Key messages

• After two years of treatment, natalizumab (NTZ) reduces the frequency of relapses and slows the progression of disability in relapsing‐remitting multiple sclerosis (RRMS) when compared with placebo (dummy treatment). After one year of treatment, there may be little to no difference between NTZ and biosimilar (medications that are nearly identical to an existing biological drug) NTZ in benefits and harms for RRMS.

• For people with secondary progressive MS (SPMS), NTZ may reduce the frequency of relapses, but may result in little to no difference in disability progression at two years.

• Longer studies with more non-white populations are needed to assess the benefits and harms of NTZ in people with MS.

What is multiple sclerosis (MS)?

MS is the most frequent central nervous system disease in young, white adults. It mainly affects the brain and spinal cord, leading to a range of physical and cognitive (thinking) problems. Inflammation and damage to the nervous system gradually affects all neurological functions, such as movement, a person's senses, and thinking and emotions. The most common type of MS is relapsing‐remitting multiple sclerosis (RRMS), where there are episodes of symptom flare-ups (relapses) followed by periods of remission (lack of symptoms). Over time, some people with RRMS transition to secondary progressive MS (SPMS). In SPMS, neurologic function worsens over time and disability increases.

How is MS treated?

There is no cure for MS at present, so treatment focuses on managing symptoms, reducing inflammatory disease activity, and slowing down the course of the disease. This is done with medications known as disease-modifying treatments (DMTs), which aim to reduce the frequency of relapses and development of new and/or growing existing lesions (damage to the brain) on magnetic resonance imaging (MRI) and slow down disability progression. Natalizumab (NTZ) is a DMT approved for the treatment of RRMS.

What did we want to find out?

We wanted to find out the benefits and harms of NTZ used alone or in combination with other treatments for people with any form of MS.

We were interested in the:

• number of people who had relapses;

• number of people whose disability worsened;

• number of people who experienced serious unwanted effects;

• impact on quality of life;

• number of people who developed active lesions confirmed by MRI;

• number of people who stopped treatment (treatment discontinuation) due to unwanted effects.

What did we do?

We searched for studies that looked at NTZ for people with any form of MS. We analysed and compared the results of the included studies and assessed how much confidence we had in the evidence based on study methods and sizes.

What did we find?

We found five studies involving a total of 3255 people. The studies were mostly conducted in Europe and North America in white women.

For RRMS:

• Compared to placebo at two-year follow-up, NTZ:

  • reduces the risk of relapses and disability;

  • probably slightly reduces serious unwanted effects;

  • results in a very slight improvement in quality of life;

  • decreases MRI disease activity;

  • probably has little to no effect on treatment discontinuation due to unwanted effects.

• Compared to biosimilar-NTZ (a medication nearly identical to NTZ) at one-year follow-up, NTZ:

  • may result in little to no difference in benefits and harms.

For SPMS:

• Compared to placebo at two-year follow-up, NTZ:

  • may reduce relapse rates;

  • may result in little to no difference in disability progression, serious unwanted effects, or treatment discontinuation due to unwanted effects;

  • probably results in little to no difference in quality of life.

What are the limitations of the evidence?

We had mixed confidence in the evidence. In cases where our confidence was limited, this was mainly due to the small size of the included studies. Also, we were worried that the financial interests of pharmaceutical companies might have influenced how the results were reported. Lastly, the studies were relatively short, lasting no more than 24 months.

How up-to-date is this evidence?

The evidence is current to February 2024.