Results from a second clinical trial that focused on preventing or slowing the development of multiple sclerosis
have been published. Oral teriflunomide (Aubagio
®, Sanofi Genzyme) significantly extended the time before the development of a first neurological symptom compared to placebo. This second completed trial supports the concept that early treatment is protective against disease activity.
Participants had a rare condition called radiologically isolated syndrome, with MS-like brain lesions on MRI but no detectable symptoms. Additional research should help determine who among those with RIS may benefit from early treatment.
- Background: Although not yet considered to be MS, radiologically isolated syndrome (RIS) is a rare condition involving people who show lesions on MRI of the brain and/or spinal cord that are consistent with those found in MS but they have no detectable neurological symptoms. Previous research suggests that about half of those classified as having RIS are likely to develop definite MS within ten years. A previous trial, involving some of the same investigators, found that dimethyl fumarate, which has a different mode of action than teriflunomide, could delay the development of MS.
- The Study: Dr. Christine Lebrun-Frénay (Université Cote d’Azur, Nice, France) and international collaborators recruited 89 people with RIS from MS Centers in France, Switzerland, and Turkey. Participants were randomly assigned to receive either daily oral teriflunomide or inactive placebo for 96 weeks, with an optional third year if no symptoms had yet occurred.
- The primary goal of the study was to determine whether treatment would extend the time it took for participants to develop a first neurological symptom. The team also assessed disease activity on MRI scans and participant-reported impressions (“patient reported outcomes”).
- Nine people in each group did not complete the study for various reasons.
- Results: Significantly fewer participants (72%) who received teriflunomide experienced a neurological symptom compared to those on placebo. There was no significant difference in the occurrence of MRI-detected disease activity or other outcomes.
- Moderate adverse effects were more common in people taking teriflunomide, and included gastrointestinal problems, menstrual cramps, and mild respiratory infections. One person in the treatment group developed a severe COVID-19 infection, possibly due to teriflunomide.
Why does this study matter? This second completed trial adds to evidence that early treatment with an MS disease-modifying therapy results in improved outcomes. It also supports the idea that MS can begin well before symptoms emerge, and it may provide clues for how to predict who will go on to develop MS.
The authors caution that before treatment of RIS is considered, individuals with nonspecific MRI abnormalities should be assessed by experts at MS centers, who are likely better equipped to make the tricky diagnosis of RIS.
“Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome,” by Christine Lebrun-Frénay, Aksel Siva, Maria Pia Sormani, Cassandre Landes-Chateau, Lydiane Mondot, Francesca Bovis, Patrick Vermersch, Caroline Papeix, Eric Thouvenot, Pierre Labauge, Françoise Durand-Dubief, Husnu Efendi, Emmanuelle Le Page, Murat Terzi, Nathalie Derache, Bertrand Bourre, Robert Hoepner, Rana Karabudak, Jérôme De Seze, Jonathan Ciron, Pierre Clavelou, Sandrine Wiertlewski, Omer Faruk Turan, Nur Yucear, Mikael Cohen, Christina Azevedo, Orhun H. Kantarci, Darin T. Okuda, Daniel Pelletier, for the TERIS Study Group, was published in
JAMA Neurology (online August 21, 2023).