Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study.

BACKGROUND: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics. PURPOSE: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics. DESIGN: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network. METHODS: Adults with a confirmed diagnosis of severe asthma for at least 12 months' duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders. RESULTS: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma. CONCLUSION: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

Understanding maternal mortality in women with obesity and the role of care they receive: a national case-control study.

OBJECTIVE: Obesity has significant implications for the health of pregnant women. However, few studies have quantified its association with maternal mortality or examined the relevant underlying causes and the role of care, although this remains the most severe maternal outcome. Our objectives were to quantify the risk of maternal death by prepregnancy body mass index and to determine whether obesity affected the quality of care of the women who died. DESING: This is a national population-based case-control study in France. Cases were 364 maternal deaths from the 2007-2012 National Confidential Enquiry. Controls were 14,681 parturients from the nationally representative 2010 perinatal survey. We studied the association between categories of prepregnancy BMI and maternal death by multivariable logistic regression, estimating adjusted odds ratios and 95% confidence intervals, overall and by specific causes of death. Individual case reviews assessed the quality of care provided to the women who died, by obesity status. RESULTS: Compared with women with normal BMI, underweight women (<18.5 kg/m2) had an adjusted OR of death of 0.75 (95% CI, 0.42-1.33), overweight women (25-29.9 kg/m2) 1.65 (95% CI, 1.24-2.19), women with class 1 obesity (30-34.9 kg/m2) 2.22 (95% CI, 1.55-3.19) and those with class 2-3 obesity (≥35 kg/m2) 3.40 (95% CI, 2.17-5.33). Analysis by cause showed significant excess risk of maternal death due to cardiovascular diseases, venous thromboembolism, hypertensive complications and stroke in women with obesity. Suboptimal care was as frequent among women with (35/62, 57%) as without obesity (136/244, 56%), but this inadequate management was directly related to obesity among 14/35 (40%) obese women with suboptimal care. Several opportunities for improvement were identified. CONCLUSIONS: The risk of maternal death increases with BMI; it multiplied by 1.6 in overweight women and more than tripled in pregnant women with severe obesity. Training clinicians in the specificities of care for pregnant women with obesity could improve their outcomes.

Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort.

BACKGROUND: Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations. OBJECTIVE: To assess changes in asthma control between baseline and 12 months of treatment. METHODS: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447). RESULTS: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators. CONCLUSION & CLINICAL RELEVANCE: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia.

Effect of Early Initiation of Varenicline on Smoking Cessation in COPD Patients Admitted for Exacerbation: The Save Randomized Clinical Trial.

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation.Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT01694732.