CD4 cell response to interval therapy with natalizumab

Regina Berkovich, Daniel M Togasaki, Steven Y Cen, Lawrence Steinman, Regina Berkovich, Daniel M Togasaki, Steven Y Cen, Lawrence Steinman

Abstract

Natalizumab treatment alters peripheral CD4 cells counts in multiple sclerosis (MS) patients, providing a way to monitor the pharmacodynamic effects of the drug. The study was undertaken to assess whether CD4 cell counts correlate with different phases of natalizumab treatment of relapsing MS patients, including during a 12-week planned treatment interruption, and whether that might provide insights on lymphocyte trafficking. Clinical outcomes, MRI data, and CD4 cell counts were assessed at baseline prior to initiating natalizumab, while on regular dosing, at the end of the 12-week extended dosing interval, and at the time of reinitiation of natalizumab. The 12-week interruption was well tolerated and not associated with return of MS activity, disability progression, or new or worsened MRI data. Observed significant shifts in CD4 counts - dramatically increasing from the baseline while on treatment and decreasing back to the baseline level off treatment, then rising in a similar manner on natalizumab reinitiation, suggest that these measurements may aid in monitoring modulation of lymphocyte trafficking and cell redistribution.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
CD4 cell counts for patients with multiple sclerosis in each of four phases of treatment with natulizamab: before initial treatment (Baseline), during the first 48-week-long treatment phase (ON1), during a subsequent 12-week drug-free interval (OFF), and after reinitiation of treatment (ON2). Results are displayed as mean of 19 patients with error bars (A) showing standard error of the mean (SEM). Cell counts during the treatment phases (ON1 and ON2) differ from Baseline (P < 0.001), whereas counts during the drug-free interval do not (P = 0.281) (A, B).
Figure 3
Figure 3
Trajectory of CD4 cell counts in patients with multiple sclerosis treated with natalizumab. During the first drug administration period, CD4 cell counts increased with a trend of square root of time. The trajectory of CD4 counts after reinitiation of natalizumab is close to linear.

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Source: PubMed

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