Florence Le Maulf

Bio: Florence Le Maulf is an academic researcher from Boehringer Ingelheim. The author has contributed to research in topics: Nintedanib & FEV1/FVC ratio. The author has an hindex of 7, co-authored 9 publications receiving 3384 citations.

Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis

Abstract: Background Nintedanib (formerly known as BIBF 1120) is an intracellular inhibitor that targets multiple tyrosine kinases. A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. Methods We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. The primary end point was the annual rate of decline in forced vital capacity (FVC). Key secondary end points were the time to the first acute exacerbation and the change from baseline in the total score on the St. George’s Respiratory Questionnaire, both assessed over a 52-week period. Results A total of 1066 patients were randomly assigned in a 3:2 ratio to receive nintedanib or placebo. The adjusted annual rate of change in FVC was −114.7 ml with nintedanib versus −239.9 ml with placebo (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) in INPULSIS-1 and −113.6 ml with nintedanib versus −207.3 ml with placebo (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001) in INPULSIS-2. In INPULSIS-1, there was no significant difference between the nintedanib and placebo groups in the time to the first acute exacerbation (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P = 0.67); in INPULSIS-2, there was a significant benefit with nintedanib versus placebo (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P = 0.005). The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. Conclusions In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. (Funded by Boehringer Ingelheim; INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.)

Treatment of Acute Venous Thromboembolism With Dabigatran or Warfarin and Pooled Analysis

Abstract: Background—Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings. Methods and Resu...

Effect of Nintedanib in Subgroups of Idiopathic Pulmonary Fibrosis by Diagnostic Criteria.

Abstract: Rationale: In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia (UIP), on high-resolution computed tomography (HRCT). Thus, the patients in these trials represented patients with definite UIP and a large subgroup of patients with possible UIP.Objectives: To investigate the potential impact of diagnostic subgroups on the progression of IPF and the effect of nintedanib.Methods: We conducted a post hoc subgroup analysis of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy versus patients without either, using pooled data from the INPULSIS trials.Measurements and Main Results: Seven hundred twenty-three (68.1%) patients had honeycombing and/or biopsy, and 338 (31.9%) patients had no honeycombing or biopsy. In these subgroups, respecti...

Design of the PF-ILD trial: A double-blind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease

Abstract: 600 patients aged ≥18 years will be randomised in a 1:1 ratio to nintedanib or placebo. Patients with diagnosis of IPF will be excluded. The study population will be enriched with two-thirds having a usual interstitial pneumonia-like pattern on HRCT. The primary endpoint is the annual rate of decline in forced vital capacity over 52 weeks. The main secondary endpoints are the absolute change from baseline in King’s Brief Interstitial Lung Disease Questionnaire total score, time to first acute interstitial lung disease exacerbation or death and time to all-cause mortality over 52 weeks. Ethics and dissemination The trial is conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guideline for Good Clinical Practice (GCP) and Japanese GCP regulations. Trial registration number NCT02999178.

Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Abstract: Background: This document provides clinical recommendations for the diagnosis of idiopathic pulmonary fibrosis (IPF). It represents a collaborative effort between the American Thoracic Society, Eur...

2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism

Abstract: ACS : acute coronary syndrome AMPLIFY : Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-line Therapy aPTT : activated partial thromboplastin time b.i.d. : bis in diem (twice daily) b.p.m. : beats per minute BNP : brain natriuretic peptide BP : blood pressure CI : confidence interval CO : cardiac output COPD : chronic obstructive pulmonary disease CPG : Committee for Practice Guidelines CRNM : clinically relevant non-major CT : computed tomographic/tomogram CTEPH : chronic thromboembolic pulmonary hypertension CUS : compression venous ultrasonography DSA : digital subtraction angiography DVT : deep vein thrombosis ELISA : enzyme-linked immunosorbent assay ESC : European Society of Cardiology H-FABP : heart-type fatty acid-binding protein HIT : heparin-induced thrombocytopenia HR : hazard ratio ICOPER : International Cooperative Pulmonary Embolism Registry ICRP : International Commission on Radiological Protection INR : international normalized ratio iPAH : idiopathic pulmonary arterial hypertension IVC : inferior vena cava LMWH : low molecular weight heparin LV : left ventricle/left ventricular MDCT : multi-detector computed tomographic (angiography) MRA : magnetic resonance angiography NGAL : neutrophil gelatinase-associated lipocalin NOAC(s) : Non-vitamin K-dependent new oral anticoagulant(s) NT-proBNP : N-terminal pro-brain natriuretic peptide o.d. : omni die (every day) OR : odds ratio PAH : pulmonary arterial hypertension PE : pulmonary embolism PEA : pulmonary endarterectomy PEITHO : Pulmonary EmbolIsm THrOmbolysis trial PESI : pulmonary embolism severity index PH : pulmonary hypertension PIOPED : Prospective Investigation On Pulmonary Embolism Diagnosis PVR : pulmonary vascular resistance RIETE : Registro Informatizado de la Enfermedad Thromboembolica venosa RR : relative risk rtPA : recombinant tissue plasminogen activator RV : right ventricle/ventricular SPECT : single photon emission computed tomography sPESI : simplified pulmonary embolism severity index TAPSE : tricuspid annulus plane systolic excursion Tc : technetium TOE : transoesophageal echocardiography TTR : time in therapeutic range TV : tricuspid valve UFH : unfractionated heparin V/Q scan : ventilation–perfusion scintigraphy VKA : vitamin K antagonist(s) VTE : venous thromboembolism Guidelines summarize and evaluate all available evidence at the time of the writing process, on a particular issue with the aim of assisting health professionals in selecting the best management strategies for an individual patient, with a given condition, taking into account the impact on outcome, as well as the risk-benefit-ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help the health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate. A great number of Guidelines have …

2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS)

Abstract: Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

A framework for advancing our understanding of cancer-associated fibroblasts

Abstract: Cancer-associated fibroblasts (CAFs) are a key component of the tumour microenvironment with diverse functions, including matrix deposition and remodelling, extensive reciprocal signalling interactions with cancer cells and crosstalk with infiltrating leukocytes. As such, they are a potential target for optimizing therapeutic strategies against cancer. However, many challenges are present in ongoing attempts to modulate CAFs for therapeutic benefit. These include limitations in our understanding of the origin of CAFs and heterogeneity in CAF function, with it being desirable to retain some antitumorigenic functions. On the basis of a meeting of experts in the field of CAF biology, we summarize in this Consensus Statement our current knowledge and present a framework for advancing our understanding of this critical cell type within the tumour microenvironment.