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1.
Artigo em Inglês | MEDLINE | ID: mdl-31351189

RESUMO

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200mg/300mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures in patients with uncontrolled, moderate-to-severe asthma, with greater efficacy observed in those with a high baseline type 2 phenotype. OBJECTIVE: To assess the efficacy and safety of dupilumab in uncontrolled, moderate-to-severe asthma patients with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). METHODS: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV1, patient-reported outcomes, type 2 biomarkers, and safety were assessed. RESULTS: CRS was self-reported by 382/1902 (20.1%) patients. Dupilumab 200mg/300mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P<.001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured timepoints and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. CONCLUSION: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS.

3.
Laryngoscope ; 129(9): 1969-1975, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30720213

RESUMO

OBJECTIVES/HYPOTHESIS: Establish treatment patterns and economic burden in US patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) versus without chronic rhinosinusitis (CRS). Determine comparative costs of subgroups with high clinical burden. STUDY DESIGN: Observational, retrospective, case-control study. METHODS: This study matched patients with CRSwNP to patients without CRS (1:1) using the Truven Health MarketScan US claims database. Categorical and continuous variables were compared using McNemar test and paired t test (normal distribution) or Wilcoxon signed rank tests (non-normal distribution). Within subgroups, χ2 and Wilcoxon or t tests were used (normal distribution). RESULTS: There were 10,841 patients with CRSwNP and 10,841 patients without CRS included. Mean age in the CRSwNP cohort was 45.8 years; 56.2% were male. During follow-up, patients with CRSwNP had an increased diagnosis of asthma versus patients without CRS (20.8% vs. 8.1%, respectively; P < .001). Annual incremental costs were $11,507 higher for patients with CRSwNP versus those without CRS. Costs were higher in subgroups of patients with CRSwNP undergoing functional endoscopy sinus surgery (FESS), with a comorbid diagnosis of asthma, receiving oral corticosteroids, or macrolides versus the overall CRSwNP group. Patients with CRSwNP undergoing FESS had the highest costs of the four subgroups ($26,724, $22,456, $20,695, and $20,990, respectively). CONCLUSIONS: Annual incremental costs were higher among patients with CRSwNP versus without CRS. Patients with CRSwNP with high clinical burden had higher overall costs than CRSwNP patients without. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1969-1975, 2019.

4.
J Allergy Clin Immunol ; 142(1): 171-177.e1, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29355679

RESUMO

BACKGROUND: Dupilumab, an anti-IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting ß2-agonists. OBJECTIVE: To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). METHODS: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE ≥0.35 Ku/L). RESULTS: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, -5.98; 95% CI, -10.45 to -1.51; P = .009) and all 4 AR-associated symptoms evaluated (nasal blockage, -0.60; 95% CI, -0.96 to -0.25; runny nose, -0.67; 95% CI, -1.04 to -0.31; sneezing, -0.55; 95% CI, -0.89 to -0.21; postnasal discharge, -0.49; 95% CI, -0.83 to -0.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (-1.82; 95% CI, -6.46 to 2.83; P = .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no differences were observed for these measures versus placebo. CONCLUSIONS: Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.

5.
Artigo em Inglês | MEDLINE | ID: mdl-25018629

RESUMO

PURPOSE: Breathlessness is a predominant symptom of chronic obstructive pulmonary disease (COPD), making it a valuable outcome in addition to lung function to assess treatment benefit. The phosphodiesterase-4 inhibitor roflumilast has been shown to provide small but significant improvements in dyspnea, as measured by the transition dyspnea index (TDI), in two 1-year studies in patients with severe to very severe COPD. PATIENTS AND METHODS: To provide a more comprehensive assessment of the impact of roflumilast on dyspnea, post hoc analyses of four 1-year roflumilast studies (M2-111, M2-112, M2-124, and M2-125) in patients with moderate to very severe COPD were conducted. RESULTS: In this pooled analysis (N=5,595), roflumilast significantly improved TDI focal scores versus placebo at week 52 (treatment difference, 0.327; P<0.0001). Roflumilast was associated with significantly greater TDI responders and significantly fewer TDI deteriorators (≥1-unit increase or decrease from baseline, respectively) versus placebo at week 52 (P<0.01, both); these significant differences were apparent by week 8 and maintained until study end (P<0.05, all). At study end, the postbronchodilator forced expiratory volume in 1 second improvement in TDI responders was significantly greater with roflumilast versus placebo (P<0.05). Similar to the overall population, improvements in TDI focal scores at week 52 were small but consistently significant over placebo in patients with chronic bronchitis, regardless of exacerbation history, concomitant treatment with short-acting muscarinic antagonists or long-acting ß2-agonists, or pretreatment with inhaled corticosteroids. CONCLUSION: This analysis shows that patients treated with roflumilast to reduce exacerbation risk may also experience small but significant improvements in dyspnea, with accompanying improvements in lung function.


