Nanoencapsulated sirolimus plus pegadricase helps patients with uncontrolled gout

Treatment with nanoencapsulated sirolimus plus pegadricase yields higher response rates compared with placebo in patients with uncontrolled gout, according to the phase III DISSOLVE I and II studies.

A total of 265 patients were randomly assigned to receive infusions of high- or low-dose nanoencapsulated sirolimus plus pegadricase or placebo. Treatment was administered intravenously, every 4 weeks, for a total of six doses.

The primary endpoint was maintenance of serum urate levels below 6 mg/dL for at least 80 percent of the time during weeks 21–24. Secondary endpoints included health-related quality of life, tophus resolution, tender joints, and gout flares. Safety was also evaluated.

The percentage of patients who achieved the primary endpoint was significantly higher with nanoencapsulated sirolimus plus pegadricase than with placebo: 51 percent in the high-dose group and 43 percent in the low-dose group vs 8 percent in the placebo group (p<0.0001 for both).

During weeks 1–12, flares occurred in a similar number of patients across the three treatment groups. Thereafter, the incidence decreased among patients treated with nanoencapsulated sirolimus plus pegadricase but remained unchanged among those who received placebo.

In terms of safety, common adverse events included gout flares (42.5 percent in the high-dose group, 44.3 percent in the low-dose group, 43.3 percent in the placebo group), infections (23 percent, 18.2 percent, and 16.7 percent), and stomatitis (9.2 percent, 3.4 percent, and 0 percent). Infusion reactions within 1 h were infrequent (4 percent) among patients treated with nanoencapsulated sirolimus plus pegadricase.

The findings demonstrate that nanoencapsulated sirolimus plus pegadricase treatment has the potential to alleviate disease burden in patients with uncontrolled gout.