WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include duration of therapy, prior use of immunosuppressants, and presence of anti-JCV antibodies. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI [
see Warnings and Precautions (
Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadolinium-enhanced magnetic resonance imaging (MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [
see Contraindications (4), Warnings and Precautions (5.1)
Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH Prescribing Program [
see Warnings and Precautions (5.2)
TYSABRI (natalizumab) is a recombinant humanized IgG4? monoclonal antibody produced in murine myeloma cells. Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to α4-integrin. The molecular weight of natalizumab is 149 kilodaltons. TYSABRI is supplied as a sterile, colorless, and clear to slightly opalescent concentrate for intravenous infusion.
Each 15 mL dose contains 300 mg natalizumab; 123 mg sodium chloride, USP; 17.0 mg sodium phosphate, monobasic, monohydrate, USP; 7.24 mg sodium phosphate, dibasic, heptahydrate, USP; 3.0 mg polysorbate 80, USP/NF, in water for injection, USP at pH 6.1.
Multiple Sclerosis (MS)
TYSABRI is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis. Tysabri increases the risk of PML. When initiating and continuing treatment with Tysabri, physicians should consider whether the expected benefit of Tysabri is sufficient to offset this risk. See important information regarding the risk of PML with TYSABRI [ see Warnings and Precautions (5.1) ].
Crohn's Disease (CD)
TYSABRI is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α. TYSABRI should not be used in combination with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α [ see Warnings and Precautions (5.1) ].
Media Articles Related to Tysabri (Natalizumab)
New EMA Advice for PML Prevention With Tysabri in MS
Source: Medscape NeurologyHeadlines [2016.02.12]
The European Medicines Agency has released new recommendations on PML prevention with natalizumab in multiple sclerosis.
MS drug tied to rising JC virus antibody levels: virus may induce deadly brain infection
Source: Multiple Sclerosis News From Medical News Today [2016.01.27]
People who take the drug natalizumab for multiple sclerosis may have up to a 10 times greater risk of developing a risk biomarker for activity of a virus that can lead to an often fatal brain...
Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2016
Source: Medscape Headlines [2016.02.12]
Read clinically focused news coverage of key developments from ACTRIMS 2016.
New Recommendations on MRI Diagnosis of Multiple Sclerosis
Source: Medscape NeurologyHeadlines [2016.02.09]
New revisions to imaging criteria for the diagnosis of MS should lead to more accurate diagnosis of the disease, experts say.
Medscape Medical News
New MRI technique offers faster diagnosis of multiple sclerosis
Source: MRI / PET / Ultrasound News From Medical News Today [2016.02.02]
A new way of using MRI scanners to look for evidence of multiple sclerosis in the brain has been successfully tested by researchers at The University of Nottingham and Nottingham University...
Published Studies Related to Tysabri (Natalizumab)
Low-contrast acuity measures visual improvement in phase 3 trial of natalizumab
in relapsing MS. 
prespecified tertiary outcome measure in AFFIRM... CONCLUSION: Low-contrast letter acuity detected treatment effects on sustained
Efficacy of natalizumab therapy in patients of African descent with relapsing multiple sclerosis: analysis of AFFIRM and SENTINEL data. [2011.04]
BACKGROUND: Patients with multiple sclerosis (MS) who are of African descent experience a more aggressive disease course than patients who are of white race/ethnicity. In phase 3 clinical trials (Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing Remitting Multiple Sclerosis [SENTINEL]), natalizumab use significantly improved clinical and magnetic resonance imaging outcomes over 2 years in patients with relapsing MS. Because patients of African descent may be less responsive to interferon beta treatment than patients of white race/ethnicity, the efficacy of natalizumab therapy in this population is clinically important. OBJECTIVE: To evaluate the efficacy of natalizumab use in patients of African descent with relapsing MS... CONCLUSION: Natalizumab therapy significantly improved the relapse rate and accumulation of brain lesions in patients of African descent with relapsing MS.
Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis. [2010.05.15]
The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS) who had experienced disease activity while receiving interferon beta-1a (IFNbeta-1a) alone... Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNbeta-1a alone.
Demographic and clinic characteristics of French patients treated with natalizumab in clinical practice. [2010.02]
Natalizumab is the first selective adhesion molecule inhibitor indicated for treatment of active relapsing-remitting multiple sclerosis (RRMS)... Tolerability was similar to that observed in AFFIRM.
Multiple sclerosis associated fatigue during natalizumab treatment. [2009.10.15]
OBJECTIVE: To assess multiple sclerosis (MS) associated fatigue after the first 6 months of natalizumab treatment... CONCLUSION: Fatigue and well-being improved after treatment initiation with natalizumab. A randomized controlled trial is necessary to come to definite conclusions as to a potential effect of natalizumab on fatigue in MS.
