Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis.

Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis.

Publication date: Apr 01, 2019

Treating patients with relapsing multiple sclerosis (MS) with cladribine tablets (two times 4 or 5 days of treatment each year for 2 years) results in long-lasting efficacy, with continued stability in many patients for 4 or more years. Safety and tolerability outcomes from individual clinical studies with cladribine tablets have been reported previously.

Report safety data from an integrated analysis of clinical trials and follow-up in patients with MS to further characterize the safety profile of cladribine tablets.

Data for patients treated with cladribine tablets 10 mg (MAVENCLAD; 3.5 mg/kg cumulative dose over 2 years, referred to as cladribine tablets 3.5 mg/kg) as monotherapy (n = 923) or placebo (n = 641) in Phase III clinical trials (CLARITY, CLARITY Extension and ORACLE-MS) and followed up in the PREMIERE registry were aggregated (Monotherapy Oral cohort). To better characterize rare events, additional data from earlier studies which involved the use of parenteral cladribine in patients with MS, and the ONWARD study, in which patients were given cladribine tablets in addition to interferon (IFN)-β or placebo plus IFN-β were included in an All Exposed cohort (cladribine, n = 1926; placebo, n = 802). Adjusted adverse events incidences per 100 patient-years (Adj-AE per 100 PY) were calculated for the integrated analyses.

The incidence rate of treatment-emergent adverse events (TEAEs) in the Monotherapy Oral cohort was 103.29 vs. 94.26 Adj-AEs per 100 PY for placebo. TEAEs that occurred more frequently with cladribine tablets were mainly driven by the TEAEs of lymphopenia (Adj-AE per 100 PY 7.94 vs. 1.06 for placebo) and lymphocyte count decreased (Adj-AE per 100 PY 0.78 vs. 0.10 for placebo) as anticipated due to the mode of action of cladribine. An increase in TEAE incidence rate was also observed in the cladribine tablets 3.5 mg/kg group vs. placebo for herpes zoster (Adj-AE per 100 PY 0.83 vs. 0.20, respectively). There were no cases of systemic, serious disseminated herpes zoster attributed to treatment with cladribine tablets. In general there was no increase in the risk of infections including opportunistic infections with cladribine tablets versus placebo, except for herpes zoster. Periods of severe lymphopenia (

Cook, S., Leist, T., Comi, G., Montalban, X., Giovannoni, G., Nolting, A., Hicking, C., Galazka, A., and Sylvester, E. Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis. 17608. 2019 Mult Scler Relat Disord (29):

Concepts Keywords
Cladribine Placebo
Clinical Trials Shingles
Cohort RTT
Disseminated Herpes Zoster Clinical medicine
Herpes Zoster Medicine
Incidence Health
Interferon Purines
Lymphocyte Organochlorides
Lymphopenia Cladribine
Monotherapy Herpes zoster
Multiple Sclerosis Opportunistic infections
Opportunistic Infections MS
ORACLE 5mg kg


Type Source Name
disease MESH opportunistic infections
disease MESH infections
disease DOID herpes zoster
disease MESH herpes zoster
disease DOID lymphopenia
disease MESH lymphopenia
drug DRUGBANK Tropicamide
disease DOID multiple sclerosis
disease MESH multiple sclerosis
drug DRUGBANK Cladribine


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