References of "Louis, Renaud"
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See detailNecitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.
Thatcher, Nick; Hirsch, Fred R.; Luft, Alexander V. et al

in The Lancet. Oncology (2015), 16(7), 763-74

BACKGROUND: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus ... [more ▼]

BACKGROUND: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. METHODS: We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m(2) administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m(2) administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash--a class effect of EGFR antibodies--that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. FINDINGS: Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients and randomly assigned them to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11.5 months [95% CI 10.4-12.6]) vs 9.9 months [8.9-11.1]; stratified hazard ratio 0.84 [95% CI 0.74-0.96; p=0.01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group (333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3-4 hypomagnesaemia (47 [9%] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and cisplatin group) and grade 3 rash (20 [4%] vs one [<1%]). Including events related to disease progression, adverse events with an outcome of death were reported for 66 (12%) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 (11%) of 541 patients in the gemcitabine and cisplatin group; these were deemed to be related to study drugs in 15 (3%) and ten (2%) patients, respectively. Overall, we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations. INTERPRETATION: Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease. FUNDING: Eli Lilly and Company. [less ▲]

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See detailAsthma Control and Sputum Eosinophils: a Longitudinal Study in Daily Practice
Demarche, Sophie ULiege; SCHLEICH, FLorence ULiege; HENKET, Monique ULiege et al

Scientific conference (2015, June 12)

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See detailClinically relevant subgroups in COPD and asthma.
Turner, Alice M.; Tamasi, Lilla; SCHLEICH, FLorence ULiege et al

in European respiratory review : an official journal of the European Respiratory Society (2015), 24(136), 283-98

As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD) nor asthma is a simple, easily defined disease. In the past, treatment options ... [more ▼]

As knowledge of airways disease has grown, it has become apparent that neither chronic obstructive pulmonary disease (COPD) nor asthma is a simple, easily defined disease. In the past, treatment options for both diseases were limited; thus, there was less need to define subgroups. As treatment options have grown, so has our need to predict who will respond to new drugs. To date, identifying subgroups has been largely reported by detailed clinical characterisation or differences in pathobiology. These subgroups are commonly called "phenotypes"; however, the problem of defining what constitutes a phenotype, whether this should include comorbid diseases and how to handle changes over time has led to the term being used loosely. In this review, we describe subgroups of COPD and asthma patients whose clinical characteristics we believe have therapeutic or major prognostic implications specific to the lung, and whether these subgroups are constant over time. Finally, we will discuss whether the subgroups we describe are common to both asthma and COPD, and give some examples of how treatment might be tailored in patients where the subgroup is clear, but the label of asthma or COPD is not. [less ▲]

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See detailActivity of the alpha-1 antitrypsin deficiency registry in Belgium.
Hutsebaut, Jacques; Janssens, Wim; Louis, Renaud ULiege et al

in COPD : Journal of Chronic Obstructive Pulmonary Disease (2015), 12(S1), 10-14

A Belgian alpha-1-antitrypsin (AAT) deficiency registry has been established in 2003. Currently 55 patients are included. At the same time, a working group has been set up for publishing national ... [more ▼]

A Belgian alpha-1-antitrypsin (AAT) deficiency registry has been established in 2003. Currently 55 patients are included. At the same time, a working group has been set up for publishing national guidelines. In 2014, several Belgian patients founded Alpha-1 Global. We hope that the integrated activities of all the stakeholders involved in AAT deficiency will permit a high quality care for all patients suffering from this disabling disease. [less ▲]

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See detailTraitement personnalisé dans l'asthme : le cas des anticorps monoclonaux dirigés contre l'interleukine-5.
LOUIS, Renaud ULiege; Demarche, Sophie ULiege; Van Hees, Thierry ULiege et al

in Revue Médicale de Liège (2015), 70(5-6), 306-9

Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab ... [more ▼]

Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia. When administered monthly by intravenous or subcutaneous injection in severe eosinophilic asthmatic patients, they reduce severe exacerbation rate by 50 %, improve asthma control and quality of life, and have an oral glucocorticoids sparing effect in those requiring oral corticoids as maintenance therapy. [less ▲]

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See detailDevelopment of recombinant stable house dust mite allergen Der p 3 molecules for component resolved diagnosis and specific immunotherapy
Bouaziz, Ahlem ULiege; Galleni, Moreno ULiege; Louis, Renaud ULiege

in Clinical and Experimental Allergy (2015), 45

Abstract BACKGROUND: The allergen Der p 3 is underrepresented in house dust mite (HDM) extracts probably due to autolysis. Recombinant stable molecule of the allergen is thus needed to improve the ... [more ▼]

