Low-Dose IL-2 May Be Safe, Effective in the Treatment of Systemic Lupus Erythematosus

Researchers evaluated the safety and efficacy of low-dose IL-2 therapy in systemic lupus erythematosus in a double-blind and placebo-controlled trial.

Low-dose interleukin-2 (IL-2) may be safe and effective in the treatment of systemic lupus erythematosus (SLE), according to results of a clinical trial published in the Annals of Rheumatic Diseases.

In this prospective, randomized, double-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02465580), researchers sought to verify the clinical response and safety of low-dose IL-2 (recombinant human IL-2 from Escherichia coli) in patients aged 18 to 65 years with active SLE (n=60).

Patients were randomly assigned to receive either low-dose IL-2 or placebo; both groups of patients were administered subcutaneously every other day for 2 weeks, followed by a 2-week interval. All patients were treated for the first 12 weeks, which included 3 treatment cycles, and followed up for an additional 12 weeks without study medicine. Patients were evaluated at screening, every 2 weeks until week 12, and every 4 weeks after that until week 24. Laboratory tests included peripheral blood mononuclear cells (T cells and natural killer cells), complete blood count, complete metabolic profile, urinalysis, serum immunoglobulin, complement component 3 (C3) and C4, anti-dsDNA antibodies, and antinucleosome antibodies.

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At week 12, the SLE Responder Index-4 (SRI-4) response rates of IL-2 were 55.17% for patients receiving IL-2 compared with 30.00% for patients receiving placebo (P =.052). By the end of the trial at week 24, 65.52% of patients in the low-dose IL-2 group reached SRI-4 response, compared with 36.67% of patients in the placebo group (P =.027). The rate of complete remission of lupus nephritis was significantly higher in the IL-2 group than in the placebo group at week 12 (53.85% vs 8.33%; P =.013) and week 24 (53.85% vs 16.67%; P =.036). A lower incidence of infection was indicated in patients receiving IL-2 compared with the placebo group (6.9% vs 20.0%), but without statistical significance. No serious adverse events were observed in the IL-2 group, but 2 patients in the placebo group had serious infections that required hospitalization.

Study limitations affecting trial outcomes included the possibility that patients could have responded differently to dosage regimen, and no dose-ranging comparison was designed in the trial. Background treatments such as calcineurin inhibitors may have affected the efficacy of low-dose IL-2. Researchers indicated that future clinical studies involving low-dose IL-2 therapy should recruit a larger cohort and stratify patients based on background treatments.

Low-dose IL-2 has the potential to become a new therapy to treat a broad range of inflammatory and autoimmune disorders refractory to current therapies. “Distinct from immunosuppressants and biologics which often increased infection incidence, low-dose IL-2 treatment was effective in SLE and was probably not accompanied with increased infection incidence,” the researchers concluded.


He J, Zhang R, Shao M, et al. Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial [published online September 19, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-215396