Profile of Women Initiated on Denosumab and Pattern of Use in a Restricted Postmenopausal Osteoporosis Indication: A French Database Analysis Over the Period 2013-2014.

INTRODUCTION: French authorities have approved the reimbursement of denosumab as a second-line therapy after bisphosphonates (BPs) in women presenting with postmenopausal osteoporosis (PMO) at high risk of fracture. By using a nationally representative claims database, we analyzed the pattern of denosumab use. The objectives of this study were to describe the profile of women initiated with denosumab over the 14-month period after launch and to check as far back as possible for the appropriateness of its use regarding the restrictions brought by French health authorities. METHODS: A retrospective study using a national representative claims database, i.e., the "Echantillon Généraliste des Bénéficiaires" (EGB), was performed. The population was composed of women aged ≥ 40 years old who had an initiation of a PMO treatment in 2013 or 2014. The denosumab women's profiles were compared with those of women that started any other PMO treatment (except denosumab) over the same period. RESULTS: In 2013 and 2014, we identified 256 women who initiated denosumab. Denosumab was primarily prescribed by specialists (75%) compared with the other PMO treatments (37.6%). Patients on denosumab were significantly older, 73.2 versus 69.1 years old, and they more frequently had a history of fractures (20.7% versus 17.4%, NS) and chronic uptake of high-dose steroids (25% versus 22.8%, NS). Of the women initiated with denosumab, 93.8% had undergone a previous PMO treatment (during the 2005-2014 period). In 92.9% of cases, it was a BP alone or in association. CONCLUSION: This study suggests satisfactory compliance of prescribers concerning the restriction of the reimbursed indication of denosumab in second line after bisphosphonates with 6.2% possible inappropriate prescriptions. FUNDING: Amgen.

Health-Related Quality of Life of Patients With Multiple Myeloma Treated in Routine Clinical Practice in France.

INTRODUCTION: New therapies for multiple myeloma (MM) have improved life expectancy, but health-related quality of life (HRQoL) data from patients with MM in the real-world setting are lacking. This study, conducted in France, explored the associations between treatment outcomes and HRQoL in patients with MM. PATIENTS AND METHODS: This observational, cross-sectional, multicenter study enrolled patients (≥ 18 years old) with symptomatic MM who had consulted a physician at least once between February and March 2016. HRQoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (QLQ-C30) and the Quality of Life Multiple Myeloma module (QLQ-MY20). RESULTS: In total, 445 patients were included in the study; 402 (90%) completed the EORTC QLQ-C30 and QLQ-MY20 questionnaires. HRQoL decreased significantly with treatment line. Patients in the first treatment-free interval had relatively high scores. At later lines, patients receiving active treatment had better scores than those whose treatment had ended. High EORTC QLQ-C30 global health status scores were associated with good treatment response, few adverse events, and long duration of treatment, and were strongly influenced by the Eastern Cooperative Oncology Group performance status. Global health status scores correlated well with the 4 items of the QLQ-MY20 (future perspective, 0.46; body image, 0.41; disease symptoms, -0.57; side effects of treatment, -0.53). CONCLUSION: Effective treatment options in MM can help maintain HRQoL by influencing treatment response levels and delaying disease progression.

Going the distance: Are we losing patients along the multiple myeloma treatment pathway?

Despite data suggesting that individuals with multiple myeloma can benefit from receiving several lines of therapy, and guidelines recommending treatment after relapse, a recent European patient chart review found that only 61% of patients receive second-line treatment. The review found that factors such as old age and previous adverse events lead to physicians deciding not to treat after relapse. However, given the large number of regimens available, treatment can be tailored to individual patients' needs and supportive care measures can help with the management of adverse effects. If approved therapies are not suitable for a patient, guidelines recommend registration in a clinical trial, yet only 7% of patients in the review were participating in such studies. A need for better education on the range of treatments available and their risk-benefit profiles is suggested. Access to new drugs should be examined to maximise the number of patients benefitting from them.

