Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
Tysabri® (natalizumab) is a disease-modifying treatment by Biogen for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and secondary progressive multiple sclerosis (SPMS).1,2
The US Food and Drug Administration (FDA) approved Tysabri as a monotherapy for the treatment of MS in November 2004.3 The European Medicines Agency (EMA) followed suit in June 2006.4
Tysabri is an intravenous injection. The recommended dosage is 300 mg infused over 1 hour, once a month.5
Tysabri’s Mechanism of Action
Multiple sclerosis is characterized by inflammation and neurodegeneration caused by an immune system attack against the myelin sheath.
Tysabri is a monoclonal antibody designed to block the movement of immune cells from the bloodstream into the central nervous system (CNS) to minimize the damage they cause.2 It targets the α4β1 integrin protein.4
Get detailed prescribing information on the Tysabri monograph page on Rare Disease Advisor.
Some patients treated with Tysabri can develop neutralizing antibodies against the treatment, which can lead to reduced effectiveness.6
Warnings, Precautions, and Adverse Reactions
Tysabri can cause serious side effects.1 These include herpes infections, liver damage, weakened immune system, low platelet counts, and allergic reactions such as hives, itching, trouble breathing, chest pain, dizziness, wheezing, chills, rash, nausea, flushing, and hypotension.
The most common side effects of Tysabri are headaches, rash, urinary and respiratory tract infections, vaginitis, nausea, diarrhea, fatigue, depression, and stomach, joint, arm, and leg pain.
Tysabri can also increase the risk of progressive multifocal leukoencephalopathy (PML), which can lead to severe disability or death. The risk of PML is higher in patients with John Cunningham virus (JCV) infections, those who have used Tysabri for 2 years or more, and those who have been treated with immunosuppressants before Tysabri. Because of this risk, Tysabri is only available through a restricted distribution program called the TOUCH Prescribing Program.7
It is not known whether Tysabri can cause harm to the fetus or whether it passes into breast milk.
The safety and effectiveness of Tysabri in pediatric patients are also not known.
Efficacy in Clinical Trials
The safety and efficacy of Tysabri have been tested in two main phase 3 clinical trials.
The first trial, AFFIRM, was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study that recruited 942 participants with MS aged 18 to 50 years at 53 sites across the US, Canada, Europe, and the UK.8
Participants were randomly assigned to either receive Tysabri or placebo by intravenous infusion every 4 weeks for more than 2 years.
The primary objective of the trial was to determine whether Tysabri was effective in reducing the rate of clinical relapses at 1 year and in slowing the progression of disability at 2 years in comparison with the placebo. The secondary outcome measure was a reduction in magnetic resonance imaging (MRI) changes and clinical relapses.
The results showed that Tysabri treatment reduced the risk of sustained progression of disability by 42% over 2 years.9 The cumulative probability of progression was 17% in patients receiving Tysabri and 29% in those receiving the placebo. Tysabri also reduced the rate of clinical relapse at 1 year by 68%, and it led to an 83% reduction in the accumulation of new or enlarging hyperintense lesions over 2 years. There were 92% fewer lesions in the Tysabri group compared with the placebo group at both 1 and 2 years.
The second trial, SENTINEL, assessed the safety and efficacy of Tysabri in combination with Avonex® (interferon beta-1a) in the treatment of MS.10 This was also a randomized, double-blind, placebo-controlled, parallel-group, multicenter study in patients aged 18 to 55 years with MS.
The trial recruited 1171 patients who were already being treated with interferon beta-1a therapy but still had at least 1 relapse in the last year. Participants were randomized to continue on their current therapy and also receive either Tysabri or a placebo intravenously every 4 weeks for up to 116 weeks.
Like the AFFIRM study, the primary objective of SENTINEL was to determine whether Tysabri was effective in reducing the rate of clinical relapses at 1 year and in slowing the progression of disability at 2 years. The secondary outcome was whether the combination therapy reduced MRI lesions and the overall rate of clinical relapses.
The results showed that Tysabri plus interferon beta-1a led to a 24% reduction in the relative risk of sustained disability progression. It was also associated with a lower annualized relapse rate over 2 years compared to interferon beta-1a plus placebo.11 There were also fewer new or enlarging lesions on T2-weighted MRI in the Tysabri plus interferon beta-1a group compared to the interferon beta-1a plus placebo group.
- Tysabri® (natalizumab). Biogen. Accessed June 15, 2021.
- Tysabri. National Multiple Sclerosis Society. Accessed June 15, 2021.
- Tysabri FDA approval history. Drugs.com. Accessed June 15, 2021.
- Tysabri: natalizumab. European Medicines Agency. Updated June 15, 2021. Accessed June 15, 2021.
- Tysabri dosage. Drugs.com. Updated June 30, 2020. Accessed June 15, 2021.
- Tysabri. MS Society of Canada. Accessed June 15, 2021.
- TYSABRI® (natalizumab) is available only through the TOUCH Prescribing Program, which stands for TYSABRI Outreach: Unified Commitment to Health. Touch On-Line. Accessed June 15, 2021.
- Safety and efficacy of natalizumab in the treatment of multiple sclerosis. ClinicalTrials.gov. December 3, 2001. Updated January 9, 2017. Accessed June 15, 2021.
- Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899-910. doi:10.1056/NEJMoa044397
- Safety and efficacy of natalizumab in combination with Avonex in the treatment of multiple sclerosis. ClinicalTrials.gov. February 18, 2002. Updated June 18, 2009. Accessed June 15, 2021.
- Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):911-923. doi:10.1056/NEJMoa044396
Reviewed by Harshi Dhingra, MD, on 7/1/2021.