This study is a randomized, controlled, single-center clinical study to evaluate the short-term efficacy of low-dose Interleukin-2 injection as an add-on therapy for the treatment of patients aged 18-75 who have been diagnosed with CSU and remain symptomatic despite oral antihistamine treatment .

Backgrounds:

Urticaria is a common disorder that present with localized edema reaction caused by dilatation and increased permeability of small blood vessels in skin and mucosa. The main clinical manifestations are wheal and erythema reaction.

Chronic spontaneous urticaria (CSU) is defined as the recurrent, transient (<24h), pruritic wheals of the skin and mucosa lasting for more than 6 weeks ,with or without angioedema, excluding chronic inducible urticaria and urticarial vasculitis. Among all patients with chronic urticaria, CSU patients accounts for about 80%. Although the pathogenesis of CSU is still unclear, increasing evidence has shown an autoimmune feature of this chronic disease. Oral antihistamines are the mainstay of treatment for patients with CSU. However, a proportion of patients with CSU remain symptomatic despite treatment with standard- or doubled-dose of antihistamines. In recent years, studies have shown that low-dose recombinant human IL-2 (rhIL-2) treatment has good therapeutic effect in a variety of autoimmune diseases, such as systemic lupus erythematosus, type 1 diabetes, without serious side reactions. Therefore, we propose low-dose rhIL-2 as an add-on treatment for patient with CSU that are recalcitrant to treatment with antihistamines. Here we designed this clinical trial to explore its therapeutic effect as well as therapeutic mechanisms.

Design of Study:

This is a randomized, controlled, single-center clinical trial to assess the short-term efficacy of rhIL-2 treatment for patients with CSU.

Methods:

RhIL-2 injection combined with the current dose of antihistamine (Use one kind or two to three kinds in combination, and use one or two doses of each kind of antihistamine，keeping doses before enrollment) will be applied to CSU patients meeting the inclusion criteria. The end points include clinical response and immunological changes, as well as safety.

Inclusion Criteria:

1. Age: between 18- and 75-years old;
2. Patients definitely diagnosed with chronic spontaneous urticaria according to 'Guideline for diagnosis and treatment of urticaria in China (2018) '; or chronic spontaneous urticaria has been diagnosed in the past.
3. Patients taking antihistamines daily ( one kind or two to three kinds in combination, with a standard- or doubled-dose of each kind of antihistamines) for at least one week and remain symptomatic with a UAS7 score of not less than 16;
4. Written informed consent was obtained, and the patient volunteers to participate in the project and complete the project as required.

Exclusion Criteria:

1. Patients with severe diseases of heart, brain, lungs, liver, kidney or blood system; patients experienced organ transplantation;
2. Patients with any acute severe infection such as pyemia and cellulitis, active tuberculosis, or an infection history of human immunodeficiency virus (HIV);
3. Patients have a clear history of allergy to rhIL-2;
4. Patients receiving Interleukin-2 treatment in the last 3 months by subcutaneous or intramuscular injection；
5. Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment;
6. Pregnant women, lactating women or women who are willing to conceive within 3 months;
7. Patients receiving glucocorticoid treatment in the last 4 weeks; Patients receiving cyclosporin treatment in the last 90 days；Patients receiving tripterygium wilfordii polyglycoside treatment in the last 6 months；Patients receiving Omalizumab treatment in the last 1 year；Other drugs used previously should be identified whether they are in the washout period one by one, and patients who have taken drugs that may have an impact on the study should be excluded during the washout period or screened again for enrollment after the washout period；
8. Patients who have participated in other clinical trials within 3 months before the screening.