Department of Rheumatologic and Immunologic Disease, Cleveland Clinic, Cleveland, OH, USA.
Division of Rheumatology, Hospital for Special Surgery, New York, NY, USA.
Clin Exp Rheumatol. 2021 Sep-Oct;39(5):1085-1092. doi: 10.55563/clinexprheumatol/b7jjnb. Epub 2021 Jan 6.
To determine factors associated with gout flares in subjects treated with pegloticase.
Gout flares from two randomised controlled trials comparing pegloticase (8 mg every 2 weeks [q2] or monthly [q4]) versus placebo were analysed. Responders had persistent urate lowering (<6mg/dL) whereas, non-responders had transient urate lowering during the 6-month RCTs. Gout flares (self-reported) were defined as acute joint pain and swelling requiring treatment. Gout flare prophylaxis (colchicine, 0.6 mg once or twice daily, or a non-steroidal anti-inflammatory drug) was initiated 1 week before the first infusion and continued throughout the study. Plasma urate at the time of flare and the change in urate preceding a flare were analysed.
Mean flare rates increased with pegloticase versus placebo during the first 3 months followed by marked reductions during months 4-6. The increase in flares with pegloticase during the first 3 months was most evident (p=0.0006) and the decrease during the second 3 months was least marked (p=0.0006) in subjects receiving monthly pegloticase. Fluctuation in urate levels was highest in monthly responders (p=0.002) and was associated with flare occurrence. Multivariate linear regression analysis indicated the only variables significantly associated with flares were treatment group and absolute change in plasma urate before flares.
Pegloticase treatment increased flares during the first 3 months of treatment in all groups when plasma urate was significantly lowered and was followed by a decline in months 4-6 in patients maintaining a low plasma urate. Flares associated with pegloticase treatment were associated with decreases and fluctuations in plasma urate levels.
确定接受培戈洛酶治疗的受试者中痛风发作的相关因素。
分析了两项随机对照试验中培戈洛酶（每 2 周[q2]或每月[q4]8mg）与安慰剂相比的痛风发作情况。应答者持续降低尿酸（<6mg/dL），而非应答者在 6 个月 RCT 期间尿酸短暂降低。痛风发作（自述）定义为需要治疗的急性关节疼痛和肿胀。痛风发作预防（秋水仙碱，0.6mg 每日一次或两次，或非甾体抗炎药）在第一次输注前 1 周开始，并持续整个研究过程。分析发作时的血浆尿酸和发作前尿酸的变化。
与安慰剂相比，培戈洛酶组在头 3 个月的平均发作率增加，随后在第 4-6 个月显著降低。在接受每月培戈洛酶治疗的患者中，前 3 个月培戈洛酶治疗引起的发作增加最为明显（p=0.0006），而第 2 个 3 个月的下降幅度最小（p=0.0006）。每月应答者的尿酸水平波动最大（p=0.002），与发作的发生有关。多变量线性回归分析表明，唯一与发作显著相关的变量是治疗组和发作前血浆尿酸的绝对变化。
在所有组中，当血浆尿酸显著降低时，培戈洛酶治疗在治疗的头 3 个月内增加了发作，并且在第 4-6 个月期间，在维持低血浆尿酸的患者中下降。与培戈洛酶治疗相关的发作与血浆尿酸水平的降低和波动有关。
