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

Autor: Tatsuya Atsumi, Yoshinori Katada, Norihiko Watanabe, Jun Kishi, Kimito Kawahata, Kenji Itoh, Michito Hirakata, Taichi Hayashi, Atsushi Kawakami, Satoshi Ito, Hiroyuki Yamashita, Nobuyuki Miyasaka, Kazuki Takada, Yoshinari Takasaki
Rok vydání: 2019
Předmět:
Adult
Male
medicine.medical_specialty
dermatomyositis
Comorbidity
Kaplan-Meier Estimate
Risk Assessment
Polymyositis
Disease-Free Survival
Tacrolimus
polymyositis
03 medical and health sciences
0302 clinical medicine
Japan
Rheumatology
Cause of Death
Internal medicine
Outcome Assessment
Health Care
medicine
Humans
Pharmacology (medical)
Prospective Studies
030212 general & internal medicine
Adverse effect
Glucocorticoids
Survival rate
Aged
interstitial lung disease
interstitial pneumonia
030203 arthritis & rheumatology
business.industry
Retrospective cohort study
Clinical Science
Middle Aged
Dermatomyositis
medicine.disease
Respiratory Function Tests
Survival Rate
Clinical trial
Prednisolone
Drug Therapy
Combination
Female
Lung Diseases
Interstitial
business
Immunosuppressive Agents
medicine.drug
Zdroj: Rheumatology (Oxford, England)
ISSN: 1462-0332
1462-0324
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: