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Prediction of natalizumab anti-drug antibodies persistency

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  • Florian Deisenhammer
  • Marlies Jank
  • Anna Lauren
  • Anders Sjödin
  • Malin Ryner
  • Anna Fogdell-Hahn
  • Claudia Sievers
  • Raija Lindberg
  • Poul Erik Hyldgaard Jensen
  • Finn Sellebjerg
  • Louis Christodoulou
  • Mary Birchler
  • Marc Pallardy
  • Michael Auer
  • Roland Liblau
  • ABIRISK Consortium
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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.

Original languageEnglish
JournalMultiple sclerosis (Houndmills, Basingstoke, England)
Volume25
Issue number3
Pages (from-to)392-398
Number of pages7
ISSN1352-4585
DOIs
Publication statusPublished - Mar 2019

ID: 58577086