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.

Case Report: A Case of Sintilimab-Induced Cystitis/Ureteritis and Review of Sintilimab-Related Adverse Events

“…For the cases reviewed, the demographic features, clinical manifestations and treatment of irAEs were summarized ( Table 1 ). From these case reports, sintilimab has been shown to induce various immune-associated disorders, including autoimmune diabetes ( 18 , 26 , 30 ), pneumonitis ( 27 , 28 ), pulmonary fibrosis ( 20 ), cytokine release syndrome and multiple organ failure ( 20 , 21 ), myocarditis ( 24 , 29 ), hypothyroid myopathy ( 19 ), myasthenia gravis and myasthenia crisis ( 22 ), paraneoplastic neurological syndrome and enteric neuropathy ( 23 ), psoriasis exacerbation ( 25 ). Some literatures previously indicated that patients with irAEs usually showed a markedly better efficacy than those without irAEs, known as higher overall response rate, longer PFS and better overall survival ( 31 , 32 ).…”

Analysis of Corticosteroids in Immune Checkpoint Inhibitors (ICE) Induced Myocarditis – A Systematic Review of 352 Screened Articles

“…Steroid use is based on its anti-inflammatory action and decreasing inflammation size. In addition to corticosteroid, immunosuppressive agents as infliximab [15, 17, 18, 31, 37, 38], intravenous immunoglobulin (IVG) [11, 13, 22, 24, 37, 38, 41], antithymocyte [35], and plasma exchange [19, 24, 33], and plasmapheresis [36, 38] are used as a secondary treatment after corticosteroid trial. [11] Also, myco-phenolate mofetil (MMF) [27, 28, 30] and tacrolimus [11, 20, 24, 41], tofacitinib [41], and abatacept [32] were used and they helped in the management and controlling the inflammation.…”

“…In addition to corticosteroid, immunosuppressive agents as infliximab [15, 17, 18, 31, 37, 38], intravenous immunoglobulin (IVG) [11, 13, 22, 24, 37, 38, 41], antithymocyte [35], and plasma exchange [19, 24, 33], and plasmapheresis [36, 38] are used as a secondary treatment after corticosteroid trial. [11] Also, myco-phenolate mofetil (MMF) [27, 28, 30] and tacrolimus [11, 20, 24, 41], tofacitinib [41], and abatacept [32] were used and they helped in the management and controlling the inflammation. The rationale for using infliximab and anti-TNF drug based on IC-induced myocarditis microscopic finding, these drugs decrease T-lymphocyte activity and have been considered for the treatment of myocarditis related to autoimmune or infectious disease, therefore, it is recommended to be used in IC-induced myocarditis.…”

An Emergent Form of Cardiotoxicity: Acute Myocarditis Induced by Immune Checkpoint Inhibitors

“…Both patients responded poorly to the treatment with steroids, plasma exchange, and intravenous immunoglobulin (IVIG), while they had significant and rapid clinical and biochemical improvement with Tofacitinib, at 5 mg twice daily. Tofacitinib may be a new option for the treatment of refractory ICI-associated myocarditis, but it needs more evidence by randomized clinical trials [ 59 ].…”