Provide continual presentation of new safety data concerning cladribine tablets 3.5mg/kg (CladT) as they become available.

Several integrated analyses have reported on the safety of CladT during the clinical development program for relapsing multiple sclerosis. As of July 2022, an estimated 56,300 patients have received CladT with 95,664 patient-years of exposure since approval in 2017.

Adverse events (AEs) from post-approval sources (spontaneous individual case safety reports, non-interventional post-marketing studies, reports from other solicited sources) are presented to July 2022. For AEs of special interest, adjusted incidences per 100 patient-years are reported; crude values are shown for hypersensitivity and liver AEs.

Adjusted incidence rates for AEs of special interest were: herpes zoster (514 reports), 0.54 (95% confidence interval: 0.49,0.59); opportunistic infections (15 reports), 0.02 (0.01,0.03); progressive multifocal leukoencephalopathy, 0; tuberculosis (23 reports), 0.02 (0.02,0.04); serious infections (754 reports), 0.79 (0.73,0.85); serious lymphopenia (112 reports), 0.12 (0.10,0.14); malignancies (187 reports), 0.20 (0.17,0.23); congenital anomalies (3 reports), 0.003 (0.001,0.010). A total of 1810 reports of hypersensitivity AEs were noted (mainly pruritus [536] and rash [410]). Liver AEs (generally enzyme elevations) were uncommonly reported in temporal association with CladT. Most cases of liver injury (according to CIOMS DILI grade) were Grade 1 (mild, 43 reports) or 2 (moderate, 14 reports); there were two Grade 3 reports (severe) and one Grade 4 report (fatal, attributed to isoniazid toxicity). Most liver AEs occurred within 8 weeks of initiating the first course of treatment in Year 1.

Cumulative to July 2022, the safety profile of CladT is consistent with findings from the clinical development program. Liver toxicity, while uncommon, was noted as an important identified risk of CladT as part of a cumulative post-approval safety review; further guidance on monitoring of liver function is now provided as part of updated prescribing information.