Abstract BACKGROUND: The allergen Der p 3 is underrepresented in house dust mite (HDM) extracts probably due to autolysis. Recombinant stable molecule of the allergen is thus needed to improve the diagnosis of allergy and the safety and efficacy of immunotherapy. OBJECTIVE: The current study reports the immunological characterization of two recombinant molecules of the HDM allergen Der p 3 as useful tools for diagnosis and immunotherapy. METHODS: Recombinant mature (rDer p 3) and immature (proDer p 3) Der p 3 and their corresponding S196A mutants were produced in Pichia pastoris and purified. The stability, IgE-binding capacity and allergenicity of the different proteins were analysed and compared with those of the major mite allergen Der p 1 used as a reference. Additionally, the immunogenicity of the different allergens was evaluated in a murine model of Der p 3 sensitization. RESULTS: Compared to the IgE reactivity to recombinant and natural Der p 3 (nDer p 3), the mean IgE binding of patient's sera to rDer p 3-S196A (50%) was higher. The poorly binding to nDer p 3 or rDer p 3 was due to autolysis of the allergen. Contrary to Der p 3, proDer p 3 displayed very weak IgE reactivity, as measured by sandwich ELISA and competitive inhibition, rat basophil leukaemia degranulation and human basophil activation assays. Moreover, proDer p 3 induced a TH 1-biased immune response that prevented allergic response in mice but retained Der p 3-specific T-cell reactivity. CONCLUSION: rDer p 3-S196A should be used for the diagnosis of HDM allergy elicited by Der p 3, and proDer p 3 may represent a hypoallergen of Der p 3. [less ▲]

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See detailNecitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study.
Paz-Ares, Luis; Mezger, Jorg; Ciuleanu, Tudor E. et al

in The Lancet. Oncology (2015), 16(3), 328-37

BACKGROUND: Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. We aimed to compare necitumumab plus pemetrexed and ... [more ▼]

BACKGROUND: Necitumumab is a second-generation recombinant human immunoglobulin G1 EGFR monoclonal antibody that competitively inhibits ligand binding. We aimed to compare necitumumab plus pemetrexed and cisplatin with pemetrexed and cisplatin alone in patients with previously untreated, stage IV, non-squamous non-small-cell lung cancer (NSCLC). METHODS: We did this randomised, open-label, controlled phase 3 study at 103 sites in 20 countries. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function, were randomly assigned 1:1 to treatment with a block randomisation scheme (block size of four) via a telephone-based interactive voice-response system or interactive web-response system. Patients received either cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 of a 3-week cycle for a maximum of six cycles alone, or with necitumumab 800 mg on days 1 and 8. Necitumumab was continued after the end of chemotherapy until disease progression or unacceptable toxic effects. Randomisation was stratified by smoking history, ECOG performance status, disease histology, and geographical region. Patients and study investigators were not masked to group assignment. The primary endpoint was overall survival. Efficacy analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00982111. FINDINGS: Between Nov 11, 2009, and Feb 2, 2011, we randomly assigned 633 patients to receive either necitumumab plus pemetrexed and cisplatin (n=315) or pemetrexed and cisplatin alone (n=318). Enrolment was stopped on Feb 2, 2011, after a recommendation from the independent data monitoring committee. There was no significant difference in overall survival between treatment groups, with a median overall survival of 11.3 months (95% CI 9.5-13.4) in the necitumumab plus pemetrexed and cisplatin group versus 11.5 months (10.1-13.1) in the pemetrexed and cisplatin group (hazard ratio 1.01 [95% CI 0.84-1.21]; p=0.96). The incidence of grade 3 or worse adverse events, including deaths, was higher in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group; in particular, deaths regarded as related to study drug were reported in 15 (5%) of 304 patients in the necitumumab group versus nine (3%) of 312 patients in the pemetrexed and cisplatin group. Serious adverse events were likewise more frequent in the necitumumab plus pemetrexed and cisplatin group than in the pemetrexed and cisplatin group (155 [51%] of 304 vs 127 [41%] of 312 patients). Patients in the necitumumab plus pemetrexed and cisplatin group had more grade 3-4 rash (45 [15%] of 304 vs one [<1%] of 312 patients in the pemetrexed and cisplatin alone group), hypomagnesaemia (23 [8%] vs seven [2%] patients), and grade 3 or higher venous thromboembolic events (23 [8%] vs 11 [4%] patients) than did those in the pemetrexed and cisplatin alone group. INTERPRETATION: Our findings show no evidence to suggest that the addition of necitumumab to pemetrexed and cisplatin increases survival of previously untreated patients with stage IV non-squamous NSCLC. Unless future studies identify potentially useful predictive biomarkers, necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin. FUNDING: Eli Lilly and Company. [less ▲]

