The first randomized discontinuation trial of MS drugs — DISCOMS — provided insight about whether people with MS should continue disease-modifying therapy (DMT) as they age.
Although stopping DMT was not inferior to continuing, non-inferiority of stopping DMT was not demonstrated, reported John Corboy, MD, of the Rocky Mountain MS Center at the University of Colorado in Westminster, in a late-breaking presentation at the Consortium of Multiple Sclerosis Centers (CMSC) annual meeting.
New or worsening clinical activity was relatively uncommon in either group, and relapses were very uncommon. DMT discontinuation was not associated with a difference in adverse events, MS symptoms, or quality of life.
Whether it’s logical and safe to consider a discontinuation trial in stable MS patients as they age is a question that’s been asked for about 10 years, Corboy observed.
“The decision to stay on or go off medications is potentially associated with risks related to the disease versus the treatment because the benefits — at least those we can identify — appear to dwindle with age,” he told MedPage Today.
“There is also a financial issue in that the costs of indefinite ongoing treatment are very high,” Corboy added. “If the benefit is very low or really not demonstrated at all, that’s a large burden for patients and for society.”
DISCOMS was conducted at 20 U.S. centers and recruited participants from May 2017 through 2021. Its primary outcome was any new relapse or brain lesion on MRI over 2 years.
“The study is somewhat unique in the MS world, as it is a so-called non-inferiority analysis,” Corboy said. “The hypothesis is that going off DMT will produce a worse outcome than staying on DMT. We were attempting to disprove this, to show non-inferiority.”
Participants were at least age 55 and had no new scan change for at least 3 years and no relapse for at least 5 years. Most participants were women (83%), white (89%), and were using older, injectable medicines at baseline. The average time from last relapse was about 14 years. On average, participants had moderate disability with an Expanded Disability Status Scale (EDSS) score of 3.4 on a 10-point scale. Most people (83%) had relapsing MS.
Corboy and colleagues randomized 259 participants: 128 continued treatment and 131 did not. Mean age at randomization was 63 and there were no significant differences at baseline between the groups. The study used a noninferiority margin of 8%.
Overall, 4.69% (95% CI 1.74-9.92) of those continuing and 12.21% (95% CI 7.15-19.08) of those discontinuing treatment had new disease activity. “Statistically, discontinuation was not proven inferior and not proven not inferior,” Corboy said. “Stated another way, discontinuation could be inferior to continuation, but this is not clear statistically.”
One patient who continued treatment and three who discontinued had relapse. “When looking at relapses alone, the outcome in discontinuers was not inferior to continuers,” Corboy noted.
“The total number of events was six in continuers and 16 in discontinuers, and 15 of the 22 total events consisted of one or two new brain lesions but no clinical relapse,” he added.
EDSS scores showed no difference in progression between groups; 14 continuers and 16 discontinuers had disability progression confirmed at 6 months. There was no relationship between MRI changes or relapse and disability progression.
Only two of the 30 people with confirmed disability progression also had at least one new brain lesion. None had relapse and disability progression.
The findings should help guide patients and providers with decision-making but will not answer all questions, Corboy pointed out.
“And while we did not get a perfect answer either way, this is perhaps the most likely outcome we might have expected — that is, a small amount of new MRI activity primarily, but of unclear clinical significance,” he said.
The study had several limitations, including its small subgroup numbers and its lack of brain volume data and neurofilament light or other biomarker information.
Two other randomized discontinuation trials are underway, one focusing on inactive secondary progressive MS, the other on relapsing-onset disease. “These will further offer help in making decisions about potential discontinuation of MS treatment,” Corboy said.
The research was funded through a Patient-Centered Outcomes Research Institute (PCORI) award and supported in part by the National Multiple Sclerosis Society (NMSS).
Corboy disclosed relationships with MedDay, Novartis, EMD Serono, NMSS, PCORI, NIH, Immune Tolerance Network, Neurology: Clinical Practice, Annals of Neurology, and Bristol Myers Squibb.