1 / 19

Measles Antibody Titers in PIDD Patients

Measles Antibody Titers in PIDD Patients. Othmar Zenker, MD. Introduction. Falling measles titers are anticipated over time in normal donors Measles antibody titers serve as a potency test for immunoglobulin lot release with a cut-off level of 0.6 x CBER Standard Lot 176

keegan
Télécharger la présentation

Measles Antibody Titers in PIDD Patients

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Measles Antibody Titers in PIDD Patients Othmar Zenker, MD

  2. Introduction • Falling measles titers are anticipated over time in normal donors • Measles antibody titers serve as a potency test for immunoglobulin lot release with a cut-off level of 0.6 x CBER Standard Lot 176 • Reduction in plasma titers will make it difficult to achieve product specifications in the future • Increased risk of immunoglobulin shortage

  3. Protective anti measles titers • 0.12 IU/mL has been associated with protection against clinical measles disease (Chen 1990) • Measles is currently no concern for PIDD patients • Protective titer for PIDD patients is unknown • Retention samples of two clinical studies were tested in functional assay and ELISA • Obtain results on anti-measles trough levels after IGSC and IGIV treatment of PIDD patients

  4. Methods used for testing of clinical samples • ELISA • Commercial kit manufactured by Dade Behring • Calibrator: in-house plasma standard calibrated against 3rd WHO standard • Neutralization Assay • Potency testing of immunoglobulins for neutralizing antibodies against Measles virus in cell culture • The content of anti-Measles in IgG is measured in relation to the Reference Immune Globulin Lot 176 • Converted in IU/mL by using a factor of 2.54 for 1%Ig

  5. Subcutaneous study • 20 subjects with available retention sample were chosen • 20 samples were analyzed by NT • 60 samples were analyzed by ELISA • Demographic data typical for PIDD • CVID/XLA = 14 / 6 • Age: Median 26 years (9 – 62) • IgG trough level: Median 9.2 g/L (5.7 – 18.1) • Weekly IGSC dose: Median 164 mg/kg (60 - 326) • Treatment every week • Weekly dose of anti measles antibodies infused was calculated using the neutralization test results obtained at lot release

  6. All patients are well protected Mean titer is 3.17 IU/mL Good correlation between dose and titer IGSC – Dose response (NT)

  7. IGSC - anti measles and trough level (NT)

  8. Intravenous study • 53 subjects with available retention sample were chosen • 58 samples were analyzed by NT • 140 samples were analyzed by ELISA • Demographic data typical for PIDD • CVID/XLA = 42 / 11 • Age: Median 20 years (4 – 66) • IgG trough level: Median 9.7 g/L (5.5 – 17.4) • Monthly IVIG dose: Median 528 mg/kg (304 – 996) • Treatment every three or four weeks • Samples were chosen only if the same lot was given on three consecutive infusions prior to the sampling

  9. Intravenous – dose response (NT) • All patients are well protected • Mean titer is 2.98 IU/mL • Good correlation between dose titer • Higher measles titer during SC treatment

  10. Trough level simulation • Assumptions • Hypothetical lot with a potency of 0.3 x CBER Standard Lot 176 • Dose of anti measles antibodies according to this lot • Linear dose – titer correlation • No endogenous anti measles antibody titer • Methods • Calculation of the hypothetical dose of anti measles antibodies for every infusion • Calculation of the hypothetical trough anti measles titer by linear interpolation

  11. Trough level simulation

  12. Trough level simulation

  13. Summary • All samples tested are well above the protective level • IGSC results in a higher trough level than IGIV • 3 or 4 weekly IGIV treatment with product under current specification obtained trough levels far above the protective titer of 0.12 IU/mL • Even with a lot with a potency of 0.3 x CBER lot 176 patients would be protected as shown in a simulation • Based on this model even a cut off level lower than 0.48 x CBER lot 176 would be adequate

  14. Acknowledgements • Karl Fickenscher, PhD • Kathrin Minnig • Thomas Nowak, PhD • Fritz Schindel • Brigitte Siani • Roland Zehnder

  15. Back Up

  16. IGIV - Correlation ELISA and NT

  17. IGSC – Correlation ELISA and NT

  18. IGIV – Dose response (ELISA)

  19. IGSC – Dose reponse (ELISA)

More Related