Effect of anakinra on recurrent pericarditis among patients with colchicine resistance and corticosteroid dependence : the AIRTRIP randomized clinical trial

IMPORTANCE Anakinra, an interleukin 1â recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis. OBJECTIVE To determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis. DESIGN, SETTING, AND PARTICIPANTS The Anakinra-Treatment of Recurrent Idiopathic Pericarditis (AIRTRIP) double-blind, placebo-controlled, randomized withdrawal trial (open label with anakinra followed by a double-blind withdrawal step with anakinra or placebo until recurrent pericarditis occurred) conducted among 21 consecutive patients enrolled at 3 Italian referral centers between June and November 2014 (end of follow-up, October 2015). Included patients had recurrent pericarditis (with-3 previous recurrences), elevation of C-reactive protein, colchicine resistance, and corticosteroid dependence. INTERVENTIONS Anakinra was administered at 2mg/kg per day, up to 100mg, for 2 months, then patients who responded with resolution of pericarditis were randomized to continue anakinra (n = 11) or switch to placebo (n = 10) for 6 months or until a pericarditis recurrence. MAIN OUTCOMES AND MEASURES The primary outcomeswere recurrent pericarditis and time to recurrence after randomization. RESULTS Eleven patients (7 female) randomized to anakinra had a mean age of 46.5 (SD, 16.3) years; 10 patients (7 female) randomized to placebo had a mean age of 44 (SD, 12.5) years. All patients were followed up for 12 months. Median follow-up was 14 (range, 12-17) months. Recurrent pericarditis occurred in 9 of 10 patients (90%; incidence rate, 2.06%of patients per year) assigned to placebo and 2 of 11 patients (18.2%; incidence rate, 0.11% of patients per year) assigned to anakinra, for an incidence rate difference of.1.95%(95%CI,.3.3%to.0.6%). Median flare-free survival (time to flare) was 72 (interquartile range, 64-150) days after randomization in the placebo group and was not reached in the anakinra group (P >.001). During anakinra treatment, 20 of 21 patients (95.2%) experienced transient local skin reactions: 1 (4.8%) herpes zoster, 3 (14.3%) transaminase elevation, and 1 (4.8%) ischemic optic neuropathy. No patient permanently discontinued the active drug. No adverse events occurred during placebo treatment. CONCLUSION AND RELEVANCE In this preliminary study of patients with recurrent pericarditis with colchicine resistance and corticosteroid dependence, the use of anakinra compared with placebo reduced the risk of recurrence over a median of 14 months. Larger studies are needed to replicate these findings as well as to assess safety and longer-term efficacy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02219828.