Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis: a single-arm clinical trial.

Autor:	Takada K; Department of Professional Development in Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo., Katada Y; Department of Rheumatology and Clinical Immunology, Sakai City Medical Center, Osaka., Ito S; Department of Rheumatology, Niigata Rheumatic Center, Niigata., Hayashi T; Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki., Kishi J; Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima., Itoh K; Division of Hematology and Rheumatology, Department of Internal Medicine, National Defense Medical College, Saitama., Yamashita H; Division of Rheumatic Diseases, National Center for Global Health and Medicine, Tokyo., Hirakata M; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo., Kawahata K; Division of Rheumatology and Allergology, Department of Internal Medicine, St Marianna University School of Medicine, Kanagawa., Kawakami A; Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki., Watanabe N; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba., Atsumi T; Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine, Hokkaido University, Hokkaido., Takasaki Y; Department of Internal Medicine, Juntendo University Koshigaya Hospital, Saitama., Miyasaka N; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2020 May 01; Vol. 59 (5), pp. 1084-1093.
DOI:	10.1093/rheumatology/kez394
Abstrakt:	Objective: Interstitial pneumonia is common and has high short-term mortality in patients with PM and DM despite glucocorticoid (GC) treatment. Retrospective studies suggested that the early use of immunosuppressive drugs with GCs might improve its short-term mortality. Methods: A multicentre, single-arm, 52-week-long clinical trial was performed to test whether the initial combination treatment with tacrolimus (0.075 mg/kg/day, adjusted for the target whole-blood trough levels between 5 and 10 ng/ml) and GCs (0.6-1.0 mg/kg/day of prednisolone followed by a slow taper) improves short-term mortality of PM/DM-interstitial pneumonia patients. The primary outcome was overall survival. We originally intended to compare, by using propensity-score matching, the outcome data of clinical trial patients with that of historical control patients who were initially treated with GCs alone. Results: The 52-week survival rate with the combination treatment (N = 26) was 88.0% (95% CI, 67.3, 96.0). Safety profiles of the combination treatment were consistent with those known for tacrolimus and high-dose GCs individually. Serious adverse events occurred in 11 patients (44.0%), which included four opportunistic infections. Only 16 patients, including only 1 deceased patient, were registered as historical controls, which precluded meaningful comparative analysis against the clinical trial patients. Conclusion: Our study provided findings which suggest that initial treatment with tacrolimus and GCs may improve short-term mortality of PM/DM-interstitial pneumonia patients with manageable safety profiles. This was the first prospective clinical investigation conducted according to the Good Clinical Practice Guideline of the International Conference on Harmonization for the treatment of this potentially life-threatening disease. Trial Registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00504348. (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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