The role of infliximab in treating refractory cardiac sarcoidosis

Abstract

Abstract Introduction Cardiac sarcoidosis (CS) is associated with therapeutic challenges, and a high morbidity and mortality. Tumour necrosis factor alpha inhibitors like infliximab may be a treatment option for patients with persistent myocardial inflammatory activity despite conventional immunosuppressive treatment with steroids and steroid-sparing agents. Purpose To identify the safety and efficacy of infliximab in the treatment of refractory cardiac sarcoidosis. Methods We conducted a review of refractory CS patients who had been or were actively on treatment with Infliximab at our specialist tertiary care hospital from January 2017 to January 2023. Serial echocardiographic and FDG-PET scan changes as well as long term clinical data on morbidity and mortality was recorded. Results Six CS patients on infliximab were retrospectively identified. The mean age at CS diagnosis was 47.0±5.9 years and mean duration between CS diagnosis and starting infliximab was 21.4±14.2 months (Table 1). Infliximab was commenced due to persistent inflammation on FDG-PET scan and/or CMR despite being on at least two agents (prednisolone and methotrexate ± hydroxychloroquine) in 5 cases and prednisolone alone (intolerance to methotrexate) in one case. At baseline, 3 patients presented with ventricular arrhythmias, 2 with atrioventricular block and 2 with heart failure. After a mean follow up of 21.2±15.5 months of being on infliximab, 5/6 CS patients had decreased myocardial uptake on PET (1 was awaiting a scan) which included complete resolution of FDG-PET signal in one patient (Table 2). A trend in improvement of mean LVEF [52.7±6.6% to 60.2±5.9%, p = 0.10] and reduction of mean prednisolone dose [19.2±6.6mg to 11.3±7.0mg, p = 0.08] was observed during Infliximab treatment. None of the patients had worsening of LVEF or admission with acute heart failure whilst being on infliximab. A total of 4/6 patients had an Implantable Cardioverter Defibrillator device in situ at the time of Infliximab initiation. No major arrhythmias were observed during follow up. One patient died following complications of patent foramen ovale repair. There were three new cases of infection (1 pneumonia and 2 COVID-19 pneumonitis) and one case of renal cell carcinoma diagnosis three years after Infliximab treatment initiation. The drug safety was overall satisfactory since none of the patients required hospitalisation (Table 2). Case 2 patient stopped infliximab after 13 months of treatment and was found to have disease relapse seven months later. During a 20 month follow up of being on infliximab again, he demonstrated complete resolution of FDG uptake on subsequent FDG-PET scan. Conclusion This study supports the use of infliximab in refractory CS by demonstrating improvement in clinical, functional and tissue characterization parameters. However, infliximab is associated with an increased risk of infections.