Clinical Trials Related to Tysabri (Natalizumab)
A Proof of Concept Study to Evaluate the Effectiveness of Tysabri in Relapsing Remitting Multiple Sclerosis (RRMS) Patient Bladder Function [Completed]
The primary objective of the study was to measure the change in bladder function as measured
by Urogenital Distress Inventory (UDI)-6 compared to baseline over 6 months of Tysabri
treatment. Secondary objectives were to (i) measure change from baseline over 6 months of
Tysabri treatment in the number of urinary incontinence episodes per participant per week,
(ii) measure change from baseline over 6 months of Tysabri treatment in the number of
micturitions per participant per day, (iii) measure change in The North American Research
Committee on Multiple Sclerosis (NARCOMS) bladder/bowel subscale (PSB) scores from baseline
over 6 months of Tysabri treatment and (iv) measure change in Incontinence Impact
Questionnaire (IIQ)-7 scores from baseline over 6 months of Tysabri treatment.
Effect of Tysabri in Patients With Relapsing-Remitting Multiple Sclerosis: A Follow-up Magnetization Transfer Imaging (MTI) Study [Completed]
The primary objective of this study is to define the effect of Tysabri in patients with
relapsing-remitting (RR) multiple sclerosis (MS) over 2 years. The investigators will also
explore the extent of remyelination in MS patients treated with Tysabri over 2 years.
A secondary objective of this study is to investigate differences in the capacity for
remyelination between patients who do or do not respond to Tysabri monotherapy during the
same 24 months.
A tertiary objective of this study is to monitor Tysabri effect in MS antiphospholipid
antibodies positive and MS antiphospholipid antibodies negative patients and to determine
perfusion differences according to the antiphospholipid antibodies positivity status.
Effects of Tysabri (BG00002) Over 12 Months on MS Related Fatigue in Participants With RRMS [Completed]
The primary objective of this trial is to observe the Multiple Sclerosis (MS) related
fatigue during treatment with Tysabri as measured by changes in the fatigue scale for motor
and cognitive functions (FMSC) over the course of 12 months. The secondary objectives are:
To investigate changes in fatigue, capacity for work, Health Related Quality of Life
(HRQol), sleepiness, cognitive impairment, physically activity induced exhaustion, speed of
walking, status of MS disease progression and amount of walking at different times points
after initiation of Tysabri treatment in participants diagnosed with Relapsing-Remitting
Multiple Sclerosis (RRMS). Changes in fatigue are measured at 3, 6 and 9 months, whereas
changes in capacity for work, HRQoL, sleepiness, cognitive impairment, physical activity
induced exhaustion, speed of walking, status of MS disease progression and amount of walking
are measured at 6 and 12 months. To investigate correlation between fatigue and cognitive
impairment, depression and physically activity induced exhaustion and status of MS disease
progression in participants at baseline, 6 and 12 month of treatment with Tysabri and to
document any changes in fatigue related medication.
Safety Study of Natalizumab to Treat Multiple Sclerosis (MS) [Completed]
The primary objective of this study is to compare the pharmacokinetic (PK) and
pharmacodynamics (PD) of single subcutaneous (SC) and intramuscular (IM) doses of 300 mg
natalizumab to intravenous (IV) administration of 300 mg natalizumab in multiple sclerosis
(MS) participants. The secondary objectives are to investigate the safety, tolerability and
PK of repeated natalizumab doses administered SC and IM, to investigate the immunogenicity
of repeated natalizumab doses administered SC and IM, to explore proof of concept within the
secondary progressive multiple sclerosis (SPMS) population using change from baseline in
clinical measures including: expanded disability status scale (EDSS), multiple sclerosis
functional composite scale (MSFC), symbol digit modalities test (SDMT), visual analogue
scale (VAS), and visual function test; and brain magnetic resonance imaging (MRI) measures
including: number of new or newly-enlarging T2 hyperintense lesions, number of new T1
hypointense lesions, number of new gadolinium-enhancing (Gd+) lesions, whole brain atrophy,
magnetization transfer ratio (MTR), and diffusion tensor imaging (DTI) and to observe the
effect of natalizumab administered IV and SC on brain MRI measures in participants with
relapsing forms of MS.
Tysabri Effects on Cognition and Neurodegeneration in Multiple Sclerosis [Recruiting]
The long-term objective is to further establish the role of Tysabri in preventing
neurological degeneration in multiple sclerosis (MS) and to establish powerful and efficient
new markers for neurological degeneration in MS. The study intends to correlate cognition
with two instruments and their measurements-MRI and OCT (optical coherence tomography).
Reports of Suspected Tysabri (Natalizumab) Side Effects
Multiple Sclerosis Relapse (2537),
Gait Disturbance (1328),
Progressive Multifocal Leukoencephalopathy (1184),
Urinary Tract Infection (1118),
Multiple Sclerosis (1056),
Malaise (1001), more >>
Page last updated: 2016-02-12