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See detailComment je traite ... une mucoviscidose
BENDAVID, G.; VANDERHELST, E.; LOUIS, Renaud ULiege et al

in Revue Médicale de Liège (2015), 70(3), 108-114

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See detailChylothorax et pseudochylothorax: contraste a partir de deux observations.
Berg, J.; GUIOT, Julien ULiege; HEINEN, Vincent ULiege et al

in Revue Médicale de Liège (2015), 70(2), 73-7

We report two cases of lipidic pleural effusion: an arthritis-associated pseudochylothorax and a chylous pleural effusion in a HIV seropositive patient. The incidence of lipidic pleural effusions is low ... [more ▼]

We report two cases of lipidic pleural effusion: an arthritis-associated pseudochylothorax and a chylous pleural effusion in a HIV seropositive patient. The incidence of lipidic pleural effusions is low, especially for pseudochylothorax. We review their clinical characteristics and management. [less ▲]

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See detailLa thermoplastie bronchique dans le traitement de l'asthme sévère de l'adulte.
Chanez, P.; Boulet, L.-P.; Brillet, P.-Y. et al

in Revue des maladies respiratoires (2015), 32

Bronchial thermoplasty is a recent endoscopic technique for the treatment of severe asthma. It is an innovative treatment whose clinical efficacy and safety are beginning to be better understood. Since ... [more ▼]

Bronchial thermoplasty is a recent endoscopic technique for the treatment of severe asthma. It is an innovative treatment whose clinical efficacy and safety are beginning to be better understood. Since this is a device-based treatment, the evaluation procedure of risks and benefits is different that for pharmaceutical products; safety aspects, regulatory requirements, study design and the assessment of the magnitude of effects may all be different. The mechanism of action and optimal patient selection need to be assessed further in rigorous clinical and scientific studies. This technique is in harmony with the development of personalised medicine in the 21st century. It should be developed further in response to the numerous challenges and needs not yet met in the management of severe asthma. [less ▲]

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See detailEtude du phénotype mixte BPCO-asthme dans une série de patients BPCO en état stable
Nguyen, M.-S.; NGUYEN DANG, Delphine ULiege; SCHLEICH, FLorence ULiege et al

in Revue Médicale de Liège (2015), 70(1), 37-43

Résumé : Le but de ce travail était d’évaluer la prévalence et de décrire les caractéristiques du phénotype mixte BPCO-asthme parmi les patients BPCO stables de stade II à IV selon la classification de ... [more ▼]

Résumé : Le but de ce travail était d’évaluer la prévalence et de décrire les caractéristiques du phénotype mixte BPCO-asthme parmi les patients BPCO stables de stade II à IV selon la classification de GOLD. Matériel et méthodes : entre mai 2013 et avril 2014, 46 patients consécutifs furent recrutés à partir des consultations de Pneumologie du CHU de Liège. Ils étaient considérés comme présentant un syndrome mixte BPCO-asthme si leur indice de Tiffeneau était < 70% après bronchodilatation et s’accompagnait soit d’un antécédent d’asthme avant l’âge de 40 ans, soit d’au moins deux des trois critères suivants: 1) réversibilité bronchique significative (changement du VEMS après la bronchodilatation ≥ 200 ml et ≥ 12%), 2) inflammation éosinophilique: éosinophiles dans les expecto-rations ≥ 3% ou/et éosinophiles dans le sang ≥ 400/μl ou/et FENO ≥ 45 ppb, 3) histoire d’allergie respiratoire, ou IgE sériques totales ≥ 113 KU/l, ou RAST ≥ 0,35 KU/l à l’égard d’un des principaux aéroallergènes. Le phénotype mixte BPCO-asthme fut observé chez 37% des patients. L’expression symptomatique était plus marquée dans le groupe de phénotype mixte que dans le groupe de BPCO pure (CAT 24,6 ± 8,1 vs 19,4 ± 8, p < 0,05) en dépit d’un déficit spiro-métrique identique. Le coefficient de transfert alvéolo-capillaire (DLCO/VA%) était préservé dans le phénotype mixte (97 ± 24%) et supérieur à celui mesuré chez les patients BPCO pure (80 ± 20%) (p < 0,05). La prévalence du phéno-type mixte est voisine d’un tiers chez les patients BPCO et ces sujets ont une expression symptomatique plus marquée, sans signe d’obstruction bronchique plus sévère. [less ▲]

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See detailLes corticoïdes inhalés sont-ils suffisants pour traiter l'asthme? Perspective historique
LOUIS, Renaud ULiege; Demarche, Sophie ULiege; SCHLEICH, FLorence ULiege

in Vaisseaux, Coeur, Poumons (2015), 20(4), 66-68

Cet article retrace l'évolution du traitement médicamenteux de l'asthme depuis l'avènement des corticoïdes inhalés à la fin des années 80. Une meilleure compréhension de la maladie, de ses différents ... [more ▼]

