Novel SEL-212 Therapy Improves Quality of Life in Patients with Gout
Reductions in the mean number of tender joints from baseline to month 6 were greater among patients in the treatment groups compared with placebo.
Puja Khanna, MD, MPH
Credit: University of Michigan
Patients with gout refractory to standard treatment receiving SEL-212 in either low dose (LD; 0.1 mg/kg) or high dose (HD; 0.15 mg/kg) formulations showed improvements in health-related quality of life (HRQoL) and tender joint count, according to data presented at the 2024 European Congress of Rheumatology (EULAR).1 A decline in urate over time was observed based on the similar rates of gout flare during the first 3 months of treatment and subsequent reductions in frequency of flare at the end of the trial.
Hyperuricemia, defined as serum uric acid (sUA) levels of ≥ 6.8 mg/dL, can lead to the accumulation of monosodium urate crystals in the cartilage, soft tissue, and joints, and may result in the formation of tophi, tender and swollen joints, gout flares, and diminished HRQoL.1
“Uricase-based therapies effectively lower sUA in patients with clinical manifestations of gout refractory to conventional sUA-lowering therapies; however their use is limited by immunogenicity-related efficacy reductions and infusion reactions,” wrote a team of investigators led by Puja Khanna, MD, MPH, a clinical professor of rheumatology at the University of Michigan.1
SEL-212, a novel, once-monthly, uricase-based infusion treatment, is comprised of an infusion of SEL-110 followed by a pegylated uricase (SEL-037). The combination allows for targeted immunomodulation that maintains sUA without needing broader immunosuppression.1
Investigators used aggregated data from the DISOLVE I and DISOLVE II trials to analyze HRQoL at 6 months among patients with gout treated with SEL-212. The placebo-controlled, double-blind, replicate-design, phase 3 clinical trials assessed the safety and efficacy of both HD and LD in adults with sUA ≥ 7 mg/dL with inadequate symptom control despite receiving medically appropriate doses of traditional gout treatments.1
Patients were randomized 1:1:1 to receive SEL-110 HD or LD prior to SEL-037 (0.2 mg/kg) infusion, or placebo, administered intravenously every 28 days for 6 treatments. In DISSOLVE 1, patients continued in a 6-month blinded extension phase, and the primary endpoint was the percentage of patients who achieved and maintained sUA <6 mg/dL for ≥ 80% of the treatment period. Tolerability and safety were determined using the monitoring of adverse events.2
Analyses of these trials included changes from baseline to treatment period in health assessment scores, such as the Health Assessment Questionnaire Disability Index (HAQ-DI) and the 36-item Short Form Survey (SF-26) physical component summary score, and tender joints. Changes in flare incidence were assessed for months 1 – 3 and months 4 – 6.1
In total, 87 patients in the pooled intent-to-treat (ITT) cohort were placed in the HD group, 88 were placed in the LD group, and 90 received placebo. Among these patients, 60, 60, and 70, respectively, completed 6 months of treatment. These patients were mostly White, male, and had ≥ 1 tophus coupled with an impaired HRQoL at baseline. The mean age ranged from 52.2 to 55.3 years and the mean duration of gout ranged from 11.3 to 12.3 years. Patient characteristics were generally comparable across treatment groups.1
Reductions in the mean number of tender joints from baseline to month 6 were greater among patients in the HD and LD cohorts (5.3 and 6.7, respectively) compared with placebo (2.7). The mean gout flare incidence was 0.3 for all treatment groups during the first treatment period and 0.1 (HD), 0.0 (LD), and 0.2 (placebo) during months 4 through 6.1
References
- Khanna P, Patel A, Singhal A, Kivitz A, et al. Health-Related Quality of Life (HRQoL) and Other Secondary Clinical Outcomes in Adults with Gout Refractory to Conventional Therapy Treated with SEL-212: Pooled 6-Month Data from the Phase 3 DISSOLVE I & II Clinical Trials. Presented at: EULAR. Vienna, Austria. June 12 – 15, 2024.
- Pine L. SEL-212 shows significant response rates, sua reductions in patients with gout. HCP Live. November 13, 2023. Accessed July 11, 2024. https://www.hcplive.com/view/sel-212-shows-significant-response-rates-sua-reductions-in-patients-with-gout.
