Abstract:Cladribine tablets (CladT) preferentially reduce B and T lymphocyte levels. As aging is associated with a decline in immune function, the effect of CladT on lymphocyte levels may differ by age. This post hoc analysis combined data from the Phase 3 CLARITY, CLARITY Extension, and ORACLE-MS studies to examine the effect of age (≤50 or >50 years) on lymphopenia following CladT 3.5 mg/kg (CladT3.5; cumulative dose over 2 years) treatment over 96 weeks. Both CladT3.5 and placebo were given over Weeks 1 and 5… Show more
“…Post hoc integrated analyses of data from the CLARITY and ORACLE-MS studies showed that the aggregate incidence of lymphopenia as an SAE was 0.1 event/100 patient-years for CladT [ 24 ] and 0/100 patient-years for placebo (Fig. 2 ) and that the time course of effects of CladT on immune cells was similar for patients above or below age 50 years [ 42 ].…”
Section: Adverse Events Of Special Interestmentioning
confidence: 99%
“…These data confirmed the results of earlier integrated analyses [ 91 , 92 ]. There has been no suggestion of clustering of specific cancer types or haematological cancers in CladT-treated populations to date [ 24 , 42 ]. Fig.…”
Section: Adverse Events Of Special Interestmentioning
Cladribine tablets (CladT) is a highly active oral disease-modifying therapy (DMT) for the management of relapsing multiple sclerosis (RMS). CladT acts as an immune reconstitution ther-
“…Post hoc integrated analyses of data from the CLARITY and ORACLE-MS studies showed that the aggregate incidence of lymphopenia as an SAE was 0.1 event/100 patient-years for CladT [ 24 ] and 0/100 patient-years for placebo (Fig. 2 ) and that the time course of effects of CladT on immune cells was similar for patients above or below age 50 years [ 42 ].…”
Section: Adverse Events Of Special Interestmentioning
confidence: 99%
“…These data confirmed the results of earlier integrated analyses [ 91 , 92 ]. There has been no suggestion of clustering of specific cancer types or haematological cancers in CladT-treated populations to date [ 24 , 42 ]. Fig.…”
Section: Adverse Events Of Special Interestmentioning
Cladribine tablets (CladT) is a highly active oral disease-modifying therapy (DMT) for the management of relapsing multiple sclerosis (RMS). CladT acts as an immune reconstitution ther-
“…Cladribine treatment is one of the most recently approved MS medicine. The mechanism of action of cladribine results in profound, rapid and long-lasting reductions of CD4 + and CD8 + T cells, as well as B cells, each in their magnitude and kinetics [17] , [34] , [35] . Cladribine is widely recognized as a T and B cell inhibitor, particularly emphasizing its T cell inhibitory effects as the primary mechanism of action.…”
“… Reproduced from ref. [ 64 ] according to the terms of the Creative Commons Attribution License (CC BY) ( http://creativecommons.org/licenses/by/4.0/ ) …”
Section: Changes In the Efficacy Of Disease-modifying Therapy With Agementioning
confidence: 99%
“…A real-world analysis comprising data from spontaneous adverse event reporting and post-marketing studies estimated the incidence of severe lymphopenia as 0.12 events/100,000 person-years of treatment [ 63 ]. A pooled analysis estimated the incidence of lymphopenia in those who received CladT according to age [ 64 ] using data from the CLARITY study [ 55 ] and its extension [ 65 ] and the ORACLE study in clinically isolated syndrome (total N = 1564) [ 66 ]. The incidence of grade 3 lymphopenia during year 1 of treatment with CladT was 8.3% (age < 50 years) and 10.0% (age ≥ 50 years) and no grade 4 lymphopenia occurred at this time.…”
Section: Changes In the Efficacy Of Disease-modifying Therapy With Agementioning
The number of ageing people with relapsing multiple sclerosis (RMS) is increasing. The efficacy of disease-modifying therapies (DMTs) for RMS declines with age. Also, older persons with MS may be more susceptible to infections, hospitalisations and malignancy. Aging people with MS have higher rates of comorbidities versus aged-matched controls, increasing the individual risk of disability. We review the therapeutic properties of cladribine tablets (CladT) in ageing people with RMS, with regard to their utility for allowing these individuals to cease continuous administration of a DMT (i.e. to act as an “exit therapy”). CladT is thought to be an immune reconstitution therapy, in that two short courses of oral treatment 1 year apart provide suppression of MS disease activity in responders that far outlasts the duration of treatment and post-treatment reductions in lymphocyte counts. Post hoc analyses, long-term follow-up of populations with RMS in randomised trials, and real-world evidence suggest that the efficacy of CladT is probably independent of age, although more data in the elderly are still needed. No clear adverse signals for lymphopenia or other adverse safety signals have emerged with increasing age, although immunosenescence in the setting of age-related “inflammaging” may predispose elderly patients to a higher risk of infections. Updating vaccination status is recommended, especially against pneumococci and herpes zoster for older patients, to minimise the risk of these infections. CladT may be a useful alternative treatment for ageing people with MS who often bear a burden of multiple comorbidities and polypharmacy and who are more exposed to the adverse effects of continuous immunosuppressive therapy.
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