Anakinra in Paediatric Rheumatology and Periodic Fever Clinics: Is the Higher Dose Safe?

Abstract

ObjectiveAnakinra has been increasingly used in off-label indications as well as dosing and mode of administration in a variety of inflammatory conditions. We aimed to review our clinical practice and compare treatment outcomes with published data.MethodsClinical data from electronic records were retrospectively reviewed for patients treated with anakinra over the past 6 years for autoinflammatory diseases (AID).ResultsFrom 47 eligible patients (27 female patients), 32 were children. Macrophage activation syndrome (MAS) was the indication for anakinra therapy in 42.6% of patients. Systemic juvenile idiopathic arthritis (SJIA) was the most common underlying diagnosis (19/47) followed by the spectrum of AID. Off-label use was noted in 38.3% patients. Recommended dose was exceeded in 21 children (mean induction dose 5.1, highest dose 29.4 mg/kg/day) and two adults; five patients were treated intravenously. The mean treatment duration for SJIA was 1.4 years, that for AID was 2.2 years, and that for patients with higher anakinra dose was 9.7 (19.3) months. The mean follow-up duration was 2.7 (1.7) years. Treatment was effective in the majority of SJIA and cryopyrinopathy patients as well as those with MAS. Anakinra was well-tolerated without any major adverse effects even in patients with long-term administration of higher than recommended doses including two infants treated with a dose of over 20 mg/kg/day.ConclusionOur results support early use of anakinra in the individually tailored dosing. In patients with hyperinflammation, anakinra may be lifesaving and may even allow for corticosteroid avoidance. Further studies are needed in order to set up generally accepted response parameters and define condition-specific optimal dosing regimen.

Patient Experiences and Challenges in the Management of Autoinflammatory Diseases—Data from the International FMF & AID Global Association Survey

“…Individual patients may tolerate or respond differently to the various preparations [ 7 , 8 , 9 , 10 , 11 ]. However, certain patients may not tolerate or respond effectively to colchicine and, therefore, require alternative treatments such as IL-1 targeting agents [ 13 , 14 , 15 , 16 ]. Patients requiring biological drugs often encounter accessibility challenges, such as physicians refusing to prescribe medications due to high costs, insurance companies not approving biological medications, limited approval (only a small number of patients are allocated to receive medication), or the drugs not being available in the patient’s country of residence.…”

“…Interleukin (IL)-1 inhibitors such as anakinra, canakinumab, and rilonacept are effective in the treatment of many different AIDs [ 6 , 7 , 8 , 9 , 10 ]. However, these biological drugs are not available in all countries, making effective disease control difficult [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

Use of Continuous Intravenous Anakinra Infusion in Multisystem Inflammatory Syndrome in Children

“…Schmitz et al's study shows that the blockage of IL-1 has been associated with the reversal of acute lung injury in avian influenza [ 23 ]. Fingerhutová et al's study demonstrated that aggressive therapy of MAS using continuous IV anakinra infusions in higher doses successfully reverses the cytokine storm, especially in the pediatric population [ 24 ]. In the case of our patient, treatment with different modalities like upgrading antibiotics, two courses of corticosteroid, IVIG, and SQ with IV push of anakinra did not provide clinical improvement immediately.…”