Mike: Hello, I’m Mike Clarke, podcast editor for the Cochrane Library. There are more than 60 Cochrane Reviews relevant to multiple sclerosis and, one of these, a network meta-analysis of immunomodulators and immunosuppressants for progressive multiple sclerosis, was updated in September 2024. We asked one of the authors, Francesco Nonino from the Istituto delle Scienze Neurologiche di Bologna in Italy, to tell us about the condition and the latest evidence in this podcast.

Francesco: Multiple sclerosis, or MS, is caused by an inflammation of the brain and spinal cord which leads to damage that impairs important activities of daily living, such as walking and taking care of oneself. Worldwide, approximately 2.8 million people are living with MS. It typically affects young people, mainly women, in the most active stage of their life, between the age of 20 and 40 years.
People with MS experience weakness, tiredness, painful cramps in their muscles, and reduced sensitivity in parts of their body. In time, their symptoms may worsen and lead to the need for a wheelchair. The most common form of MS is called "relapsing-remitting" because the symptoms come and go over the years, with each appearance of symptoms being called a "relapse".  When recovery doesn't happen or is incomplete between relapses, the condition is known as “progressive” MS, which is the focus of our review.
Although, currently, there is no cure for MS, several drugs are available to reduce inflammation in the brain or spinal cord. These are called ‘disease-modifying’ because they are aimed at reducing the frequency of relapses and slowing the progression of disability. In our review, we used a network meta-analysis to try to put these drugs in order of their effectiveness for reducing relapses and slowing progression, and to see if any drug is better tolerated or causes fewer unwanted events.
We found 23 studies involving a total of more than 10,000 people with progressive MS who were treated with a disease‐modifying drug or placebo for at least one year. Twenty studies compared disease‐modifying treatments to placebo, and three studies compared different disease‐modifying treatments to each other. The studies ranged in size from 27 to 1651 participants. Most studies lasted 12 or 24 months, with only four lasting more than 24 months; and most studies were conducted by drug companies to obtain regulatory approval to sell the drug.
Overall, we are very uncertain about the effects of the drugs on relapses and on slowing the worsening of disability. However, we did find evidence that two years of rituximab and three years of interferon beta‐1b probably slightly reduce the number of people who experience relapses.
The number of people who stopped taking a drug because of harmful events was slightly higher with interferon beta‐1a than with placebo, and probably slightly higher than placebo for interferon beta‐1b, rituximab, immunoglobulins, glatiramer acetate, natalizumab, fingolimod, siponimod, and ocrelizumab.
Overall, our confidence in the effects of the disease‐modifying drugs for patients with progressive MS is very limited. This is because the evidence was based on relatively low numbers of people experiencing events such as relapses and worsening of disability; and insufficient evidence over a longer term than two years. This is particularly relevant for a chronic condition such as MS that develops over decades. We are also concerned that the interests of drug companies may have influenced the reporting of results.
In conclusion, there is an ongoing need for longer studies that make comparisons between different disease-modifying treatments if we are to have reliable evidence on benefits and harms over time for people with progressive MS. Future studies should also give more consideration to effects that are important to these patients, such as their quality of life and cognitive performance.

Mike: If you would like to read the full version of this review, and watch for future updates if those much-needed studies become available, it’s free to view at CochraneLibrary.com. If you go to the website and search “immunomodulators for progressive multiple sclerosis”, you’ll see a link to it.