AMSTERDAM — Anti-inflammatory immunosuppressant anakinra (Kineret) held no survival benefit for Acute Myocarditis, the randomized phase IIb ARAMIS trial showed.

The interleukin-1 receptor antagonist yielded a median 30 days alive and free of complications compared with 31 in the placebo group (P=0.168), Mathieu Kerneis, MD, PhD, of Pitie Salpetriere AP-HP University Hospital in Paris, reported here at the European Society of Cardiology (ESC) congress.

Frequency of the composite of heart failure, ventricular arrhythmia, chest pain requiring medication, or left ventricular ejection fraction less than 50% at 28 days post-discharge was 41% less frequent in the anakinra arm (10.5% vs 16.7%), though this secondary endpoint was not powered to be able to show significance. This was driven by less new medication for chest pain.

“I don’t think that ARAMIS ends the story of the anti-inflammatory drug in Acute Myocarditis; I think that it’s just the beginning,” Kerneis told MedPage Today at an ESC press conference.

Still promising was also the conclusion of press conference chair Carlos Aguiar, MD, of Hospital Santa Cruz in Lisbon, Portugal, who suggested that a determination that inflammation has been sufficiently taken care of would be the right moment to discontinue medication rather than at discharge.

Another possible way forward is to target higher-risk patients, suggested ESC hotline session study discussant Enrico Ammirati, MD, PhD, of ASST Great Metropolitan Niguarda in Milan.

The trial enrolled 120 patients, making it the largest-ever randomized controlled trial in acute myocarditis, and was the first to include an all-comer acute myocarditis population diagnosed on cardiac MRI (CMR) rather than biopsy. Within 72 hours of diagnosis, patients were randomized double blind to anakinra at the usual 100 mg subcutaneous dose once-daily or placebo, both along with standard of care, including beta-blockers and ACE inhibitors.

Importantly, Kerneis noted no safety issues with anakinra administered during the acute phase of myocarditis diagnosed with CMR rather than endomyocardial biopsy, and thus no proof of absence of viral replication.

However, it was a trial in patients mostly at low risk of events: all had chest pain, but 11% had dyspnea and median left ventricular ejection fraction (LVEF) by echocardiography was 60%, with only 9.4% complicated by an LVEF under 50%. Less than 1% had a fulminant presentation. There were no deaths in the trial.

“It’s very challenging first to do a trial with patients at very high risk of events,” Kerneis told MedPage Today. “In fact, there is only one ongoing study — the MYTHS trial — … and it’s struggling to recruit patients at high risk because there are very few patients with a fulminant form of myocarditis.”

The MYTHS (Myocarditis Therapy With Steroids) trial will carry the story of inflammation targeting and immunosuppression forward in acute myocarditis, said Ammirati, who is the trial’s primary investigator. It is testing steroid therapy for suspected acute myocarditis complicated by acute heart failure or cardiogenic shock with an LVEF under 41% and left ventricular end-diastolic diameter less than 56 mm on echocardiography.

“It’s an important area where we have so many gaps in knowledge,” concluded ESC session moderator Christopher Granger, MD, of Duke University in Durham, North Carolina.