T-Cell Count With Natalizumab In MS: Predictor Of Non-CNS Opportunistic Infections?

Background: It is known that based on its mechanism of action, Natalizumab reduces T-cell counts in the CSF of patients as observed by Stuve et al.¹As such, much concern has been placed over PML resulting from JCV infection, but no other infections. In theory, the T-cell count of peripheral blood should remain constant.

Objectives: To observe that if within the first 1 to 2 years of treatment, the CD4/CD8 T-cell count in peripheral blood reduces significantly enough in patients to allow for increased susceptibility to non-CNS opportunistic infections.

Methods: Retrospective analysis of Fraser Health MS clinic patients that had been or are ongoing treatment with Natalizumab was completed as to observe the changes of T lymphocytes over time and by number of doses.

Results: Of the patients followed, 64% saw a decrease in the CD4/CD8 levels, while 29% saw no observable change and 7% saw an increase within the first 1-2 years of treatment. It was seen that by the 2nd to 3rd year of treatment with Natalizumab the CD4/CD8 ratio’s re-stabilized to just below their initial value. It was also found that in years 2 and 3 there is a normal distribution between patients that over-shoot their initial CD4/CD8 ratio, those that re-stabilize to their initial value and those that are still lower then their initial value after an extended dosage period. Final analysis of the data will be presented at the conference

Conclusions: The T-cell count of peripheral blood did not remain constant during the first 2 years of treatment and may increase risk of non-CNS opportunistic infections due to the lower lymphocyte levels. Final results of this study will identify if physicians should place greater concern for patients under treatment with Natalizumab, specifically within the first 1-2 years of treatment, with regards to non-CNS opportunistic infections.

Reference: Stuve O, Marra CM, Bar-Or A, et al. Altered CD4+/CD8+ T-Cell Ratios in Cerebrospinal Fluid of Natalizumab-Treated Patients With Multiple Sclerosis. Arch Neurol. 2006;63(10):1383-1387.