L-Glutamine and Crizanlizumab for Adults with Sickle Cell Disease (SCD) in Qatar: A Cost Effectiveness Analysis

Abstract

Background :Sickle cell disease (SCD) is a hereditary disease that is caused by autosomal recessive gene fault in the beta (β) allele of the hemoglobin (Hb) gene. As a result, sickled cells are characterized by easy and abnormal hemolysis with resultant varying degrees of anemia. Globally, the incidence of SCD is estimated to reach 400,000 persons per year, and in the United States alone, for example, the prevalence estimation is approximately 100,000 patients. Possible clinical presentations of SCD may come from different pathophysiologic mechanisms: the disfiguration of the RBC with subsequent loss of function can lead to vascular occlusion and a short lifetime of these RBCs that leads to hemolysis. The most severe and serious manifestation of SCD is the recurrent acute pain, or better known as vaso-occlusive crisis (VOC). Additionally, other clinical manifestations that SCD patients may show are acute complications such as acute chest syndrome (ACS), recurrent infections, kidney necrosis, and stroke. Such complications may affect multiple organs and can result in early death. Acute pain crisis is another common complication of SCD and is usually managed with pain medications, especially opioids,This is the first study to address two of novel therapies in patients with SCD in the Middle East. Our study was comprehensive in terms of outcome mostly encountered by SCD patients which is VOC and inclusivity of interventions mostly used for its management and was focused on the target population of in one of areas of high prevalence of SCD in the world. Our analysis tracked the CHEERS guidelines and checklist for reporting. To be also complete, we used only RCT evidence in our analysis. Additionally, in considering VOC, we ensured only studies with a definition compatible with that of the principal Crizanlizumab study were analyzed.Objectives:Treatment options for preventing vaso-occlusive crises (VOC) among sickle cell disease (SCD) patients are on the rise, especially if hydroxyurea treatment has failed. This economic analysis is conducted to assess the comparative clinical effectiveness, safety and acquisition cost of L-glutamine and Crizanlizumab for older adolescent and adults (≥16 years old) SCD in Qatar, with an emphasis on treatment costs and acute pain crises.Methods:We conduct a decision tree model, where we compare the clinical and economic outcomes of two novel FDA-approved medications which are available in Qatar; L-glutamine and Crizanlizumab over a time horizon of one year in a hypothetical cohort of adult SCD patients from a Qatar healthcare perspective. The main outcome is incremental cost per SCD-related acute pain crises averted. Model clinical parameters were derived from individual drug randomized trials, published literature, whereas cost parameters from Qatar healthcare payer system. A sensitivity analysis was carried out, and the study results were robust around model inputs. Costs were converted to 2020 US dollars.Results:Study results showed that both treatment modalities' costs were the main driver of this analysis, with average annual cost of the treatments per patient being $189,014 for Crizanlizumab (5mg/Kg), $143,798 Crizanlizumab (2.5mg/Kg) and $74,323 for L-glutamine. The probability of no first time SCD-related VOC averted were 0.001/year for Glutamine, 0.26/year for Crizanlizumab (5mg/Kg) and 0.34/year for Crizanlizumab (2.5mg/Kg). Lower dose Crizanlizumab (2.5mg/Kg) dominated the higher one (5mg/Kg). The ICER of Crizanlizumab (2.5mg/Kg), when compared to L-Glutamine was $81,265 per SCD-related VOC averted. When comparing Crizanlizumab (5mg/Kg) and L-Glutamine, Crizanlizumab (5mg/Kg) showed higher efficacy, yet the Crizanlizumab ICER was at $459,620 than L-glutamine.Conclusions:Crizanlizumab (2.5mg/Kg) may be cost-effective interventions yet it is not the approved dose for preventing VOC in adolescents and adults with sickle cell disease. Crizanlizumab (5mg/Kg) was more cost effective than the approved L-glutamine per SCD vaso-occlusive crisis prevented. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.