Economic Evaluation of Cladribine Tablets in Patients With High Disease Activity-Relapsing-Remitting Multiple Sclerosis in the Kingdom of Saudi Arabia.

OBJECTIVE: Cladribine tablets are the first short-course oral treatment approved for high disease activity relapsing-remitting multiple sclerosis (HDA-RRMS) across various countries. This analysis assessed the cost-effectiveness of introducing cladribine tablets as a treatment option for patients with high disease activity compared with other HDA-RRMS therapies in the Kingdom of Saudi Arabia (KSA). METHODS: The cost-effectiveness model was adapted from the KSA payer's perspective. Data for the model's adaptation were retrieved from the literature and validated by key opinion leaders. The comparators considered in the model were alemtuzumab, dimethyl fumarate, fingolimod, interferon beta-1a (subcutaneous and intramuscular) and beta-1b, natalizumab, and teriflunomide. A sensitivity analysis was also performed to assess the robustness of the analysis. RESULTS: The cost-effectiveness results showed cladribine tablets as the dominant strategy (ie, less costly and more effective) versus all the comparators. The incremental cost and quality-adjusted life-years gained were largely driven by drug acquisition cost and delayed expanded disability status scale progression, respectively. Cladribine tablets showed an 81% to 100% probability of being cost-effective at a threshold of Saudi Riyal 225 326 per quality-adjusted life-years gained against different comparators. CONCLUSIONS: Cladribine tablets are a dominant treatment option for patients with HDA-RRMS from the payer perspective in the KSA.

Correction to: Cost Effectiveness of Cladribine Tablets for the Treatment of Relapsing-Remitting Multiple Sclerosis in The Netherlands.

The second author's name should be "Maria De Francesco" rather than "Maria de Fransesco".

Cost Effectiveness of Cladribine Tablets for the Treatment of Relapsing-Remitting Multiple Sclerosis in The Netherlands.

BACKGROUND: Cladribine tablets have recently become available in The Netherlands for patients with relapsing-remitting multiple sclerosis (RRMS) as a disease-modifying agent that reduces the frequency and severity of relapses and delays disability progression. OBJECTIVE: The aim of this study was to evaluate the cost effectiveness of cladribine tablets, compared with alternative options, in the treatment of RRMS patients with high disease activity (HDA) and patients with rapidly evolving severe (RES) MS in The Netherlands. METHODS: A Markov model was developed simulating the costs and effects of RRMS treatment. For HDA, alemtuzumab and fingolimod were used as comparators; natalizumab was used for the RES subpopulation. The analysis included a societal perspective and a value-of-information (VOI) analysis. RESULTS: For the HDA subpopulation, treatment with cladribine tablets was the cost-effective (dominant) strategy compared with alemtuzumab and fingolimod, with 50.9% and 98.2%, respectively, probability of being cost effective at a threshold of €50,000/QALY gained and a net monetary benefit (NMB) of €10,866 and €151,115, respectively. For the RES subpopulation, treatment with cladribine tablets dominated treatment with natalizumab, with 94.1% probability of being cost effective at a threshold of €50,000/QALY gained and an NMB of €122,986. Note that these outcomes are driven by the lower costs of cladribine tablets. Efficacy differences were small, very uncertain, and likely not clinically meaningful. The probabilistic sensitivity analyses showed significant overlap in the credible intervals for total lifetime QALY outcomes and costs of cladribine tablets and all relevant comparators. The population-level VOI amounted to €19,295,441. CONCLUSIONS: The base-case analysis shows that treatment of RRMS with cladribine tablets is cost effective versus alemtuzumab and fingolimod in HDA patients, and cost effective versus natalizumab in RES patients, at a threshold of €50,000. Driven by the lower costs, cladribine tablets were cost effective (dominant) in all base-case analyses. However, given that outcomes are based on indirect comparisons and post hoc subgroup analysis, as well as the uncertainty surrounding the outcomes, the results presented in this paper should be interpreted with caution.

Potent and Selective Inhibitors of Long Chain l-2-Hydroxy Acid Oxidase Reduced Blood Pressure in DOCA Salt-Treated Rats.

l-2-Hydroxy acid oxidase (Hao2) is a peroxisomal enzyme with predominant expression in the liver and kidney. Hao2 was recently identified as a candidate gene for blood pressure quantitative trait locus in rats. To investigate a pharmacological role of Hao2 in the management of blood pressure, selective Hao2 inhibitors were developed. Optimization of screening hits 1 and 2 led to the discovery of compounds 3 and 4 as potent and selective rat Hao2 inhibitors with pharmacokinetic properties suitable for in vivo studies in rats. Treatment with compound 3 or 4 resulted in a significant reduction or attenuation of blood pressure in an established or developing model of hypertension, deoxycorticosterone acetate-treated rats. This is the first report demonstrating a pharmacological benefit of selective Hao2 inhibitors in a relevant model of hypertension.