A question of class: Treatment options for patients with relapsed and/or refractory multiple myeloma.

Multiple classes of agent with distinct mechanisms of action are now available for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM), including immunomodulatory agents, proteasome inhibitors, histone deacetylase inhibitors and monoclonal antibodies. Additionally, several different drugs may be available within each agent class, each with their own specific efficacy and safety profile. This expansion of the treatment landscape has dramatically improved outcomes for patients. However, as the treatment options for RRMM become more complex, choosing the class of agent or combination of agents to use in the relapsed setting becomes increasingly challenging. Furthermore, treatment options for specific patient populations such as the elderly, those with high-risk cytogenetic abnormalities and those with refractory disease are yet to be defined in the current treatment landscape. When choosing an appropriate treatment approach, physicians must consider multiple criteria including both patient-related and disease-related factors. The aim should be to provide patient-specific treatment in order to gain a clinical benefit while minimizing toxicity. This review provides an overview of the mechanism of action and efficacy and safety profiles of each class of agent and of treatment regimens that combine different classes of agent, with a special focus on treating specific patient populations.

Management of immune thrombocytopenia in adults: a population-based analysis of the French hospital discharge database from 2009 to 2012.

The present study describes the current clinical practice and hospital management of adults with immune thrombocytopenia (ITP) between 2009 and 2012 in France, based on the national discharge hospital database. Adult ITP patients were managed almost exclusively in public hospitals. A relatively stable number of patients, around 3200 per year, were hospitalized for ITP annually over the 4-year period, about two-thirds of whom were newly-diagnosed ITP. Re-hospitalizations tended to decrease over the study period. Intravenous immunoglobulin administration, concerning half of ITP hospitalized patients, and rituximab administration were stable over time, whereas a slight decrease of splenectomies was observed.

Use of clinical practice guidelines on long-term prophylaxis in severe hemophilia in France: a retrospective audit.

OBJECTIVES: To evaluate the impact of the 2002 guidelines on the current status of prophylaxis in French children with severe hemophilia A or B. STUDY DESIGN: Clinical information was captured, in a prospective way, using FranceCoag Network. We retrospectively studied 291 patients with severe (<1 IU/dL) hemophilia A and B, with no history of inhibitors. RESULTS: Our results demonstrate that the availability of national medical guidelines has improved clinical practice in France. In the past decade, the proportion of children with severe hemophilia undergoing prophylaxis has shown a significant 2- to 3-fold increase: ∼80% of these children>3 years of age are now receiving prophylaxis. In severe hemophilia A and B, the age at which prophylaxis commences has significantly decreased: 4.0 and 6.1 years for the period 1996-1999 as opposed to 1.8 and 1.4 years for the period 2004-2007 (P=.0001). CONCLUSIONS: Long-term clinical and physical evaluations of patients will be necessary to establish the benefits of this increase in prophylactic treatment on the prevention of hemophilic arthropathy.

Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri.

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.

Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer.

PURPOSE: To determine the risk factors for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after breast cancer. PATIENTS AND METHODS: We conducted a case-control study among women treated for breast cancer between 1985 and 2001 in French general hospitals, cancer centers, or clinics. We included 182 AML and MDS patients and 534 matched controls. Breast cancer characteristics, type of treatment, and family history of cancer were compared in both groups. RESULTS: The risk of AML/MDS was increased after topoisomerase-II inhibitor-based chemotherapy (P < 10-16) and was higher for mitoxantrone-based chemotherapy than for anthracycline-based chemotherapy (relative risk [RR] = 15.6; 95% CI, 7.1 to 34.2; and RR = 2.7; 95% CI, 1.7 to 4.5, respectively). After adjustment for other treatment components, the risk of AML/MDS in patients who received radiotherapy was multiplied by 3.9 (95% CI, 1.4 to 10.8) but was not increased by alkylating agents. Patients receiving granulocyte colony-stimulating factor (G-CSF) support had an increased risk of AML/MDS (RR = 6.3; 95% CI, 1.9 to 21), even when controlling for chemotherapy doses. Similar results were obtained when AML and MDS were considered separately. CONCLUSION: This large case-control study demonstrates that the risk of AML/MDS is much higher with mitoxantrone-based chemotherapy than with anthracyclines-based chemotherapy in a population of women recently treated for breast cancer. The risk of AML/MDS associated with mitoxantrone must be kept in mind when using this drug to treat diseases other than breast cancer (eg, prostate cancer or multiple sclerosis). In addition, our study suggests the need to monitor the long-term effects of G-CSF therapy.

