TYSABRI (natalizumab)

– a four weekly infusion for RRMS patients with highly active disease1

Indication

TYSABRI is indicated as single disease modifying therapy in adults with highly active relapsing remitting multiple sclerosis for the following patient groups:

  • Patients with highly active disease despite a full and adequate course of treatment with at least one disease modifying therapy (DMT)
  • or
  • Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1
    or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI.

Posology

TYSABRI 300 mg is administered by intravenous infusion once every four weeks.1

Efficacy

TYSABRI has demonstrated sustained efficacy across measures of ARR, disability progression and MRI indicators of disease activity compared with placebo.2-5

TYSABRI- SUMMARY OF 2 YEAR EFFICACY DATA FOR OVERALL POPULATION 2-4

TYSABRI- SUMMARY OF 2 YEAR EFFICACY DATA FOR HIGHLY ACTIVE PATIENT FROM A SUB-ANALYSIS OF AFFIRM ‡ 1,2

The highly active subgroup is a post-hoc analysis of treatment-naïve patients with ≥2 relapses in the previous year and ≥1 Gd+ lesion

TYSABRI AND NEDA5

No evidence of disease activity (NEDA) has been defined as5:
absence of relapses + absence of increased disability* + absence of radiological disease activity

Proportion of patients with NEDA over 2 years: post-hoc analysis of AFFIRM‡5

Overall population

Highly active patients

The highly active subgroup is a post-hoc analysis of treatment-naïve patients with ≥2 relapses in the previous year and ≥1 Gd+ lesion.

Adapted from Havrdova E et al., 2009 – a post hoc analysis of the AFFIRM study
  
*   No progression of disability sustained for 12 weeks
*   No Gd+ lesions and no new or enlarging T2-hyperintense lesions
** Highly active = two or more disabling relapses in one year and disease activity shows up on an MRI scan

 

Safety Profile

TYSABRI has a manageable tolerability and safety profile elucidated by over 11 years of documented clinical experience in the post-marketing setting.1,6-8

In placebo-controlled trials in 1,617 MS patients treated with natalizumab for up to 2 years (placebo: 1,135), adverse events leading to discontinuation of therapy occurred in 5.8% of patients treated with natalizumab (placebo: 4.8%). Over the 2-year duration of the studies, 43.5% of patients treated with natalizumab reported adverse reactions (placebo: 39.6%).

The highest incidence of adverse reactions identified from placebo-controlled trials in multiple sclerosis patients with natalizumab given at the recommended dose, are reported as dizziness, nausea, urticaria and rigors associated with infusions.1

In the first 5 years of the TOP study (TYSABRI Observational Programme – a multinational, open-label, ten-year prospective study carried out in the clinical setting), safety findings were consistent with previous studies, and no new safety concerns were identified.6

Safety data in STRATA (an observational, prospective, open-label extension study in patients treated with TYSABRI in previous studies) are consistent with TYSABRI’s known safety profile.7

TYSABRI is associated with an increased, but manageable risk of PML. Clinicians have access to clear management guidelines to help them manage the risks to their patients.8

See the SmPC (UK | ROI ) and PI for more information.

Other

It is estimated that over 181,300 patients have been treated with TYSABRI worldwide resulting in an acccumulated post-marketing exposure of over 638,838 patient-years. These figures do not include 5,100 patients treated with TYSABRI in clinical trials.9

Study designs*: 
Data presented above is taken from the AFFIRM study: The Natalizumab Safety and Efficacy in RRMS study. A two-year, multinational, phase III trial designed to confirm the efficacy and evaluate the safety of long-term TYSABRI treatment. RRMS patients were randomly assigned in a 2:1 ratio to receive either 300mg TYSABRI (n=627) or placebo (n=315) by IV infusion every 4 weeks for up to 116 weeks. Primary endpoints were rate of clinical relapse at 12 months and EDSS score at 24 months. Secondary endpoints at 12 months were: number of new or enlarging hyperintense T2 lesions; number of Gd+ lesions; and the proportion of relapse-free patients. Secondary endpoints at 24 months were: rate of clinical relapse; volume of T2 lesions; number of new hypointense T1 lesions; and progression of disability as measured by the the Multiple Sclerosis Functional Composite.4

Abbreviations:
ARR: Annualised Relapse Rate; CI: Confidence Interval; DMT: Disease Modifying Therapy; EDSS: Expanded Disability Status Scale; Gd+: Gadolinium Enhancing; HR: Hazard Ratio; IV: Intravenous Therapy; MRI: Magnetic Resonance Imaging; MS: Multiple Sclerosis;
NEDA: No Evidence of Disease Activity; PML: Progressive Multifocal Leukoencephalopathy; RRMS: Relapsing Remitting Multiple Sclerosis

MSP-PAN-0010i Date of prep: September 2018