iMED.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Avenida Gama Pinto, 1640-019, Lisbon, Portugal.
Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal.
BioDrugs. 2021 Jan;35(1):35-45. doi: 10.1007/s40259-020-00458-3.
The reported immunogenicity rates of adalimumab differ significantly between studies because of a wide variety of factors related to the disease, patients, study design, and products.
The objective of this study was to characterize this variability and identify the major factors that contribute to these fluctuations.
A systematic literature review was conducted using the MEDLINE, Clinicaltrials.gov, and Cochrane Library databases. Studies that reported the immunogenicity rates of adalimumab were selected, and data pertaining to publication details, study characteristics, characteristics of the cohort at baseline, and immunogenicity were extracted. Records were sorted according to the immunogenicity assay type, and mean immunogenicity values for each assay type were calculated. Normalised immunogenicity was calculated for each report by subtracting the appropriate mean immunogenicity value. Collected data were subjected to statistical analysis, namely analysis of variance (ANOVA) and principal component analysis, to unveil immunogenicity rate patterns across studies from a multivariate perspective.
In total, 130 publications were identified, from which 165 data records were extracted and included in the analysis. The immunogenicity rates of adalimumab averaged 24.9% across studies and varied significantly over time, ranging between 0 and 87%. An increase across time in the reported immunogenicity rates was detected, and the assay used to detect anti-adalimumab antibodies was a significant (but not exclusive) contributor to this trend. Furthermore, the principal components analysis revealed that the type of study and the exposure time were associated with the assay-normalised immunogenicity rates of adalimumab. Nonetheless, neither these nor the remaining factors included in this analysis seem to contribute to the temporal increase in reported immunogenicity rates.
Future studies that evaluate the patient-, product-, and disease-related factors behind the immunogenicity of adalimumab are required because the evidence published so far does not completely explain the temporal increase in immunogenicity rates detected in this analysis.
由于与疾病、患者、研究设计和产品相关的各种因素，阿达木单抗的报道免疫原性率在不同研究中差异很大。
本研究旨在描述这种变异性，并确定导致这些波动的主要因素。
使用 MEDLINE、Clinicaltrials.gov 和 Cochrane Library 数据库进行系统文献回顾。选择报告阿达木单抗免疫原性率的研究，并提取与出版物细节、研究特征、基线队列特征和免疫原性相关的数据。根据免疫原性测定类型对记录进行排序，并计算每种测定类型的平均免疫原性值。通过从每个报告中减去适当的平均免疫原性值来计算归一化免疫原性。对收集的数据进行统计分析，即方差分析（ANOVA）和主成分分析，以从多变量角度揭示研究之间免疫原性率模式。
共确定了 130 篇出版物，从中提取了 165 份数据记录并纳入分析。研究中阿达木单抗的免疫原性率平均为 24.9%，且随时间变化显著，范围在 0 到 87%之间。检测到报告的免疫原性率随时间增加，用于检测抗阿达木单抗抗体的测定是导致这种趋势的一个重要（但不是唯一）因素。此外，主成分分析显示，研究类型和暴露时间与阿达木单抗的测定归一化免疫原性率相关。然而，包括在本分析中的这些因素和其余因素似乎都没有导致报告的免疫原性率随时间增加。
需要进行评估阿达木单抗免疫原性背后的患者、产品和疾病相关因素的未来研究，因为迄今为止发表的证据并不能完全解释本分析中检测到的免疫原性率随时间增加的情况。
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