Central Dermatology, St. Louis, MO 63117, USA.
Am J Clin Dermatol. 2011 Oct 1;12(5):321-37. doi: 10.2165/11587890-000000000-00000.
A favorable benefit-risk profile has been established for adalimumab, with up to 5 years of treatment in 13 clinical trials in patients with moderate to severe chronic plaque psoriasis.
The aim of this analysis was to assess the long-term safety of all adalimumab exposure in all psoriasis clinical trials.
A total of six sets of data were analyzed as follows: (i) all cumulative safety data from all exposure for all adalimumab-treated patients in the 13 clinical trials in moderate to severe psoriasis (All Adalimumab Treatment Population) through April 2007, November 2008, and November 2009, respectively; (ii) longitudinal data for 1403 patients treated with adalimumab 40 mg every other week (eow) dosing (Every Other Week Population) through June 2007 and April 2010; and (iii) data from placebo-controlled periods of clinical trials. Adverse events that occurred up to 70 days after the final dose of adalimumab were analyzed.
During placebo-controlled periods, a total of 572 patients had 173.0 patient-years (PYs) of exposure to placebo and 1188 patients had 370.5 PYs of exposure to adalimumab. Adverse event incidence rates, expressed as events per 100 PYs (events/100 PYs), for placebo- and adalimumab-treated patients for serious adverse events were 7.52 and 8.64, and for serious infectious adverse events were 2.89 and 2.43, respectively. In the 2007, 2008, and 2009 All Adalimumab Treatment Population there were, respectively, 1819 patients (2424.7 PYs), 2197 patients (4351.9 PYs), and 3010 patients (4844.7 PYs), with serious adverse event incidence rates of 6.51, 7.22, and 8.36 events/100 PYs, and serious infectious adverse event rates of 1.32, 1.38, and 1.65 events/100 PYs. In the 2007 and 2010 Every Other Week Population (n = 1403), there were 1883.5 and 2854.1 total PYs of exposure, respectively, with serious adverse event incidence rates of 6.32 and 6.87 events/100 PYs, and serious infectious adverse event rates of 1.33 and 1.37 events/100 PYs, respectively.
Multiple lines of evidence from a total of six sets of safety data, with treatment for up to 5 years, including results from all adalimumab-treated patients, and a subset of patients treated with 40 mg eow dosing, did not show evidence of cumulative toxicity, and showed adverse event rates that were generally stable or decreased with increased mean per-patient exposure.
阿达木单抗具有良好的获益风险比，在 13 项中重度慢性斑块型银屑病临床试验中，患者接受长达 5 年的治疗。
本分析旨在评估阿达木单抗所有暴露的长期安全性。
共分析了六组数据：（i）截至 2007 年 4 月、2008 年 11 月和 2009 年 11 月，所有阿达木单抗治疗的中重度银屑病临床试验中所有患者的所有累积安全性数据（所有阿达木单抗治疗人群）；（ii）接受阿达木单抗 40mg 每两周（每两周一次）治疗的 1403 例患者的纵向数据（每两周一次人群）至 2007 年 6 月和 2010 年 4 月；和（iii）来自临床试验的安慰剂对照期的数据。分析了阿达木单抗末次给药后 70 天内发生的不良事件。
在安慰剂对照期，572 例患者接受安慰剂治疗，暴露 173.0 患者年（PYs），1188 例患者接受阿达木单抗治疗，暴露 370.5 PYs。接受安慰剂和阿达木单抗治疗的患者严重不良事件的不良事件发生率，以每 100PYs（事件/100PYs）表示，分别为 7.52 和 8.64，严重感染性不良事件分别为 2.89 和 2.43。2007 年、2008 年和 2009 年的所有阿达木单抗治疗人群中，分别有 1819 例（2424.7PYs）、2197 例（4351.9PYs）和 3010 例（4844.7PYs），严重不良事件发生率分别为 6.51、7.22 和 8.36 事件/100PYs，严重感染性不良事件发生率分别为 1.32、1.38 和 1.65 事件/100PYs。在 2007 年和 2010 年的每两周一次人群（n=1403）中，分别有 1883.5 和 2854.1 总 PYs 暴露，严重不良事件发生率分别为 6.32 和 6.87 事件/100PYs，严重感染性不良事件发生率分别为 1.33 和 1.37 事件/100PYs。
共有六组安全性数据提供了多种证据，最长治疗时间达 5 年，包括所有接受阿达木单抗治疗的患者的数据，以及接受 40mg 每两周一次治疗的患者的一个亚组的数据，没有累积毒性的证据，并且表明不良事件发生率通常稳定或随着患者平均暴露量的增加而降低。