[The heat wave of August 2003: what happened?]. / La vague de chaleur d'août 2003: que s'est-il passe?

A heat wave of exceptional intensity occurred in France in August 2003, 2003 was the warmest of the last 53 years in terms of minimal, maximal and average temperatures, and in terms of duration. In addition, high temperatures and sunshine, causing the emission of pollutants, significantly increased the atmospheric ozone level. Some epidemiological studies were rapidly implemented during the month of August in order to asses the health impact of this heat wave. Excess mortality was estimated at about 14 800 additional deaths. This is equivalent to a total mortality increase of 60% between August 1st and 20th, 2003 (Inserm survey). Almost the whole country was concerned by this excess-mortality, even in locations where the number of very hot days remained low. Excess-mortality clearly increased with the duration of extreme temperatures. These studies also described the features of heat-related deaths. They showed that the death toll was at its highest among seniors and suggested that less autonomous or disabled or mentally ill people were more vulnerable. So, they provided essential information for the setting up of an early warning system in conjunction with emergency departments. The public health impact of the Summer 2003 heat wave in various European countries was also assessed. Different heat waves in term of intensity had occurred at different times in many countries with each time deaths in excess. But, it does seem that France was the most affected country. However, implementation of standardized methods of data collection through all countries is necessary to afford further comparisons. Collaborative studies will be conducted in this way. After theses first descriptive studies, further etiologic studies on risk factors and heat-related deaths were launched and are now in progress. Considering the health impact of the heat wave, national health authorities decided to launch an Heat Wave National Plan including a provisional Heat Watch Warning System (HWWS) for 2004. Developed in collaboration with Metéo France, this HWWS is based upon an analysis of historical daily mortality data and meteorological indicators in 14 French cities in order to define the best indicators and triggers. The public health impact of the heat wave of August 2003 was major. This exceptional event raises questions about anticipating phenomena which are difficult to predict. The collaborative efforts which were developed and the group of actions and studies which were implemented in a context of emergency are now useful for the setting up of early warning strategies and thus efficient prevention.

Mortality in 13 French cities during the August 2003 heat wave.

We observed the daily trend in mortality rates during the 2003 heat wave in 13 of France's largest cities. Mortality data were collected from July 25 to September 15 each year from 1999 through 2003. The conjunction of a maximum temperature of 35 degrees C and a minimum temperature of 20 degrees C was exceptional in 7 cities. An excess mortality rate was observed in the 13 towns, with disparities from +4% (Lille) to +142% (Paris).

Long-term complete haematological and molecular remission after allogeneic bone marrow transplantation in a patient with a stem cell myeloproliferative disorder associated with t(8;13)(p12;q12).

A rare atypical myeloproliferative disorder (aMPD) associated with chromosomal translocations involving the short arm of chromosome 8, region p11-p12 has been described. In most patients, the cytogenetic abnormality is a t(8;13)(p12;q12) that fuses fibroblast growth factor receptor 1, the 8p12 key gene, to FIM/ZNF198 gene. Prognosis is poor with frequent evolution to acute myeloid leukaemia within 1 year of diagnosis. We report a new patient with aMPD with a t(8;13) translocation. Complete haematological, cytogenetic and molecular remission was demonstrated 39 months after allogeneic bone marrow transplantation. This is the first report to demonstrate a molecular remission in this disorder.