Real-World Safety and Effectiveness of Cladribine Tablets in Older (≥ 50 Years) Patients with Relapsing Multiple Sclerosis: Results from the “Aging” Study—A Multicenter, Single-Arm, Phase 4 Observational Study

Older patients with relapsing multiple sclerosis (PwRMS) are often underrepresented in clinical trials, limiting evidence on the safety and effectiveness of disease-modifying therapies. This study characterized the safety and effectiveness of short-course treatment with cladribine tablets (CladT) over 24 months in PwRMS aged ≥ 50 years. “Aging” was a 24-month observational, single-arm, real-world, phase 4 study conducted at 14 centers in the USA. PwRMS aged ≥ 50 years who initiated CladT (cumulative dose 3.5 mg/kg over 2 years) on/before January 31, 2022 were included. The primary endpoint was annualized relapse rate (ARR) at 24 months after CladT initiation. Additional clinical, imaging, disability, and safety endpoints were assessed. Post hoc subgroup analyses were conducted by age. Of 115 PwRMS included, 84 (73.0%) were aged < 65 years and 31 (27.0%) ≥ 65 years. At 24 months, mean ARR was low overall and in both subgroups—total: 0.07 (95% confidence interval [CI] 0.03–0.12), < 65 years: 0.10 (95% CI 0.03–0.16), ≥ 65 years: 0.02 (95% CI − 0.02 to 0.05). Safety profiles were comparable across age groups: ≥ 1 adverse event (AE) occurred in 80/115, 69.6% of PwRMS (< 65 years: 60/84, 71.4%; ≥ 65 years: 20/31, 64.5%), and serious AEs in 8/115, 7.0% (< 65 years: 6/84, 7.1%; ≥ 65 years: 2/31, 6.5%). Lymphopenia (51/115, 44.3%), COVID-19 (15/115, 13.0%), and urinary tract infections (7/115, 6.1%) were the most frequent AEs and predominantly mild-to-moderate; PwRMS aged ≥ 65 years had lower incidences than those < 65 years. Median lymphocyte counts were stable; most lymphopenia events were grade 1–2; no grade 4 lymphopenia occurred. AE-related treatment discontinuation rates were low and similar across age groups. No unexpected safety concerns, malignancies, opportunistic infections, or deaths occurred. In older PwRMS, CladT was found to be effective with a favorable safety profile at 2 years, including in PwRMS aged ≥ 65 years. These findings support the therapeutic value of CladT in older PwRMS. Infographic available for this article. Older patients with relapsing multiple sclerosis (a form of multiple sclerosis where symptoms flare up, during relapses) are often underrepresented in clinical trials, so there is less evidence about how safe and effective treatments are in this age group. This 24-month real-world study in the USA included 115 patients aged ≥ 50 years who started short-course treatment with cladribine tablets of 3.5 mg/kg over 2 years for the treatment of their relapsing multiple sclerosis. The main outcome was the annualized relapse rate (average number of relapses per year). Over 24 months, the annualized relapse rate was low (roughly 7 in 100), and most patients had no relapses. Patients aged ≥ 65 years had fewer relapses, and more of them had no relapses, than those < 65 years. Safety results were similar across the age groups. About 7 in 10 patients had at least 1 adverse event (an unwanted medical problem during treatment) but serious adverse events were uncommon (7%). The most frequent adverse events were low lymphocyte counts (lymphocytes are a type of white blood cell that help fight infection; a known side effect of cladribine tablets), COVID-19, and urinary tract infections. Most adverse events were mild-to-moderate in severity; lymphocyte counts remained stable over time. Only a few patients stopped treatment because of adverse events, and there were no unexpected safety concerns, cancers, serious unusual infections, or deaths. Overall, cladribine tablets showed a favorable safety profile and effectiveness in patients aged ≥ 50 years with relapsing multiple sclerosis, including those aged ≥ 65 years.