Interleukin-2 on Active Dermatomyositis

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

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

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.

Inclusion Criteria:

1. Age 18-75 years old (including 18 and 75 years old);

2. 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.

3. 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.

4. 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.

5. 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:

1. Received intravenous glucocorticoid (> 1 mg/kg/d) within 4 weeks;
2. 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.
3. Dermatomyositis patients with other connective tissue diseases or tumors;
4. Allergic constitution or allergic to multiple drugs;
5. 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;
6. Those who are positive for hepatitis B surface antigen or hepatitis C antibody;
7. Persons with mental illness or other reasons who cannot cooperate with treatment.