Switching to Cladribine Safe and Effective in Older Persons With MS, Real-World Data Show

Donald Negroski, MD

Findings from a single-center, real-world cohort of older patients with relapsing multiple sclerosis (MS) showed that cladribine (Mavenclad; EMD Serono) was safe and well tolerated for a 2-year period after switching from a previous disease-modifying therapy (DMT). These data appear encouraging, as an aging population often faces increased comorbid conditions and immunosenescence.¹

Presented at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29-June 2, in Nashville, Tennessee, mean duration follow-up was 1125 days, with nearly 70% of patients in stratification years 3, 4, or 5 at data cutoff. Cladribine, a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes, was well tolerated, with lymphopenia, upper respiratory tract infection, urinary tract infection, fatigue, and headache occurring in less than 5% of both the full cohort (n = 75) and a subgroup of those older than 50 (n = 40).

Led by Donald Negroski, MD, a neurologist at the Multiple Sclerosis Center of Sarasota, the prospective and retrospective study aimed to understand the benefit/risk profile of cladribine, a noncontinuous immunosuppressive DMT. Cladribine, which has been on the market since 2019, is administered in 4 courses of 4 to 5 days each over 2 years, with no treatment in years 3 and 4. In the study, after switching from a previous DMT, the mean age at cladribine initiation was 51.9 years for all patients and 60.7 years for the older subgroup.

In the analysis, the median disease duration was 11 and 13.5 years, respectively, for the overall cohort and older subgroup. Through the available follow-up period, more than 85% of all patients were relapse free, had a stable or improved MRI result, and had an annualized relapse rate of 0.11 in year 2 and 0.03 in year 3. The study is still ongoing, and additional results will be presented in the future as more patients increase the time from their last cladribine dose.

READ MORE: MAGNIFY-MS Analysis Further Demonstrates Cladribine’s Direct Impact on Central Nervous System in MS

Cladribine is thought to be an immune reconstitution therapy, in that 2 short course of oral treatment 1 year apart provide suppression of MS disease activity in responders that outlasts the duration of treatment and post-treatment reductions in lymphocyte counts. The randomized CLARITY study was the pivotal phase 3 clinical trial that underpinned the approval of cladribine for therapeutic use in relapsing MS. The study included 1326 patients who had received no more than 1 DMT previously who were randomly assigned to placebo or 1 of 2 doses of cladribine (cumulative total doses of 3.5 or 5.25 mg/kg, given as two 4–5-day courses 1 month apart at the start of the first and second years of treatment).

A post-hoc analysis of CLARITY stratified the trial population by age (≤45 years: n = 649; >45 years: n = 221), with findings showing that the risk of MS relapses was significantly reduced in both groups. In addition, there were significant (P <.0001) reductions in the mean number of active T2 MRI lesions in those aged less than 45 years (–0.667; 95% CI, –0.67 to –0.5) and greater than 45 years (–0.167; 95% CI, –0.33 to 0.00), as well as significant (P <.0001) reductions in the number of combined unique lesions in each group (–0.667 [95% CI, 1.00 to –0.67] and –0.333 [95% CI, –0.33 to 0.00], respectively).²

In a recently published narrative review on the use of cladribine tablets as exit therapy for stable elderly patients with MS, investigators wrote that "There is also no indication of an increased risk of serious safety issues in older people receiving cladribine, though this also requires further study. In addition to its more usual role earlier in the MS disease course, cladribine appears to be a rational therapeutic option for selected older people with RMS, including as an “exit therapy” for those with low and stable clinical and radiological MS disease activity on previous continuous DMT."³

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REFERENCES
1. Negroski, D. Long-Term Follow-Up of Cladribine Tablets in a Real-World Aging Patient Population. Presented at: 2024 CMSC Annual Meeting; May 29-June 2; Nashville, TN. ABSTRACT CS08
2. Giovanonni G, Rammohan K, Cook S, et al. Cladribine tablets 35 mg/kg is efficacious in patients aged above and below 45 years with relapsing multiple sclerosis in the clarity study. Mult Scler Relat Disord. 2018;26:P262.
3. de Seze J, Dive D, Ayrignac X, et al. Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis. Neurology & Ther. 2024;13(519-533). doi:10.1007/s40120-024-00603-y