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Abstract Details

Serum Natalizumab and Anti-Natalizumab Antibody Concentrations May Be Useful in Patient Management
Multiple Sclerosis
P1 - Poster Session 1 (8:00 AM-9:00 AM)

NTZ is a monoclonal antibody directed against the a4-integrin subunit of a4b1 and a4b7 integrins.  NTZ is used to treat relapsing and remitting forms of multiple sclerosis. Although a majority of patients on standard dosing (intravenous 300 mg, every 4 weeks) reach therapeutic drug concentrations, about 10% of patients will eventually fail NTZ therapy due to the development of anti-NTZ antibodies.

Natalizumab (NTZ) and anti-natalizumab antibody concentrations in serum are used together to provide patient-specific pharmacokinetic and immunogenic assessment to aid in patient management.

Serum measurements of NTZ and anti-NTZ antibody levels are performed by novel lab developed electro-chemiluminescent immunoassays. The natalizumab drug assay is validated to measure free drug (pharmacodynamically active) level in serum.  The anti-natalizumab antibody assay is quantitative and drug-tolerant, meaning that circulating drug in patient serum does not interfere with anti-NTZ detection and quantitation.

Here, we report concomitant measurement of NTZ and anti-NTZ antibody in 160 patient serum samples.  Positive anti-NTZ levels from 24 to 235 ng/mL were found in 7.5% (12/160) patients. Anti-NTZ-free samples (148/160) had NTZ drug levels ranging from undetectable (<1.0) to 85 ug/mL. The mean and median drug level in 90 samples (results >1.0) was 10.8 and 2.7, respectively. 61/90 samples had therapeutic drug concentrations (at least 2.0 ug/mL). In the presence of anti-NTZ, 67% (8/12) had undetectable drug level and (4/12) had mean and median drug levels of 1.2 and 1.3, respectively, which is 9- or 2-fold lower than the mean and median drug levels of the anti-NTZ Ab -free group.  

Low serum NTZ and high anti-NTZ are associated with loss of clinical efficacy, while elevated NTZ may increase progressive multifocal leukoencephalopathy risk.  Assays to measure biologic drugs and their anti-drug antibodies in patient serum may be useful tools in dose optimization and patient management.
Jane Yang, MD (Labcorp)
Dr. Yang has received personal compensation for serving as an employee of Labcorp.
Kelly Y. Chun, PhD (Labcorp) Dr. Chun has nothing to disclose.