Anakinra safe but did not increase days free from acute myocarditis complications
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Key takeaways:
- Anakinra did not increase days free from complications vs. placebo in patients with acute myocarditis.
- The drug was safe, with only one instance of a treatment-related serious adverse event.
Anakinra, an interleukin-1R antagonist, was shown to be a safe treatment in patients with acute myocarditis, but did not change the number of days free from complications compared with placebo, a speaker reported.
The results of the phase 2b ARAMIS trial were presented at the European Society of Cardiology Congress.
Image: Adobe Stock
“Myocarditis is an inflammation of the heart that can cause life-threatening events among young patients, frequently hospitalized for the first time of their lives in an intensive care unit and exposed to a 3% event rate of deaths and heart transplantation at 1 month,” Mathieu Kerneis, MD, PhD, interventional cardiologist and head of the cardiac intensive care unit at the Pitié Salpêtrière Hospital, Sorbonne University, Paris, said during a press conference. “The problem is that there is no specific treatment for these patients. There is no evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis or inflammatory cardiomyopathy. In fact, a strategy of immunomodulation has never been evaluated in an acute setting or in patients with heart biopsy.”
Kerneis and colleagues hypothesized that inhibition of the interleukin-1 (IL-1) beta pathway with the IL-1R antagonist anakinra (Kineret, Swedish Orphan Biovitrum), a drug already used to treat inflammatory disease with an acceptable safety profile, may be an effective treatment for acute myocarditis.
To test this hypothesis, the researchers enrolled 117 patients hospitalized with acute myocarditis and randomly assigned them to anakinra 100 mg or placebo on top of standard of care with beta-blockers and ACE inhibitors. Participants were followed for up to 28 days after hospital discharge.
The primary outcome was survival time free of myocarditis-related complications.
The median number of days free from myocarditis-related complications was 30 in the anakinra group and 31 in the placebo group (mean, 29.75 in anakinra; 29.72 in placebo), with no significant difference between the two study groups (P = .168).
The composite outcome of clinical events, including HF, ventricular arrhythmia, chest pain requiring medication or ventricular dysfunction (left ventricular ejection fraction < 50%) occurred in 10.5% of the anakinra group and 16.7% of the placebo group (OR = 0.59; 95% CI, 0.19-1.78) at 28 days, Kerneis said during the press conference.
Incidents of chest pain requiring new medication was numerically lower in the anakinra arm (3.5% vs. 10%) while incidence of ventricular dysfunction was numerically higher compared with placebo (8.5% vs. 7.4%), he said.
The rates of serious adverse events were similar between the groups (adjusted OR = 1.2; 95% CI, 0.35-4.07).
The researchers reported one incident of mild hepatic cytolysis in the anakinra arm, which was the only serious adverse event potentially related to use of the drug.
“ARAMIS is the largest randomized controlled trial in acute myocarditis and probably the first ever in an acute setting, enrolling, for the first time, an all-comers acute myocarditis population diagnosed based on [cardiac magnetic resonance], not biopsy, and patients who are mostly at low risk of events,” Kerneis said during the press conference. “A short administration of anakinra did not increase the number of days free of myocarditis complications. There was no safety issue with anakinra when administrated during the acute phase of myocarditis without biopsy. ... Further randomized controlled studies are needed to explore the potential benefit of such strategies among patients at higher risk of events or with a prolonged strategy of anti-inflammatory drug use.”
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Kerneis M, et al. Hot line 7. Presented at: European Society of Cardiology Congress; Aug. 25-28, 2023; Amsterdam (hybrid meeting).
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