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

• Published in: Rheumatology (Oxford, England) Vol. 59; no. 5; pp. 1084 - 1093
• Main Authors: Takada, Kazuki, Katada, Yoshinori, Ito, Satoshi, Hayashi, Taichi, Kishi, Jun, Itoh, Kenji, Yamashita, Hiroyuki, Hirakata, Michito, Kawahata, Kimito, Kawakami, Atsushi, Watanabe, Norihiko, Atsumi, Tatsuya, Takasaki, Yoshinari, Miyasaka, Nobuyuki
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2020
• Subjects: Adult; Aged; Cause of Death; Clinical Science; Comorbidity; Dermatomyositis - diagnosis; Dermatomyositis - drug therapy; Dermatomyositis - epidemiology; Disease-Free Survival; Drug Therapy, Combination; Female; Glucocorticoids - administration & dosage; Humans; Immunosuppressive Agents - administration & dosage; Japan; Kaplan-Meier Estimate; Lung Diseases, Interstitial - diagnosis; Lung Diseases, Interstitial - drug therapy; Lung Diseases, Interstitial - epidemiology; Male; Middle Aged; Outcome Assessment, Health Care; Polymyositis - diagnosis; Polymyositis - drug therapy; Polymyositis - epidemiology; Prospective Studies; Respiratory Function Tests; Risk Assessment; Survival Rate; Tacrolimus - administration & dosage; Tacrolimus - adverse effects; Japan; polymyositis; dermatomyositis; interstitial lung disease; tacrolimus; interstitial pneumonia
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/kez394

Abstract 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.