Tofacitinib for treatment in immune-mediated myocarditis: The first reported cases

Abstract

Introduction: Immune checkpoint inhibitors (ICI) has demonstrated significant clinical benefit in advanced cancer. Despite favorable benefits, the use of ICI is accompanied by various side effects, which are inflammatory side effects potentially affecting any organ. Among which myocarditis is the most severe and has a relatively high mortality. However, there is no effective treatments, and many patients respond poorly to glucocorticoids and immunosuppressants. Therefore, it is urgent to explore effective treatments.

Cases report: Here we describe two patients with metastatic cancer who developed immune-mediated myocarditis after receiving anti-programmed cell death protein (PD)-1 antibody. The main clinical manifestations are dyspnea. All patients had an elevation of cardiac enzyme, a variety of atypical electrocardiographic (ECG) abnormalities and preserved left ventricular ejection fraction (LVEF). All our patients underwent cardiac MRI (CMRI) and suggested typical features of myocarditis, including myocardial oedema and delayed enhancement.Management and outcome: All patients were treated promptly with glucocorticoids, followed by other immunosuppressive treatments include plasma exchange and intravenous immunoglobulin (IVIG). However, no significant improvement was observed and we then administered tofacitinib 5 mg twice daily to treat the refractory myocarditis and the elevated levels of pro-inflammatory cytokines. All patients recovered and were discharged. No major adverse reaction was reported during tofacitinib therapy.

Discussion: To our knowledge, this is the first report in the world of patients with ICI-associated myocarditis treated with oral tofacitinib. Our results can at least provide a new option for clinical treatment of refractory myocarditis or other immune-related adverse events.

Keywords: Immune checkpoint inhibitor; myocarditis; tofacitinib.