SAN DIEGO — Cladribine may be a good option for older patients with multiple sclerosis (MS) who want to discontinue their disease-modifying therapy (DMT) without increasing their risk of relapse, a retrospective study showed.

A small study of 32 patients showed that only 4% of patients aged 50 and older who were taking cladribine developed new disease activity after finishing and discontinuing therapy. However, younger patients aged 45-49 had higher rates of breakthrough disease, with 25% developing new lesions.

“Cladribine may provide a viable exit strategy for DMT discontinuation in people with MS ages 50 and older,” corresponding author Nabeela Nathoo, MD, PhD, a neurologist and assistant professor at the University of Alberta, Edmonton, told Medscape Medical News. 

The findings were presented February 6 at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2026. 

A Closer Look at Cladribine 

The findings address a dilemma in MS therapy: As patients get older and their symptoms improve as their immune systems weaken and slow inflammatory activity, when is it appropriate to discontinue therapy?

As reported previously by Medscape Medical News, the evidence to date is mixed. Some studies suggest DMT discontinuation may be a viable option for adults over age 55 with stable disease, while others point to an increased risk of new disease activity when patients stop taking DMTs. 

“A common question we get asked by patients in the MS clinic is ‘Do I have to take medication for the rest of my life?’” lead author Samantha Dolter, MD, a neurology resident at University of Alberta, told Medscape Medical News. 

“One of our MS neurologists had been offering cladribine to patients who wish to try discontinuing medications but are understandably nervous about the risk of relapse, given its potential to allow several years of protection from inflammation after the final dose. We wanted to study the use of cladribine at our site and let other clinicians know what our results have been using this strategy,” Dolter said.Research has shown that cladribine’s protection against inflammation continues for several years after the final treatment. Although commonly used in Canada and Europe, cladribine is not widely used in the US.

To learn more about patient outcomes after stopping cladribine, researchers tracked 32 patients (81% female; 97% White) who received at least two cycles of cladribine between January 2018 and July 2025 at the Northern Alberta MS Clinic. All patients were 45 or older when they began treatment; 75% were aged 50 or older.

Prior to treatment with cladribine in the study, patients reported receiving platform therapy, such as interferons and glatiramer acetate, dimethyl fumarate, teriflunomide, and/or CD20 therapy. 

Promising, but Not for Everyone 

Investigators found that clinical relapse was reported in fewer patients in the older age group vs younger patients (4% vs 25%). Specifically, only one of the 24 patients in the older than 50 group developed clinical relapses and new MRI lesions compared to two of the eight patients in the 45-49 age group who had new MRI lesions only. 

The relapse rate in the older group is lower than what was reported in two large studies on DMT discontinuation, the DOT-MS trial (20% in people ≥ 50 years) and the DISCOMs trial (12.2% in people ≥ 55 years). 

Adverse events were reported in 97% of the participants, including lymphopenia, elevated liver enzymes, or both. 

“These results align with research to date suggesting cladribine may be a safe and effective method to transition [people with MS] off of DMTs,” researchers wrote, noting that the strategy should be used with caution in patients aged 45 or younger. 

“We would recommend close follow-up clinically and with MRI if people are treated with cladribine as there is still a propensity for developing new inflammation several years later,” Nathoo said. 

Investigators said more study of cladribine is needed, including randomized controlled trials with more ethnically diverse patient cohorts. 

“It would be interesting to see if using cladribine as an exit strategy vs simply discontinuing a DMT would help reduce the risk of new inflammation — clinical and MRI,” Nathoo said.

‘No Warning Signs’ 

Asked to comment, John R. Corboy, MD, a professor at the University of Colorado Anschutz School of Medicine, Aurora, noted the study is small, based on findings from a single center, and has the weaknesses of observational research. 

“We don’t have a lot of data on cladribine when people stop the drug. At least there are no warning signs here,” said Corboy, who led the 2024 DISCOMS trial on DMT discontinuation but was not part of the new study. 

He added that “larger and longer-term studies need to be done” in light of the fact that patients with MS may live for several decades with the disease. 

For now, though, cladribine “maybe be useful to consider” in cases where clinicians want to discontinue patients from DMTs, especially in light of evidence that some other MS drugs — such as natalizumab and fingolimod — have significant “rebound” effects after discontinuation, Corboy said. Cladribine “doesn’t appear to act like those drugs,” he added.

Corboy noted that cladribine likely does as well as anti-CD20 drugs such as rituximab, ocrelizumab, and alemtuzumab.

"But we don’t really know how long at this point. A recent couple of papers suggest possible return of disease activity after ocrelizumab discontinuation, starting about 19-24 months later. But this is very preliminary and in certain subsets of people with MS," he said. 

The study has no funding. Nathoo disclosed relationships with MS Canada, Canadian Institutes of Health Research, Novartis, and Roche. Dolter reported no disclosures. Corboy disclosed a relationship with EMD Serono.