Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis

Abstract

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone, <10 mg/day). Adalimumab was added in 19 patients with persistently active CS or in those with intolerance to methotrexate. Methotrexate±low-dose prednisone resulted in initial reduction (88%) or elimination (60%) of 18-fluorodeoxyglucose uptake, and patients receiving adalimumab-containing regimens experienced improved (84%) or resolved (63%) 18-fluorodeoxyglucose uptake. Radiologic relapse occurred in 8 of 9 patients after immunosuppression cessation, 4 patients on methotrexate-containing regimens, and in no patients on adalimumab-containing regimens. Conclusions Corticosteroid-sparing regimens containing methotrexate with or without adalimumab is an effective maintenance therapy in patients after an initial response is confirmed. Disease recurrence in patients on and off immunosuppression support need for ongoing radiologic surveillance regardless of immunosuppression regimen.

Keywords: immunosuppression; sarcoidosis; ventricular arrhythmia.

Figure 1

Association between immunosuppression regimen and complete resolution of 18‐fluorodeoxyglucose uptake on positron emission tomography in patients with cardiac sarcoidosis. All patients were initially treated with a methotrexate‐containing regimen except for 2 patients, who were initially treated with an adalimumab‐containing regimen. Persistent, decreased, or no 18‐fluorodeoxyglucose resolution in each patient stratified on maintenance immunosuppression. FDG indicates fluorodeoxyglucose; LDP, low‐dose prednisone; MTX, methotrexate.

Figure 2

Cardiac sarcoidosis (CS) disease activity determined by 18‐fluorodeoxyglucose positron emission tomography (18F‐FDG PET) throughout treatment course. Serial positron emission tomography scans obtained in a single patient with different immunosuppression regimens, with the short‐axis view visualized, from apex to base. The image on top is perfusion imaging, and the bottom demonstrates 18F‐FDG uptake. A, De novo CS: Initial positron emission tomography demonstrates 18F‐FDG uptake in the anteroseptum with a corresponding perfusion defect (myocardial maximal standardized uptake value [SUVmax]=2.85, SUVmax/standardized uptake value(liver)=1.08). B, CS suppression: Complete resolution of 18F‐FDG uptake on methotrexate maintenance therapy, with persistent perfusion defect, consistent with treated CS with residual scar. There is only mild 18F‐FDG uptake seen in the blood pool (myocardial SUVmax 0.77, SUVmax/standardized uptake value (liver)=0.31). C, CS recurrence: After immunosuppression discontinuation, there is new 18F‐FDG uptake in the basal to mid‐anterolateral wall with a new perfusion defect (myocardial SUVmax 4.78, SUVmax/SUV(liver)=1.53). FDG indicates fluorodeoxyglucose; SUVmax, maximal standardized uptake value.

Figure 3

FDG quantification and immunosuppression status in cardiac sarcoidosis. A, Normalized maximal standardized uptake valuefor each subject at the time of cardiac sarcoidosis diagnosis and after initial immunosuppression treatment. B, In those subjects who discontinued immunosuppression, normalized maximal standardized uptake value is reported before and after immunosuppression discontinuation. SUV indicates standardized uptake value; SUVmax, maximal standardized uptake value.