Reslizumab in the management of poorly controlled asthma: the data so far.
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ABSTRACT:
SUBMITTER: Maselli DJ
PROVIDER: S-EPMC5012840 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Reslizumab in the management of poorly controlled asthma: the data so far.
Maselli Diego Jose DJ Velez Maria Ines MI Rogers Linda L
Journal of asthma and allergy 20160831
Interleukin-5, an important cytokine in the pathophysiology of asthma, participates in terminal maturation and increases chemotaxis, endothelial adhesion, and activation of eosinophils. Blockade of interleukin-5 activity with monoclonal antibodies have been successful in decreasing eosinophil counts. Reslizumab, a monoclonal antibody that targets interleukin-5, has been studied for the treatment of severe asthma. Several studies have shown that reslizumab can effectively treat severe asthma with ...[more]
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Project description:Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem - with considerable effect on morbidity, mortality, as well as a high burden on health care resources. Regardless of effective treatments being widely available and the existence of treatment guidelines, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients is, therefore, of utmost importance. The recognition of distinct inflammatory phenotypes within this population has driven the development of targeted biological therapies - particularly, selective targeted monoclonal antibodies (mAbs). It is noteworthy that in approximately 50% of these patients, there is strong evidence of the pathogenic role of T helper type-2 (Th2) cytokines, such as interleukin (IL)-4 and IL-13, orchestrating the eosinophilic and allergic inflammatory processes. Among the recently developed antiasthma biologic drugs, the mAb dupilumab is very promising given its ability to inhibit the biological effects of both IL-4 and IL-13. In this review, we focused on IL-4 and IL-13, as these interleukins are considered to play a key role in the pathophysiology of asthma, and on dupilumab, an anti-IL-4 receptor human mAb, as a forthcoming treatment for uncontrolled severe asthma in the near future.
| S-EPMC5589101 | biostudies-literature
Project description:Patients with severe eosinophilic asthma have an unmet need for novel and efficacious treatments. Reslizumab is one of the three monoclonal antibodies targeting the IL-5 pathway and has been found in Phase IIIb clinical trials to reduce asthma exacerbations, control asthma-related symptoms and improve pulmonary function in patients with eosinophilic asthma.In this article, we discuss the results of asthma clinical trials using reslizumab, beginning with a discussion of the relationship between eosinophils, IL-5 and asthma. We conducted PubMed searches using the terms 'reslizumab', 'anti-IL-5', 'eosinophilic asthma', 'IL-5 asthma'. We also searched ClinicalTrials.gov for 'reslizumab', 'reslizumab asthma', 'SCH 55700', 'SCH 55700 asthma', 'Cinquil' and 'Cinquil asthma'.Reslizumab and other anti-IL-5 therapies have seen success in recent trials through more stringent study participant selection targeting eosinophilic inflammation. This selection can now be based on simple blood counts. These drugs have shown a very good safety profile, but long-term safety data are not yet available. Approval for these drugs is eagerly awaited by clinicians and patients alike.
| S-EPMC5161345 | biostudies-other
Project description:Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control.To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.The Study of Acid Reflux in Children With Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization.Participating children were randomly assigned to receive either lansoprazole, 15 mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n = 149), or placebo (n = 157).The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control.The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, -0.1 to 0.1 L), asthma-related quality of life (-0.1; 95% CI, -0.3 to 0.1), or rate of episodes of poor asthma control (relative risk, 1.2; 95% CI, 0.9-1.5). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]).In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events.clinicaltrials.gov Identifier: NCT00442013.
