial the safety profile of daily anakinra (Kineret) use in patients with active rheumatoid arthritis (RA) and concurrent comorbid conditions.Methods. In 169 centers in 9 countries, 1,414 patients with active RA were randomly assigned to receive either anakinra (100 mg) or placebo treatment (4:1 anakinra-to-placebo allocation ratio), with study drug administered by daily subcutaneous injection for 6 months. The current post hoc analysis assessed baseline comorbid conditions, and patients were considered at high risk for the occurrence of adverse events if they had a history of at least one of the following: cardiovascular event, pulmonary event, central nervous system-related event, infection, diabetes, malignancy, or renal impairment. Within each treatment group (anakinra or placebo), incidence rates were summarized for serious adverse events, infectious events, and serious infectious events in high-risk patients and compared with these incidence rates in patients without comorbid conditions.Results. The majority of patients in the trial had one or more comorbid conditions. In these high-risk patients, there were no differences in the incidence of serious adverse events or infectious events between treatment groups. The incidence of serious infectious events with anakinra use was similar between high-risk patients (2.5%) and the entire study population (2.1%) and was not attributable to any single comorbidity. Conclusion.Results of the analysis of adverse events in patients with active RA and coexisting comorbidities suggest that the favorable safety profile of anakinra is maintained in a high-risk patient population.

Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet's disease

“…Though IL-1 appears to be involved in the delayed hypersensitivity to Mtb, this cytokine does not appear to play a key role in the control of Mtb infection, thus explaining the little or absent risk of developing tuberculosis in patients treated with anti-IL-1 agents [85]. Notably, anakinra has been used on a large number of patients with several diseases (7964 with rheumatoid arthritis, 216 with juvenile idiopathic arthritis, 35 with adultonset Still's disease, and -more recently -in different autoinflammatory diseases and in gout) without showing cases of active tuberculosis [87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106]. Furthermore, data from a Canadian registry have disclosed that the use of biological and traditional disease-modifying antirheumatic drugs is associated with an increased risk of developing tuberculosis in patients with rheumatoid arthritis, mainly among noncurrent users of corticosteroids [107].…”

Cryopyrinopathies: update on pathogenesis and treatment

“…The safety and tolerability of this drug has been established in patients with arthritis, and it has been extensively used to treat patients with rheumatoid arthritis. 46,47 Treatment of familial cold autoinflammatory syndrome and Muckle-wells syndrome with anakinra Anakinra was first used to treat two adult patients with a MWS phenotype; the drug was given daily by subcutaneous injection at a dose of 100 mg. The efficacy of this treatment was remarkable: all inflammatory symptoms (rash, fever and arthralgia) ceased a few hours after the first injection, and serum amyloid A protein levels normalized in a few days.…”

Der Zusammenhang zwischen rheumatoider Arthritis und Krebs

“…In vorläufigen Studien zur Sicherheit erwies sich der IL-1-Rezeptor-Antagonist Anakinra als nicht mit einem erhöhten Malignitätsrisiko assoziiert [28]. Aber hier gilt es, weiterführende Untersuchungen dieser Substanz abzuwarten, bevor endgültige Schlüsse gezogen werden können.…”