Ocrelizumab Benefit Confirmed in Older Patients With MS
MILAN — Ocrelizumab (Ocrevus) effectively prevents relapse in older patients with multiple sclerosis, researchers have shown for the first time, although the extremely low risk for relapse in this population should be taken into account, they say.
The researchers studied about 700 patients with multiple sclerosis aged 60 years and older from an international database, comparing outcomes with the anti-CD20 monoclonal antibody ocrelizumab vs those for interferon/glatiramer acetate (BRACE).
They found ocrelizumab significantly reduced the annual rate of relapses, although after adjustments, patients overall faced a relapse rate of less than 0.1 per year. There were also no significant differences in either disability progression or improvement between the two treatments.
“We believe this study is unique in that ocrelizumab demonstrates a very clear differential treatment benefit in this age group,” said study presenter Yi Chao Foong, MD, PhD candidate, Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia.
“However, this has to be balanced against the fact that overall relapse activity is extremely low in people with multiple sclerosis over the age of 60,” he added.
“We believe that this study adds valuable, real-world data for nuanced benefit vs risk DMT discussions with for older adults with multiple sclerosis.”
The findings were presented at the 9th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2023.
Lack of Data in Older Patients
Fong explained the comparative efficacy of disease-modifying therapies (DMTs) has not been demonstrated in older people with multiple sclerosis, as all landmark trials to date have excluded people older than age 60 years.
He underlined, however, that the inflammatory aspect of multiple sclerosis reduces with age, when neurodegenerative processes begin to predominate.
“This, combined with increased risk of acute infections in older adults have raised concerns over the benefit ratios of DMTs in this age group,” Fong said.
This has led to several de-escalation studies in older patients already on treatment for multiple sclerosis, but with “varied results.”
One study, published earlier this year, was unable to conclude whether DMT discontinuation was non-inferior to continuation in older patients with no recent relapse or new MRI activity.
To investigate further, the Australian team used the MSBase database to study patients with a confirmed multiple sclerosis diagnosis who had started or switched to ocrelizumab or BRACE when older than 60 years of age.
They were also required to have undergone an Expanded Disability Status Scale (EDSS) assessment around the time of the initiation of DMT. In all, 675 patients met the inclusion criteria, of whom 248 started with ocrelizumab and 427 with BRACE.
The treatment groups were well balanced, although baseline EDSS scores were higher in patients given ocrelizumab, at 5.22 vs 3.89 with BRACE (P = .05), and they had a lower relapse rate prior in the year (P = .01) and 2 years (P = .02) prior to baseline.
Only Relapse Rates Reduced
Over 571 patient-years of follow-up, there were eight relapses in patients treated with ocrelizumab, compared with 182 relapses during 2238 patient-years among those given BRACE.
The team then performed propensity matching based on patient age, disease duration, sex, baseline EDSS, prior relapses, and prior DMTs.
They found that, over a median follow-up of 2.47 years for ocrelizumab and 4.48 years for BRACE, there was a lower rate of relapse with ocrelizumab, at a weighted annualized relapse rate (ARR) of 0.01 vs 0.08 (P < .0001).
This, they calculated, equated to an ARR ratio in favor of ocrelizumab of 0.15 (P < .01).
The time to first relapse was also longer for ocrelizumab vs BRACE, at a weighted hazard ratio for relapse of 0.11 (P < .001) and with, as Fong highlighted, separation of the curves at 5 months.
Over a follow-up duration of 3.6 years, there was, however, no significant difference in confirmed disability progression (CDP) between the two treatments (P = .31), with similar results seen for confirmed disability improvement (CDI) (P = .92).
Fong noted the study was limited by an inherent treatment indication bias, affecting the sensitivity analysis and weighing, while assessment of CDP and CDI was hampered by the relatively short follow-up period and the lack of data on comorbidities.
He also highlighted the lack of safety data for the study population, as well as the lack of MRI.
Muddling the Data
Approached for comment, Pavan Bhargava, MBBS, MD, associate professor of neurology, Johns Hopkins Precision Medicine Center of Excellence for Multiple Sclerosis, Baltimore, pointed out the study is based on retrospective data.
“The main question that we normally come up against in clinical practice, once people are older, is: What do you do with their treatment?” he told Medscape Medical News.
This, Bhargava said, was the question that was addressed in the previous de-escalation studies.
The current study, he noted, “actually answered a completely different question: If you were starting or changing a treatment after 60, which one would be better to choose?” This is a “much rarer scenario,” he said.
The results nevertheless showed what is seen in younger patients; in other words, “a more efficacious treatment is more effective at reducing relapses than a less efficacious treatment, even though overall the number of relapses is quite low,” Bhargava said.
“The other problem,” he added, is the study included “not just relapsing but also progressive patients, so that kind of muddles the data a little bit.”
Consequently, “it’s hard to really make a definitive conclusion” from the results, Bhargava concluded.
No funding was declared. Fong declares relationships with Biogen, National Health and Medical Research Council, Multiple Sclerosis Research Australia, and the Australian and New Zealand Association of Neurologists. Several co-authors also declared financial relationships with industry.
9th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2023: Abstract O045. Presented October 11, 2023.
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