Hugo Neffen

Efficacy and Safety of Subcutaneous Omalizumab vs Placebo as Add-on Therapy to Corticosteroids for Children and Adults With Asthma: A Systematic Review

BACKGROUND Omalizumab is a humanized monoclonal anti-IgE for the treatment of severe allergic asthma. Because omalizumab targets an immune system molecule, there has been particular interest in the drugs safety. METHODS To establish the efficacy and safety of subcutaneous omalizumab as add-on therapy to corticosteroids, a systematic review of placebo-controlled studies was performed. Primary outcomes were reduction of steroid use and asthma exacerbations. Secondary outcome measures included lung function, rescue medication use, asthma symptoms, health-related quality of life, and adverse effects. RESULTS Eight trials (3,429 participants) fulfilled the selection criteria. At the end of the steroid-reduction phase, patients taking omalizumab were more likely to be able to withdraw from corticosteroids completely compared with those taking placebo (relative risk [RR] = 1.80; 95% CI, 1.42-2.28; P = .00001). Omalizumab patients showed a decreased risk of asthma exacerbations at the end of the stable (RR = 0.57; 95% CI, 0.48-0.66; P = .0001) and adjustable-steroid phases (RR = 0.55; 95% CI, 0.47-0.64; P = .0001); post-hoc analysis suggests this effect was independent of duration of treatment, age, severity of asthma, and risk of bias. The frequency of serious adverse effects was similar in the omalizumab (3.8%) and placebo (5.3%) groups. However, injection site reactions were more frequent in the omalizumab patients (19.9% vs 13.2%). There were no indications of increased risk of hypersensitivity reactions, cardiovascular effects, or malignant neoplasms. CONCLUSIONS Data indicate that the efficacy of add-on omalizumab in patients with moderate-to-severe allergic asthma is accompanied by an acceptable safety profile.

Asthma control in Latin America: the Asthma Insights and Reality in Latin America (AIRLA) survey

OBJECTIVES The aims of this survey were (1) to assess the quality of asthma treatment and control in Latin America, (2) to determine how closely asthma management guidelines are being followed, and (3) to assess perception, knowledge and attitudes related to asthma in Latin America. METHODS We surveyed a household sample of 2,184 adults or parents of children with asthma in 2003 in 11 countries in Latin America. Respondents were asked about healthcare utilization, symptom severity, activity limitations and medication use. RESULTS Daytime asthma symptoms were reported by 56% of the respondents, and 51% reported being awakened by their asthma at night. More than half of those surveyed had been hospitalized, attended a hospital emergency service or made unscheduled emergency visits to other healthcare facilities for asthma during the previous year. Patient perception of asthma control did not match symptom severity, even in patients with severe persistent asthma, 44.7% of whom regarded their disease as being well or completely controlled. Only 2.4% (2.3% adults and 2.6% children) met all criteria for asthma control. Although 37% reported treatment with prescription medications, only 6% were using inhaled corticosteroids. Most adults (79%) and children (68%) in this survey reported that asthma symptoms limited their activities. Absence from school and work was reported by 58% of the children and 31% of adults, respectively. CONCLUSIONS Asthma control in Latin America falls short of goals in international guidelines, and in many aspects asthma care and control in Latin America suffer from the same shortcomings as in other areas of the world.

Comparison of Indacaterol With Tiotropium or Twice-Daily Long-Acting β-Agonists for Stable COPD: A Systematic Review

BACKGROUND Bronchodilators are central to the symptomatic management of patients with COPD.Previous data have shown that inhaled indacaterol improved numerous clinical outcomes over placebo. METHODS This systematic review explored the efficacy and safety of indacaterol in comparison with tiotropium or bid long-acting β 2 -agonists (TD-LABAs) for treatment of moderate to severe COPD. Randomized controlled trials were identified after a search of different databases of published and unpublished trials. RESULTS Five trials (5,920 participants) were included. Compared with tiotropium, indacaterol showed statistically and clinically significant reductions in the use of rescue medication and dyspnea(43% greater likelihood of achieving a minimal clinically important difference [MCID] in the transitional dyspnea index [TDI]; number needed to treat for benefit [NNTB] 5 10). Additionally,the MCID in health status was more likely to be achieved with indacaterol than with tiotropium (OR = 1.43; 95% CI, 1.22–1.68; P = .00001; [NNTB ]= 10). Trough FEV 1 was significantly higher at the end of treatment with indacaterol than with TD-LABAs (80 mL, P = .00001). Similarly, indacaterol signifi cantly improved dyspnea (61% greater likelihood of achieving an MCID in TDI, P = .008) and health status (21% greater likelihood of achieving an MCID in St. George’s Respiratory Questionnaire, P 5 .04) than TD-LABA. Indacaterol showed similar levels of safety and tolerability to both comparators. CONCLUSIONS Available evidence suggests that indacaterol may prove useful as an alternative to tiotropium or TD-LABA due to its effects on health status, dyspnea, and pulmonary function.

