Takeda Development Center Americas Inc., Cambridge, Massachusetts, USA.
Takeda Pharmaceuticals International Inc., Cambridge, Massachusetts, USA.
J Clin Pharmacol. 2021 Sep;61(9):1174-1181. doi: 10.1002/jcph.1877. Epub 2021 Jul 14.
Patients in the GEMINI 1 or 2 study (NCT00790933; Eudra CT2008-002784-14) with ulcerative colitis or Crohn disease had low immunogenicity rates after vedolizumab treatment for up to 52 weeks. We report immunogenicity rates from the GEMINI long-term safety (LTS) study using a new drug-tolerant electrochemiluminescence assay, including analyses in patients who received continuous vedolizumab induction and maintenance in GEMINI 1 or 2 and long term safety, or vedolizumab induction and placebo maintenance in GEMINI 1 or 2 followed by re-treatment in long term safety (treatment interruption). Patients were enrolled in GEMINI long term safety from GEMINI 1, 2, or 3, or as de novo vedolizumab-treated patients; all received vedolizumab 300 mg intravenously every 4 weeks. Vedolizumab antidrug antibody (ADA) status was determined by electrochemiluminescence assay; ADA-positive samples were characterized by neutralizing activity. Vedolizumab ADA data were available for 1753 patients: 1513 continuously treated with vedolizumab before/during GEMINI long term safety, 240 re-treated after treatment interruption. Among continuously treated patients, 36 (2.4%) were ADA positive (15 persistently, 20 neutralizing ADA positive). Among re-treated patients, 53 (22.1%) were ADA positive (42 persistently, 40 neutralizing ADA positive). Longitudinal immunogenicity rates increased during placebo maintenance (19.4% at week 52), then decreased in GEMINI long term safety to rates (0 at the final visit) similar to continuously treated patients. ADA positivity was 1.1% vs 2.5% (continuous treatment) and 23.1% vs 22.0% (re-treatment) among patients with and without infusion-related reactions, respectively. Long-term vedolizumab treatment was associated with generally low immunogenicity rates; vedolizumab-re-treated patients had higher rates during placebo maintenance, which decreased during re-treatment. No relationship was observed between immunogenicity and infusion-related reactions.
在 GEMINI 1 或 2 研究（NCT00790933；Eudra CT2008-002784-14）中，患有溃疡性结肠炎或克罗恩病的患者在接受维得利珠单抗治疗长达 52 周后，其免疫原性率较低。我们报告了使用新的药物耐受电化学发光测定法的 GEMINI 长期安全性（LTS）研究中的免疫原性率，包括在 GEMINI 1 或 2 中接受连续维得利珠单抗诱导和维持治疗以及在 GEMINI 1 或 2 中接受维得利珠单抗诱导和安慰剂维持治疗后进行长期安全性再治疗（治疗中断）的患者的分析。患者从 GEMINI 1、2 或 3 入组 GEMINI 长期安全性研究，或作为新接受维得利珠单抗治疗的患者；所有患者均接受静脉内维得利珠单抗 300mg，每 4 周 1 次。通过电化学发光测定法确定维得利珠单抗抗药物抗体（ADA）状态；ADA 阳性样本通过中和活性进行特征分析。1753 例患者有维得利珠单抗 ADA 数据：1513 例在 GEMINI 长期安全性之前/期间连续接受维得利珠单抗治疗，240 例在治疗中断后再治疗。在连续治疗的患者中，36 例（2.4%）ADA 阳性（15 例持续阳性，20 例中和 ADA 阳性）。在再治疗的患者中，53 例（22.1%）ADA 阳性（42 例持续阳性，40 例中和 ADA 阳性）。在安慰剂维持期间（第 52 周时为 19.4%），免疫原性率呈纵向增加，然后在 GEMINI 长期安全性中降至与连续治疗患者相似的水平（最后一次就诊时为 0）。在有和无输注相关反应的患者中，ADA 阳性率分别为 1.1%比 2.5%（连续治疗）和 23.1%比 22.0%。长期接受维得利珠单抗治疗与总体较低的免疫原性率相关；在安慰剂维持期间，再治疗患者的比率较高，在再治疗期间下降。未观察到免疫原性与输注相关反应之间存在关系。
