IL-1抑制剂Rilonacept在降尿酸初期可预防痛风急性发作

IL-1抑制剂Rilonacept在降尿酸初期可预防痛风急性发作

张警丰

        摘要  目的：评估IL-1抑制剂rilonacept在初始降尿酸治疗的几个月中预防痛风急性发作的作用。

        方法：入组条件为高尿酸血症的成年痛风患者，按照1：1的比例随机分配至实验组与对照组，采用随机对照双盲法，实验周期为16周。实验组每周予皮下注射rilonacept一次（负荷量320mg，以后每周160mg）,对照组予安慰剂注射。治疗初始均予别嘌醇300mg/d，至血清尿酸浓度低于6mg/dl。观察指标包括体格检查、实验室指标和不良反应发生情况。

        结果：rilonacept组（n=41）与对照组（n=42）基线资料无差异。在12周的初始有效终点内，痛风急性发作的患者比例，rilonacept组显著低于对照组（0.15[6例]vs 0.79[33例]，P=0.001）。在初始治疗后4周rilonacept组的痛风急性发作率即低于对照组（P=0.007）。12周以后rilonacept组痛风急性发生率亦低于对照组（14.6% vs 45.2%, P=0.004）。在16周时rilonacept组及对照组均停药，之后随访6周未见痛风急性发作反弹。两组间副反应相当，无死亡及严重感染副反应报道。最常见的副反应是感染（rilonacept组14.6%，对照组26.2%）及骨骼肌异常（rilonacept组14.6%，对照组21.4%）。Rilonacept组的12周评估完成率要高于对照组（98% vs 79%,P=0.015）。

        结论：Rilonacept可显著降低初始降尿酸治疗时急性痛风发作率，并且具有很好的安全性。

        附原文  Abstract  OBJECTIVE: To evaluate the interleukin-1 inhibitor rilonacept (IL-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy (ULT).METHODS: Adult hyperuricemic patients with gout were randomized 1:1 to 16 weeks of once-weekly subcutaneous treatment with double blind rilonacept (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). Study visits included physical examination, laboratory assessments, review of adverse events.RESULTS: Baseline characteristics were similar between rilonacept (n=41) and placebo (n=42) groups. The mean number of gout flares per patient through week 12 (primary efficacy endpoint) was markedly lower in the rilonacept group relative to placebo (0.15 [6 flares] versus 0.79 [33 flares]; P=0.001). Fewer flares were observed with rilonacept as early as 4 weeks after initiating treatment (P=0.007). The proportion of patients with flares was lower with rilonacept relative to placebo over 12 weeks (14.6% versus 45.2%; P=0.004). No rebound in flare rate was observed for 6 weeks after rilonacept or placebo were discontinued at week 16. Adverse events were similar between groups, no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% rilonacept and 26.2% placebo) and musculoskeletal disorders (14.6% rilonacept and 21.4% placebo). A higher percentage of rilonacept-treated patients (98%) compared with placebo (79%) completed the primary 12-week evaluation period (P=0.015).CONCLUSION: Rilonacept significantly reduced gout flares during initiation of ULT and demonstrated a favorable safety profile. (NCT00610363 [ClinicalTrials.gov Identifier].

        引自：Schumacher HR Jr, Sundy JS, Terkeltaub R, et al.Rilonacept (IL-1 Trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: results of a Phase 2 clinical trial. Arthritis Rheum. 2012 Jan 4. doi: 10.1002/art.33412.