Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.
Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.
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乌司奴单抗抗体对银屑病的临床影响：一项观察性、横断面、多中心研究。
DOI：
10.1016/j.jid.2020.03.957
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Loeff FC
中科院分区：
文献类型：
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作者：
Loeff FC
乌司奴单抗是治疗银屑病的有效药物，但患者之间的反应不同。抗药抗体（ADA）的形成可通过降低游离乌司奴单抗水平来解释部分变异。目前，已发表的ADA临床影响分析尚不完整。在这项针对340名患者的观察性横断面多中心研究中，我们评估了ADA对乌司奴单抗水平和PASI评估的临床反应的影响。使用两种测定法测量循环ADA水平：药物敏感性放射免疫测定法和药物耐受性ELISA法。使用ELISA测量循环乌司奴单抗水平。使用放射免疫分析法和药物耐受ELISA法分别在3.8%（95%置信区间[CI] = 3.2-4.2）和10.6%（95% CI = 7.9-13.9）的患者中检出ADA。至少85%的ADA具有中和作用。与ADA阴性患者相比，放射免疫测定和耐药ELISA中ADA阳性与较低的乌司奴单抗中位水平相关（−0.62 μg/ml [95% CI = −1.190至−0.30]和−0.74 μg/ml [95% CI = −1.09至−0.47]，和更高的绝对PASI（分别为6.6 [95% CI = 3.0-9.9]和1.9 [95% CI = 0.4-4.0]）。无论ADA状态如何，无法检出乌司奴单抗与临床结局较差相关（与乌司奴单抗阳性患者相比，中位样本PASI为10.1，6.5 [95% CI = 3.9-8.8]）。总之，ADA形成导致的药物暴露量大幅降低与临床应答受损相关。
Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2–4.2) and in 10.6% (95% CI = 7.9–13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (−0.62 μg/ml [95% CI = −1.190 to −0.30] and −0.74 μg/ml [95% CI = −1.09 to −0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0–9.9] and 1.9 [95% CI = 0.4–4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9–8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.