Rheumatology, Center for Rheumatology and Bone Research, Wheaton, MD, USA.
Rheumatology, George Washington University, Washington DC, USA.
Rheumatology (Oxford). 2024 Apr 2;63(4):1058-1067. doi: 10.1093/rheumatology/kead333.
Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase.
COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety.
During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only.
SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase.
NCT03905512.
聚乙二醇尿酸酶可降低痛风患者的血清尿酸（SU）水平，减少痛风发作和痛风石。然而，治疗中出现的抗药物抗体会对安全性和疗效产生不利影响，目前已批准的聚乙二醇尿酸酶培戈洛酶需要每两周输注一次。研究中的 SEL-212 疗法旨在通过每月顺序输注专有雷帕霉素纳米颗粒（ImmTOR）和 pegadricase 来促进尿酸酶特异性耐受。
COMPARE 是一项随机、2 期、开放性 SEL-212 与培戈洛酶治疗难治性痛风的临床试验。SEL-212[ImmTOR（0.15mg/kg）和 pegadricase（0.2mg/kg）]每月输注一次，或培戈洛酶（8mg）每两周输注一次，共 6 个月。主要终点是在 3 个月和 6 个月期间 SU＜6mg/dl 的参与者比例≥80%。次要结局是平均 SU、痛风发作、压痛和/或肿胀关节的数量以及安全性。
在 3 个月和 6 个月联合期间，与培戈洛酶相比，用 SEL-212 治疗的参与者达到并维持 SU＜6mg/dl 的时间比例更高（53.0%vs46.0%，P=0.181）。SEL-212 与培戈洛酶相比，在 3 个月和 6 个月期间 SU 水平的降低百分比具有统计学意义（-73.79%和-47.96%，P=0.0161）。两种治疗方法在痛风发作发生率和压痛和/或肿胀关节数量方面的降低情况相当。SEL-212 和培戈洛酶最常见的治疗相关不良事件之间存在数值差异：痛风发作（60.2%vs50.6%）、感染（25.3%vs18.4%）和输注相关反应（15.7%vs11.5%）。SEL-212 有 8 名（9.6%）参与者出现痛风，培戈洛酶有 0 名参与者出现痛风。与雷帕霉素相关的口腔炎（及其相关术语）在 8 名（9.6%）接受 SEL-212 治疗的患者中出现，而在接受培戈洛酶治疗的患者中则没有。口腔炎是雷帕霉素的已知事件，仅与 ImmTOR 相关。
在难治性痛风中，SEL-212 的疗效和耐受性与培戈洛酶相当。由于与培戈洛酶相比，SEL-212 的输注频率降低，因此治疗负担显著减轻。
NCT03905512。