| S-EPMC4153372 | biostudies-literature
Project description:BackgroundGastroesophageal reflux is common among patients with asthma but often causes mild or no symptoms. It is not known whether treatment of gastroesophageal reflux with proton-pump inhibitors in patients who have poorly controlled asthma without symptoms of gastroesophageal reflux can substantially improve asthma control.MethodsIn a parallel-group, double-blind trial, we randomly assigned 412 participants with inadequately controlled asthma, despite treatment with inhaled corticosteroids, and with minimal or no symptoms of gastroesophageal reflux to receive either 40 mg of esomeprazole twice a day or matching placebo. Participants were followed for 24 weeks with the use of daily asthma diaries, spirometry performed once every 4 weeks, and questionnaires that asked about asthma symptoms. We used ambulatory pH monitoring to ascertain the presence or absence of gastroesophageal reflux in the participants. The primary outcome was the rate of episodes of poor asthma control, as assessed on the basis of entries in asthma diaries.ResultsEpisodes of poor asthma control occurred with similar frequency in the placebo and esomeprazole groups (2.3 and 2.5 events per person-year, respectively; P=0.66). There was no treatment effect with respect to individual components of the episodes of poor asthma control or with respect to secondary outcomes, including pulmonary function, airway reactivity, asthma control, symptom scores, nocturnal awakening, or quality of life. The presence of gastroesophageal reflux, which was documented by pH monitoring in 40% of participants with minimal or no symptoms, did not identify a subgroup of patients that benefited from treatment with proton-pump inhibitors. There were fewer serious adverse events among patients receiving esomeprazole than among those receiving placebo (11 vs. 17).ConclusionsDespite a high prevalence of asymptomatic gastroesophageal reflux among patients with poorly controlled asthma, treatment with proton-pump inhibitors does not improve asthma control. Asymptomatic gastroesophageal reflux is not a likely cause of poorly controlled asthma. (ClinicalTrials.gov number, NCT00069823.)
| S-EPMC2974569 | biostudies-literature
Project description:BackgroundObesity increases asthma risk, and may alter asthma severity. In adults, sex appears to modify the effect of obesity on asthma. Among children, the effect of sex on the relationship between obesity and asthma severity remains less clear, particularly when considering race.ObjectiveTo determine how obesity affects disease characteristics in a diverse cohort of children with poorly controlled asthma, and if obesity effects are altered by sex.DesignWe analyzed 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month trial assessing lansoprazole for asthma control. In this secondary analysis, we determined associations between obesity and symptom severity, spirometry, exacerbation risk, airway biomarkers, bronchial reactivity, and airflow perception. We used both a multivariate linear regression and longitudinal mixed-effect model to determine if obesity interacted with sex to affect asthma severity.ResultsRegardless of sex, BMI >95th percentile did not affect asthma control, exacerbation risk or airway biomarkers. Sex changed the effect of obesity on lung function (sex × obesity FEV1%, interaction P-value < 0.01, sex × obesity FEV1/FVC, interaction P-value = 0.03). Obese males had significantly worse airflow obstruction compared to non-obese males, while in females there was no obesity effect on airflow obstruction. In females, obesity was associated with significantly greater FEV1 and FVC, and a trend toward reduced airway reactivity.ConclusionsObesity did not affect asthma control, airway markers or disease stability; however obesity did affect lung function in a sex-dependent manner. In males, obesity associated with reduced FEV1/FVC, and in females, obesity associated with substantially improved lung function.
| S-EPMC3578966 | biostudies-literature
Project description:BackgroundVery poorly controlled (VPC) asthma in children is associated with ongoing acute exacerbations but factors associated with VPC are understudied.ObjectiveTo examine the risk factors associated with VPC asthma in urban minority children.MethodsThis descriptive study examined asthma control levels (well-controlled [WC], not well-controlled [NWC], and VPC) at baseline and 6 months in children participating in an ongoing randomized controlled trial of an emergency department/home environmental control intervention. Data collection occurred during the index emergency department visit and included allergen-specific IgE and salivary cotinine testing and caregiver interview of sociodemographic and child health characteristics. Follow-up data were collected at 6 months. Unadjusted analyses examined the association of sociodemographic and health characteristics by level of asthma control. Multivariate analysis tested significant factors associated with VPC asthma at 6 months.ResultsAt baseline most children were categorized with VPC asthma (WC, 0%; NWC, 47%; VPC, 53%) and rates of VPC minimally improved at 6 months (WC, 13%; NWC, 41%; VPC, 46%). Risk for VPC asthma was twice as likely in children with allergic rhinitis (odds ratio [OR], 2.42), having 2 or more primary care provider asthma visits within the past 3 months (OR, 2.77), or caregiver worry about medication side effects (OR, 2.13) and 3 to 4 times more likely when asthma control was assessed during the fall or spring season (OR: fall, 3.32; spring, 4.14).ConclusionsImproving asthma control in low-income, high-risk children with VPC asthma requires treatment of comorbidities, attention to caregiver medication beliefs, and adept use of stepwise therapy.
