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.
他指出，该研究的主要目标是证明4个周期治疗后CD25hi/ CD3+CD4+Foxp3+CD127lo Treg比率至少比基线时增加2倍，次要目标包括通过SLEDAI评估临床应答、血清学以及其他免疫学指标改变等。
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.
来源： Frontline Medical News