• Antonio Brucato, Massimo Imazio, Marco Gattorno, George Lazaros, Silvia Maestroni, Mara Carraro, Martina Finetti, Davide Cumetti, Alessandra Carobbio, Nicolino Ruperto, Renzo Marcolongo, Monia Lorini, Alessandro Rimini, Anna Valenti, Gian Luca Erre, Maria Pia Sormani, Riccardo Belli, Fiorenzo Gaita, and Alberto Martini.
• Internal Medicine Division, Research Foundation, and Clinical Pharmacology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
• JAMA. 2016 Nov 8; 316 (18): 1906-1912.

ImportanceAnakinra, an interleukin 1β recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis.ObjectiveTo determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis.Design, Setting, And ParticipantsThe 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.InterventionsAnakinra was administered at 2 mg/kg per day, up to 100 mg, 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 MeasuresThe primary outcomes were recurrent pericarditis and time to recurrence after randomization.ResultsEleven 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 RelevanceIn 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 Registrationclinicaltrials.gov Identifier: NCT02219828.

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