Prediction of natalizumab anti-drug antibodies persistency
| Autor: | Louis Christodoulou, Anna Lauren, Claudia Sievers, Michael Auer, Mary Birchler, Anna Fogdell-Hahn, Anders Sjödin, Malin Ryner, Poul Erik Jensen, Marc Pallardy, Roland S. Liblau, Marlies Jank, Finn Sellebjerg, Raija L.P. Lindberg, Florian Deisenhammer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Drug
Oncology Adult Male medicine.medical_specialty Treatment response Multiple Sclerosis media_common.quotation_subject Enzyme-Linked Immunosorbent Assay Sensitivity and Specificity Antibodies 03 medical and health sciences Young Adult 0302 clinical medicine Natalizumab Internal medicine Outcome Assessment Health Care medicine Humans Immunologic Factors 030212 general & internal medicine media_common Immunoassay biology business.industry Multiple sclerosis Middle Aged medicine.disease Neurology biology.protein Female Neurology (clinical) Antibody business 030217 neurology & neurosurgery medicine.drug Follow-Up Studies |
| Zdroj: | Multiple sclerosis (Houndmills, Basingstoke, England). 25(3) |
| ISSN: | 1477-0970 |
| Popis: | Background: Anti-drug antibodies (ADA) against natalizumab develop early during treatment. ADA persistency is defined by two consecutive positive results as performed by the current qualitative ELISA assay (positive/negative). Very little is known about the magnitude of the natalizumab ADA response and persistency. Design/methods: We developed a highly sensitive natalizumab ADA titration assay on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We included 43 patients with a positive ELISA-ADA result within 6 months of treatment initiation (baseline) of whom a follow-up serum sample was available 12–30 months after treatment start. MSD-ADA titres and drug levels were measured. Results: Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA persistency. Reversion to ADA negativity occurred in 10 patients with mean drug levels of 10.8 μg/mL. The median trough drug level in ADA-positive samples was 0 µg/mL. PK levels and ADA titres correlated strongly negatively ( r = −0.67). Conclusion: High baseline natalizumab ADA titres accurately predict persistency. Despite continuous treatment, the majority of patients with persistent ADA had no detectable drug levels indicating loss of efficacy in line with phase 3 study results. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|