Reich Kristian, Papp Kim A, Griffiths Christopher E M, Szapary Philippe O, Yeilding Newman, Wasfi Yasmine, Ott Elyssa, Hsu Ming-Chun, Lebwohl Mark, Gordon Kenneth B
Dermatologikum Hamburg, Germany.
J Drugs Dermatol. 2012 Mar;11(3):300-12.
The efficacy and safety profile of ustekinumab with up to three years of exposure suggested a favorable benefit-risk profile in patients with moderate to severe psoriasis.
To evaluate the safety of ustekinumab in patients with moderate to severe psoriasis treated for up to four years.
Safety data were pooled across four Phase II/III randomized controlled trials. Rates over time and cumulative rates of adverse events (AEs), AEs leading to treatment discontinuation, serious adverse events (SAEs), serious infections, malignancies, and major adverse cardiovascular events (MACE) (i.e., cardiovascular death, myocardial infarction [MI], or stroke as adjudicated by an independent panel of academic cardiologists) were evaluated. Observed rates of AEs of interest were compared with those expected in the general (malignancies, MI, and stroke) and psoriasis (serious infections, MI, and stroke) populations.
Overall, 3,117 patients were followed for up to four years (6,791 patient-years). Rates of AEs, AEs leading to treatment discontinuation, and SAEs remained stable over time, whereas cumulative rates were generally comparable between patients who received 45 mg and 90 mg of ustekinumab. The rates of AEs of interest also remained stable over time, and cumulative rates per 100 patient-years were 0.80 and 1.32 (serious infections), 0.70 and 0.53 (nonmelanoma skin cancer), 0.63 and 0.61 (other malignancies), and 0.56 and 0.46 (MACE) in patients treated with 45 mg and 90 mg, respectively. Rates of AEs of interest were consistent with those in the general and psoriasis populations.
The safety profile of long-term ustekinumab treatment with up to four years of continuous use remains consistent with previous reports, with no evidence of cumulative toxicity.
使用优特克单抗长达三年的疗效和安全性表明，中度至重度银屑病患者的获益风险比良好。
评估优特克单抗治疗中度至重度银屑病患者长达四年的安全性。
汇总四项II/III期随机对照试验的安全性数据。评估不良事件（AE）、导致治疗中断的AE、严重不良事件（SAE）、严重感染、恶性肿瘤和主要不良心血管事件（MACE，即由学术心脏病专家独立小组判定的心血管死亡、心肌梗死[MI]或中风）随时间的发生率以及累积发生率。将观察到的感兴趣AE的发生率与一般人群（恶性肿瘤、MI和中风）和银屑病患者人群（严重感染、MI和中风）中预期的发生率进行比较。
总体而言，3117例患者随访长达四年（6791患者年）。AE、导致治疗中断的AE和SAE的发生率随时间保持稳定，而接受45mg和90mg优特克单抗的患者累积发生率总体相当。感兴趣AE的发生率也随时间保持稳定，45mg和90mg治疗的患者每100患者年的累积发生率分别为0.80和1.32（严重感染）、0.70和0.53（非黑色素瘤皮肤癌）、0.63和0.61（其他恶性肿瘤）以及0.56和0.46（MACE）。感兴趣AE的发生率与一般人群和银屑病患者人群中的发生率一致。
连续使用长达四年的长期优特克单抗治疗的安全性与既往报告一致，无累积毒性证据。
