Gottlieb Alice B, Cooper Kevin D, McCormick Thomas S, Toichi Eiko, Everitt Daniel E, Frederick Bart, Zhu Yaowei, Pendley Charles E, Graham Martin A, Mascelli Mary Ann
Department of Dermatology, Tufts-New England Medical Center, Boston, MA 02111, USA.
Curr Med Res Opin. 2007 May;23(5):1081-92. doi: 10.1185/030079907x182112.
To evaluate safety, pharmacokinetics, pharmacodynamics, and clinical response of single subcutaneous (s.c.) administrations of a human monoclonal antibody against the p40 subunit of IL-12/23 (IL-12/23 mAb) in subjects with moderate-to-severe psoriasis.
Twenty-one subjects were enrolled sequentially into 4 dose cohorts (0.27, 0.675, 1.35, and 2.7 mg/kg) and randomized to IL-12/23 mAb or placebo in a 4:1 ratio. Laboratory/clinical parameters and pharmacokinetics were evaluated through Week 24; mRNA cytokine expression was measured in psoriatic plaques at Week 1.
Mostly mild adverse events and no serious adverse events were reported. The pharmacokinetics (Cmax and AUC) of IL-12/23 mAb increased in an approximately dose-proportional manner. Of the 17 subjects who received IL-12/23 mAb, 13 achieved PASI 75 (compared with no placebo subjects). mRNA expression of IL-8, IL-18, and IFN-gamma in psoriatic plaques decreased in subjects with sustained Psoriasis Area and Severity Index (PASI) improvement.
Interpretation of results is limited due to the small sample size in each dose cohort.
A single s.c. administration of IL-12/23 mAb was well tolerated and showed clinical response in subjects with moderate-to-severe psoriasis.
评估皮下注射单剂量抗白细胞介素12/23（IL-12/23）p40亚基人单克隆抗体（IL-12/23单克隆抗体）在中重度银屑病患者中的安全性、药代动力学、药效学及临床反应。
21名受试者按顺序入组4个剂量组（0.27、0.675、1.35和2.7mg/kg），并以4:1的比例随机分为IL-12/23单克隆抗体组或安慰剂组。在第24周前评估实验室/临床参数及药代动力学；在第1周测量银屑病斑块中的mRNA细胞因子表达。
报告的大多为轻度不良事件，无严重不良事件。IL-12/23单克隆抗体的药代动力学（Cmax和AUC）以近似剂量比例的方式增加。在接受IL-12/23单克隆抗体的17名受试者中，13名达到了银屑病面积和严重程度指数改善75%（PASI 75）（相比之下，安慰剂组无受试者达到）。银屑病面积和严重程度指数（PASI）持续改善的受试者中，银屑病斑块中IL-8、IL-18和干扰素-γ的mRNA表达下降。
由于每个剂量组的样本量较小，结果的解释受到限制。
皮下注射单剂量IL-12/23单克隆抗体耐受性良好，在中重度银屑病患者中显示出临床反应。
