Post-marketing safety profile of cladribine in multiple sclerosis: a disproportionality analysis based on the FDA...

Cladribine has been widely recognized as a therapeutic option for relapsing-remitting multiple sclerosis (MS), but there is still a dearth of real-world data regarding its safety profile.

This study aimed to assess adverse events (AEs) linked to cladribine in MS patients, utilizing data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

AE reports identifying cladribine as the primary suspect drug were extracted from the U.S. FAERS, covering the period from the first quarter of 2019 to the third quarter of 2024. Four disproportionality methods-reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean-were employed to evaluate the association between cladribine and AEs. Furthermore, the Weibull distribution model was applied to analyze time-to-onset patterns, and subgroup analyses were conducted based on sex and age.

After screening 4,833 cladribine-related reports, 113 preferred terms (PTs) were identified as positive across all four disproportionality methods. Known AEs such as pneumonia (n = 190, ROR 2.85), lymphopenia (n = 111, ROR 4.19), and drug-induced liver injury (n = 22, ROR 5.94). Unexpected events, including rheumatoid arthritis (ROR 5.64), hypothyroidism (ROR 5.04), eye hemorrhage (ROR 6.88), uveitis (ROR 4.86), retinal detachmen (ROR 4.37), brain edema (ROR 6.12), acute myocardial infarction (ROR 3.70), and completed suicide (ROR 7.46), were also reported. Stratified analysis revealed that females were at a higher risk of nausea, alopecia, and migraine, while males were more susceptible to gait disturbance and sepsis. Older adults (≥ 65 years) faced increased risks of leukopenia and urinary tract infections (UTIs). The median onset of AEs was 152 days, with the highest proportion (28.18%) reported in the first month. Weibull analysis indicated an early peak (shape parameter 0.72).

This study not only corroborates previously established risks associated with cladribine but also uncovers new potential safety signals, highlighting the importance of vigilance for early acute toxicity.