In the 2-year AFFIRM pivotal trial:

Relapsing MS patients received TYSABRI every 28 days (n=627) or placebo (n=315). Patients with PPMS, SPMS, and PRMS were excluded.

83% of patients taking TYSABRI had no sustained disability progression for 12 weeks vs 71% with placebo (primary endpoint: 17% vs 29%; p<0.001)1,2


Data from the AFFIRM and RESTORE trials were used to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of TYSABRI

Effects of TYSABRI on circulating immune cell counts were reversible, returning to baseline levels within 16 weeks of discontinuation1,3

Study description:The RESTORE study was an exploratory, randomized, multicenter, partially blinded, parallel-group study that assessed the timing of pharmacokinetic and pharmacodynamic changes based upon TYSABRI initiation and interruption in 175 patients with RMS

  • Patients were randomized (1:1:2) to receive 300 mg TYSABRI IV (n=45), placebo (n=42), or an alternate therapy (n=88) every 4 weeks
  • The patients who interrupted TYSABRI treatment and switched to placebo or alternate therapies in RESTORE were combined in analyses. In the alternate therapy arm, patients and neurologists selected the therapy, hence, leading to unbalanced groups
    • After 28 weeks, patients on placebo or an alternate therapy resumed treatment with open-label TYSABRI
    • Clinical, MRI, blood sample, and laboratory evaluations were performed at baseline and every 4 weeks up to Week 28, through which pharmacokinetics (PK), pharmacodynamics (PD), time course of drug concentration, and changes in peripheral immune cells upon natalizumab treatment initiation and interruption were assessed

Study limitations:

  • Patients were already receiving TYSABRI at the start of the study; therefore, pretreatment levels were not available
    • Total lymphocyte counts were performed at baseline in AFFIRM, yielding data that served as surrogate pretreatment levels
  • Baseline patient characteristics, such as age, race, and disease severity, differed in AFFIRM and RESTORE and may have impacted circulating lymphocyte counts
  • These data are limited in their ability to inform clinical practices other than discontinuation following monthly TYSABRI administration

TYSABRI inhibits the migration of lymphocytes into the CNS by binding to the α4 integrin1

TYSABRI retains lymphocytes in the periphery without destroying them3

  • TYSABRI is believed to suppress inflammation within the CNS by targeting and binding to the surfaces of lymphocytes and blocking their transmigration across the blood-brain barrier1
  • TYSABRI binds to the α4 subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s)3

Because TYSABRI does not destroy lymphocytes, counts remain within the normal range and usually return to pretreatment levels within 16 weeks after the last dose1,3

In an exploratory analysis, total lymphocyte counts remained in the normal range with TYSABRI, and changes were reversible1,3

  • After interrupting treatment, total lymphocyte counts returned to baseline levels by Week 16

aThe blue, dashed line indicates total lymphocyte counts prior to TYSABRI treatment in the AFFIRM TYSABRI treatment arm.

  • For the duration of the RESTORE trial, lymphocyte counts in both arms remained within the normal range of healthy individuals as provided by Covance3

Understanding the reversibility of TYSABRI may help to inform clinicians when making decisions for their patients with RMS3

Study was funded by Biogen.