Session Type: Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Immunogenicity and development of anti-drug antibodies have been associated with treatment failure and adverse events during biologic treatment. Anti-drug antibodies (ADAs) have been reported in 21% of Juvenile Idiopathic Arthritis patients treated with Adalimumab. However, their role in reducing adalimumab efficacy is still debated due to conflicting results. No study has been directed toward identification of neutralizing ADAs in paediatric rheumatic disorders.
Aim of our study was to detect ADAs, along with their clinical relevance, using a new theranostic peptide-base assay in a cohort of children with inflammatory chronic diseases on Adalimumab treatment.
Methods: ix candidate Adalimumab derived peptide antigens (HC-CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR 2, LC CDR3) have been developed and optimized to be tested. Their performance has been compared with commercial ELISA kit and a SPR-based optical assay (Biacore®). Assays have been performed in sera of a cohort of children receiving Adalimumab due to an inflammatory chronic disease. Mean age, disease duration, concomitant treatment with methotrexate (MTX), ANA positivity, disease activity parameters and scores at the time of ADA determination have been recorded. Chi-square, and Fisher exact test were used to compare data. Pearson’s and Spearman’s correlation tests were used to determine correlation coefficients for entered variables.
Results: Eighteen (14 F, median age 12.6, range 3.8-16, yrs) patients were enrolled: 16 affected by Juvenile Idiopathic Arthritis, 7 of whom complicated by JIA -associated chronic uveitis, and 2 patients affected by chronic idiopathic uveitis. Peptide assay revealed ADAs in 8 children, Biacore in 6, commercial Elisa in 5. Of note, we found total concordance among the 3 tests just in 2 patients. No significant correlation has been proven among the 3 ADA determinations. Biacore and ELISA determination showed significant concordance (rs: 0.72, p< 0.006). The presence of HC CDR3 and LC CDR 3 resulted significantly correlated with disease activity (rs: 0.57, p< 0.05), and, inversely, with disease remission on treatment (rs= -0.523, p< 0.05). No patient experienced severe adverse events and no correlation with ADAs has been revealed.
Conclusion: In chronic rheumatic disorders, novel reliable methods are urgently required to guide clinical decision and support decisions about switching within or between drugs in refractory children. The 3 different methods, since based on different antigenic probes, detect different antibody populations. The present peptide-based assays might contribute to identify neutralizing ADAs in patients treated with Adalimumab. Further validation in larger cohort is required.
To cite this abstract in AMA style:Marrani E, Rusche H, Terzani F, Peroni E, Real-Fernandez F, Monasson O, Ponti R, Simonini G, Papini A, Rovero P. Anti-adalimumab Antibodies Detection Using a Novel Peptide-based Assay in a Cohort of Pediatric Patients with Chronic Rheumatic Disorders: A Pilot Study [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/anti-adalimumab-antibodies-detection-using-a-novel-peptide-based-assay-in-a-cohort-of-pediatric-patients-with-chronic-rheumatic-disorders-a-pilot-study/. Accessed January 22, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-adalimumab-antibodies-detection-using-a-novel-peptide-based-assay-in-a-cohort-of-pediatric-patients-with-chronic-rheumatic-disorders-a-pilot-study/