Real-life use of ruxolitinib in GVHD: A retrospective study of prescribing practices, dosages and adverse drugs reactions

Details

Supervisors

Dachy, François ; Spinewine, Anne

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master de spécialisation en pharmacie hospitalière

Abstract

Background: Ruxolitinib was recently approved for GVHD (Graft-Versus-Host Disease) treatment, with adverse drugs reactions (ADRs) described in different trials. While dosage adjustment and tapering recommendations have been established, real-world adherence and their association with ADRs remain unexplored. Objectives: To assess real-life adherence to recommendations and describe ADRs occurrence. The secondary objective was to assess whether non-adherence to dosage recommendations during initiation or maintenance was associated with ADRs. Method: We conducted a retrospective study of patients aged 16 or older who initiated ruxolitinib between 2017 and 2023 for GVHD in two Belgian hospitals. Dosage adjustments recommendations at initiation, maintenance and tapering were compiled through a literature review. ADRs occurrence and severity were identified from medical records and included cytopenias, renal and hepatic toxicities and infections. Each ADR was modeled using a separate mixed logistic model, with dose deviation as a fixed effect, using marginal effects at the means to interpret the predicted probability of ADRs. Results: Fifty-seven patients were enrolled, accounting for 61 ruxolitinib treatments and 881 one-month periods. All-grade ADRs occurred in all aGVHD patients and 97.7% of cGVHD patients: grade ≥3 ADRs affected 88.2% and 75.0%, respectively. Dosage deviations occurred in 41.8% of periods. During initiation and maintenance, lower-than-recommended doses was observed in 23.8% and higher-than-recommended doses in 6.0% of periods. Higher-thanrecommended doses in these phases were significantly associated with increased rates of grade ≥3 ADRs, all-grade and grade ≥3 cytopenias, and hepatotoxicity. In contrast, lower doses showed no decreased ADRs risk compared to guideline-concordant dosing. During tapering, higher-than-recommended doses (i.e., slow tapering) was observed in 63.8% of periods. Conclusion: Frequent non-adherence to dosage recommendations was observed and associated with increased ADRs risk. These findings underscore the need for adherence to established dosing recommendations and question current prescribing practices.