THU0570 EFFICACY AND SAFETY OF ANAKINRA IN THE TREATMENT OF AUTOIMMUNE MYOCARDITIS
Authors: Giacomo De Luca, Corrado Campochiaro, Giulio Cavalli, Silvia Sartorelli, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Virus-negative or “autoimmune” myocarditis(VNM) is a severe, inflammatory heart disease with a poor prognosis, and is a leading cause of inflammatory dilated cardiomyopathy(i-DCM). Therapies are limited. Preliminary data indicate that interleukin-1(IL-1) plays a key role in the initiation and maintainance of the inflammatory heart response, sustaining an auto-inflammatory cycle<sup>[1,2]</sup>. Objectives: to evaluate the efficacy and safety of anakinra(ANK) in improving Left Ventricular Ejection Fraction(LVEF) on transthoracic echocardiography(TTE) in patients with VNM. <h3>Methods</h3> Biopsy-proven VNM patients were enrolled and treated with ANK 100 mg daily subcutaneously. All patients received treatment with the maximum tolerated dose of any beta blockers and ACE-inhibitors, according to current guidelines. At baseline and 8±4 weeks after ANK therapy, all patients underwent a full evaluation with assessment of functional status(New York Heart Association[NYHA]), measurement of high-sensitive troponin T(hs-TnT) and NT-proBNP serum levels, electrocardiography(ECG), 24h-ECG-Holter, TTE and cardiac magnetic resonance(CMR). Any myocarditis-related complication, cardiovascular deaths and adverse events(AEs) was recorded during follow-up. Continuous variables were assessed with the Wilcoxon signed-rank test for non-parametric tests and a p value&lt;0.05 was considered statistically significant. <h3>Results</h3> Eleven patients(F/M=5/6, mean age 46,2±12,2 years) diagnosed with EBM-proven VNM were enrolled. Nine patients received ANK as first line therapy, and in 5 cases ANK was used as monotherapy; ANK was combined with prednisone(mean dose 31,7±16,7 mg daily) in 6 patients, 5 of them were concomitantly treated with azathioprine. On EMB, 6 patients were classified as i-DCM, 3 with acute VNM e 1 with active and chronic VNM<sup>[3-4]</sup>. Clinical onset was characterized by congestive heart failure in the most cases(72.7%). The majority of patients(72.7%) was in NYHA class III-IV. Mean LV-EF on TTE at baseline was 38,7%±19,6, with comparable findings on CMR(36,45%±18,0), and 8 patients(72.7%) had a depressed LV-EF(&lt;55%). At baseline, mean levels of hs-TnT and NT-proBNP were 150,0±153,9 ng/L and 6968,8±10788,4 pg/ml, respectively. Hs-TnT and NT-proBNP levels were elevated in 10(90.9%) and 9 patients(81.8%) respectively. At 8 weeks, LV-EF improved in 10 patients(90.9%). The LV-EF increase was&gt;10% in 5 patients(45.5%) and between 5-10% in 5 cases(45.5%); only 1 patient showed a &lt;10% LV-EF decrease. Mean LV-EF at the end of follow-up improved to 49,4%±10,8(p=0.059). When evaluating the 8 patients with baseline reduced LV-EF, the LV-EF improvement was statistically significant (baseline 29,2%±12,9; after ANK 45.2%±9.2,p=0.025). The LV-EF amelioration was paralleled by clinical improvements in all patients, since the majority of them(90.9%) were in NYHA class I-II at the end of follow-up. Consistently, hs-TnT declined after 8 weeks(64,6±100,7 ng/L,p=0,028), and a similar trend was observed for NT-proBNP, even though not statistical significant(2582,6±5048,1 pg/ml,p=0,06). We did not observe any myocarditis-related death or complications, nor any ANK-related AEs. <h3>Conclusion</h3> Our pilot study supports the efficacy and safety of ANK in the treatment of inflammatory heart failure in VNM and provides the first clinical evidence to support the therapeutic blockade of IL-1 in myocarditis. <h3>References</h3> [1] De LucaG,et al.Ann Intern Med.2018;169:819-820. [2] De LucaG,et al. Front Immunol.2018;9:1335. [3] RichardsonP,et al. Circulation.1996;93:841-2. [4] AretzHT,et al. Am J Cardiovasc Pathol.1987;1:3-14. <h3>Acknowledgement</h3> Dr Giovanni Peretto and Dr Simone Sala from Unit of Arrhythmology and Cardiac Electrophysiology <h3>Disclosure of Interests</h3> Giacomo De Luca Consultant for: Dr Giacomo De Luca received consultation honoraria from Pfizer and SOBI., Corrado Campochiaro Consultant for: Dr Corrado Campochiaro received consultation honoraria from Pfizer., Giulio Cavalli Consultant for: Dr Giulio Cavalli received consultation honoraria from Pfizer, Novartis and SOBI., Silvia Sartorelli: None declared, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI.