一项比较 Briakinumab 与甲氨蝶呤治疗银屑病患者的 52 周临床试验。
A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis.
机构信息
Dermatologikum Hamburg, Hamburg, Germany.
出版信息
N Engl J Med. 2011 Oct 27;365(17):1586-96. doi: 10.1056/NEJMoa1010858.
BACKGROUND
Briakinumab is a monoclonal antibody against the p40 molecule shared by interleukin-12 and interleukin-23, which is overexpressed in psoriatic skin lesions. We assessed the efficacy and safety of briakinumab as compared with methotrexate in patients with psoriasis.
METHODS
In this 52-week trial, we randomly assigned 317 patients with moderate-to-severe psoriasis to briakinumab, at a dose of 200 mg at weeks 0 and 4 and 100 mg at week 8 and every 4 weeks thereafter (154 patients), or methotrexate, at a dose of 5 to 25 mg weekly (163 patients). The primary end points were the percentages of patients with at least 75% improvement in the score on the psoriasis area-and-severity index (PASI) at weeks 24 and 52 and a score on the physician's global assessment of 0 (clear; i.e., no apparent disease) or 1 (minimal disease) at weeks 24 and 52. A total of 248 patients were enrolled in an ongoing 160-week open-label continuation study.
RESULTS
At week 24, a total of 81.8% of the patients in the briakinumab group versus 39.9% in the methotrexate group had at least 75% improvement in the PASI score, and 80.5% versus 34.4% had a score of 0 or 1 on the physician's global assessment. The corresponding percentages at week 52 were 66.2% versus 23.9% with at least a 75% improvement in the PASI score and 63.0% versus 20.2% with a score of 0 or 1 on the physician's global assessment (P<0.001 for all comparisons). During the 52-week study, serious adverse events occurred in 9.1% of the patients in the briakinumab group (12.9 events per 100 patient-years) and in 6.1% in the methotrexate group (10.6 events per 100 patient-years). Serious infections occurred in 2.6% of the patients in the briakinumab group (4.1 events per 100 patient-years) and in 1.8% in the methotrexate group (2.7 events per 100 patient-years); cancers occurred in 1.9% (2.0 events per 100 patient-years) versus 0%.
CONCLUSIONS
Briakinumab showed higher efficacy than methotrexate in patients with moderate-to-severe psoriasis. Serious infections and cancers occurred more frequently with briakinumab, but the differences were not significant. (Funded by Abbott Laboratories; ClinicalTrials.gov number, NCT00679731.).
背景
布利akinumab 是一种针对白细胞介素-12 和白细胞介素-23 共同的 p40 分子的单克隆抗体，在银屑病皮损中过度表达。我们评估了 briakinumab 与甲氨蝶呤在银屑病患者中的疗效和安全性。
方法
在这项为期 52 周的试验中，我们将 317 名中重度银屑病患者随机分为 briakinumab 组（200mg 剂量，第 0 周和第 4 周，第 8 周和此后每 4 周 100mg，154 例）或甲氨蝶呤组（每周 5 至 25mg，163 例）。主要终点是第 24 周和第 52 周时，银屑病面积和严重程度指数（PASI）至少改善 75%的患者比例，以及第 24 周和第 52 周时医生整体评估为 0（清除；即无明显疾病）或 1（最小疾病）的患者比例。共有 248 名患者参加了正在进行的 160 周开放标签延续研究。
结果
第 24 周时，briakinumab 组共有 81.8%的患者 PASI 评分至少改善 75%，而甲氨蝶呤组为 39.9%；briakinumab 组有 80.5%的患者医生整体评估得分为 0 或 1，而甲氨蝶呤组为 34.4%。第 52 周时，PASI 评分至少改善 75%的患者比例分别为 66.2%和 23.9%，医生整体评估得分为 0 或 1的患者比例分别为 63.0%和 20.2%（所有比较均<0.001）。在 52 周的研究期间，briakinumab 组有 9.1%的患者（每 100 患者年发生 12.9 例）发生严重不良事件，而甲氨蝶呤组为 6.1%（每 100 患者年发生 10.6 例）。briakinumab 组有 2.6%的患者（每 100 患者年发生 4.1 例）发生严重感染，而甲氨蝶呤组为 1.8%（每 100 患者年发生 2.7 例）；briakinumab 组有 1.9%的患者（每 100 患者年发生 2.0 例）发生癌症，而甲氨蝶呤组为 0%。
结论
与甲氨蝶呤相比，布利akinumab 在中重度银屑病患者中显示出更高的疗效。布利akinumab 组发生严重感染和癌症的频率更高，但差异无统计学意义。（由 Abbott Laboratories 资助；临床试验.gov 编号，NCT00679731）。
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