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Project description:Poor adherence to asthma controller medications results in poor treatment outcomes.To compare controller medication adherence and clinical outcomes in 612 adults with poorly controlled asthma randomized to one of two different treatment decision-making models or to usual care.In shared decision making (SDM), nonphysician clinicians and patients negotiated a treatment regimen that accommodated patient goals and preferences. In clinician decision making, treatment was prescribed without specifically eliciting patient goals/preferences. The otherwise identical intervention protocols both provided asthma education and involved two in-person and three brief phone encounters.Refill adherence was measured using continuous medication acquisition (CMA) indices-the total days' supply acquired per year divided by 365 days. Cumulative controller medication dose was measured in beclomethasone canister equivalents. In follow-up Year 1, compared with usual care, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.46; P < 0.0001) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.40; P = 0.0225); higher cumulative controller medication dose (canister equivalent, 10.9 vs. 5.2; P < 0.0001); significantly better clinical outcomes (asthma-related quality of life, health care use, rescue medication use, asthma control, and lung function). In Year 2, compared with usual care, SDM resulted in significantly lower rescue medication use, the sole clinical outcome available for that year. Compared with clinician decision making, SDM resulted in: significantly better controller adherence (CMA, 0.67 vs. 0.59; P = 0.03) and long-acting beta-agonist adherence (CMA, 0.51 vs. 0.41; P = 0.0143); higher cumulative controller dose (CMA, 10.9 vs. 9.1; P = 0.005); and quantitatively, but not significantly, better outcomes on all clinical measures.Negotiating patients' treatment decisions significantly improves adherence to asthma pharmacotherapy and clinical outcomes. Clinical trials registered with www.clinicaltrials.gov (NCT00217945 and NCT00149526).
| S-EPMC2841026 | biostudies-literature
Project description:BackgroundMorbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.MethodsWe conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.ResultsWhen quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.ConclusionsIn contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).
| S-EPMC7026584 | biostudies-literature
Project description:Asthma is the most common non-communicable pulmonary condition, affecting prepubertal boys more often than girls. This study explored how maternal and perinatal risk factors are linked to poorly controlled childhood asthma in a sex dependent manner. This single centre study was performed at a metropolitan teaching hospital in Western Sydney, Australia, using electronical obstetric records from 2000 to 2017 and electronical pediatric records from 2007 to 2018. The data of 1694 children with complete entries were retrospectively analysed. Risk factors for multiple hospital admission for asthma were selected by backward-eliminated Poisson regression modelling. Selection stability of these parameters was independently confirmed using approximated exhaustive search. Sex-specific regression models indicated that most notably parity (RR[95%CI] for parity = 3; 1.85[1.22-2.81]), birth length z-score (1.45[1.23-1.70]) and birth weight z-score (0.77[0.65-0.90]) contributed to multiple asthma admissions in girls, while boys were affected most prominently by maternal BMI (e.g. BMI 35-39.9; 1.92[1.38-2.67]) and threatened preterm labor (1.68[1.10-2.58]). Allergic status was a risk factors for both boys and girls (1.47[1.18-1.83] and 1.46[1.13-1.89]). Applying ROC analysis, the predictive modelling of risk factors for hospital admissions showed an incremental increase with an AUC of 0.84 and 0.75 for girls and boys respectively for >3 hospital admissions. Multiple hospital admissions for asthma are associated with maternal and perinatal risk factors in a sex and birth order dependent manner. Hence, prospective risk stratification studies aiming to improve childhood asthma control are warranted to test the clinical utility of these parameters. Furthermore, the influence of the early in utero environment on male-female differences in other communicable and non-communicable respiratory conditions should be considered.
| S-EPMC8158992 | biostudies-literature