IL-1 BLOCKADE IN PEDIATRIC RECURRENT PERICARDITIS: A MULTICENTRIC RETROSPECTIVE STUDY ON THE ITALIAN COHORT

Abstract

Background: Acute pericarditis is an inflammatory condition causing the occurrence of pericardial effusion. In a third of patients, the disease is recurrent. Most of the cases are idiopathic or occur after a pericardial procedure. First line treatment of idiopathic pericarditis consists in NSAIDs and colchicine; glucocorticoids represent the second line treatment in resistant or intolerant cases. The use of different biologics and immunosoppressant has been reported, with variable responses. A recent clinical trial has enlightened the effectiveness of anakinra in patients with colchicine-resistant recurrent pericarditis. Objectives: To describe the clinical characteristics and response to treatment in a cohort of paediatric patients with recurrent pericarditis treated with IL inhibitors. Methods: Pediatric patients with recurrent pericarditis followed at 19 Italian centers of paediatric rheumatology or cardiology and treated with IL1 inhibitors were included in the study. Demographic, clinical and response to treatment data were retrospectively collected. Results: 55 patients were included in the study. The mean age at onset of the first episode of pericarditis was 12.53 years. The mean number of relapses of pericarditis before the beginning of treatment with IL1 inhibitors was of 3.4. 53 out of 55 patients had previously received treatment with NSAIDS and 44 colchicine. 44 patients received steroidal treatment: 2 of them displayed a steroidal-resistance and 39 steroidal-dependence with reoccurrence of the symptoms following any attempt to reduce or withdraw this treatment. Anakinra (mean dosage of 1.67 mg/kg/day) was used as first Il-1 inhibitor in 54 of the 55 patients, Canakinumab (150 mg every 4 weeks) in one. 53 out of 54 patients treated with anakinra displayed a complete clinical response to treatment within a mean of 2 days: NSAIDs, glucocorticoids and colchicine were withdraw in 25 out of 26, 31 out of 35 and 15 out of 32 patients respectively. 50 of 54 patients displayed a complete response; among these, three were switched to Canakinumab, 17 patients continued treatment at the same dosage while in 30 patients a reduction of treatment was attempted. 12 patients presented, during anakinra tapering, a disease flare, promptly resolved after an increasing of the dosage. The remaining 18 patients did not present any flare despite the reduction of the drug. Anakinra was withdrawn in 16 patients, with recurrence of the symptoms in 11 (9 restarted anakinra, 2 were treated with glucocorticoids and colchicine, with good response). 5 patients were treated with Canakinumab: 1 as first anti-IL1 drug, 4 were switched from anakinra (two for poor compliance, one for side effects and one for incomplete control of the disease). 2 out of five patients had a complete control of the diseases, 2 patients discontinued the treatment because of inefficacy and 1 patient required low dose of glucocorticoids to control the disease. At last follow-up 34 patients were on anakinra, 7 on anakinra and colchicine, 2 on canakinumab, 1 on canakinumab plus colchicine and NSAIDs. In 9 patients all treatments were withdrawn for complete control of the disease. Conclusion: This study confirm the effectiveness of IL-1 blockade in paediatric patients with recurrent pericarditis. However, most of the patients require prolonged treatment to maintain clinical remission. Moreover, in our cohort of patients the rate of response was higher for anakinra then for canakinumab, suggesting a possible role of IL1a in the pathogenesis of this condition.