Combination of ruxolitinib and abatacept with glucocorticoids for the treatment of immune checkpoint inhibitor associated myocarditis

Introduction and Objectives

Immune checkpoint inhibitor (ICI)–related myocarditis is a rare but potentially fatal immune-related adverse event. While high-dose corticosteroids represent the cornerstone of treatment, the optimal first-line immunosuppressive strategy remains uncertain.

The aim of this study was to evaluate the effectiveness of first-line combination therapy with ruxolitinib and abatacept in addition to corticosteroids in patients with ICI-related myocarditis.

Methods

We conducted a retrospective analysis of consecutive patients admitted to a tertiary referral center with suspected ICI-related myocarditis from August 2023 onwards. Clinical presentation, electrocardiographic findings, imaging data, treatment strategies, and in-hospital outcomes were analyzed.

Results

Among 26 patients with initial suspicion of ICI-related myocarditis, 3 were diagnosed with alternative conditions, and 23 were classified as having definite or probable myocarditis. Three patients only received corticosteroids: two because the involvement was mild and without electrocardiographic changes, and one due to a fulminant course resulting in death within less than 24 hours.

All the other 20 patients received methylprednisolone combined with ruxolitinib, and abatacept was additionally administered in 13 patients (65%).

The main presenting manifestations were myositis or myasthenic syndrome in 70%, respiratory failure in 5%, and asymptomatic cardiac troponin I elevation in 25%.

Respiratory failure requiring non-invasive ventilatory support occurred in 8 patients (40%), while one patient developed cardiogenic shock.

Electrocardiographic abnormalities were observed in 16 patients (80%), including ventricular arrhythmias in 4 (20%) and conduction disorders in 12 (60%). Complete atrioventricular block developed in 4 patients, leading to permanent pacemaker implantation in 3 cases.

Left ventricular systolic dysfunction was present in three patients (15%). Pericardial effusion was detected in 2 patients (10%), with no cases of cardiac tamponade.

Four patients (20%) died during hospitalization, one due to refractory ventricular arrhythmias.

Conclusions

In this cohort of patients with definite or probable ICI-related myocarditis, characterized by a high burden of arrhythmic complications, first-line combination immunosuppressive therapy with corticosteroids, ruxolitinib, and abatacept was associated with favorable in-hospital outcomes and low mortality.