Real-World Findings Show Numerous Benefits for Older Patients With MS Switching to Teriflunomide

Daniel Becker, MD

Data from a multicenter, real-world, longitudinal study of patients with relapsing multiple sclerosis (MS) aged 55 who switched over to teriflunomide (Aubagio; Sanofi) showed significant improvements in annualized relapse rare (ARR), stable disability, and reduced occurrences of lymphopenia.¹

Teriflunomide, a once-daily oral immunomodulator, was approved in September 2012, becoming the second oral DMT greenlit for relapsing forms of MS. In the newly published analysis, senior investigator Daniel Becker, MD, assistant professor of neurology, Johns Hopkins School of Medicine, and colleagues performed chart reviews of 182 patients with relapsing MS from 4 MS centers who switched from other disease-modifying treatments (DMTs) to teriflunomide.

The mean age at index was 62.5 (±5.4) years, 76.4% were female, and 85.2% were White. Injectables like Glatiramer acetate and interferon-beta-1 were among the most used DMTs prior to switching (70%), followed by other oral DMTs such as fingolimod (19.2%), and infusibles like alemtuzumab, natalizumab, and ocrelizumab (7.8%). The primary reasons for switching from other DMTs were relapse (22.5%), needle fatigue (20.0%), and tolerability (18.1%), with others switching because of safety concerns.

In terms of ARR, there was a significant decrease observed from the start of teriflunomide treatment (mean, 0.43 [±0.61]) to year 1 post-index (mean, 0.13 [±0.65]) and year 2 post-index (mean, 0.05 [±0.28]). There were 16 people who reported relapses from index to post-index year 1, 12 of which who were on teriflunomide. Six of these patients had relapses occur within 4 months of treatment.

Expanded Disability Status Scale (EDSS) scores, which also evaluated efficacy, stayed the same from index (mean, 4.5 [±1.8]) to 1 year post-treatment (mean, 4.5 [±1.8]) and increased slightly at 2 years post-treatment (mean, 4.7 [±1.7]). There were no notable differences in ARR or EDSS score in the subgroup analyses of age group (55-64, ≥ 64 years), sex, MS type (relapsing-remitting, secondary progressive), and route of administration of prior DMT. All told, a majority of patients that had stable or improved MRI outcomes at index (90.4%) remained stable or improved after switching to teriflunomide at years 1 (96.0%) and 2 (93.6%). Subgroup analyses of MRI data by age group, sex, MS type, and route of administration of prior DMT did not show marked differences.

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Investigators observed that the frequency of lymphopenia decreased over time, from 23.5% at index, 21.4% at 1 year, and 14.8% at the end of the 2-year observation period. There were fewer patients with grade 3 or 4 lymphopenia by the 1-year mark, and no patients with this status at 2 years post-index. Notably, most patients were within the normal range of 4.0-11.0 x 109 cells/L for white blood cell count.

For patients who switched from oral DMTs to teriflunomide, there was an increase in normal ALC from index (9 of 28; 32.1%) to 1 year post-index (17 of 31; 54.8%) and to 2 years post-index (19 of 26; 73.1%). Lymphocyte counts remained stable from index to post-index for those who switched from injectables or infusions. Less than a quarter of the cohort (22.0%) reported infections throughout the study, the most common of which were urinary tract infections (12.6%). None of the infections were related to teriflunomide, and no patient reported more than 1 infection throughout the 2-year treatment period.

There were several noted limitations to the study, including the fact that it was retrospective and observational in design, which may have led to selection bias. The results were also based on medical review charts from multiple centers, so data available from the medical records may have varied. Additionally, the study took place across 4 centers, which may limit the generalizability of the findings, for which the study investigators noted, "A larger study could further substantiate the conclusions."

REFERENCE
1. Berkovich R, Negroski D, Wynn D, et al. Effectiveness and safety of switching to teriflunomide in older patients with relapsing multiple sclerosis: a real-world retrospective multicenter analysis. Mult Scler & Relat Disord. 2023;70:104472. doi:10.1016/j.msard.2022.104472