Cet article retrace l'évolution du traitement médicamenteux de l'asthme depuis l'avènement des corticoïdes inhalés à la fin des années 80. Une meilleure compréhension de la maladie, de ses différents phénotypes et des cytokins et médiateurs protéiques impliqués dans les différentes voies inflammatoires, a ouvert la porte à une prise en charge plus pointue de la maladie et plus particulièrement de ses formes sévères. A l'heure actuelle, le traitement des patients atteints d'asthme sévère requiert une caractérisation plus poussée de la maladie. [less ▲]

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See detailFirst-line crizotinib versus chemotherapy in ALK-positive lung cancer.
Solomon, Benjamin J.; Mok, Tony; Kim, Dong-Wan et al

in The New England journal of medicine (2014), 371(23), 2167-77

BACKGROUND: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. METHODS: We ... [more ▼]

BACKGROUND: The efficacy of the ALK inhibitor crizotinib as compared with standard chemotherapy as first-line treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC) is unknown. METHODS: We conducted an open-label, phase 3 trial comparing crizotinib with chemotherapy in 343 patients with advanced ALK-positive nonsquamous NSCLC who had received no previous systemic treatment for advanced disease. Patients were randomly assigned to receive oral crizotinib at a dose of 250 mg twice daily or to receive intravenous chemotherapy (pemetrexed, 500 mg per square meter of body-surface area, plus either cisplatin, 75 mg per square meter, or carboplatin, target area under the curve of 5 to 6 mg per milliliter per minute) every 3 weeks for up to six cycles. Crossover to crizotinib treatment after disease progression was permitted for patients receiving chemotherapy. The primary end point was progression-free survival as assessed by independent radiologic review. RESULTS: Progression-free survival was significantly longer with crizotinib than with chemotherapy (median, 10.9 months vs. 7.0 months; hazard ratio for progression or death with crizotinib, 0.45; 95% confidence interval [CI], 0.35 to 0.60; P<0.001). Objective response rates were 74% and 45%, respectively (P<0.001). Median overall survival was not reached in either group (hazard ratio for death with crizotinib, 0.82; 95% CI, 0.54 to 1.26; P=0.36); the probability of 1-year survival was 84% with crizotinib and 79% with chemotherapy. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema, and the most common events with chemotherapy were nausea, fatigue, vomiting, and decreased appetite. As compared with chemotherapy, crizotinib was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life. CONCLUSIONS: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC. (Funded by Pfizer; PROFILE 1014 ClinicalTrials.gov number, NCT01154140.). [less ▲]

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See detailHeterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR).
SCHLEICH, FLorence ULiege; Brusselle, G.; Louis, Renaud ULiege et al

in Respiratory medicine (2014), 108(12), 1723-32

The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its ... [more ▼]

The Belgian severe asthma registry is a web-based registry encompassing demographic, clinical, functional and inflammatory data of severe asthmatics (SA), aiming at improving awareness, knowledge on its natural history and subphenotypes, and offering tools to optimize care of this asthma population. METHODS: The cross-sectional analyses of this registry included 350 SA as defined by the ATS (2000) from 9 Belgian centres, with at least one year follow up. RESULTS: Mean age was 55 +/- 14 yrs. SA were more frequently female (57%) and atopic (70%). Late-onset asthma (>/=40 yr) was observed in 31% of SA. Current smokers represented 12% while 31% were ex-smokers. In addition to high doses ICS + LABA, 65% of patients were receiving LTRA, 27% anti-IgE and 24% maintenance oral corticosteroids (8 mg (Interquartile range-IQR:4-8) methylprednisolone). Despite impaired airflow (median FEV1:67%; IQR: 52-81) only 65% had a post-bronchodilator FEV1/FVC ratio <70%. The median blood eosinophil count was 240/mm(3). The median FENO was 26 ppb (IQR: 15-43) and 22% of SA had FENO >/= 50 ppb. Induced sputum was successful in 86 patients. Eosinophilic asthma (sputum Eos >/= 3%) was the predominant phenotype (55%) while neutrophilic (sputum Neu >/= 76%) and paucigranulocytic asthma accounted for 22% and 17% respectively. Comorbidities included rhinitis and chronic rhinosinusitis (49%), nasal polyposis (19%), oesophageal reflux (36%), overweight and obesity (47%) and depression (19%). In addition, 8% had aspirin-induced asthma and 3% ABPA. Asthma was not well-controlled in 83% according to ACT < 20 and 77% with ACQ > 1.5. CONCLUSION: In this cohort of patients with severe asthma, the majority displayed indices of persistent airflow limitation and eosinophilic inflammation despite high-dose corticosteroids, suggesting potential for eosinophil-targeted biotherapies. [less ▲]

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