Background/Purpose: Urate-lowering therapy is recommended to lower serum urate (sUA) and for long-term prevention of gout flares (FitzGerald et al. Arthritis Care Res (Hoboken) 2020; Dalbeth et al. Lancet 2021), though an initial increase in gout flares after ULT initiation has been documented (Feng et al. Int J Clin Exp Med 2015; Schlesinger et al. Nat Rev Rheumatol 2023). NASP (formerly SEL-212) is an investigational, every 4-week, sequential infusion therapy designed to reduce sUA levels in patients (pts) with uncontrolled gout (UG), consisting of targeted immunomodulating, nanoencapsulated sirolimus (NAS; formerly SEL-110), sequentially administered with pegadricase (a pegylated uricase; formerly SEL-037). Gout flare incidence in pts receiving NASP has been previously reported (Baraf et al. British Society for Rheumatology (BSR) 2024 Annual Meeting; Poster P084). Here, we report gout flare outcomes in pts who received 6 doses of NASP or placebo (PBO).

Methods: This post hoc analysis of pooled data from DISSOLVE I (NCT04513366) and DISSOLVE II (NCT04596540) focuses on gout flare outcomes in pts who received 6 doses of NASP (high-dose [HD]: sequential infusions, 0.15 mg/kg NAS and 0.2 mg/kg pegadricase; low-dose [LD]: sequential infusions, 0.10 mg/kg NAS and 0.2 mg/kg pegadricase) or PBO every 4 weeks. Flares were assessed using a validated definition in pts with gout (Gaffo et al. Arthritis Rheumatol 2018).

Results: Overall, 42, 35 and 67 pts received 6 doses in the HD, LD, and PBO groups, respectively. At treatment initiation (weeks 1–4), the proportion of pts who experienced a gout flare was similar in the three treatment arms: 23.8%, 28.6% and 20.9% in pts treated with HD NASP, LD NASP and PBO, respectively. Over the study period (up to week 24), the proportion of pts experiencing flares decreased for NASP and remained consistent for PBO: 4.8%, 5.7% and 22.4% of pts in the HD, LD, and PBO arms, respectively, experienced a flare during weeks 21-24. During weeks 13–24, the average number of gout flares per patient was 2.3 and 5.7 times fewer on HD and LD, respectively, vs PBO (HD: 12 flares in 42 pts, rate of 0.29 gout flares per patient; LD: 4 in 35 pts, rate of 0.11; PBO: 44 in 67 pts, rate of 0.66). Cumulative gout flare rates over time were similar between NASP- and PBO-treated pts through Day 100. Between days 100–200, cumulative gout flare rates plateaued in NASP-treated pts but continued to increase in PBO-treated pts (Figure 1). Across all treatment arms, most flares ranged from mild to moderate intensity.

Conclusion: The proportion of pts with flares and number of flares decreased with NASP compared to PBO over the course of the study, with 95.2% and 94.3% of HD and LD-treated pts being flare-free during weeks 21–24. These results highlight the potential of NASP as an effective therapy for reducing disease burden and improving a key clinical outcome in pts with UG.

Figure 1. Cumulative mean estimate of gout flares in patients who completed 6 doses of study drug.

Cumulative mean function estimate of gout flares per patient is shown for patients receiving 6 doses of HD NASP (yellow), LD NASP (teal) or PBO (dark gray). The event of interest is gout flare, and multiple gout flares are taken into consideration in the cumulative mean function. The analysis relative day is the number of days since the first dose of treatment.

HD NASP, sequential infusions of 0.15 mg/kg nanoencapsulated sirolimus and 0.2 mg/kg pegadricase, LD NASP, sequential infusions of 0.10 mg/kg nanoencapsulated sirolimus and 0.2 mg/kg pegadricase; PBO, placebo.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/nanoencapsulated-sirolimus-plus-pegadricase-nasp-demonstrates-a-reduction-in-gout-flares-results-from-the-phase-3-dissolve-studies/