Data from 5 clinical trials and their extensions along with 1 real-world study suggest that treatment with teriflunomide can help patients of varying ages maintain low annualized relapse rates and stable EDSS scores.
Jiwon Oh, MD, PhD
Results of a new pooled analysis consisting of real-world data and clinical trial data have shown that treatment with teriflunomide (Aubagio, Sanofi Genzyme) for multiple sclerosis (MS) is not only effective, but that efficacy can be maintained long-term across multiple patient age groups.
Utilizing datasets from a phase 2 study (NCT01487096), the phase 3 TEMSO (NCT00134563; NCT00803049), TOWER (NCT00751881), TOPIC (NCT00622700), and TENERE (NCT00883337) studies and their respective extensions, and the phase 4 Teri-PRO (NCT01895335) study, the findings revealed that patients given 14-mg teriflunomide maintained low annualized relapse rates (ARR; range 0.096 to 0.352) across all age groups. As well, the Expanded Disability Status Scale (EDSS) scores remained stable for all age groups.
The investigators, led by Jiwon Oh, MD, PhD, of the Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, also noted that “similar overall safety profiles were observed in teriflunomide-treated patients regardless of age in the core and extension studies,” though individual adverse events (AEs) differed by age in some instances. The overall rates of AEs were consistent between the clinical trials and the real-world data.
The data were presented in a poster at the 2019 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), May 28-June 1, in Seattle, Washington.
The patient population in the pooled clinical trials included 1978 patients, while the real-world Teri-PRO study included an additional 928 patients. When stratified by age, there were 232 patients aged ≤25 years (209 pooled, 23 real-world), 718 aged >25 to ≤35 years (593 pooled, 125 real-world), 999 aged >35 to ≤45 years (719 pooled, 280 real-world), and 745 aged >45 years (457 pooled, 288 real-world). Additionally, the real-world cohort included 212 patients aged >55 years.
ARRs were significantly reduced for patients administered teriflunomide by 55.5% (P =.0005), 26.8% (P =.0148), 35.9% (P =.0002), and 35.8% (P = 0096) in patients aged ≤25 years, >25—≤35 years, >35– ≤45 years, and >45 years, respectively, compared to placebo. When exploring data from the core studies and their extensions, the unadjusted ARR was 0.228 (95% CI, 0.216-0.241) overall for patients receiving teriflunomide.
When subgrouping patients by age, the unadjusted ARRs were 0.269 (95% CI, 0.220-0.317) for those ≤25 years, 0.303 (95% CI, 0.275-0.330) for those >25— ≤35 years, 0.201 (95% CI, 0.182-0.219) for those >35–≤45 years, and 0.181 (95% CI, 0.159-0.202) for those >45 years.
Meanwhile, in the real-world Teri-PRO study, the annualized rate of treated relapses was 0.096 in patients aged ≤25 years, 0.352 in patients aged >25 to ≤35 years, 0.234 in patients aged >35 to ≤45 years, 0.186 in patients aged >45 to ≤55 years, and 0.114 in patients aged >55 years.
As for EDSS scores, there was observed stability across age groups over a 7-year period. Those aged ≤25 years had the lowest mean score of 2.00 (standard deviation [SD], 0.97) at year 7, up from 1.92 (SD, 1.16) at baseline. At year 7, those aged >35 to ≤45 years had a mean score of 2.84 (SD, 1.60), those aged >25 to ≤35 years had mean score of 2.61 (SD, 1.80), and those aged >45 years had a mean score of 3.47 (SD, 1.54). Those were up from baseline scores of 2.57 (SD, 1.44), 2.34 (SD, 1.33), and 3.05 (SD, 1.45), respectively.
Oh and colleagues noted that the most common safety events reported in all age groups were nasopharyngitis, headache, diarrhea, and increased alanine aminotransferase. “Diarrhea, back pain, and hypertension were more common in the older age groups than the younger age groups. Hypertension and musculoskeletal pain are also more common with increasing age in the general population,” they wrote.
In Teri-PRO, 82.6% of patients aged ≤25 years experienced an AE, with those rates being 78.4% of those aged >25 to ≤35 years, 85% of those aged >35 to ≤45 years, 83.3% of those aged >45 to ≤55 years and 81.1% of those older than 55 years.
All told, Oh et al noted that the data collected in clinical trials was reinforced by the real-world data of teriflunomide, supporting its use in patients with MS. They added that as of January 2019, more than 96,800 patients were being treated with teriflunomide, with a total real-world exposure of approximately 237,400 patient-years as of September 2018.
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Oh J, Vukusic S, Tiel-WIlck K, et al. Efficacy and Safety of Teriflunomide in Patients of Different Ages:Analysis of Pooled Clinical Trials and Real-World Data. Presented at: 2019 CMSC Annual Meeting. May 28-June 1, 2019; Seattle, WA. Abstract DXT27.