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Can MS Treatment Be Stopped?

— Pendulum keeps swinging on risks from drug discontinuation

Last Updated December 2, 2019
MedpageToday

DALLAS -- Patients with stable relapsing-remitting multiple sclerosis (MS) who stopped disease-modifying therapies (DMTs) showed similar times to relapses, inflammatory events, and disability progression as stable patients who remained on treatment, according to a presented here.

In addition, patients who were older -- ages >45 -- when they stopped treatment appeared to have better outcomes, reported Hajime Yano, MD, of Brigham and Women's Hospital in Boston, and colleagues, at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) forum.

"There's been a lot of interest in the last 5 years about this issue," said co-author Tanuja Chitnis, MD, also of Brigham and Women's Hospital, in an interview with app. "There are questions about how safe it is to treat long-term with DMTs."

"This data suggests that younger age goes along with more inflammatory disease activity and that is the critical group that needs to be treated with DMTs," she added. "And potentially after the age of 45 or 50, in stable patients, there may be opportunities to stop or step down DMTs."

While other studies have looked at discontinuing DMTs, a key strength of this research is the MRI data, Yano said. "Our study includes MRI activity as an inclusion and also as outcome measures," he told app.

In this analysis, Yano and colleagues identified 70 relapsing-remitting MS patients who discontinued DMTs in the (Comprehensive Longitudinal Investigation of MS at the Brigham and Women's Hospital) cohort. Patients had been treated for ≥2 years and had no clinical and radiological relapses -- including no gadolinium-enhancing (Gd+) or new T2 lesions, or T2 lesion enlargement -- for ≥2 years before discontinuing. Most patients were on glatiramer acetate (Copaxone; 44.3%) or interferon beta-1a (Rebif; 41.4%).

At baseline, patients were an average of age 45, a mean disease duration of about 12.5 years, and been receiving treatment for an average of 6 years. Most (87%) were female.

The researchers matched this group with 70 patients who remained on treatment, and looked for differences between the two groups in time to clinical relapse, MRI event, disability progression, and any inflammatory event (either clinical relapse or MRI event).

Compared with those who continued treatment, patients who discontinued DMTs had similar outcomes in time to:

  • Clinical relapse: hazard ratio 0.97 (95% CI 0.49-1.90, P=0.92)
  • MRI event: HR 0.97 (95% CI 0.59-1.59, P=0.90)
  • Disability progression: HR 1.27 (95% CI 0.62-2.57, P=0.51)
  • Inflammatory event: HR 0.93 (95% CI 0.58-1.44, P=0.69)

In a subgroup analysis comparing patients ages >45 with younger patients, statistically significant differences in time to clinical relapse (P=0.032 for interaction), time to MRI event (P=0.013 for interaction), and time to any inflammatory event (P=0.0005 for interaction) emerged.

"This is consistent with many randomized controlled trials showing that disease-modifying treatments have diminished impact with greater age," noted John Corboy, MD, of the University of Colorado in Denver, who was not involved with the study.

"It is notable that the most recent demographic study of prevalence in MS in the U.S. shows that 46% of all MS patients are 55 and older, so large numbers of folks are potentially affected by research of this nature," Corboy told app.

An ongoing multicenter trial, , may shed more light about stopping treatment in older patients, he added.

DISCOMS "is a randomized controlled discontinuation trial, with blinded outcomes, in a restricted age group -- 55 and older -- with more stringent evidence of no recent inflammatory disease activity, specifically, no relapse for 5 years and no new scan lesion for 3 years," Corboy said. Patients will be followed for 2 years and the to end in 2021.

Disclosures

Yano disclosed support from the Yoshida Scholarship Foundation in Japan.

Primary Source

Americas Committee for Treatment and Research in Multiple Sclerosis

Yano H, et al "Discontinuation of disease-modifying therapy in patients with relapsing-remitting multiple sclerosis" 2019 ACTRIMS; Abstract P061.