Low-Dose IL-2 Safe, Well Tolerated Among Patients With Primary Sjögren Syndrome

Low-dose IL-2 was found to be effective and well tolerated among patients with primary Sjögren syndrome.

Low-dose interleukin (IL)-2 was found to be well tolerated and effective in the treatment of primary Sjögren syndrome (pSS), according to study findings published in JAMA Network Open.

Research has shown that IL-2 controls the homeostasis and activation of CD4+ T cells, playing a major role in the development, proliferation, and survival of regulatory T cells (Tregs). It is also known that dysregulation of T and B cells with impaired Treg cell function promotes the development of pSS.

Low-dose IL-2 improves Treg cell function and may potentially benefit patients with pSS.

Researchers in China conducted a randomized double-blind placebo-controlled trial at Peking University People’s Hospital from June 2015 to August 2017 to assess the efficacy and safety of low-dose IL-2, as well as patient immune response to treatment.

Data were collected from patients with pSS who were randomly assigned to the treatment or the placebo group. Patients in the treatment group received low-dose IL-2 at a dose of 1 million IU subcutaneously every other day for 2 weeks followed by a 2-week pause in treatment, while the placebo group received an equivalent subcutaneous injection.

In this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells.

The researchers assessed pSS disease activity levels at baseline and weeks 4, 12, and 24, using the European Alliance of Associations for Rheumatology (EULAR) Sjögrens Syndrome Disease Activity Index (ESSDAI). They evaluated the efficacy of IL-2 based on improvements on the ESSDAI by 3 or more points after 24 weeks.

In addition, the researchers evaluated changes in other clinical manifestations, such as dryness, fatigue, and pain, using the visual analog scale (VAS) on the EULAR SS Patient Reported Index (ESSPRI), the 36-Item Short Form Survey (SF-36), and the Multidimensional Fatigue Inventory (MFI-20). They also analyzed clinical data obtained from ocular examinations, salivary gland ultrasonography, lung function tests, and immunologic indexes, including immunoglobulins A (IgA), G (IgG), and M (IgM), complement 3 (C3) and complement 4 (C4), and erythrocyte sedimentation rate (ESR).

A total of 60 patients with pSS were included in the study (n=30 each in the treatment and placebo groups). After 24 weeks, ESSDAI scores improved by 3 or more points in 66.7% of the treatment group compared with 26.7% of the placebo group (P =.004). Patients in the treatment vs placebo group also demonstrated significant improvements in ESSDAI scores at week 12 (P <.001).

After 12 weeks, patients in the treatment vs placebo group demonstrated improvements in clinical manifestations of pSS, according to ESSPRI VAS scores, including dryness (difference, -18.33 points; P =.001), fatigue (difference, -11.67 points; P =.01), and pain (difference, -10.33 points; P =.03).

After 24 weeks, patients receiving treatment with IL-2 demonstrated notable improvements in quality of life and mental health on the SF-36 (difference, -0.58 points; P <.001).

Lung function improved among 12 patients with pSS in the treatment group. Improvements were also noted in capacity of diffuse carbon monoxide at weeks 12 (P =.01) and 24 (P =.003) and forced vital capacity percentage (P =.03) at week 24 compared with baseline.

More patients in the treatment vs placebo group recovered from thrombocytopenia and leukopenia by week 12. In addition, patients receiving IL-2 demonstrated trends indicative of reduced pSS disease activity, such as resolution of persistent parotid gland swelling and arthritis.

The researchers assessed treatment-associated adverse events, such as injection site reactions, infection, and other adverse reactions. No serious adverse events occurred in both groups. Patients in the treatment vs placebo group showed a decreased incidence of infection (P =.006).

Study limitations included the small cohort size resulting in insufficient statistical power and lack of clinical stratification, the lack of comprehensive comparison between dosage and interval of IL-2 administration, and the lack of follow-up after discontinuation of treatment with IL-2.

“[Low-dose] IL-2 was effective and well tolerated in patients with pSS,” the study authors said. “It restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells.”


He J, Chen J, Miao M, et al. Efficacy and safety of low-dose interleukin 2 for primary sjögren syndrome: A randomized clinical trial. JAMA Netw Open. 2022;5(11):e2241451. doi:10.1001/jamanetworkopen.2022.41451