Allergen immunotherapy on the way to product-based evaluation—a WAO statement

Allergen immunotherapy (AIT) is widely used in clinical practice for patients with moderate to severe allergic rhinitis due to inhalant allergens and may be delivered via subcutaneous (SCIT) and sublingual routes (SLIT). However, the quality of evidence for individual AIT products is very heterogeneous, and extensions of overall conclusions (“class effects”) on the efficacy and disease-modifying effects to all AIT products are unjustified. In contrast, each product needs to be evaluated individually, based on available study results, to justify efficacy and specific claims on sustained and disease modifying effects per allergen and targeted patient group (children vs. adults, allergic rhinitis vs. asthma). WAO intends to support the current development to evidence-based AIT, which ultimately will lead to a more efficacious treatment of allergic patients and the appropriate recognition of AIT.

Reliability and factor analysis of the Spanish version of the Asthma Control Test

BACKGROUND The Asthma Control Test (ACT) has been developed to evaluate asthma control and to reflect its nature. A Spanish version of the test has been widely disseminated to physicians, but it has not yet been validated. OBJECTIVES To examine the psychometric properties of the Spanish version of the ACT. METHODS A total of 322 asthmatic patients with a mean (SD) age of 43.8 (17.3) years (range, 12-84 years) with appropriate criteria for inclusion completed the ACT. Spirometric variables were measured and asthma severity was rated by physicians. RESULTS Internal consistency reliability was 0.79. The ACT showed weak correlation coefficients with forced expiratory volume in 1 second (FEV1) (p = 0.27; P = .01) and asthma severity (p = -0.19; P = .01). Almost 40% of patients with an FEV1 less than 60% of predicted rated their asthma as well or totally controlled; conversely, 70% of patients with asthma well or totally controlled showed an FEV1 less than 80% of predicted. The factor analysis revealed a 2-factor solution: the first component included the 5 items of the ACT (subjective component), and the second component included the spirometric measures (objective component). The 2-factor solution accounted for 66.2% of the total variance. CONCLUSIONS These data reveal a unidimensional structure of the ACT and do not support the use of this test without spirometry in the management of asthma. Spirometry provides important complementary information about asthma severity that may be used in conjunction with clinical assessments of controlto provide optimal management in many patients.

Systematic review on the use of omalizumab for the treatment of asthmatic children and adolescents

There are less data on omalizumab treatment in pediatric asthma than in adult population. Thus, to establish the efficacy and safety of subcutaneous omalizumab as an add‐on therapy, a systematic review of placebo‐controlled studies was performed.

Guía ALERTA 2. América Latina y España: Recomendaciones para la prevención y el Tratamiento de la exacerbación Asmática

aDepartamento de Emergencia, Hospital Central de las Fuerzas Armadas, Montevideo, Uruguay; Departamento de Asma de la Asociacion Latinoamericana del Torax (2006-2008), Montevideo, Uruguay bServicio de Neumologia, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Area de Asma de la Sociedad Espanola de Neumologia y Cirugia Toracica, Barcelona, Espana cUnidad de Neumologia, Hospital de Mataro, Sociedad Espanola de Neumologia y Cirugia Toracica, Barcelona, Espana dEscuela de Medicina, Pontificia Universidad Catolica de Chile, Asociacion Latinoamericana del Torax, Santiago, Chile eServicio de Neumologia, Hospital Universitario La Fe, Valencia, Espana, Sociedad Espanola de Neumologia y Cirugia Toracica, Barcelona, Espana fServicio de Neumologia Pediatrica, Hospital de Nens de Barcelona, Sociedad Espanola de Neumologia y Cirugia Toracica, Barcelona, Espana gServicio de Neumologia, Hospital Universitario 12 de Octubre, Madrid, Espana, Sociedad Espanola de Neumologia y Cirugia Toracica, Barcelona, Espana hSeccion de Neumonologia, Hospital G. Baigorria, Universidad Nacional de Rosario, Asociacion Latinoamericana del Torax, Santa Fe, Argentina iUnidad de Medicina Respiratoria, Hospital de Ninos O. Alassia, Asociacion Latinoamericana del Torax, Santa Fe, Argentina jInstituto Nacional de Enfermedades Respiratorias, Departamento de Asma de la Asociacion Latinoamericana del Torax (2008-2010), Mexico DF, Mexico

