Older Age at DMT Discontinuation Linked to Sustained NEDA in CIS Patients

Older Age at DMT Discontinuation Linked to Sustained NEDA in CIS Patients
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Older age at disease-modifying therapy (DMT) discontinuation is the main predictive factor of sustained “no evidence of disease activity” (NEDA) in people starting DMT immediately after being diagnosed with clinically isolated syndrome (CIS), according to a study in Austria.

In particular, patients discontinuing DMT at age 45 or older after at least five years of NEDA showed a significantly lower risk of disease reappearance than those stopping therapy before that age.

These findings may help inform treatment decisions after sustained NEDA in this patient population and suggest that DMT discontinuation with continuous monitoring may be a low-risk option for patients older than 45.

The study, “Should I stop or should I go on? Disease modifying therapy after the first clinical episode of multiple sclerosis,” was published in the Journal of Neurology.

CIS, a neurologic episode that lasts at least 24 hours, often is the first clinical presentation of multiple sclerosis (MS). Several DMTs have been approved for relapsing forms of MS, including CIS.

Notably, interferon-beta products, such as Rebif (by EMD Serono, known as Merck KGaA outside North America.), and glatiramer acetate (marketed as Copaxone by Teva Pharmaceuticals, or Glatopa, its generic form by Sandoz) were shown to significantly delay the conversion from CIS to clinically definite MS in clinical trials. Both types of therapies are available in injectable forms.

A proportion of CIS patients may achieve NEDA — a status defined by the absence of new or enlarging brain lesions, relapses, and confirmed disability progression — after DMTs and remain free of disease activity for prolonged periods.

This may prompt “consideration of DMT discontinuation in CIS patients and treating neurologists, especially if patients experience adverse events or [needle] fatigue,” the researchers wrote, noting that convenience and economic burden also may drive the discussion on whether to continue treatment. (Needle fatigue represents a waning commitment to continue with the prescribed injectable treatment.)

However, the risks of DMT discontinuation following sustained NEDA in these patients remains largely unknown.

Now, researchers at the Medical University of Vienna, in Austria, set out to evaluate potential predictive factors for sustained NEDA after stopping DMT in people diagnosed with CIS.

They retrospectively analyzed the demographic and clinical data from 49 patients (32 women and 17 men) who started DMT immediately after CIS diagnosis and discontinued it after showing NEDA for at least five years.

Patients, with a mean age of 26.3 years at symptom onset, were diagnosed between 2001 and 2011 at the University’s MS center, and started on interferon-beta medication or glatiramer acetate after a mean of 2.7 months from disease onset.

The option to stop DMT was discussed extensively with patients, who had the final say. After DMT discontinuation, patients underwent regular clinical and brain imaging (through MRI) follow-up for at least five consecutive years.

Results showed that 26 (53%) patients remained disease-activity free for at least five years after DMT discontinuation. In contrast, 23 patients (47%) showed either disease relapse or disability progression (nine patients or 18.4%), new or enlarging brain lesions (seven patients or 14.3%), or both (seven patients or 14.3%).

Age at DMT termination was the main predictive factor for sustained NEDA after discontinuation, with older age associated with a higher likelihood of remaining free of disease activity.

Being a woman also was a significant predictive factor of sustained NEDA, but this association was only modest, the team noted. No other clinical or treatment-related parameters showed a predictive value of disease reactivation after DMT stop.

Further analysis highlighted that patients 45 and older at DMT stoppage had a significantly lower risk of disease reactivation, compared with younger patients — 13% vs. 54% in the younger-than-45 group.

The mean time to show signs of disease activity was greater in older patients (37 months) compared to those at least 40 (31 months), and those younger than 31 (26 months).

Taken together, “in CIS patients with immediate DMT after their first clinical episode, older age at the time of DMT discontinuation is the main predictive factor for sustained NEDA status,” the researchers wrote.

They emphasized, however, that the findings should not encourage CIS patients to stop DMT after a long period without signs of disease activity. Instead, they may provide support to physicians in advising patients who no longer want to continue DMT due to sustained NEDA.

“In this context, neurologists should encourage younger people to continue DMT despite no overt clinical or MRI indicators of ongoing disease activity, while in patients [over] 45 years, stopping DMT together with continuous regular clinical and MRI follow-up may provide a clinically reasonable option with low risk,” the team concluded.

Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Marta Figueiredo holds a BSc in Biology and a MSc in Evolutionary and Developmental Biology from the University of Lisbon, Portugal. She is currently finishing her PhD in Biomedical Sciences at the University of Lisbon, where she focused her research on the role of several signalling pathways in thymus and parathyroid glands embryonic development.
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