ARAMIS: Anakinra is safe but does not reduce complications of acute myocarditis

By Leah Kosyakovsky on

Key Points:

  • While myocarditis is an inflammatory condition, there have not yet been trials demonstrating the benefit of anti-inflammatory therapies in the treatment of acute myocarditis.
  • In the ARAMIS study, subcutaneous anakinra was compared with placebo in patients with acute myocarditis diagnosed on CMR presenting with chest pain and troponin elevation. The primary endpoint was number of days alive free from myocarditis complications.
  • Anakinra use did not result in a significant change in number of days free from myocarditis complications but was well-tolerated and safe.

Acute myocarditis is a common inflammatory condition with numerous potential serious consequences, from arrhythmias to severe heart failure and death. However, there are no specific anti-inflammatory therapies that have been demonstrated to be effective in the treatment of acute myocarditis. Anakinra is an interleukin (IL)-1 receptor antagonist which has been previously identified to be effective in pericarditis, but it has not been tested in randomized trials in the setting of myocarditis. In a breaking presentation at the 2023 ESC Congress today, Dr. Mathieu Kerneis (Pitié Salpetrière APHP University Hospital, Paris) and his team presented their study: “ARAMIS – Anakinra versus Placebo in Acute Myocarditis.”

The ARAMIS trial (NCT03018834) was a randomized, double-blind, multicenter trial of patients with acute myocarditis comparing anakinra with placebo. Participants were required to have chest pain, troponin elevation, myocarditis diagnosed on cardiac MRI within 72 hours of admission, and either normal invasive or CT coronary angiography within the past year. Key exclusion criteria were active coronary disease, clinical suspicion of an underlying rheumatologic or infectious condition, pregnancy, or contraindication to anakinra. The primary outcome was number of days alive free from myocarditis complications. Myocarditis complications could include HF hospitalization, chest pain requiring medication, LVEF <50%, and any ventricular arrhythmia.

A total of 120 patients were 1:1 randomized across 6 academic centers in France to either subcutaneous anakinra (100mg daily) or placebo until hospital discharge, in addition to standard medical therapy (including an ACE inhibitor).  The median age was 28, and 10% were women. Participants receiving anakinra did not have a significant difference in median days free from myocarditis complications within 28 days of discharge (30 days vs 31 days, p=0.168). Anakinra was well-tolerated and safe, with no difference in the number of serious adverse events within 28 days post discharge (12.1% vs 10.2%, p>0.05).

When discussing the clinical implications of the study at the ESC Congress press conference, Dr. Kerneis stated: “ARAMIS enrolled for the first time an all-comer myocarditis population diagnosed on CMR, mostly at low risk of events….and a short administration of anakinra did not increase the number of days free of myocarditis complications…further studies are needed to explore the potential benefit of the anti-inflammatory strategy in acute myocarditis patients at higher risk of events.”