# Presentation: 685003

## 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
- Reduction in plasma titers will make it difficult to achieve product specifications in the future
- Increased risk of immunoglobulin shortage

## 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

## 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

## 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

## IGSC – Dose response (NT)

- All patients are well protected
- Mean titer is 3.17 IU/mL
- Good correlation between dose and titer

## IGSC - anti measles and trough level (NT)

## 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

## 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

## 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

## Trough level simulation

**Trough level simulation**

## Trough level simulation

## 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

## Acknowledgements

- Karl Fickenscher, PhD
- Kathrin Minnig
- Thomas Nowak, PhD
- Fritz Schindel
- Brigitte Siani
- Roland Zehnder

## Back Up

## IGIV - Correlation ELISA and NT

## IGSC – Correlation ELISA and NT

## IGIV – Dose response (ELISA)

## IGSC – Dose reponse (ELISA)