Arthritis Associates, Orlando, Florida.
CymaBay Therapeutics, Newark, California.
Arthritis Rheumatol. 2016 Aug;68(8):2027-34. doi: 10.1002/art.39684.
Arhalofenate is a novel antiinflammatory uricosuric agent. The objective of this study was to evaluate its antiflare activity in patients with gout.
This was a 12-week, randomized, double-blind, controlled phase IIb study. Eligible patients had had ≥3 flares of gout during the previous year, had discontinued urate-lowering therapy and colchicine, and had a serum uric acid (UA) level of 7.5-12 mg/dl. Patients were randomly assigned at a 2:2:2:2:1 ratio to receive 600 mg arhalofenate, 800 mg arhalofenate, 300 mg allopurinol, 300 mg allopurinol plus 0.6 mg colchicine, or placebo once a day. The primary outcome measure was the flare incidence (number of flares divided by time of exposure). The serum UA level was a secondary outcome measure.
A total of 239 gout patients were randomized and took at least 1 dose of study medication. The primary outcome measure comparing flare incidence between 800 mg arhalofenate and 300 mg allopurinol was achieved, with a 46% decrease in the 800 mg arhalofenate group (0.66 versus 1.24; P = 0.0056). Treatment with 800 mg arhalofenate was also significantly better than placebo (P = 0.049) and not significantly different from treatment with 300 mg allopurinol plus 0.6 mg colchicine (P = 0.091). Mean changes in serum UA level were -12.5% with 600 mg arhalofenate and -16.5% with 800 mg arhalofenate (P = 0.001 and P = 0.0001, respectively, versus -0.9% with placebo). There were no meaningful differences in adverse events (AEs) between groups, and there were no serious AEs related to arhalofenate. Urinary calculus occurred in 1 patient receiving 300 mg allopurinol. No abnormal serum creatinine values >1.5-fold the baseline value were observed in the arhalofenate-treated groups.
Arhalofenate at a dosage of 800 mg decreased gout flares significantly compared to allopurinol at a dosage of 300 mg. Arhalofenate was well tolerated and appeared safe. Arhalofenate is the first urate-lowering antiflare therapy.
阿法洛芬酸是一种新型的抗炎排尿酸药物。本研究的目的是评估其在痛风患者中的抗复发活性。
这是一项为期 12 周、随机、双盲、对照的 2b 期研究。合格的患者在过去一年中有≥3 次痛风发作，已停止降尿酸治疗和秋水仙碱治疗，且血清尿酸（UA）水平为 7.5-12mg/dl。患者按 2:2:2:2:1 的比例随机分配接受 600mg 阿法洛芬酸、800mg 阿法洛芬酸、300mg 别嘌醇、300mg 别嘌醇加 0.6mg 秋水仙碱或安慰剂，每日 1 次。主要结局指标为复发发生率（复发次数除以暴露时间）。血清 UA 水平是次要结局指标。
共有 239 例痛风患者随机分组并至少服用了 1 剂研究药物。800mg 阿法洛芬酸与 300mg 别嘌醇比较复发发生率的主要结局指标达到，800mg 阿法洛芬酸组复发率降低 46%（0.66 与 1.24；P=0.0056）。800mg 阿法洛芬酸治疗也明显优于安慰剂（P=0.049），与 300mg 别嘌醇加 0.6mg 秋水仙碱治疗无显著差异（P=0.091）。600mg 阿法洛芬酸治疗组血清 UA 水平平均下降 12.5%，800mg 阿法洛芬酸治疗组下降 16.5%（分别与安慰剂组比较，P=0.001 和 P=0.0001）。各组间不良事件（AE）无明显差异，阿法洛芬酸相关严重 AE 无发生。1 例接受 300mg 别嘌醇治疗的患者发生尿路结石。阿法洛芬酸治疗组未观察到血清肌酐值异常>1.5 倍基线值。
与 300mg 别嘌醇相比，800mg 阿法洛芬酸可显著降低痛风发作。阿法洛芬酸耐受性良好，安全性好。阿法洛芬酸是第一种降尿酸抗复发治疗药物。
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