ABSTRACT
Introduction: Interleukin 1 (IL-1) induced proinflammatory signals were discovered as a causative aetiology in a spectrum of diseases. Efficacy and safety of the recombinant IL-1 receptor antagonist anakinra across autoinflammatory and autoimmune diseases has been demonstrated in many studies. Despite the recommended dosage in patients above 8 months and weighing more than 10 kg, use of higher doses or earlier onset of therapy have been occasionally reported. Objectives: To an institutional review of data on efficacy, safety and tolerance of anakinra in patients with autoinflammatory diseases (AID). Methods: A single-centre retrospective review of electronic records of patients treated with anakinra between August 2007 and May 2021. Results: A total of 47 patients (30 children, 17 adults) were identified. The median follow-up was 35 months (range 1-165 months). Patients have been treated for diagnosis of systemic juvenile idiopathic arthritis (sJIA) (n = 18;38%), cryopyrinopathy (CAPS) (n = 10;21%), mevalonate-kinase deficiency (MKD) (n = 7;15%), undifferentiated AID (uAID) (n = 6;13%), PIMS-TS (n = 3;6%), NLRC4-GOF (n = 1, 2%), PAPA syndrome (n = 1;2%) and polyarticular JIA (n = 1, 2%). The most frequent indication for starting anakinra was macrophage activation syndrome (MAS) (n = 20;42,5%) which occurred in patients with sJIA (n=14, 70%), uAID (n=3, 15%), PIMS (n=1, 5%), NLRC4-GOF (n=1, 5%) or polyarticular JIA (n=1, 5%). Fourteen patients with sJIA (78%) received anakinra due to macrophage activation syndrome. MAS was the first manifestation of sJIA in 6 patients (33%). Recommended dosing of anakinra (1-4 mg/kg/day) was exceeded in 44,6% of patients (n=21) with the following dose range: 4-6 mg/kg (n = 8;38%), 6-9,9mg/kg (n = 4;19%), ≥10 mg/kg (n = 9;43%). Paediatric cohort received anakinra in very wide dosing range of 1,4 -26,1 mg/kg (average 5,59 mg/kg, median 4,15 mg/kg). The highest dose (10-26mg/kg) was required by patients with uAID (n=1, 8 days of age), sJIA/MAS (n=2, 3 and 5 years of age), CINCA (n=1, 4 years of age) and NLRC4-GOF (n=1, 4 weeks of age). The median dose of anakinra in adult patients was 1,6 mg/kg (range 0,9-7,7mg/kg). In severely sick patients the daily dose was divided into 2-4 intravenous applications, one patient received continuous anakinra i.v. infusion. Rapid therapeutic effect (within 24-48 hours from starting anakinra) was observed in all patients. The most frequent recorded adverse effects were already well-known injection-site reaction in 25,5% (n = 12) of patients which disappeared within one month in all of them. Persistent eosinophilia (highest values 3,6 and 2,3x10 ∗9 cells) was documented in 2 sJIA patients. Mild asymptomatic neutropenia (ANC min 0,8 x10 ∗9/L) and transient liver transaminase elevation (up to 3-times ULN) both occurred in 4,2% (n = 2) of patients each. Conclusion: Use of anakinra in a wide dosing range was reported. Our observation illustrates the need as well as safety of higher anakinra dosing in younger age groups including 2 newborns. No serious adverse effects that would require discontinuation or termination of anakinra were observed at all dosing regimens.