TY - JOUR
T1 - Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis
T2 - A single-arm clinical trial
AU - Takada, Kazuki
AU - Katada, Yoshinori
AU - Ito, Satoshi
AU - Hayashi, Taichi
AU - Kishi, Jun
AU - Itoh, Kenji
AU - Yamashita, Hiroyuki
AU - Hirakata, Michito
AU - Kawahata, Kimito
AU - Kawakami, Atsushi
AU - Watanabe, Norihiko
AU - Atsumi, Tatsuya
AU - Takasaki, Yoshinari
AU - Miyasaka, Nobuyuki
N1 - Funding Information:
Funding: This work was supported by the Japan Medical Association under the Large Scale Clinical Trial Network Project by the Ministry of Health, Labour and Welfare, Japan.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
KW - dermatomyositis
KW - interstitial lung disease
KW - interstitial pneumonia
KW - polymyositis
KW - tacrolimus
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U2 - 10.1093/rheumatology/kez394
DO - 10.1093/rheumatology/kez394
M3 - Article
C2 - 31539061
AN - SCOPUS:85084167527
SN - 1462-0324
VL - 59
SP - 1084
EP - 1093
JO - Rheumatology and Rehabilitation
JF - Rheumatology and Rehabilitation
IS - 5
ER -