WASHINGTON (FRONTLINE MEDICAL NEWS) – A novel biologic treatment strategy involving subcutaneous low-dose interleukin-2 therapy for refractory systemic lupus erythematosus (SLE) showed promise in a single-center, combined phase I/IIa trial.

In 12 patients with active and refractory SLE – that is, patients with SLE disease activity index (SLEDAI) score of at least 6 who were on at least two different immunosuppressive therapies – low-dose IL-2 treatment led to an effective and cycle-dependent increase in the percentage of CD25hi cells among regulatory T cells (Treg). The increase was statistically significant (P less than .001), Jens Humrich, MD, and his colleagues reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.

Further, a reduction in SLEDAI was seen in 10 patients (83.3%), and a clinical response occurred in 8 (66.7%), with complete resolution of clinical manifestations including rash, arthritis, myositis, and alopecia.

However, a reduction in levels of anti-dsDNA antibodies was not observed, said Dr. Humrich of University Hospital Schleswig-Holstein in Lubeck, Germany.

Treatment was safe; treatment-related adverse events were generally mild and transient, Dr. Humrich noted.

Study subjects received four treatment cycles each, with daily subcutaneous injections of recombinant human IL-2 (aldesleukin) at single doses of 0.75, 1.5, or 3.0 million IU on 5 consecutive days. Cycles were separated by a washout period of 9-16 days. Subjects were then followed for 9 weeks.

IL-2 is crucial for the growth and survival of Treg (and thus for the control of autoimmunity). Prior studies demonstrated the significance of acquired IL-2 deficiency and related Treg defects in the pathogenesis of SLE – and that compensation for IL-2 deficiency with low-dose IL-2 can correct these defects, he explained.

In the current study, the primary aim was to show at least a twofold increase in the percentage of CD25hi cells among CD3+CD4+Foxp3+CD127lo Treg cells after the fourth treatment cycle vs. baseline, and secondary aims included clinical responses assessed by SLEDAI and changes in serologic and other immunologic parameters, he said.

The findings suggest that low-dose IL-2 therapy can safely and selectively expand the Treg population and decrease disease activity in patients with active and refractory SLE.

“This study provides the basis for larger and placebo-controlled clinical studies aiming to prove the efficacy of this novel biologic treatment strategy,” the investigators concluded.

Dr. Humrich reported having no disclosures.