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.