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Most patients with Sjogren's syndrome treated with low doses of interleukin-2 (IL-2) in a randomized, placebo-controlled trial showed significant improvement, researchers said.

After 24 weeks in the 60-person trial, 66.7% of those assigned to IL-2 met the primary endpoint, a 3-point decrease in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) scores, compared with 26.7% of the placebo group (P=0.004), according to Jing He, MD, of Peking University People's Hospital in Beijing, and colleagues.

IL-2 treatment was also associated with improvement in other clinical and laboratory measures, including shifts in immune cell populations thought to be responsible for Sjogren's. No important safety risks were seen, the researchers .

Sjogren's syndrome is an autoimmune disease that cuts glandular fluid secretions, most prominently in the eyes and mouth, although other organs can be affected as well. The , in fact, counts effects on 12 organ systems. Current treatment typically involves corticosteroids, hydroxychloroquine, and broad-spectrum immunosuppressants, such as cyclosporine and azathioprine; while these do reduce symptoms, they are "associated with substantial adverse effects," He and colleagues noted, since treatment generally continues indefinitely.

Previous studies had shown that Sjogren's patients are deficient in regulatory T cells, which are key to immune tolerance and are induced by IL-2, leading to the hypothesis that injections of the cytokine may restore a more normal balance of immune cell populations. (The group had previously tried the patients, with encouraging results.) In the , He and colleagues hoped to show that the IL-2 treatment promotes markers of immune tolerance as well as improving the clinical symptoms.

It seems to have worked out exactly that way.

For the trial, He and colleagues enrolled 60 Sjogren's patients, all women, mean age about 50. Baseline ESSDAI scores averaged 8.0 in the intervention group and 7.0 among those assigned to placebo. Other clinical measures included patients' assessments of various symptoms, a fatigue scale, ocular and salivary gland exams, and the 36-item Short Form (SF-36) inventory for overall health. Patients also gave blood samples for immunoglobulin and complement measurements.

IL-2 was administered as subcutaneous injections of 1 million IU in 4-week cycles, consisting of doses every other day for 2 weeks followed by 2 weeks off. Placebo injections were given on the same schedule. Patients received three cycles, then were followed for an additional 12 weeks.

Overall, the mean change from baseline in ESSDAI score at week 24 was -3.67 points with IL-2 versus -1.20 points with placebo, for a mean 2.47-point advantage with the intervention (P<0.001). Most secondary clinical measures also showed significant improvement, especially patient-assessed dryness and fatigue and the SF-36's mental health component. Biomarkers such as parotid gland enlargement, leukopenia, and interstitial lung disease trended in IL-2's favor but did not reach statistical significance. "No serious adverse events were observed," the researchers reported.

With regard to immune cell effects, each dose of IL-2 led to rapid increases in regulatory T-cell counts that faded back to baseline before the next injection. Beneficial IL-10-producing B-cell populations also increased, which then appeared to suppress pathogenic effector T-cell activity. "Thus, it seems plausible that IL-2 may induce immune tolerance by targeting the CD24^highCD27+ B cell subset," He and colleagues concluded. However, they acknowledged that the persistence of these latter effects after dosing stopped was perplexing and "needs further characterization."

Limitations to the study included the small number of participants and its conduct at a single institution in China. The researchers also cautioned that the dosage and dosing schedule for IL-2 used in the trial was not necessarily optimal.

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