The study of severe asthma in Latin America and Spain (1994-2004): characteristics of patients hospitalized with acute severe asthma

OBJECTIVE Studies assessing the characteristics and management of patients hospitalized with asthma have been limited to a small number of facilities and have evaluated short time periods. The present study evaluated long-term changes among hospitalized asthma patients at a large number of facilities. METHODS This was a retrospective, hospital-based observational case series, designated the Study of Severe Asthma in Latin America and Spain, which was conducted in Spain and in eight Latin-American countries. We reviewed the hospital records of 3,038 patients (age range, 15-69 years) hospitalized with acute severe asthma at one of nineteen tertiary-care hospitals in 1994, 1999 and 2004. RESULTS Over time, the use of inhaled corticosteroids and long-acting beta2 agonists increased significantly, whereas the use of theophylline as a controller medication decreased. The utilization of pulmonary function tests also increased. There was a significant reduction in the mean hospital stay (8.5 days, 7.4 days and 7.1 days in 1994, 1999 and 2004, respectively, p = 0.0001) and a significant increase in the mean of the lowest arterial pH at hospital admission. In contrast, there was a significant decrease in the proportion of cases in which PEF was determined in the emergency room (48.6% in 1994 vs. 43.5% in 2004, p = 0.0001). We found the quality of asthma management and care to be generally better in Spain than in Latin America. CONCLUSIONS Although there have been certain improvements in the management of asthma between severe exacerbations and during hospitalization, asthma management remains suboptimal in Spain and, especially, in Latin America.

A Systematic Review of the Efficacy and Safety of a Fixed-Dose Combination of Umeclidinium and Vilanterol for the Treatment of COPD

BACKGROUND COPD guidelines recommend the combined use of inhaled long-acting β2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) if symptoms are not improved by a single agent. This systematic review tested the hypothesis that the bronchodilator effect of the LABA/LAMA combination, umeclidinium (UMEC)/vilanterol (VIL), would translate into better outcomes without incurring increased adverse events (AEs). METHODS This was a systematic review of randomized, placebo-controlled or crossover trials (> 4 weeks) involving UMEC/VIL compared with its monocomponents, tiotropium, or fluticasone/salmeterol. Primary outcomes were trough FEV1, serious adverse events (SAEs), and serious cardiovascular events (SCVEs). RESULTS Eleven trials from 10 studies (9,609 patients) showed that UMEV/VIL provided superior improvements in lung function compared with UMEC, VIL, tiotropium, and fluticasone propionate/salmeterol (mean trough FEV1, 60, 110, 90, and 90 mL, respectively; P < .0001). Also, UMEC/VIL had a greater likelihood of demonstrating a minimal clinically important difference on the Transition Dyspnea Index compared with UMEC and VIL (number needed to treat for benefit [NNTB] = 14 and 10, respectively). UMEC/VIL therapy significantly reduced the risk of COPD exacerbations compared with UMEC and VIL (NNTB = 42 and 41, respectively). On the contrary, we noted no significant differences between UMEC/VIL and tiotropium with respect to dyspnea, health status, or risk of COPD exacerbation. Regarding safety issues, the incidence of AEs, SAEs, SCVEs, and mortality on treatment was similar across treatments, suggesting reduced safety concerns with the use of the UMEC/VIL combination. CONCLUSIONS Once-daily inhaled UMEC/VIL showed superior efficacy compared with its monocomponents, tiotropium, and fluticasone/combination in patients with moderate to severe COPD.

Asthma-chronic obstructive pulmonary disease overlap syndrome: a controversial concept.

Purpose of review To illustrate the scant evidence and the shortcomings of the concept of ‘asthma-COPD overlap syndrome’ (ACOS) in terms of clinical utility. Recent findings Asthma and chronic obstructive pulmonary disease (COPD) are considered as two distinct and heterogeneous diseases. For many years, physicians have been aware that asthma and COPD can coexist in some patients. Recently, the term ACOS has been applied when a person has clinical features of both asthma and COPD. However, the lack of an accurate diagnosis has led to inconsistent data regarding reported prevalence, prognosis and therapeutics. Even today, it has not been possible to establish a phenotypic characterization of ACOS, although it is part of the overall complexity and heterogeneity of COPDs. No high quality data exist on which to base treatment recommendations for ACOS. Consequently, in clinical practice, treatment is extrapolated from the available evidence on asthma and COPD. Summary The current concept of ACOS seems clinically irrelevant because it has no influence on the prognosis and treatment of these patients. The authors concluded that the term ACOS should be avoided in the case of patients with features of both asthma and COPD.