Background/Purpose: Patients (pts) with gout have impaired health-related quality of life (HRQoL) relating to acute or chronic inflammation from elevated serum uric acid (sUA) levels. SEL-212 is a novel, once-monthly, two‐component infusion therapy of nanoparticles containing sirolimus (SEL-110) followed by pegadricase (SEL‑037, a pegylated uricase) designed to reduce sUA. Results from DISSOLVE I and II (DI and DII) Phase 3 trials demonstrated that SEL-212 significantly improved response rates (sUA <6 mg/dL for ≥80% of treatment period [TP] 6) and mean sUA levels vs placebo in pts with chronic refractory gout. Post hoc analyses were conducted in pts who received the first 3 (F3D) or 6 doses (F6D) of SEL-212, to assess effects on physical and mental functioning, daily activities and pain.

Methods: DI (US) and DII (global) were randomized, double-blind, placebo-controlled trials of pts with ≥3 gout flares within 18 months prior to screening or ≥1 tophus or a current diagnosis of gouty arthritis, in whom oral urate lowering therapy failed to normalize sUA and control symptoms, and naïve to uricase-based therapy. Pts received high- or low-dose (HD or LD) SEL‑212 (consisting of SEL-110 [0.15 or 0.1 mg/kg] plus SEL-037 [0.2 mg/kg]) or placebo on Day 0 (D0) for each of the six 28-day TPs. Patient reported outcomes (PROs: 36‑item Short Form survey [SF‑36], Health Assessment Questionnaire-Disability Index [HAQ-DI] and pain visual analogue scale [VAS]) were assessed at baseline, TP4 D0 and TP6 D28. Analyses were performed using pooled data from DI and DII and reported as least squares mean [standard error].

Results: Baseline characteristics were similar in the intent-to-treat and F3D/F6D populations and across treatment arms for the F3D/F6D subgroups (Table 1). Change from baseline in SF-36 physical component summary score was improved to a greater extent with SEL-212 LD (5.6 [0.1]) vs placebo (4.0 [0.9]) in the F3D subgroup, and further improved with SEL‑212 LD (9.0 [1.6]) and SEL-212 HD (6.8 [1.3]) vs placebo (2.7 [1.1]) in the F6D subgroup (Fig 1A). Change from baseline in SF-36 mental component summary score was improved to a greater extent with SEL-212 LD (4.7 [1.1]) and SEL-212 HD (2.9 [1.1]) vs placebo (1.6 [1.0]) in the F3D subgroup, while an improvement was observed for SEL-212 LD (4.2 [1.5]) vs placebo (2.9 [1.0]) in the F6D subgroup (Fig 1B). In the F3D subgroup, change from baseline in HAQ-DI was improved with SEL‑212 LD (-0.4 [0.1]) vs placebo (-0.1 [0.1]) (Fig 2A). In the F6D subgroup, change from baseline in HAQ‑DI was improved with SEL-212 LD (-0.4 [0.1]) and SEL-212 HD (-0.3 [0.1]) vs placebo (-0.2 [0.1]) (Fig 2A). Similar data were reported for pain VAS score, with a trend for improved outcomes observed in the F6D vs FD3 subgroup (Fig 2B).

Conclusion: Clinically meaningful changes in PROs were reported after 3 doses of SEL-212, which further improved after 3 additional doses, indicating patients reported an incremental HRQoL benefit with prolonged treatment duration. SEL-212 improved clinical and HRQoL outcomes, including functional ability, mental health and pain, in adults with refractory gout, which is likely reflective of improved urate lowering with this novel agent.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/improvements-in-patient-reported-outcomes-after-treatment-with-sel-212-in-adults-with-refractory-gout-results-from-two-randomized-phase-3-trials/