Premium
Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High‐Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti–Melanoma Differentiation–Associated Gene 5–Positive Dermatomyositis
Author(s) -
Tsuji Hideaki,
Nakashima Ran,
Hosono Yuji,
Imura Yoshitaka,
Yagita Masato,
Yoshifuji Hajime,
Hirata Shintaro,
Nojima Takaki,
Sugiyama Eiji,
Hatta Kazuhiro,
Taguchi Yoshio,
Katayama Masaki,
Tanizawa Kiminobu,
Handa Tomohiro,
Uozumi Ryuji,
Akizuki Shuji,
Murakami Kosaku,
Hashimoto Motomu,
Tanaka Masao,
Ohmura Koichiro,
Mimori Tsuneyo
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41105
Subject(s) - medicine , regimen , cyclophosphamide , tacrolimus , gastroenterology , prednisolone , interstitial lung disease , adverse effect , immunosuppression , surgery , transplantation , chemotherapy , lung
Objective Interstitial lung disease ( ILD ) accompanied by anti–melanoma differentiation–associated gene 5 (anti– MDA ‐5)–positive dermatomyositis ( DM ) is often rapidly progressive and associated with poor prognosis. Because there is no established treatment, we undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti– MDA ‐5–positive DM patients with ILD . Methods Adult Japanese patients with new‐onset anti– MDA ‐5–positive DM with ILD (n = 29) were enrolled at multiple study centers from 2014 to 2017. They were treated with a regimen of high‐dose glucocorticoids ( GC s), tacrolimus, and intravenous cyclophosphamide ( IV CYC ). Plasmapheresis was used if a patient's condition worsened after the regimen started. The primary end point was 6‐month survival, which was compared between this group of patients and a historical control group (n = 15) consisting of anti– MDA ‐5–positive DM patients with ILD who received step‐up treatment (high‐dose GC and stepwise addition of immunosuppressant). Secondary end points were 12‐month survival rate, adverse events, and changes in laboratory data. Results The combined immunosuppressive regimen group showed significantly higher 6‐month survival rates than the step‐up treatment group (89% versus 33%; P < 0.0001). Over a period of 52 weeks, improvements in anti– MDA ‐5 titers, serum ferritin levels, vital capacity, and chest high‐resolution computed tomography scores were observed. The combined immunosuppressive regimen group received IV CYC nearly 20 days earlier with shorter intervals and tended to receive plasmapheresis more often than patients undergoing step‐up treatment. Cytomegalovirus reactivation was frequently observed over 52 weeks. Conclusion A combined immunosuppressive regimen is effective for anti– MDA ‐5–positive DM patients with ILD . Plasmapheresis can be used for additional effect in intractable disease. Patients should be carefully monitored for opportunistic infections during treatment.