Assuntos
Aminopiridinas/uso terapêutico , Benzamidas/uso terapêutico , Dispneia/tratamento farmacológico , Pulmão/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Idoso , Aminopiridinas/efeitos adversos , Benzamidas/efeitos adversos , Ciclopropanos/efeitos adversos , Ciclopropanos/uso terapêutico , Dispneia/diagnóstico , Dispneia/etiologia , Dispneia/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 4/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
6.
Respir Med ; 108(2): 366-75, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24120253

RESUMO

BACKGROUND: This post-hoc analysis examined the impact of roflumilast on chronic obstructive pulmonary disease (COPD) exacerbations and lung function in patients with COPD who received concomitant long-acting ß2-agonists (LABA) with or without prior inhaled corticosteroid (ICS) and the influence of various demographic and clinical characteristics on these outcomes. METHODS: Data were pooled from 2 double-blind, placebo-controlled, 52-week studies of once-daily roflumilast 500 µg in patients with COPD. Endpoints were mean rate of exacerbations and change from baseline in pre- and postbronchodilator FEV1. RESULTS: In this pooled analysis (N = 3091), addition of roflumilast to LABAs for 1 year in patients who discontinued ICS prior to study entry (n = 945) significantly reduced the risk of COPD exacerbations vs. placebo by 19.2% (p < 0.05) and significantly improved pre- and postbronchodilator FEV1 by 40 mL and 34 mL, respectively (both, p < 0.01). Similar improvements were observed in patients who received concomitant LABAs but were not taking ICS prior to study entry (n = 597). A significant reduction in COPD exacerbation risk with roflumilast vs. placebo was observed regardless of age or smoking status, and in patients who had severe or very severe COPD. Significantly improved lung function was observed with roflumilast in all the subgroups (p < 0.05), with the exception of patients with moderate COPD. CONCLUSIONS: Roflumilast reduced exacerbation rates and improved lung function in patients with COPD who received concomitant LABA, regardless of prior ICS use, and across various patient subgroups regardless of age and smoking status. CLINICALTRIALSGOV REGISTRATION NUMBERS: NCT00297102 (M2-124) and NCT00297115 (M2-125).


Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Inibidores da Fosfodiesterase 4/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Aguda , Administração Oral , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Broncodilatadores/administração & dosagem , Ciclopropanos/administração & dosagem , Preparações de Ação Retardada , Método Duplo-Cego , Esquema de Medicação , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fumar/fisiopatologia
7.
Chest ; 144(3): 758-765, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23412642

RESUMO

BACKGROUND: Evaluation of cardiovascular safety for new therapies for COPD is important because of a high prevalence of cardiac comorbidities in the COPD population. Hence, we evaluated the effects of roflumilast, a novel oral phosphodiesterase 4 inhibitor developed for the treatment and prevention of COPD exacerbations, on major adverse cardiovascular events (MACEs). METHODS: Intermediate- and long-term placebo-controlled clinical trials of roflumilast in COPD were pooled and assessed for potential cardiovascular events. Studies comprised 14 12- to 52-week placebo-controlled trials in patients with moderate to very severe COPD. All deaths and serious nonfatal cardiovascular events were evaluated by an independent adjudication committee blinded to study and treatment. The MACE composite of cardiovascular death, nonfatal myocardial infarction, and stroke was analyzed according to treatment group. RESULTS: Of 6,563 patients receiving roflumilast, 52 experienced MACEs (14.3 per 1,000 patient-years), and of 5,491 patients receiving placebo, 76 experienced MACEs (22.3 per 1,000 patient-years). The MACE composite rate was significantly lower for roflumilast compared with placebo (hazard ratio, 0.65; 95% CI, 0.45-0.93; P = .019). CONCLUSIONS: A lower rate of cardiovascular events was observed with roflumilast than with placebo in patients with COPD, indicating the lack of a cardiovascular safety signal when treating patients with COPD. Potential cardiovascular benefits of roflumilast should be evaluated in future controlled clinical trials.


Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Doenças Cardiovasculares/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Ciclopropanos/administração & dosagem , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 4 , Prevalência , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Suíça/epidemiologia , Resultado do Tratamento
9.
Int J Surg ; 8(1): 52-5, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19883802

RESUMO

INTRODUCTION: This study aimed to assess surgical workload and risk factors for gastrointestinal bleeding in patients on warfarin admitted to a hospital. METHODS: Data was collected for all warfarinised patients admitted between April 2005 and October 2007 with gastrointestinal bleeding. RESULTS: A total of 30 patients (average 80 years) were recorded. Indications for warfarin therapy were atrial fibrillation (80%), mechanical heart valve (6.67%) and embolic disease (13.33%). Fifty percent were admitted with an INR above therapeutic range and of these patients, 83% were on one or more medications known to potentiate the anti-coagulation effect of warfarin. Nine patients were also taking anti-platelet medication. Five of these nine had an admission INR within the intended therapeutic range. Thirteen patients received blood transfusions and had a significantly higher (p<0.05) INR (average 9) than the 17 patients not requiring transfusion (average 2.8). The average cost of transfusion per patient was pound470. None of the patients required acute surgical intervention. The average length of stay was 7 days, at a total cost of pound1444 per patient. Investigations found the cause of bleeding to be diverticulosis in 9 patients and neoplastic disease in 4 patients. Almost half of the patients received no investigation due to risks from co-morbidity. CONCLUSIONS: Uncontrolled anti-coagulation, polypharmacy and age were overwhelming risk factors for major gastrointestinal bleeding. Our results show that adding anti-platelet therapy has to be clearly justified against the increased risk of bleeding. Cost to the surgical department was high and no patients required surgical or radiological intervention. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Warfarin is an important drug, but the complications of its use are difficult and expensive to deal with. Warfarin use is a risk factor for haemorrhage, and this commonly involves the gastrointestinal tract. The use of warfarin is set to increase as the population ages and atrial fibrillation and other cardiovascular risk factors become more prevalent. Consequently, one can expect a rise in warfarin-related gastrointestinal haemorrhage. WHAT DOES THIS ARTICLE ADD?: Our study aimed to assess the burden of gastrointestinal haemorrhage secondary to warfarin on our surgical department (which was high), and also to assess what the risk factors for haemorrhage for patients on warfarin. One of the risk factors we uncovered was polypharmacy, particularly involving anti-platelets e.g. aspirin. We highlight the need for further guidance with regards to managing patients on warfarin, and suggest possible solutions to the problems uncovered.


Assuntos
Anticoagulantes/efeitos adversos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Inibidores da Agregação de Plaquetas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Varfarina/efeitos adversos , Carga de Trabalho , Fatores Etários , Idoso de 80 Anos ou mais , Feminino , Humanos , Coeficiente Internacional Normatizado , Tempo de Internação/estatística & dados numéricos , Masculino , Polimedicação , Fatores de Risco , Estatísticas não Paramétricas
10.
World J Gastroenterol ; 15(5): 612-4, 2009 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-19195065

RESUMO

Endometriosis is the ectopic growth of viable endometrium outside the uterus, affecting approximately 7% of females. It commonly affects pelvic structures including the bowel. Perforation of the colon by endometriosis is very rare and the patients generally present with an asymptomatic or painful pelvic mass, often in the left iliac fossa. Our patient presented acutely unwell and her symptoms were more suggestive of pyelonephritis or diverticulitis. We therefore report an unusual cause of acute abdomen. The purpose of the following case report is to elucidate certain diagnostic and therapeutic problems of the disease, concerning both surgeons and gynaecologists. In summary, intestinal endometriosis should be considered in the differential diagnosis of all post-menarche women with episodic gastrointestinal symptoms. A past history of endometriosis or co-existent gynaecological symptoms should increase the index of suspicion, and laparoscopy prior to formal laparotomy should be considered. Our patient, in retrospect, had a history of mild endometriosis, but we feel that this case serves as a reminder of a rare, but important, differential diagnosis of acute abdomen in females.


Assuntos
Doenças do Colo/etiologia , Endometriose/complicações , Enteropatias/complicações , Perfuração Intestinal/etiologia , Adulto , Doenças do Colo/patologia , Endometriose/patologia , Feminino , Humanos , Enteropatias/patologia , Mucosa Intestinal/patologia , Perfuração Intestinal/patologia
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