Low-dose IL-2 Treatment on Behcet's Disease

Study Overview
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Brief Summary
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The study aims to explore the clinical and immunological efficacy of low-dose IL-2 on Behcet's Disease.

Detailed Description
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The investigators designed a single center, open-label, prospective study that routinely administered low-dose IL-2 therapy to monitor the improvement of clinical and laboratory parameters to explore its efficacy and to observe changes in immune cell subsets and cytokines. One million units of rhIL-2 was administered subcutaneously five days every week for 4 weeks and then twice a week for 8 weeks. All patients were followed up for 3 months after treatment.

Official Title
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Low-dose IL-2 Treatment on Behcet's Disease

Conditions
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Behcet's Disease

Intervention / Treatment
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* Drug: Low-dose IL-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 and ≤70 years of age at time of screening; Diagnosis of Behcet disease defined by the International Study Group Criteria of 1989; Patients who had active disease activity or intolerance after 3 months of conventional therapy; patients who had relapsed disease activity without treatment. Active manifestations including oral ulcers, genital ulcers, arthralgia, skin lesions and other systemic involvement manifestations. Intestinal BD-associated symptoms (abdominal pain, diarrhea, melena, etc.) and endoscopic evidence of active ulcers in the intestine. Aggravated visual acuity on a Snellen chart in at least one eye. Neurological BD (NBD) is classifies as either acute NBD (ANB) or chronic progressive NBD (CPNB) in accordance with the diagnostic criteria for NBD. Vascular BD (VBD) patients have active vasculitis lesions (deep vein thrombosis, aortic lesions, etc.) and abnormalities in inflammatory markers such as serum C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) at enrollment. Apply glucocorticoids (≤1.0mg/Kg*d prednisone or equivalent doses of other hormones) for 4 weeks. DMARDs ( methotrexate, hydroxychloroquine, azathioprine, morphine, leflunomide, cyclosporine, mycophenolate mofeti ) need to stable for 4 weeks. Other medications, such as, IVIg and cyclophosphamide need to more than 2 months, Rituximab for 6 months, other biological agents (infliximab, adalimumab, etanercept, anakinra, etc.) for 3 months. Have given written informed consent and patients are expected to be able to comply with the requirements of the study follow-up plan and other protocols. Exclusion Criteria: Stable disease activity; Received glucocorticoid >1.0mg/Kg*d within 4 weeks, used rituximab within 6 months and other biological agents within 3 months. Severe comorbidities: including Heart failure (≥ grade III NYHA); Renal insufficiency (creatinine clearance ≤30 ml/min); Hepatic insufficiency (serum ALT or AST >3 times the ULN, or total bilirubin >ULN for the central laboratory conducting the test). Other disease including hematopathy, gastrointestinal disease, endocrinopathy, pulmonary, neuropathy. Known allergies, hypersensitivity, or intolerance to IL-2 or its excipients. Severe infection, such as hepatitis, HIV, syphilis, pneumonia, bacteremia, cytomegalovirus and so on. Malignancy; Had uncontrolled psychiatric or emotional disorder; Pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose IL-2<br>One million units of rhIL-2 was administered subcutaneously five days every week for 4 weeks and then twice a week for 8 weeks. All patients were followed up for 3 months after treatment. | Drug: Low-dose IL-2<br>* One million units of rhIL-2 was administered subcutaneously five days every week for 4 weeks and then twice a week for 8 weeks. All patients were followed up for 3 months after treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Regulatory T cells at week 12 compared to baseline. | Regulatory T cell was examined by flow cytometry and the marker is CD4+CD25+FoxP3+ | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Behcet Syndrome Activity Scale (BSAS) Score. | The BSAS score comprises 10 items. Questions about oral ulcers (q1), genital ulcers (q3), skin lesions (q5), and current disease activity (q10) are scored from 0 to 10 (vi- sual analogue scale [VAS]), questions about the number of oral ulcers (q2), genital ulcers (q4), and skin lesions (q6) were scored as 0, 5, or 10, depending on which of the three were checked(0,n=0;5,n=1to3;10,n> 3 for q2 and q4; and n > 5 for q6), and questions about gastrointestinal/eye/vascular symptoms (q7, q8, and q9) were scored as 0 or 10, depending on whether or not they were present. The total score possible is 100. | Week 12 and Week 24 | 
| Change from baseline in physician global assessment activity | 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 Behcet Syndrome | Week 12 and Week 24 | 
| Change from baseline in number of oral and genital ulcers | Ulcers will be examined by a physician. | Week 12 and Week 24 | 
| Change in C-reactive protein from baseline |  | Week 12 and Week 24 | 
| Change in FoxP3+ Treg cell at week 12 and week 24 compared to baseline. |  | Week 12 and Week 24 | 
| Change in steroid dose at week 12 and week 24 compared to baseline. |  | Week 12 and Week 24 | 
| Change from baseline in simplified Behcet Disease Current Activity Form (BDCAF) Score | Simplified BDCAF score comprises 12 items of 10 systemic involvements. Question about headache, oral ulcers, genital ulcers, erythema, skin pustules, joints (arthralgia), joints (athritis), nausea/vomiting/abdominal pain, diarrhea with altered/frank blood per rectum, eye involvement, nervous system involvement, major vessel involvement are scored from 0 or 1 depending on the symptoms of previous 4 weeks by a physician. The total score possible is 12. | Week 12 and Week 24 | 
| Change from baseline in simplified electronic medical record -based activity index (EMRAI). | The EMRAI contains nine symptom scoring items and two laboratory results. Items include oral and genital ulcers, ocular symptoms, skin lesions, epididymitis, and symptoms related to the involvement of joints, the GI tract, the vascular system, and the central nervous system (CNS). laboratory results includ erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP). The presence of each item, ESR and CRP are dichotomised as 0 or 1. The total score possible is 11. | Week 12 and Week 24 | 
| Change from baseline in Behcet's disease ocular inflammatory score 24 (BOS24) | Behcet's disease ocular attack score 24 (BOS24) consists of a total 24 points divided into 6 parameters of ocular inflammatory symptoms, including anterior chamber cells (maximum 4 points), vitreous opacity (maximum 4 points), peripheral fundus lesions (maximum 8 points), posterior pole lesions (maximum 4 points), subfoveal lesions (maximum 2 points), and optic disc lesions (maximum 2 points). | Week 12 and Week 24 | 
| Change from baseline in erythrocyte sedimentation rate | erythrocyte sedimentation rate | Week 12 and Week 24 | 
| Rate of mean change in DAIBD score of 20 or more from baseline. | This primary endpoint applies to intestinal BD patients.The DAIBD will be assessed by collecting information on 8 different intestinal BD-related variables. These 8 variables are: fever, abdominal mass, abdominal tenderness, intestinal complications, extraintestinal manifestations, general well-being, abdominal pain, and total number of liquid stools. The last 3 variables are scored over 7 days by the participant on a diary card. Abdominal pain will be measured using the 11-point numeric rating scale (NRS) to standardize the evaluation of pain and the result of 11-point NRS will be divided into 4 grades (none, mild, moderate, severe) to fill out the DAIBD. where, None indicate 0; Mild indicate 1-3; Moderate indicate 4-6; Severe indicate 7-10. | week12 | 
| Rate of equal or more than 20% changes in Visual acuity. | This primary endpoint applies to ocular involvement of BD patients. | week12 | 
| Rate of participants without oral and genital ulcers. | Ulcers will be examined by a physician. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ulcers