Low-dose IL-2( Interleukin-2) Treatment in SLE

Not Applicable

Completed

Brief Summary: This clinical study will test the efficacy and safety of low dose IL-2 treatment in Systemic lupus erythematosus.

Detailed Description: Systemic lupus erythematosus (SLE) is a chronic autoimmune syndrome affecting various organs. While available therapies, such as corticosteroids and immunosuppressive agents have improved the outcome of patients, there remains a significant unmet need for safe and more effective treatments. Dysfunction of regulatory T (Treg) cells has been detected in diverse autoimmune diseases, which can be promoted by interleukin-2 (IL-2). We hypothesized that low-dose IL-2 could be a novel therapy in active SLE patients.

This is a single center, uncontrolled, open-label study to assess the efficacy/safety of low dose IL-2 plus standard therapy in active SLE.

Methods: Each SLE patients (n=40) with Scores\>=8 on the Safety of Estrogens in Lupus Erythematosus National Assessment (AELENA) version of the SLE Disease Activity Index (SLEDAI) that was refractory or relaps to glucocorticoid therapy received low-dose IL-2 (1 million units every other day subcutaneously (HrIL-2 1X 106, ip, Qod) for a period of 14 days. After a 14-day rest, another cycle started) for 3-6 cycles according to the situation of the disease. The end points were safety and clinical and immunologic response.

Expected Results: This trail will define low-dose IL-2 plus standard therapy is efficacy and safety with active lupus patients, which could be relevant to the amelioration the abnormity of T help cells in SLE patients.

Recruitment & Eligibility

Inclusion Criteria

Meet the American College of Rheumatology criteria for the diagnosis of SLE.
Under standard treatment (≥ 2 months) at the time of inclusion
Background treatment failed to control flares or to permit prednisone tapering
With at least one of the following manifestations: thrombocytopenia, disease-associated rash, mouth ulcer, non-infectious type of fever, active vasculitis, renal disorder(proteinuria>0.5g/day), neuropsychiatric SLE.
Positive for at least one of the following laboratory tests: ANA>1:160, anti-dsDNA, immunoglobulin>20g/L, decreased C3 or C4, leukopenia<3×10^9/L, thrombocytopenia<100×10^9/L;
SLE disease activity index(SLEDAI) ≥ 8.
Negative HIV test.
Negative for hepatitis B and C virus.
Written informed consent form.

Exclusion Criteria

Sever chronic liver, kidney, lung or heart dysfunction; (heart failure (≥ grade III NYHA), hepatic insufficiency (transaminases> 3N) )
Serious infection such as bacteremia, sepsis;
Cancer or history of cancer cured for less than five years (except in situ carcinoma of the cervix or Basocellular carcinoma);
High-dose steroid pulse therapy (>1.5mg/kg) or IV bolus of corticosteroids in the last 2 months.
History of administration of rituximab or other biologics;
Purified protein derivative (tuberculin) >10mm
Mental disorder or any other chronic illness or drug-abuse that could interfere with the ability to comply with the protocol or to give information;
Inability to comply with IL-2 treatment regimen.

Arm && Interventions

Group	Intervention	Description
Interleukin-2	Interleukin-2	Interleukin-2 to treat activated SLE.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Were SLE Responders (SRI)	week 2，week 4，week 6，week 8，week 10	SRI response was defined as (1) a ≥ 4-point reduction in SELENA-SLEDAI score, (2) no new BILAG A score or ≤ 1 new BILAG B score, and (3) no deterioration from baseline in the physician's global assessment by ≥ 0.3 points.

Secondary Outcome Measures

Name	Time	Method
Immunological Responses	week 0 and week 10	Analysis regulatory CD4+ T (Treg) cells , interleukin 17 (IL-17)-producing helper T (Th17) cells and follicular helper T (Tfh) cells before and during IL-2 treatment. P values below 0.05 are considered statistically significant in this study.
Safety Assessment	up to Day 180	Adverse events includes injection site reactions, influenza-like symptoms, infection, fever, tumor, cardiovascular event，drug-induced liver and kidney damage.
The Immunologic Impact of Low Dose IL-2 Treatment in SLE Patients	week 0 and week 10	Laboratory measures were detected, including, C3, C4 and anti-dsDNA titres.
SELENA SLEDAI Score	week 0, week 10	Assessment version of the SLE Disease Activity Index (SELENA-SLEDAI) change. The higher the score represent the worse of the disease. The total score ranges from 0 to 105 points, score\> 8 means the disease is moderate-to-severe active".
Number of Relapses	24 weeks	Relapses mean that if the patient's SELENA SLEDAI Score is lower than 4 during the treatment, while the SELENA SLEDAI Score increase after stopping using the study drugs in 3 months.