St Vincent's Hospital
Neurology Department

Author Of 1 Presentation

Clinical Outcome Measures Poster Presentation

P0107 - Lymphocyte response in standard and extended interval dosing of natalizumab (ID 312)

Speakers
Presentation Number
P0107
Presentation Topic
Clinical Outcome Measures

Abstract

Background

Natalizumab (Tysabri) is a humanised monoclonal IgG4 antibody used in the management of severe relapsing remitting multiple sclerosis (RRMS). It is the first in its class of selective adhesion molecules.

The four-weekly standard interval dosing (SID) of natalizumab is based on initial phase 3 trials showing that a4 integrin receptor saturation remains >70% four weeks following a 300mg infusion. Extended interval dosing (EID) e.g. six weekly infusions, can be associated with a lower integrin receptor saturation however this may not result in any clinical difference. A recent study by Yamout et al confirmed that both regimens had similar impact on MRI inflammatory activity and Expanded Disability Status Score (EDSS) outcomes. Additionally EID may be linked with a lower risk of progressive multifocal leucoencephalopathy (PML), the most worrying adverse event in natalizumab use.

Natalizumab use results in elevation of serum levels of lymphocytes, through their sequestration in peripheral blood. The lymphocytosis response has been established as a marker for therapeutic efficacy- patients displaying lower levels of natalizumab induced lymphocytosis are at greater risk for relapse.

Objectives

Given the established evidence of peripheral blood lymphocyte count as a marker of therapeutic efficacy, we sought to establish the lymphocyte response in our cohort of patients on SID, EID and those who transitioned from SID to EID.

Methods

We collected lymphocyte levels on all patients on tysabri (on standard and extended interval dosing). Lymphocyte count was tracked at three monthly intervals during natalizumab use. Lymphocyte levels on ten patients who were switched from standard dosing to extended interval dosing was also analysed.

Results

We had 92 patients using tysabri. Ten of the patients were transitioned from SID to EID.

The average lymphocyte count prior to commencement of natalizumab was 1.89.

Post two infusions at SID, this increased to 2.66, and after five infusions increased to 3.46. There was no significant change after this, with average lymphocyte counts maintained between 3 and 3.5 for the remainder of the therapy.

Of the eight patients who were transitioned from SID to EID:

-Average pre natalizumab lymphocyte level was 1.88.

-Average lymphocyte level on SID was 3.23

-Average level post two infusions on EID was 3.41

Conclusions

Our data confirms that there is no significant difference in lymphocyte count between patients on SID and EID, and similarly between patients who transition between SID and EID.

EID has been shown to be at least as effective as SID in treatment of RRMS while also lowering the risk of progressive multifocal leucoencephalopathy (PML). Studies have shown no increase in relapses. The Expanded Disability Status Scale (EDSS) also shows no difference between patients on SID and EID. Our data contributes to the evidence underlying the safety of EID use in patients with highly active relapsing remitting MS.

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