OBJECTIVES : There are 3 disease-modifying medicines for multiple sclerosis currently licensed and approved for use in Kazakhstan: natalizumab, okrelizumab, and cladribine. Only the natalizumab and cladribine are presented in the Kazakhstan National Formulary (KNF). The aim of the study was to estimate the cost-effectiveness of Cladribine Tablets in the treatment of high disease activity relapsing-remitting MS (HDA-RRMS) compared with natalizumab, from the healthcare payer perspective in the Republic of Kazakhstan. METHODS: A cohort-based Markov model was developed. The model included 10 Expanded Disability Status Scale [EDSS] states and death. Transition matrices derived from the previous economic evaluations and adjusted to HDA-RRMS patients were used to model the natural history of EDSS. The effect of the medicines compared was modelled using an indirect treatment comparison. The annual relapse rate and the probability of suffering adverse reactions were obtained from the literature. The derived costs were calculated from Kazakhstan medical tariffs and unit costs. The utilities were obtained from the clinical trials and the literature. Uncertainty was assessed via one-way deterministic sensitivity analysis. RESULTS: Under base-case assumptions, cladribine tablets were associated with modest gains in QALYs in HDA-RRMS patients. Cladribine yielded 3.20 QALYs at a cost of 24,380,274 KZT per patient, whereas natalizumab yielded 3.13 QALYs at a cost of 23,242,316 KZT. This resulted in an incremental cost-effectiveness ratio of 15,591,777 KZT/QALY gained. CONCLUSIONS: Cladribine tablets at the current declared price cannot be considered a cost-effective alternative to natalizumab in the treatment of HDA-RRMS from the healthcare payer perspective in Kazakh settings at the threshold of three times the per-capita gross GDP per QALY gained.