Budget Impact of Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia With Sustained Deep Molecular Response.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) account for the vast majority of healthcare expenditure on patients with chronic myeloid leukemia (CML), and it has been demonstrated that TKI discontinuation in patients in long-term deep molecular remission (DMR) is safe and improves quality of life. Our objective was to estimate the budget impact of TKI discontinuation in CML patients in long-term DMR from the perspective of the French healthcare system. METHODS: This analysis was conducted over a 5-year time horizon using a Markov model with cycles of 6 months. Transition probabilities were estimated through systematic reviews and meta-analyses. Costs were estimated from the French National Claims Database. Monte Carlo simulations were performed to take into account the uncertainty surrounding model parameters. Sensitivity analyses were carried out by varying the size of the target population and the cost of TKIs. RESULTS: Over a 5-year period and for a target population of 100 patients each year eligible and agreeing to stop TKI, the TKI discontinuation strategy would save €25.5 million (95% confidence interval -39.3 to 70.0). In this model, the probability that TKI discontinuation would be more expensive than TKI continuation was 12.0%. In sensitivity analyses, mean savings ranged from €14.9 million to €62.9 million. CONCLUSIONS: This study provides transparent, reproducible, and interpretable results for healthcare professionals and policy makers. Our results clearly show that innovative healthcare strategies can benefit both the healthcare system and patients. Savings from generalizing TKI discontinuation in CML patients in sustained DMR should yield health gains for other patients.

Risk of molecular recurrence after tyrosine kinase inhibitor discontinuation in chronic myeloid leukaemia patients: a systematic review of literature with a meta-analysis of studies over the last ten years.

More than 10 years ago, the first pilot observational study of imatinib discontinuation was reported in chronic myeloid leukaemia (CML) patients in deep molecular response (DMR). Several studies have been published since then, in patients treated with frontline imatinib, or second-generation tyrosine kinase inhibitors (TKI) in first or second line but also on second attempt of TKI discontinuation. Our objective was to estimate, through meta-analyses of the literature data, the probability of molecular recurrence (MolRec) in the time periods of 0-6, 6-12, 12-18 and 18-24 months after a first and second TKI discontinuation and the probability of re-acquisition of DMR after MolRec. The Medline and Scopus databases were searched up to April 2019. The studies were selected by three independent reviewers. Random-effect meta-analyses were conducted using the MetaXL software. The probability of MolRec in the time periods 0-6, 6-12, 12-18 and 18-24 months after the first attempt was respectively 35%, 8%, 3% and 3%, whereas the probability of MolRec in the time periods 0-6, 6-12 and 12-18 after the second attempt was 48%, 27% and 12% respectively. Re-acquisition of a DMR was observed in 90% of patients. Most of the MolRec occur during the first six months in case of a first attempt, whereas the second MolRec occurs over a larger window of time.

Measles outbreak linked to insufficient vaccination coverage in Nouvelle-Aquitaine Region, France, October 2017 to July 2018.

On 30 October 2017, an outbreak of measles started in the Nouvelle-Aquitaine (NA) region in France among Bordeaux University students before spreading to other regions. Until 1 July 2018, 1,101 cases were reported in NA, including 98 complications and two deaths. Cases were related to clusters (e.g. students, healthcare workers) in 16%; 81% of cases were not vaccinated against measles as recommended. Vaccination coverage above herd immunity threshold remains the main preventative outbreak measure.

Skin autofluorescence predicts cardio-renal outcome in type 1 diabetes: a longitudinal study.

BACKGROUND: We aimed to analyze the relationships between skin autofluorescence (SAF) and incident macrovascular events and renal impairment after 4 years of follow-up in patients with type 1 diabetes (T1D). METHODS: Two hundred and forty-three patients (51.2 ± 16.7 years old) with T1D participated. SAF was measured by AGE-Reader-TM at inclusion. Macrovascular events (MVE), estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER) were recorded then and 4 years later. Multivariate logistic regression was used to analyze the relationships between SAF and incident MVE and renal profile 4 years later. RESULTS: Patients with incident MVE had a higher SAF (p = 0.003). SAF predicted incident MVE after adjustment for age, sex, body mass index, tobacco, diabetes duration, hypertension, HbA1c, AER, eGFR (OR 4.84 [95 % CI 1.31-17.89], p = 0.018). However, this relation was no longer significant after adjustment for history of MVE. An inverse relation was found between SAF and incident eGFR (p = 0.0001). Patients with incident eGFR <60 ml/min/1.73 m(2) had a SAF higher than patients with normal eGFR. After adjustment for the previous criteria, SAF remained associated with the risk of impaired incident eGFR (OR 7.42 [95 % CI 1.59-34.65], p = 0.018). No relation was found between SAF and increased AER 4 years later. CONCLUSIONS: SAF predicts MVE in patients with T1D, adjusted for cardiovascular risk factors but the most powerful predictive factor remains history of MVE. SAF also predicts eGFR impairment, adjusted for initial AER and renal function. SAF could be a useful non-invasive tool for estimating risk of cardiovascular or renal impairment in patients with T1D.

Effects of a physical activity programme to prevent physical performance decline in onco-geriatric patients: a randomized multicentre trial.

BACKGROUND: Older adults with cancer experience negative long-term functional effects of both cancer and treatments. Exercise may minimize their age-related and cancer-related functional decline. METHODS: We conducted a multicentre open-label 12 month randomized clinical trial with two parallel arms including participants aged ≥70 years with lymphoma or carcinoma requiring curative treatment. The study started at the beginning of any phase of cancer treatment (surgery, chemotherapy, or radiotherapy). The usual care group (UCG) received the current national recommendations in physical activity (a guideline without specific counselling). The intervention group (IG) received 1 year phoned physical activity advice individually adapted to physical assessment (twice a month during the first 6 months and then monthly). The primary outcome was the proportion of subjects with a 1 year decreased short physical performance battery (SPPB) score of 1 point or more. Physical, cognitive, and clinical secondary outcomes were also investigated. RESULTS: We allocated 301 participants (age 76.7 ± 5.0, female 60.6%) to each group. At baseline, the median SPPB was 10/12 in both groups. Breast was the most frequent tumour site (35.7%). After 1 year, 14.0% of participants in the UCG and 18.7% in the IG had a decrease in SPPB score of 1 point or more (P = 0.772). At 2 years, there was no difference in SPPB, gait speed, International Physical Activity Questionnaire score, and verbal fluency. Subgroup analyses after 2 years showed a decline in SPPB for 29.8% of UCG and 5.0% of IG breast cancer participants (P = 0.006), in 21.7% of UCG and 6.2% of IG female participants (P = 0.019), and in 24.5% of UCG and 11.1% of IG normal nutritional status participants (P = 0.009). Falls, hospitalization, institutionalization, and death rates were similar in both groups. CONCLUSIONS: Personalized phoned physical activity advice had not reduced functional decline at 1 year but provided preliminary evidence that may prevent physical performance decline at 2 years in older adults with breast cancer.