The effect of cladribine on CD8+ T lymphocytes varied by age, with steady increases shown in the younger population whereas there were fluctuations observed in the older group.
Results from a post-hoc analysis presented virtually at the ACTRIMS Forum 2021, February 25–27, demonstrated that cladribine 10 mg (Mavenclad; EMD Serono) had a similar impact on CD19+ B and CD4+ T lymphocytes by week 96 in both older and younger patients with multiple sclerosis (MS).1
Presented by Gavin Giovannoni, MBBCh, PhD, chair of neurology, Barts and The London School of Medicine and Dentistry, the study examined the effect of age at baseline and after treatment with cladribine 10 mg (3.5 mg/kg cumulative dose over 2 years) on levels of lymphocyte subsets. Giovannoni and colleagues used combined data from 923 patients treated with cladribine from CLARITY (NCT00213135), CLARITY extension (NCT00641537), and ORACLE-MS trials (NCT00725985), as well as the PREMIERE registry (NCT01013350).
Nadir for CD19+ B lymphocytes occurred at week 9 (4 weeks after year 1 dosing) for both age groups, corresponding to a decrease from baseline (DFB) of 90.2% and 93.8% in the younger than50 and older than 50 groups, respectively.
After year 2 dosing, CD19+ B lymphocytes were lowest at week 52 (age ≤50: 84.7% DFB; age >50: 84.4% DFB), and were below the lower limit of normal (LLN) but recovered gradually to normal levels by week 96. The original median CD19+ B lymphocytes at baseline were 203.5 cells/µl (age ≤50; n = 813) and 208 cells/µl (age >50; n = 110).
At baseline, the median CD4+ T lymphocytes were 837.5 cells/µl (age ≤50) and 952 cells/µl (age >50). In year 1, CD4+ T lymphocytes were lowest at week 16 (11 weeks after year 1 dosing; age ≤50: 53.3% DFB and age >50: 60.4% DFB; both above LLN). After week 16, there was a small increase in CD4+ T lymphocytes, but levels remained low and above LLN until end of year 1.
In year 2, researchers found the nadir for CD4+ T lymphocytes to be below LLN for both age groups (age ≤50: 66.4% DFB at week 60 [8 weeks after year 2 dosing]; age >50: 73.7% DFB at week 72 [20 weeks after year 2 dosing]), with levels gradually reaching normal range by week 96.
Giovannoni and colleagues also examined the impact of cladribine on CD8+ T lymphocytes but found the effect to vary by age, with increases shown in younger patients and fluctuations occurring in older patients. Notably, despite these fluctuations, older patients had CD8+ T lymphocytes generally in the normal range, according to study authors.
At the 2020 ACTRIMS Forum, Giovannoni, lead investigator in the CLARITY studies, presented research on the durability of cladribine. All told, the treatment demonstrated the ability to be efficacious beyond 2 years in patients with relapsing-remitting MS.2
In that study, patients who switched to placebo (n = 98) in the CLARITY extension had comparable relapse-free status over time compared to those who continued on therapy (n = 186). Those who switched to placebo had an annualized relapse rate (ARR) of 0.15 (97.5% CI, 0.09–0.21), while those who continued treatment had an ARR of 0.10 (97.5% CI, 0.06–0.13).
Cladribine received FDA approval as an oral therapy for the treatment of relapsing MS and active secondary progressive MS in March 2019. The EMD Serono product was approved based on data from a trial that included more than 1300 patients with relapsing forms of MS, ultimately showing a significant decrease in the number of relapses experienced by patients who had greater than 1 relapse the previous year, compared to placebo.3
For more coverage of ACTRIMS Forum 2021, click here.