medwireNews: People aged 50 years and older with nonactive multiple sclerosis (MS) have an increased risk for relapse when they stop taking high-efficacy therapy (HET) that impacts immune cell trafficking, a study has found.
Specifically, stopping treatment with fingolimod and natalizumab increased the risk by a respective 4.5- and 7.2-fold compared with continuing the treatments. By contrast, discontinuing anti-CD20 HET, including rituximab and ocrelizumab, did not increase the risk for relapse.
“Further studies are needed to identify the best therapeutic strategy: switching to an anti-CD20 therapy as in younger patients or deescalation to an MET [medium-efficacy therapy],” write Anne Kerbrat (University Hospital of Rennes, France) and colleagues in JAMA Neurology.
They add: “The possibility of stopping anti-CD20 therapy without switching or with deescalation to an MET in older patients with MS must be investigated by studies with a longer follow-up.”
The observational study extracted clinical data from the French MS registry, with eligible patients aged 50 years and older and treated with HETs including natalizumab, fingolimod, rituximab, or ocrelizumab for at least 1 year, with no relapse or magnetic resonance imaging (MRI) activity for at least 2 years.
The patients were then classified according to whether they were discontinuing HET without initial plans to switch to another therapy (n=168) or continuing HET (n=1452).
Of the 1620 patients enrolled in the study, 75.7% had relapsing–remitting MS and the remaining 24.3% had secondary progressive MS. The mean duration of disease was 17.4 years, and the patients had significant disability at baseline, as indicated by a mean score of 4 out of a possible 10 points on the Expanded Disability Status Scale (EDSS), higher scores on which represent greater disability.
The researchers used propensity-score matching to compare 154 participants who discontinued HET with the same number who did not. They had a mean age of 57.7 years, a mean 5.6 years since the last inflammatory activity, and a mean follow-up of 2.5 years.
A total of 33% of patients were treated with fingolimod, 29% with natalizumab, and 38% with anti-CD20 therapy (rituximab or ocrelizumab). The drug dosing was in accordance with standard protocols and for rituximab it was 500–1000 mg every 6–9 months.
Among participants who discontinued HET, the risk for a first relapse at 1 year was increased a significant 4.1-fold compared with participants who continued treatment, and the probability of relapse was 33.6% for those receiving natalizumab and 16.3% for those receiving fingolimod, but 0.0% for those receiving anti-CD20 therapy. Patients discontinuing natalizumab had a peak in relapses within the first 4 months.
Kerbrat et al note that the heightened risk for relapse when discontinuing HET was seen in patients with relapsing–remitting MS (hazard ratio [HR]=4.3) but not in those with secondary progressive MS, although they add that the result “must be treated with caution” due to the transition to secondary progressive MS potentially being underestimated and difficulties in identifying relapses in this group.
The patients discontinuing HET also had a faster onset of first focal inflammatory activity (relapse and/or new or enlarged T2 lesions on an MRI scan) than those continuing HET, with an HR of 3.6. The highest likelihood of inflammatory activity according to the HET discontinued was seen in those taking fingolimod, followed by those given natalizumab and anti-CD20 therapy, with HRs of 6.2, 3.8, and 1.8, respectively.
This increased likelihood for inflammatory activity was seen for both MS phenotypes, observes the team, suggesting that “stopping natalizumab or fingolimod without switching to another treatment exposes the patient to an increased risk of inflammatory activity, even in those with nonactive secondary progressive MS.”
The researchers linked HET discontinuation to a greater likelihood of disability progression, defined as an EDSS increase of 1.0 point or 0.5 points if baseline EDSS score was 5.5 points or greater, confirmed for at least 6 months and until the end of patient follow-up, relative to HET continuation, with an HR of 2.6. This was particularly the case for patients stopping natalizumab, who had a significant HR of 5.2.
They conclude that the findings confirm the increased risk for relapse with HET discontinuation in older adults, as has been seen in younger patients, and suggest that the mechanism of action of the discontinued HET “is an important factor, independent of age.”
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