Dataset Information

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

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.

SUBMITTER: Takada K

PROVIDER: S-EPMC7850120 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Takada Kazuki K Katada Yoshinori Y Ito Satoshi S Hayashi Taichi T Kishi Jun J Itoh Kenji K Yamashita Hiroyuki H Hirakata Michito M Kawahata Kimito K Kawakami Atsushi A Watanabe Norihiko N Atsumi Tatsuya T Takasaki Yoshinari Y Miyasaka Nobuyuki N

Rheumatology (Oxford, England) 20200501 5

<h4>Objective</h4>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.<h4>Methods</h4>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 betw ...[more]

PMID: 31539061

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Project description:Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular manifestations of dermatomyositis and polymyositis and is strongly linked to poor prognosis and early mortality. We aimed to characterise the demographic and clinical characteristics, incidence, and treatment of interstitial lung disease in patients with dermatomyositis or polymyositis. We conducted a retrospective cohort study using the Japan Medical Data Center healthcare claims database. Patients in the database with dermatomyositis (International Classification of Disease version 10 M33.0, M33.1, M33.9) or polymyositis (M33.2) from 01-Jan-2011 until 31-Dec-2019 were identified and followed-up for interstitial lung disease (J84.x) until death, dis-enrolment, or study end (31 December 2020). Cumulative risk curves compared interstitial lung disease risk in dermatomyositis versus polymyositis. Risk factors were evaluated by Cox proportional hazard models. There were 886 patients with dermatomyositis and 745 patients with polymyositis included in the cohort analysis. Mean (standard deviation) age at dermatomyositis/polymyositis diagnosis was 46.0 (16.0)/49.7 (13.3) years and 300 (34%)/104 (14%) developed interstitial lung disease during follow-up. The incidence rate of interstitial lung disease per 100 person-years was 18.42 (95% CI 16.42-20.59) for dermatomyositis and 5.39 (95% CI 4.43-6.50) for polymyositis. In the analysis adjusted for sex, age, and comorbidity score, the risk of interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis (hazard ratio 2.72, 95% CI 2.18-3.41). The rate diverged markedly between the groups in the first year after diagnosis. Risk factors for interstitial lung disease were older age in dermatomyositis, female sex and rheumatoid arthritis in polymyositis. Glucocorticoids with/without tacrolimus were the most common newly prescribed drugs after the interstitial lung disease diagnosis. In conclusion, the risk of developing interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis, and risk factors were different in the 2 patient groups.

Project description:OBJECTIVES:Interstitial lung disease (ILD) is an extramuscular manifestation that results in increased morbidity and mortality from polymyositis (PM) and dermatomyositis (DM). The aim of this study was to systematically evaluate risk factors associated with the development of ILD in PM/DM. METHODS:Observational studies were identified from searching PubMed, Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) or standardized mean differences (SMDs) and corresponding 95% confidence intervals (CIs) were obtained for the relationships between risk factors and ILD in PM/DM using either fixed- or random-effects models, whichever were appropriate. Heterogeneity tests, sensitivity analyses, and publication bias assessments were also performed. RESULTS:Twenty-three studies were selected for a meta-analysis that included 834 patients and 1245 control subjects. Risk factors that may have increased the risk of developing ILD in PM/DM patients included older age at diagnosis (SMD, 0.35; 95% CI, 0.18-0.52; P < 0.0001), arthritis/arthralgia (OR, 3.17; 95% CI, 1.99-5.04; P < 0.00001), fever (OR, 2.31; 95% CI, 1.42-3.76; P = 0.0007), presence of anti-Jo-1 antibodies (OR, 3.34; 95% CI, 2.16-5.16; P < 0.00001), elevated erythrocyte sedimentation rate (ESR; SMD, 0.48; 95% CI, 0.32-0.64; P < 0.00001), presence of anti-MDA5 antibodies (OR, 18.26; 95% CI, 9.66-34.51; P < 0.00001), and elevated C-reactive protein level (CRP; OR, 3.50; 95% CI, 1.48-8.28; P = 0.004). Meanwhile, malignancy (OR, 0.36; 95% CI, 0.18-0.72; P = 0.004) reduced the risk of developing ILD in PM/DM patients. CONCLUSION:Our meta-analysis results suggest that the association between PM/DM and ILD may be due to such risk factors as older age at diagnosis, arthritis/arthralgia, fever, presence of anti-Jo-1 antibodies, elevated ESR, presence of anti-MDA5 antibodies, and elevated CRP level, while malignancy was associated with a reduced risk of developing ILD. Thus, these variables may be used to guide screening processes for ILD in patients with PM/DM.

Dataset Information

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

Objective

Methods

Results

Conclusion

Trial registration

Publications

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

Similar Datasets

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