Interleukin-2 on Active Dermatomyositis

Study Overview
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Brief Summary
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The purpose of this paper is to explore the effect of low-dose IL-2 on refractory dermatomyositis and immunological indexes.

Detailed Description
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A randomized, double-blind, placebo-controlled, multicenter clinical trial was designed. Patients were treated with low-dose IL-2 regularly to explore its efficacy and safety. The improvement of clinical and laboratory indexes was evaluated. Changes of immune cell subsets and cytokines were monitored.

Official Title
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Therapeutic Effect of Interleukin-2 on Active Dermatomyositis: A Multicenter, Randomised, Double-blind, Placebo-controlled Trial

Conditions
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Dermatomyositis

Intervention / Treatment
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* Drug: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years old (including 18 and 75 years old); The diagnosis of dermatomyositis conforms to Bohan/Peter Recommendation in 1975 or EULAR/ACR Classification Standard in 2017. Active myositis was defined by baseline Manual Muscle Testing (MMT-8) no greater than 125/150 and at least two additional abnormal CSMs. To allow the enrolment of patients with active DM with a moderate to severe rash who may not meet the MMT-8 criterion noted above, patients with DM could be enrolled if their cutaneous VAS score on the Myositis Disease Activity Assessment Tool (MDAAT) was ≥3cm on the 10cm VAS scale and at least three of the five CSMs were abnormal (excluding the MMT-8). Abnormal CSMs include: 1. patients global assessment (PGA), the minimum value of 10 cm visual analog scale (VAS) is 2.0 cm 2. Physicians global assessment (PhGA), the minimum value on the 10 cm VAS scale is 2.0 cm 3. Health Assessment Questionnaire (HAQ), with a minimum value of 0.25 4. At least one muscle enzyme [including creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] High, the lowest level is 1.3 x upper limit normal 5. Global Extra-muscle Disease Activity Score, with a minimum of 1.0 cm on the 10 cm VAS scale [This measure is a comprehensive assessment by the physician based on an assessment of the physique, skin, bone, gastrointestinal, lung and heart scale activity scores,named Myositis Disease Activity Assessment Tool (MDAAT)]. 6. Manual Muscle Testing (MMT-8) no greater than 125/150. The dose of glucocorticoid (equivalent to prednisone) was less than 0.5mg/kg/d within 4 weeks before joining the group, and/or there were no new immunosuppressants (cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus, azathioprine, methotrexate, etc.) within 12 weeks, and the dose was stable for 4 weeks. Voluntary signing of informed consent: When participating in the trial, the patient must be given a written notice of consent, and hope that the patient can comply with the requirements of the study follow-up plan and other protocols. Agree to adopt effective contraceptive measures during the study period (women of childbearing age). Exclusion Criteria: Any subject meeting any of the following criteria should be excluded: Received intravenous glucocorticoid (> 1 mg/kg/d) within 4 weeks; Serious complications: including (1). heart failure (≥ NYHA III); (2). renal insufficiency (creatinine clearance rate ≤30 ml/min); (3). liver insufficiency (excluding serum ALT or AST caused by dermatomyositis, or total bilirubin greater than normal upper limit), (4). hemoglobin < 80g/L, E. platelet count < 60. Dermatomyositis patients with other connective tissue diseases or tumors; Allergic constitution or allergic to multiple drugs; Those who are in the period of acute and chronic infection (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, Epstein-Barr virus, tuberculosis infection), or are hospitalized for infection, or use intravenous antibiotics to treat infection 2 months before the first treatment, or have a history of active tuberculosis in the past; Those who are positive for hepatitis B surface antigen or hepatitis C antibody; Persons with mental illness or other reasons who cannot cooperate with treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose IL-2<br>The first stage (double-blind treatment period): One million IU of IL-2 was injected subcutaneously once every other day for 12 weeks. The second stage (open treatment period): One million IU of IL-2 was injected subcutaneously once every other day for 12 weeks. | Drug: Interleukin-2<br>* low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10 6 IU once every other day, for 6 months.<br>* Other names: Recombinant Human Interleukin-2;|
| Placebo Comparator: Placebo<br>The first stage (double-blind treatment period): Placebo was injected subcutaneously once every other day for 12 weeks. The second stage (open treatment period): One million IU of IL-2 was injected subcutaneously once every other day for 12 weeks. | Drug: Interleukin-2<br>* low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10 6 IU once every other day, for 6 months.<br>* Other names: Recombinant Human Interleukin-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving minimal improvement (TIS≥20). | The primary outcome will be to compare the proportion of subjects achieving minimal improvement (TIS≥20). The TIS (total improvement score) is the sum of all 6 improvement scores associated with the change in each core set measure. A total improvement score of ≥20 represents minimal improvement, a score of ≥40 represents moderate improvement, and a score of ≥60 represents major improvement. | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMT-8 (Manual Muscle Testing), (potential score 0 - 80); | MMT-8 is a set of 8 designated muscles tested unilaterally; test on right side (use left side if right side cannot be tested). Higher scores mean a better outcome. | week12 and 24 | 
| CDASI activity score (cutaneous dermatomyositis disease area and severity index), (potential score 0-100 for cutaneous dermatomyositis disease area and 0-32 for severity index); | The CDASI is a clinician-scored single page instrument that separately measures activity and damage in the skin of DM patients for use in clinical practice or clinical/therapeutic studies. Higher scores mean a worse outcome. | week12 and 24 | 
| Physician's Global Disease Activity VAS, (potential score 0 - 10); | Physician's Global Disease Activity (10 cm VAS assessing global disease activity from No evidence of disease activity to Extremely active or severe disease activity; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Higher scores mean a worse outcome. | week12 and 24 | 
| Patient's Global Disease Activity VAS, (potential score 0 - 80); | Patient's Global Disease Activity (10 cm VAS assessing global disease activity from No evidence of disease activity to Extremely active or severe disease activity; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Higher scores mean a worse outcome. | week 12 and 24 | 
| Health assessment question, (potential score 0 - 3); | Patients reported how their illness affects their ability to function in daily life , Higher scores mean a better outcome. | week 12 and 24 | 
| Myositis disease activity assessment tool (MDAAT) - 2005, VERSION 2 | This is a combined tool that captures the physician's assessment of disease activity of various organ systems using (1) the 0-4 scale described below and (2) a visual analog scale (VAS) [potential score 0 - 10]. Please assess the clinical features (items 1-26) of each organ system. Higher scores mean a worse outcome. | week 12 and 24 | 
| CD4 T cells | number and proportion of CD4 T cells in peripheral blood. | week 12 and 24 | 
| Serum cytokines | concentration of serum cytokines | week 12 and 24 | 
| glucocorticoid dosage | Daily dosage of glucocorticoid | week 12 and 24 | 
| Rate of Participants with adverse effects associated with experimental drugs | Adverse effects include fever, rash, abnormal liver function, rate of new-onset infection and any abnormal measures associated with low-dose IL-2 therapy. | up to 24 weeks | 
| Proportion of subjects meeting the definition of improvement (DOI) | The DOI for this trial is a composite utilizing the six CSM: 3 of 6 CSM improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (a worsening measure cannot be the MMT). | week12 and 24 | 
| Number of subjects achieving minimal improvement (TIS≥20). | The primary outcome will be to compare the proportion of subjects achieving minimal improvement (TIS≥20). The TIS (total improvement score) is the sum of all 6 improvement scores associated with the change in each core set measure. A total improvement score of ≥20 represents minimal improvement, a score of ≥40 represents moderate improvement, and a score of ≥60 represents major improvement. | week 24 |