Treatment with Methotrexate and Low-dose Corticosteroids in Sarcoidosis Patients with Cardiac Lesions

Abstract

Objective Our objective was to evaluate the effectiveness of combination therapy consisting of low-dose corticosteroids with weekly methotrexate in patients with cardiac sarcoidosis in whom long-term therapy is required. Combination therapy was selected because long-term standard corticosteroid therapy tends to result in various adverse effects and the steroid-sparing effects of methotrexate have been reported. Methods This study was a small open-label study comparing long-term functional changes between patients who received combination therapy (5-15 mg/day of prednisolone and 6 mg/week of methotrexate) and patients who received corticosteroids alone. The comparative analysis was based on the following therapeutic indexes: ejection fraction (EF), left ventricular end-diastolic diameter (LVDd) on echocardiography, serum Nterminal fragment pro-brain natriuretic peptide (NT-proBNP) and cardiothoracic ratio (CTR) on plain chest radiographs. Patients Seventeen patients with cardiac sarcoidosis were examined in the sarcoidosis clinic. Cardiac sarcoidosis was diagnosed based on the Japanese diagnostic guidelines published in 2006. Results The EF was significantly stabilized in the combination therapy group but not in the corticosteroids alone group at three years after the first treatment. The CTR and NT-proBNP levels were significantly stabilized in the combination therapy group compared with those observed in the corticosteroids alone group at both three and five years after the first treatment. The LVDd values tended to be stable in the combination therapy group compared with those observed in the corticosteroids alone group. The combination therapy was associated with few adverse effects. Conclusion Weekly methotrexate therapy with daily small doses of corticosteroids stabilized the EF, CTR and NT-proBNP levels in the serum without eliciting adverse effects longitudinally.

Diagnosis and Therapy of Cardiac Sarcoidosis: A Clinical Perspective

“…32 Although there are no formal guidelines for medical treatment of CS, an expert consensus statement 11 and treatment protocols from major sarcoidosis centers have been published. 1,[33][34][35] Survival or improvement in LVEF with corticosteroid therapy has been demonstrated in some studies, but not others. 33,36,37 Treatment protocols vary between centers, but generally prednisone, initially at higher doses (40 mg/day) is initiated, then gradually tapered over Although there are no standardized protocols for follow up, cardiac PET may be performed 3-6 months after initiation of immunosuppressant therapy to assess response.…”

Diagnosis and treatment of cardiac sarcoidosis

“…In CS, there is one report of the combination of low-dose prednisolone (5–15 mg/day) with a weekly dose of methotrexate (6 mg/week), which stabilises the cardiac function of CS,29 but the other immunosuppressive drug effects for CS still lack sufficient data.…”

Management of Arrhythmias in Cardiac Sarcoidosis

“…Alternatives to corticosteroids are often considered in patients who experience severe side effects or refractory disease, although the efficacy of these therapies in CS is poorly understood. The most widely used immunosuppressive agent utilized for CS is methotrexate, due to efficacy in treating extracardiac sarcoidosis . One prospective study examined CS patients treated with low‐dose corticosteroids and methotrexate and found statistically significant sparing of LVEF (60.7 ± 14.3% vs 44.5 ± 13.8%; P = 0.04) and lower serum N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) levels compared with patients treated with corticosteroids alone up to 5 years after initiation of therapy .…”