Can precision medicine be integrated into routine therapeutic decisions at the bedside of patients?

Therapeutic strategies are shifting from a "one-size-fits-all" population-based approach to a stratified approach targeting groups with similar characteristics, or even individuals, tailoring treatments to the unique characteristics of each patient. Since such strategies rely on increasingly complex knowledge and healthcare technologies, along with an understanding of the tools of precision medicine, the appropriate dissemination and use of these strategies involves a number of challenges for the medical community. Having evaluation methodologies that have been jointly designed with the institutional, industrial, academic stakeholders, and also patients, like streamlining the processes and externally validating performances, could enhance the relevance of the "evaluation" aspect of precision medicine. Creating a network of expert precision-medicine centers and ensuring that precision-medicine procedures are reimbursed by social security would guarantee fair and sustainable access. Finally, training healthcare professionals, creating interfaces between precision-medicine expert centers and primary care professionals as well as patients, and integrating individual patient data into medical records are all key drivers that will enable information from precision-medicine to be made available and guarantee the proper use of these approaches.

Cost-Effectiveness of Blinatumomab in Pediatric Patients with High-Risk First-Relapse B-Cell Precursor Acute Lymphoblastic Leukemia in France.

BACKGROUND: Based on the results of the phase III randomized 20120215 trial, the European Medicines Agency granted the approval of blinatumomab for the treatment of pediatric patients with high-risk first-relapsed Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL). In France, blinatumomab received reimbursement for this indication in May 2022. This analysis assessed the cost effectiveness of blinatumomab compared with high-risk consolidation chemotherapy (HC3) in this indication from a French healthcare and societal perspective. METHODS: A partitioned survival model with three health states (event-free, post-event and death) was developed to estimate life-years (LYs), quality-adjusted life-years (QALYs) and costs over a lifetime horizon. Patients who were alive after 5 years were considered to be cured. An excess mortality rate was applied to capture the late effects of cancer therapy. Utility values were based on the TOWER trial using French tariffs, and cost input data were identified from French national public health sources. The model was validated by clinical experts. RESULTS: Treatment with blinatumomab over HC3 was estimated to provide gains of 8.39 LYs and 7.16 QALYs. Total healthcare costs for blinatumomab and HC3 were estimated to be €154,326 and €102,028, respectively, resulting in an increment of €52,298. The incremental cost-effectiveness ratio was estimated to be €7308 per QALY gained from a healthcare perspective. Results were robust to sensitivity analyses, including analysis from the societal perspective. CONCLUSIONS: Blinatumomab administered as part of consolidation therapy in pediatric patients with high-risk first-relapsed ALL is cost effective compared with HC3 from the French healthcare and societal perspective.

Trends in postmenopausal osteoporosis treatment in France during the period 2007-2016: A nationwide claims database analysis.

