Interleukin-2 on Refractory Dermatomyositis
Study Details
Study Description
Brief Summary
The purpose of this paper is to explore the effect of low-dose IL-2 on refractory dermatomyositis and immunological indexes.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: low-dose IL-2 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
low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10~6 IU once every other day, for 6 months.
Other Names:
|
| Placebo Comparator: Placebo 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
low dose interleukin-2 injected subcutaneously, at a dose of 1 x 10~6 IU once every other day, for 6 months.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of subjects achieving minimal improvement (TIS≥20). [week 12]
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.
Secondary Outcome Measures
- MMT-8 (Manual Muscle Testing), (potential score 0 - 80); [week12 and 24]
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.
- 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); [week12 and 24]
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.
- Physician's Global Disease Activity VAS, (potential score 0 - 10); [week12 and 24]
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.
- Patient's Global Disease Activity VAS, (potential score 0 - 80); [week 12 and 24]
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.
- Health assessment question, (potential score 0 - 3); [week 12 and 24]
Patients reported how their illness affects their ability to function in daily life , Higher scores mean a better outcome.
- Myositis disease activity assessment tool (MDAAT) - 2005, VERSION 2 [week 12 and 24]
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.
- CD4 T cells [week 12 and 24]
number and proportion of CD4 T cells in peripheral blood.
- Serum cytokines [week 12 and 24]
concentration of serum cytokines
- glucocorticoid dosage [week 12 and 24]
Daily dosage of glucocorticoid
- Rate of Participants with adverse effects associated with experimental drugs [up to 24 weeks]
Adverse effects include fever, rash, abnormal liver function, rate of new-onset infection and any abnormal measures associated with low-dose IL-2 therapy.
- Proportion of subjects meeting the definition of improvement (DOI) [week12 and 24]
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).
- Number of subjects achieving minimal improvement (TIS≥20). [week 24]
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.
Eligibility Criteria
Criteria
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:
-
- patients global assessment (PGA), the minimum value of 10 cm visual analog scale (VAS) is 2.0 cm
-
- Physicians global assessment (PhGA), the minimum value on the 10 cm VAS scale is 2.0 cm
-
- Health Assessment Questionnaire (HAQ), with a minimum value of 0.25
-
- 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
-
- 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)].
-
- 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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Peking University People's Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IIMIL2