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Systematic Review and Principal Components Analysis of the Immunogenicity of Adalimumab

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Abstract

Background

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.

Objective

The objective of this study was to characterize this variability and identify the major factors that contribute to these fluctuations.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

The authors express their special thanks to Joseph Smolen for his interest, availability, and support in the critical review of this manuscript.

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Authors and Affiliations

  1. iMED.ULisboa, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Avenida Gama Pinto, 1640-019, Lisbon, Portugal

    Rodrigo Borrega, Carlos Araújo, Nádia Aguiam, João Lopes & Joao Goncalves

  2. Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, Porto, Portugal

    Fernando Magro

  3. Department of Gastroenterology, Sao Joao Hospital Centre, Porto, Portugal

    Fernando Magro

  4. Center for Drug Discovery and Innovative Medicines, MedInUP, Porto, Portugal

    Fernando Magro

  5. Clinical Pharmacology Unit, São João Hospital University Center, Porto, Portugal

    Fernando Magro

  6. Rheumatology and Metabolic Bone Diseases Unit, Santa Maria University Hospital, North Lisbon Centre, Lisbon, Portugal

    João Eurico Fonseca

  7. Rheumatology Research Unit, Medical Academic Centre, Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

    João Eurico Fonseca

  8. Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy

    Silvio Danese

  9. Department of Biomedical Sciences, Humanitas University, Milan, Italy

    Silvio Danese

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  1. Rodrigo Borrega
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Correspondence to Joao Goncalves.

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Funding

No sources of funding were used to support the execution and writing of this research.

Conflict of interest

JG has received speaker honoraria and consulting fees from Amgen, Biogen, Novartis, Sanofi, Mylan, and Samsung Bioepis. JEF has received unrestricted research grants or acted as a speaker for Abbvie, Ache, Amgen, BIAL, Biogen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, and UCBF. FM has served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratórios Vitória, Ferring, Hospira, and Biogen. SD has served as a speaker, a consultant, and an advisory board member for Schering-Plough, Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alphawasserman, Genentech, Grunenthal, Pfizer, Astra Zeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson. RB, CA, NA, and JL have no conflicts of interest that are directly relevant to the content of this article.

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All data generated or analysed during this study are included in this published article and its supplementary information files.

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Conception and design of the study: RB, SD, JG. Acquisition of data: RB, CA. Interpretation and analysis of data: RB, CA, NA, JL, JG. Drafting the article or revising it critically for important intellectual content the article: all authors. Final approval of the version to be published: all authors.

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Borrega, R., Araújo, C., Aguiam, N. et al. Systematic Review and Principal Components Analysis of the Immunogenicity of Adalimumab. BioDrugs 35, 35–45 (2021). https://doi.org/10.1007/s40259-020-00458-3

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