DESENSITIZATION TO ANAKINRA IN REFRACTORY RECURRENT PERICARDITIS

Introduction: Recurrent pericarditis (RP) is a possible complication of acute pericarditis (15–30%). It can be idiopathic or it can occur after a pericardial procedure (post-pericardiotomic). First line treatment consists of a combination of high-doses of NSAIDs with colchicine; corticosteroids represent the second line in resistant or intolerant cases. Different biologics and immunosoppressant have been used as third line treatment, with variable responses: by now the most promising results have been obtained with anakinra, enlightening the possible role of IL-1 in the pathogenesis of this condition. Objectives: To describe the clinical course and the outcome of desensitization procedure to anakinra in a patient with steroid- dependent pericarditis, who withdrawn anakinra for adverse reactions and did not respond to IL-1β blockade with canakinumab. Methods: A 9-years old girl started to complain with recurrent pericarditis at the age of 6 years old, after surgical correction of an atrial septal defect. NSAIDs were not effective and colchicine was withdrawn for intolerance; oral steroids were started with good response, then gradually tapered, with prompt relapse after the steroid discontinuation, requiring pericardiocentesis. The child showed a steroid-dependent course of the disease, with several relapses after tapering attempts. In March 2016, after 5 relapses, anakinra (2 mg/kg/day) was started with a fast and complete clinical response; however, it was discontinued after 2 weeks for the appearance of severe local side effects. She was firstly evaluated in our Center in April 2016; in July 2016 therapy with canakinumab 150 mg (4 mg/kg) every 4 weeks was started. She experienced four relapses during this treatment (July 2016 -December 2017), following every attempt to reduce steroidal dosage, despite the modification of the schedule (4 mg/kg every three weeks) and the reintroduction of colchicine. Due to inadequate response, canakinumab was withdrawn and, in light of the effectiveness previously demonstrated by anakinra, it was decided, after an allergologic consultation, to attempt to reintroduce this therapy, performing a process of desensitization as reported by Mendonca et al (J clin immunology, 2017) . Results: In January 2018 desensitization to anakinra was started. The patient received five to three consecutive injections per day of gradually increasing anakinra doses and dilutions from days 1 to 9. Each injection was spaced by 15 minutes intervals, raising the dose at each step. On Day 2, due to the appearance of skin reactions at injection site, it was decided to enlarge the interval between the injections (30 minutes) and increase the dilution, restarting desensitization protocol. The full target dosage (80 mg/day; 2mg/kg/day) at standard dilution (divided in 4 different administrations) was reached on Day 8. Since Day 11 anakinra was administrated twice a day, once a day after one month. Antihistaminic and steroids were administrated during all the desensitization process, then discontinued, without recurrence of both skin reactions and disease manifestations. In June 2018 low-dose colchicine was progressively tapered and finally discontinued. Conclusion: Desensitization process to anakinra allowed to achieve full control of the disease in a patient with severe refractory recurrent pericarditis, not responding neither to first line treatment nor to IL-1β blockade and becoming steroids-dependant. Even further data are required, the divergent response to the two antagonists of IL-1 could suggest a prominent role of IL-1α in the pathogenesis of this disease.