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 relapsing‐remitting multiple sclerosis, was updated in January 2024. We asked the lead author, Francesco Nonino from the Institute of Neurological Science in Bologna, Italy, to tell us more 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. There are approximately 2.8 million people living with MS worldwide. 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 multiple sclerosis experience weakness, tiredness, painful cramps in their muscles, and reduced sensitivity in parts of their body. In time, such symptoms may worsen and lead to the need for a wheelchair. The most common form of multiple sclerosis is called "relapsing-remitting" because the symptoms come and go over the years, with each appearance of symptoms being called a "relapse".  Although, currently, there is no treatment that can cure for multiple sclerosis, several drugs are available to reduce inflammation in the brain or spinal cord. These are called "disease-modifying" in that 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 find out if any of these drugs is better than the others in achieving these outcomes, and if any drug is better tolerated or causes fewer unwanted events.
The previous version of the review was published in 2016 and we now include 50 randomised trials, that tested 29 pharmacological treatments, and included a total of more than 36,000 people with multiple sclerosis. About two thirds of the research participants were female. Twenty-five studies compared a "disease-modifying" drug with placebo, while the other 25 tested "disease-modifying" drugs directly against each other. Most studies lasted 12 or 24 months, with only four following the patients for as long as 36-months; and most studies were performed by pharmaceutical companies in order to obtain regulatory authorization to market the studied drug.
We found three drugs, natalizumab, cladribine and alemtuzumab, to be more effective than other drugs for reducing the frequency of relapses after two years of treatment. Two years of natalizumab may also be effective in slowing the worsening of disability. People taking fingolimod, teriflunomide, glatiramer acetate, interferon beta-1a, laquinimod, natalizumab and daclizumab may more likely discontinue the drug because of unwanted effects.
However, our confidence in the desirable and undesirable effects of all these "disease-modifying" drugs is limited, mainly because the evidence is based on few cases of relapse and worsening of disability, and there is insufficient evidence on a longer term than two years, which is particularly relevant for a chronic condition such as multiple sclerosis that develops over decades. We were also concerned that the interests of pharmaceutical companies may have influenced the reporting of the study results.
Finally, there is an ongoing need for more studies directly comparing active agents, with follow-up of at least three years, and assessment of other patient-relevant outcomes, such as quality of life and cognitive status, and particular focus on the impact of sex and gender on treatment effects.

Mike: If you would like to read the full version of this review, and watch for future updates if such studies become available, it's free to view at Cochrane Library dot com. If you go to the website and search 'immunomodulators for relapsing remitting multiple sclerosis', you'll see a link to it near the top of the list.