Morimoto R, Unno K, Fujita N, Sakuragi Y, Nishimoto T, Yamashita M, Kuwayama T, Hiraiwa H, Kondo T, Kuwatsuka Y, Okumura T, Ohshima S, Takahashi H, Ando M, Ishii H, Kato K, and Murohara T
Background: Fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) can noninvasively assess active inflammatory myocardium in patients with cardiac sarcoidosis (CS). Prednisolone (PSL) is the initial drug of choice for active CS; however, its efficacy has not been prospectively evaluated. Moreover, there are no alternative systematic treatment strategies., Objectives: The goal of this study was to evaluate the efficacy of methotrexate (MTX) in patients refractory to PSL assessed by using cardiac metabolic activity (CMA) in 18 F-FDG-PET., Methods: A total of 59 patients with active CS were prospectively enrolled. CMA (standardized uptake value × accumulation area) was used as an indicator of active inflammation, and a 6-month regimen of PSL therapy was introduced, followed by a second FDG scan. Poor responders to PSL therapy (CMA reduction rate <70%) and patients with recurrent CS (CMA reduction rate ≥70% after initial PSL therapy but CMA recurred after an additional 6 months of therapy) were randomly assigned to the MTX or repeat PSL (re-PSL) therapy groups for another 6 months., Results: Fifty-six patients completed the initial 6-month PSL therapy regimen. Median CMA reduced from 203.3 to 1.0 (P < 0.001), and 47 patients were allocated to the response group, 9 to the poor response group, and 2 to the recurrent group. Accordingly, 11 patients were randomly assigned to the MTX (n = 5) or re-PSL (n = 6) groups. After 6 months, neither group showed a significant reduction in CMA values. MTX was comparable to re-PSL in reducing CMA., Conclusions: The 6-month regimen of PSL was a potent therapeutic tool for active CS. When MTX was added to low-dose PSL in patients refractory to the initial PSL therapy, there was no significant difference compared with re-PSL. Further studies are needed to evaluate the therapeutic potential of MTX for active CS, including how MTX works when it is administered in higher doses or for longer periods., Competing Interests: Funding Support and Author Disclosures This work was supported by the Japan Society for the Promotion of Science KAKENHI grants JP18K15387 and JP22K08178 (to Dr Morimoto). Dr Okumura has received lecture fees from Ono Pharma Co Ltd, Novartis Pharma KK, Otsuka Pharma Co Ltd, and AstraZeneca Co Ltd; and research grants from Ono Pharma Co Ltd, Amgen Astellas BioPharma KK, Pfizer Japan Inc, Alnylam, and Alexion (not in connection with the submitted work). Dr Ishii has received lecture fees from AstraZeneca Inc, Bayer Pharmaceutical Co Ltd, Boehringer Ingelheim Japan, Bristol Myers Squibb Inc, Daiichi Sankyo Pharma Inc, MSD KK, Mitsubishi Tanabe Pharma Co Ltd, Mochida Pharmaceutical Co Ltd, Novartis Japan, and Pfizer Japan Inc; and has received scholarship funds or donations from Boehringer Ingelheim Japan and Bristol Myers Squibb Inc. Dr Murohara has received lecture fees and unrestricted research grants from Bayer Pharma Co Ltd, Daiichi Sankyo Co, Ltd, Dainippon Sumitomo Pharma Co Ltd, Kowa Co Ltd, MSD KK, Mitsubishi Tanabe Pharma Co, Boehringer Ingelheim Co Ltd, Novartis Pharma KK, Pfizer Japan Inc, Sanofi, Takeda Pharma Co Ltd, Astellas Pharma Inc, Otsuka Pharma Ltd, and Teijin Pharma Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)