A single-arm, pilot study to evaluate the efficacy and safety of induction therapy of corticosteroids, tacrolimus, and mycophenolate mofetil in patients with anti-ARS antibody syndrome.
Efficacy and safety of induction therapy of corticosteroids, tacrolimus, and mycophenolate mofetil for anti-ARS antibody syndrome.
Furuta Shunsuke
Chiba University Hospital
1-8-1, Inohana, Chuo-ku, Chiba-shi, Chiba
+81-43-222-7171
shfuruta@chiba-u.jp
Takahashi Tatsuro
Chiba University Hospital
1-8-1, Inohana, Chuo-ku, Chiba-shi, Chiba
+81-43-222-7171
tatsuro.takahashi@chiba-u.jp
Recruiting
Dec. 25, 2024
Jan. 08, 2025
15
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
The following criteria apply to patients who meet all of the following conditions
1) The patient is at least 18 years old at the time of obtaining consent
2) The patient is newly diagnosed with anti-ARS antibody syndrome based on the following criteria
The patient is positive for serum anti-ARS antibodies and has at least one of the following findings (i-ii)
i. Progressive interstitial pneumonia: Findings of interstitial pneumonia on chest CT, and worsening over time of any of the following respiratory symptoms, imaging findings, or respiratory function test values associated with interstitial pneumonia
ii. Myositis: definite or probable according to the diagnostic criteria for polymyositis/dermatomyositis of Bohan & Peter (1-2)
3) Patients who have given their written consent freely and of their own accord after being fully informed of the study and its procedures
1) Received corticosteroids for inflammatory muscle disease or interstitial lung disease within 1 week prior to obtaining consent
2) Received immunosuppressive drugs, TNF inhibitors, IL-6 inhibitors, anti-CD20 monoclonal antibody products, JAK inhibitors, intravenous immunoglobulin or plasma exchange therapy within 12 weeks prior to obtaining consent
3) Comorbidity of other systemic autoimmune diseases (except rheumatoid arthritis and Sjogren's syndrome)
4) On maintenance dialysis or with chronic kidney disease with eGFR less than 30 mL/min/1.73 m2
5) HIV infection, hepatitis B virus or hepatitis C virus infection or history of infection
6) Coexisting active tuberculosis
7) History of malignancy within 5 years (except for intraepithelial carcinoma that is considered curatively resected)
8) Patient has uncontrollable complications
9) Pregnant, seeking pregnancy, within 28 days postpartum, or breastfeeding
10) In the opinion of the principal investigator or subinvestigators, is unfit to safely conduct this study
18age old over
No limit
Both
anti-synthetase syndrome
Start corticosteroids from Day 1, add tacrolimus and mycophenolate mofetil by Day 14, and continue until the end of the study.
The percentage of patients who maintained remission at 52 weeks with only the treatment specified in the protocol and who were not receiving corticosteroids
Definition of remission
The dose of corticosteroids must be 5 mg/day or less (prednisolone equivalent) and there must be no evidence of disease activity as defined below
Findings of disease activity
At least one of the following findings is present due to the activity of anti-ARS antibody syndrome (excluding cases caused by factors other than anti-ARS antibody syndrome)
1) A clear worsening of interstitial pneumonia is observed on a simple chest X-ray or chest CT scan compared to the most recent scan (however, clinically exclude infectious pneumonia, drug-induced pneumonia, and hypersensitivity pneumonia)
2) A decrease of 10 points or more in %FVC or 15 points or more in %DLco compared to the most recent value in respiratory function tests
3) A decrease in the number of muscle groups assessed by MMT-8 compared to the previous assessment, or the presence of obvious muscle pain
4) Two or more consecutive increases in myogenic enzymes (CK or ALD) of more than three times the upper limit of normal
5) Active arthritis
6) Active skin lesions that are difficult to control with topical medication
Definition of relapse
The appearance of disease activity after achieving remission, requiring intensification of systemic treatment
Secondar efficacy endpoints
1) Percentage of patients achieving remission at 52 weeks
2) TIS at 8 weeks and 52 weeks
3) Changes in each core set endpoint included in the TIS at 8 and 52 weeks
4) Percentage of patients showing TIS20, TIS40, and TIS60 at 8 and 52 weeks
5) Changes in %FVC and %DLco
6) Changes in blood laboratory values (CK, ALD, LDH, KL-6)
7) Percentage of relapse and relapse-free survival up to 52 weeks
8) Symptoms, corticosteroid dose and total dose of corticosteroids at relapse
9) Dose of corticosteroids at 52 weeks
10) Cumulative dose of corticosteroids at 52 weeks
The secondary safety endpoint is the Incidence of adverse events.
Chiba University Hospital
Not applicable
Chiba University Certified Clinical Research Review Board
