Effect of Anakinra on Recurrent Pericarditis Among Patients With Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial.
Anakinra, an interleukin 1β recombinant receptor antagonist, may have potential to treat colchicine-resistant and corticosteroid-dependent recurrent pericarditis.



To determine the efficacy of anakinra for colchicine-resistant and corticosteroid-dependent recurrent pericarditis.



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.



Anakinra 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.



The primary outcomes were recurrent pericarditis and time to recurrence after randomization.



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.



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.



clinicaltrials.gov Identifier: NCT02219828.
Internal Medicine Division, Research Foundation, and Clinical Pharmacology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Antonio
A
Brucato
Cardiology Department, Maria Vittoria Hospital and Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
Massimo
M
Imazio
IRCCS Istituto G. Gaslini, Pediatria II, Genova, Italy.
Marco
M
Gattorno
Cardiology Department, Maria Vittoria Hospital and Department of Public Health and Pediatrics, University of Torino, Torino, Italy4Department of Cardiology, University of Athens Medical School, Hippokration Hospital, Athens, Greece.
George
G
Lazaros
Internal Medicine Division, Research Foundation, and Clinical Pharmacology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Silvia
S
Maestroni
Cardiology Department, Maria Vittoria Hospital and Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
Mara
M
Carraro
IRCCS Istituto G. Gaslini, Pediatria II, Genova, Italy.
Martina
M
Finetti
Internal Medicine Division, Research Foundation, and Clinical Pharmacology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Davide
D
Cumetti
Internal Medicine Division, Research Foundation, and Clinical Pharmacology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Alessandra
A
Carobbio
IRCCS Istituto G. Gaslini, Pediatria II, Genova, Italy.
Nicolino
N
Ruperto
Clinical Immunology, Department of Medicine, Azienda Ospedaliera-Università, Padova, Italy.
Renzo
R
Marcolongo
Internal Medicine Division, Research Foundation, and Clinical Pharmacology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Monia
M
Lorini
IRCCS Istituto G. Gaslini, Pediatria II, Genova, Italy.
Alessandro
A
Rimini
Internal Medicine Division, Research Foundation, and Clinical Pharmacology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
Anna
A
Valenti
Reumatologia, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy.
Gian Luca
GL
Erre
IRCCS Istituto G. Gaslini, Pediatria II, Genova, Italy.
Maria Pia
MP
Sormani
Cardiology Department, Maria Vittoria Hospital and Department of Public Health and Pediatrics, University of Torino, Torino, Italy.
Riccardo
R
Belli
University Cardiology Division, Department of Medical Sciences, Città della Scienza e della Salute, Torino, Italy.
Fiorenzo
F
Gaita
IRCCS Istituto G. Gaslini, Pediatria II, Genova, Italy8University of Genova, Genova, Italy.
Alberto
A
Martini
D002657:Child Development; D003071:Cognition; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight / Q000254:growth & development*; D007804:Language Development; D008297:Male; D008895:Milk, Human; D009864:Ontario