Original Title: Dosage sanguin du ruxolitinib par chromatographie liquide de haute performance couplée à la spectrométrie de masse en tandem (HPLC-MS/MS)

Authors' objectives: A request to introduce a new test to the Répertoire québécois et système de mesure des procédures de biologie médicale (hereinafter referred to as the “Répertoire”) has been submitted to the Institut national d'excellence en santé et en services sociaux (INESSS) in accordance with the evaluation mechanism for new biomedical tests. The mandate given was to evaluate the relevance of introducing the ruxolitinib blood test by highperformance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) to the Répertoire.

Authors' results and conclusions: RESULTS (#1 POPULATION DIMENSION): Ruxolitinib is indicated for the treatment of graft-versus-host disease in patients aged 12 and over. According to the literature and clinicians, this drug is also used exceptionally to prevent and treat GVHD or another rare immune disorder in children under 12 years of age (off-label). • Ruxolitinib is a targeted therapy for hematological malignancies and is metabolized by the liver enzyme CYP3A4, among others, which predisposes it to drug interaction with any inhibitor or inducer of this enzyme. • Drug interaction and toxicity are associated with considerable inter-individual variability in pharmacokinetic parameters. • Therapeutic monitoring of ruxolitinib could be beneficial for groups of patients likely to develop toxicities. (#2 CLINICAL DIMENSION): In the clinical setting, several factors such as weight, drug dose, elimination halflife and drug-drug interactions are likely to increase inter-individual variability in pharmacokinetic parameters. • Blood quantification of ruxolitinib could potentially allow better control of drug interactions. • According to some clinicians consulted, ruxolitinib blood quantification could promote judicious and optimal use of this treatment in young children under 12 years of age (off-label). (#3 ORGANIZATIONAL DIMENSION): Should ruxolitinib be included in the Répertoire, blood quantification would remain infrequent in the context of a rare disease. For the moment, clinicians believe that the availability of services at a single center would meet all the needs of the province. • The interpretation of test results should be harmonized across Quebec. (#4 SOCIO-CULTURAL DIMENSION): To date, no guidelines, clinical practice guidelines or expert consensus recommending ruxolitinib blood quantification by HPLC-MS/MS have been identified. • The little known and little used ruxolitinib test is emerging. • In Quebec, ruxolitinib may be used exceptionally in off-label clinical situations through special access programs. (#5 ECONOMIC DIMENSION): The cost-effectiveness of the proposed analysis cannot be evaluated, as no reliable data are available to accurately quantify health benefits and costs. • The weighted value of this analysis is 85.86. To this can be added the transportrelated value of 4.4. • The introduction of the analysis recommended in the Répertoire could generate additional costs of $74,000 over the first three years, for 828 analyses. Sensitivity analyses show that the net variation could be between $62,000 and $82,000. CONCLUSION: Members of the INESSS CDP-ADD recognize the innovative potential of HPLC-MS/MS blood determination of ruxolitinib in young children, while emphasizing: • the inadequacy and prematurity of scientific data from the literature and the impossibility of supporting the validity and clinical utility of the test to date; • the test's development stage, which is still in the research stage and not yet ready for use as a routine clinical test; • the early nature of introducing this test into the Répertoire; • the continued collection of scientific research evidence, which is strongly recommended to support a future request for re-evaluation of this test.

Authors' recommendations: In light of the findings stated above, INESSS recommends that the Minister not introduce ruxolitinib blood testing by HPLC-MS/MS into the Répertoire.

Authors' methods: To fulfil the mandate, a rapid review of the scientific literature was conducted, based on publications listed in bibliographic databases and other information sources. Ad hoc consultations were also conducted with specialist clinicians and other stakeholders. The methodology was developed around eight evaluation questions covering the five dimensions of the statement of principles of the INESSS framework for evaluating the value of interventions. A budgetary impact analysis was realized, taking into account the costs associated with introducing this analysis into the Répertoire. Costs were projected over a three-year time frame from a healthcare system perspective. All scientific, contextual and experiential data were interpreted and evaluated using a value-based approach, defined based on the five dimensions, to guide the deliberation process of members of the Standing Deliberative Committee - Diagnostic Approaches and Screening (CDP-ADD) in developing the recommendation.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-sanguin-du-ruxolitinib-par-chromatographie-liquide-de-haute-performance-couplee-a-la-spectrometrie-de-masse-en-tandem-hplc-ms-ms.html

Year Published: 2024

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/dosage-sanguin-du-ruxolitinib-par-chromatographie-liquide-de-haute-performance-couplee-a-la-spectrometrie-de-masse-en-tandem-hplc-ms-ms.html

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: L'Institut national d'excellence en sante et en services sociaux (INESSS)