PURPOSE: To describe the trends in the pharmacological management of postmenopausal osteoporosis in France during the period 2007-2016. METHOD: This cross-sectional, yearly repeated study of patients in France used the nationwide claims database 'Échantillon Généraliste de Bénéficiaires' (EGB), covering a 1 in 97 representative sample of approximately 600,000 individuals insured by the main French public insurance scheme. For women aged 50-89 years, prescriptions for all anti-osteoporosis medications (AOMs) marketed in France during the study period (bisphosphonates alone or used in combination with calcium, selective estrogen receptor modulators, strontium ranelate, teriparatide or denosumab) were identified in each calendar year. Initiation of any AOM in a calendar year was defined by the absence of a prescription for any AOM within the 2 previous calendar years. Incidence was calculated for all AOM prescriptions and initial prescriptions for AOM. RESULTS: Marked changes were observed in the rates of women receiving any AOM, with a slight increase from 2007 to 2009 (from 10.22 to 10.42 per 100 patient-years [PY]), then a plateau in 2009-2010, followed by a rapid and more than twofold decrease until 2016 (from 10.39 to 5.02 per 100 PY). The decrease in the overall rate of women initiating an AOM showed a rapid halving from 2007 to 2012 (from 2.56 to 1.15 per 100 PY), followed by a plateau in the range of 0.90-1.0 per 100 PY during the period 2013-2016. In contrast, the use of calcium/vitamin D has been rapidly increasing as the only prevention and exclusive intervention for postmenopausal osteoporosis, from 10.6% of women in 2007 to 47.7% in 2016. The profile of patients initiating AOM changed substantially over the 10-year period. Despite a stable mean age of approximately 69 years, an increasing proportion of women with severe chronic comorbidities (from 34.9% to 43.3%), history of fractures (from 7.8% to 13.3%) or high-dose steroid use (from 2.9% to 8.4%) was observed. The decline of AOM initiation was associated with a marked reduction of prescriptions during the study period: by 64.2% for primary care physicians; by 36.7% for specialty doctors; and by 18.4% for rheumatologists. CONCLUSION: These findings suggest a general trend toward an AOM uptake that is increasingly limited to a fraction of patients who are at high risk of fractures. In the context of an aging population and declining prescription rates for AOM, these data highlight an increasing treatment gap among women in France with osteoporosis, which is similar to that seen in other European countries and in the USA.

Screening and treatment of familial hypercholesterolemia in a French sample of ambulatory care patients: A retrospective longitudinal cohort study.

BACKGROUND AND AIMS: Untreated Familial Hypercholesterolemia (FH) leads to premature morbidity and mortality. In France, its epidemiology and management are understudied in ambulatory care. We described the clinical profile, pharmacological management, and clinical outcomes in a French sample of FH patients. METHODS: This was a retrospective longitudinal study on patients from The Health Improvement Network (THIN®) database in France, between October 2016-June 2019. Patients ≥18 years, with probable/definite FH based on the Dutch Lipid Clinic Network (DLCN) criteria were included. Baseline characteristics, lipid profile, lipid-lowering therapy (LLT), low-density lipoprotein-cholesterol (LDL-C) goal achievement; and disease management at 6-month of follow-up were analyzed. RESULTS: 116 patients with probable (n = 70)/definite (n = 46) FH were included (mean age:57.8±14.0 years; 56.0% women; 9.5% with personal history of cardiovascular events); 90 patients had data available at follow-up. At baseline, 77.6% of patients had LDL-C>190 mg/dL, 27.6% were not receiving LLTs, 37.9% received statins alone, 20.7% statins with other LLTs, and 7.7% other LLTs. High-intensity statins were prescribed to 11.2% of patients, 30.2% received moderate-intensity statins, and 8.6% low-intensity statins. Only 6.0% of patients achieved LDL-C goal. At 6-month of follow-up, statins discontinuation and switching were 22.7% and 2.3%, respectively. None of the patients received proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors at baseline nor follow-up. CONCLUSIONS: Despite the existence of effective LLTs, FH patients are suboptimally-treated, do not achieve LDL-C goal, and exhibit worsened pharmacological management over time. Future studies with longer follow-up periods and assessment of factors affecting LDL-C management, including lifestyle and diet, are needed.

Quality of life in adults with acute lymphoblastic leukemia in France: results from a French cross-sectional study.

In recent years, treatment of acute lymphoblastic leukemia (ALL) has improved substantially, leading to longer survival. This has necessitated a greater focus on health-related quality of life (HRQoL), but data are lacking. In a part-prospective, part-retrospective study, we enrolled 219 adults with ALL in France to assess the impact of key disease and treatment characteristics on HRQoL. Overall HRQoL and most specific QoL domain scores were consistently better among patients receiving front-line therapy, those currently in complete remission, and those who had previously received hematopoietic stem-cell transplantation. Furthermore, HRQoL was consistently impaired in patients with minimal residual disease present (MRD+). In multivariate analyses, multiple lines of therapy, MRD+, leukopenia, comorbidities, and anemia were significantly associated with impaired HRQoL. This study provides real-world data on HRQoL in adults with ALL in France and shows the positive impact of MRD-negative status on HRQoL.

Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France - a cohort study using the French National Healthcare database (SNDS).

Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2-33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.

Clinical impact and room for improvement of intensity and adherence to lipid lowering therapy: Five years of clinical follow-up from 164,565 post-myocardial infarction patients.

BACKGROUND: In patients at risk of cardiovascular (CV) events, the effectiveness of lipid-lowering therapies (LLT) is affected by both intensity and adherence. Our study evaluated the association between LLT intensity (statin and/or ezetimibe) and adherence, and CV events in patients with a history of myocardial infarction (MI) in France. METHODS: Using the French national healthcare database (SNDS), we included patients with a history of MI, an initial LLT prescription in 2011-2013, and a second prescription within one year. LLT intensity was defined using the expected percent reduction in low-density lipoprotein cholesterol; adherence was measured as the proportion of days covered. Cox proportional hazards models were used to assess associations between intensity and/or adherence, and the risk of major adverse CV event (MACE). RESULTS: 164,565 patients were included; mean (SD) age, 66·3 (13·8) years; 73·6% men. Following an MI, only half of patients were treated with high-intensity LLT and approximately 40% of those on LLT remained non-adherent during follow-up (mean (SD) follow-up, 2·6 (1·4) years). Each 10% increase in treatment intensity, adherence, or adherence-adjusted intensity was respectively associated with a 16% (HR 0.84, 95%CI 0.84-0.85), 7% (HR 0.93, 95%CI 0.93-0.94), and 15% (HR 0.85, 95%CI 0.84-0.86) decrease in the risk of MACE. CONCLUSIONS: Among patients with a history of MI, prescriptions of high-intensity LLT were limited and adherence to LLT was low. Higher intensity and/or adherence to statins was associated with a significantly lower risk of MACE, highlighting the importance of compliance with clinical guidelines to improve patient outcomes.

High persistence over two years with denosumab among postmenopausal women with osteoporosis in France: A prospective cohort study.

PURPOSE: To assess the 12 and 24-month persistence with denosumab in postmenopausal women with osteoporosis in real-world clinical practice in France, and to describe characteristics and management of these patients. METHODS: This prospective, multicenter cohort study evaluated persistence with denosumab at 12 months (primary endpoint) and 24 months (secondary endpoint), defined as at least 2 or 4 injections respectively, and time elapsed between 2 consecutive injections did not exceed 6 months +8 weeks. Other endpoints included patients' characteristics at baseline, medical history, concomitant and previous treatments, and incidence of adverse drug reactions (ADR), serious adverse events and fractures. RESULTS: 478 patients were enrolled by 86 physicians between June 2015 and February 2016. The mean follow-up was 28 months. Mean age was 72 years and 91% of patients had been previously treated for osteoporosis. The persistence with denosumab was 86% (95%CI: 83%-89%) at 12 months and 72% (95%CI: 68%-76%) at 24 months. Using the Kaplan-Meier estimates, the persistence probability over time was 86% at 12 months and 76% at 24 months. During the study, 78 patients discontinued therapy. No multiple vertebral fractures were reported upon discontinuation. ADR were reported for 55 patients, 4 being serious, and 27 patients discontinued denosumab due to an ADR. Among patients who received at least one injection, 10 died. None of the deaths were attributable to denosumab. CONCLUSION: Persistence with denosumab at 12 and 24 months was high, and the treatment was well tolerated among postmenopausal women with osteoporosis treated in routine clinical practice in France.

Treatment of tuberculosis with levofloxacin or moxifloxacin: report of 6 pediatric cases.

We report 6 pediatric cases of tuberculosis caused by Mycobacterium tuberculosis and treated them with levofloxacin or moxifloxacin in the mother-child unit of a university hospital in France between 2005 and 2011. We assess the clinical efficacy and safety of fluoroquinolones and the benefit-risk ratio for their use as second-line antituberculosis drugs in children and adolescents.