Prediction of natalizumab anti-drug antibodies persistency
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Prediction of natalizumab anti-drug antibodies persistency. / ABIRISK Consortium.
In: Multiple Sclerosis Journal, Vol. 25, No. 3, 03.2019, p. 392-398.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Prediction of natalizumab anti-drug antibodies persistency
AU - Deisenhammer, Florian
AU - Jank, Marlies
AU - Lauren, Anna
AU - Sjödin, Anders
AU - Ryner, Malin
AU - Fogdell-Hahn, Anna
AU - Sievers, Claudia
AU - Lindberg, Raija
AU - Jensen, Poul Erik
AU - Sellebjerg, Finn
AU - Christodoulou, Louis
AU - Birchler, Mary
AU - Pallardy, Marc
AU - Auer, Michael
AU - Liblau, Roland
AU - ABIRISK Consortium
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - anti-drug antibodies
KW - Natalizumab
KW - outcome measurement
KW - treatment response
U2 - 10.1177/1352458517753721
DO - 10.1177/1352458517753721
M3 - Journal article
C2 - 29336205
AN - SCOPUS:85043373173
VL - 25
SP - 392
EP - 398
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
SN - 1352-4585
IS - 3
ER -
ID: 241100185