Biologics In Asthma Research Articles

Asthma and COVID-19 in the elderly: course, survival, predictors of mortality

Bronchial asthma occurs in 0.9 – 17% of patients hospitalized with COVID-19. However, it is not clear whether asthma is a risk factor for the development and severity of COVID-19. Studies have shown that patients with asthma appear to be more susceptible to COVID-19 infection, but severe disease progression is not related to medication use, including asthma biologics, but rather to older age and comorbidities.Aim.To evaluate the clinical course of SARS-CoV-2 infection in elderly patients with asthma, to examine the effect of asthma and comorbidities on COVID-19related outcomes, and to determine predictors of mortality.Methods.Elderly patients [WHO, 2020] (> 60 years,n= 131, median age 74 (67; 80) years; 59 men, 72 women) with asthma hospitalized for COVID-19 were included in the study. COVID-19 was confirmed by laboratory tests (PCR smear) and/or clinical and radiological examinations. All patients had a history of a documented diagnosis of asthma (GINA, 2020).Results.Out of 131 patients, 30 (22.9%) died in the hospital, and 15 (14.9%) died after discharge from the hospital (within 90 days). The group of patients with lethal outcome showed the following differences from those who recovered: values of Charlson index, respiration rate, degree of lung damage on CT scan, absolute number of leukocytes, neutrophils and neutrophils-to-lymphocytes ratio, C-reactive protein on the 5th day of hospitalization, and LDH were statistically significantly higher, while absolute number of eosinophils, total protein content, SpO2and SpO2/FiO2levels were lower; steroid intake during the year and non-atopic asthma were more common. Multivariate and ROC analysis revealed the most significant predictors of hospital mortality and their thresholds: Charlson comorbidity index ≥ 6 points, neutrophil/lymphocyte ratio ≥ 4.5, total protein ≤ 60 g/l, eosinophil level ≤ 100 cells/μL.Conclusion.The most significant predictors of hospital mortality in elderly patients with severe COVID-19 against asthma are Charlson comorbidity, neutrophil/lymphocyte ratio; lower eosinophil and total protein levels. Survival time of patients has an inverse correlation with the number of mortality risk factors present.

Perceptions on Home-Administration of Biologics in the Context of Severe Asthma: An International Qualitative Study

Biologics are an effective therapy for severe asthma. Home administration of biologics by patients is likely to facilitate their accessibility. Yet little is known about patients' and health care providers' (HCPs) perceptions regarding home administration of biologics. The aim of this study is to create more insight into the perceptions and experiences of patients and HCPs regarding home administration of biologics in the context of the treatment of severe asthma. A qualitative international study was performed in the Netherlands, United States, Australia, and United Kingdom. In each country, 2 focus groups were held with potential/recent and long-term users of biologics at home. Prior to the focus groups, patients were prompted with themes on online forums. For triangulation purposes, interviews were held with HCPs to discuss salient findings from forums and focus groups. Data were analyzed with qualitative content analysis. In total, 75 patients participated in the forums, of which 40 participated in the focus groups. Furthermore, 12 HCPs were interviewed. The following overarching themes were identified: living with severe asthma; practical aspects of using biologics; the role of HCPs regarding biologics; social support from family, friends, and others; effectiveness of biologics and other treatments; side effects of biologics. This study showed that, for those using biologics for severe asthma, the benefits of home administration of biologics usually outweigh inconvenience and side effects. Guided practice, accessible support contact, and monitoring including social support should be central in the transition from hospital to home administration of asthma biologics.

Development of methodology for assessing steroid-tapering in clinical trials for biologics in asthma

BackgroundLong-term use of oral corticosteroids (OCS) is associated with a risk of adverse events and comorbidities. As such, a goal in assessing the efficacy of biologics in severe asthma is often to monitor reduction in OCS usage. Importantly, however, OCS dose reductions must be conducted without loss of disease control.Main bodyHerein, we describe the development of OCS-sparing study methodologies for biologic therapies in patients with asthma. In particular, we focus on four randomized, placebo-controlled, parallel-group studies of varying sizes (key single-center study [n = 20], SIRIUS [n = 135], ZONDA [n = 220], VENTURE [n = 210]) and one open-label study (PONENTE [n = 598]), which assessed the effect of asthma biologics (mepolizumab, benralizumab or dupilumab) on OCS use using predefined OCS-tapering schedules. In particular, we discuss the evolution of study design elements in these studies, including patient eligibility criteria, the use of tailored OCS dose reduction schedules, monitoring of outcomes, the use of biomarkers and use of repetitive assessments of adrenal function during OCS tapering.ConclusionTaken together, these developments have improved OCS-sparing asthma studies in recent years and the lessons learned may help with optimization of further OCS-sparing studies, and potentially clinical practice in the future.

Efficacy of Biologics on Refractory Eosinophilic Otitis Media Associated with Bronchial Asthma or Severe Uncontrolled CRSwNP.

Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is resistant to conventional treatments and strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of our study is to evaluate the effectiveness of biologics drugs in the control of EOM. This is a retrospective no-profit real-life observational study, involving patients affected by refractory EOM and in treatment with different biologics for concomitant severe eosinophilic asthma or severe uncontrolled CRSwNP (Dupilumab: n = 5; Omalizumab: n = 1; Mepolizumab: n = 1; Benralizumab: n = 1). We analyzed data at baseline and at the 6-month follow-up, including specific nasal and otological parameters. We observed an improvement of all nasal outcomes, including NPS, SNOT-22, VAS, and smell function. Regarding specific otological parameters, we observed a significant reduction in the mean value of COMOT-15 score and of Otitis Severity Score at 6-month follow-up compared to baseline (p < 0.05). Finally, we observed an improvement in terms of air conduction hearing levels during the treatment. Our results demonstrated that anti type-2 inflammatory pathway biologics can be effective in improving symptoms control and in reducing the severity of eosinophilic otitis media when treating coexisting type-2 diseases, such as asthma and or CRSwNP.

Clinical Characteristics of Patients and Factors Associated with Switching Biologics in Asthma.

PurposeBiologics have been used increasingly for the treatment of severe asthma. However, established guidelines for the selection, switching, or discontinuation of biologics do not exist. We aimed to identify the clinical characteristics of patients with asthma who required switching biologics and the factors associated with switching biologics.Patients and MethodsThis was a retrospective study of 42 patients with severe asthma treated with biologics at the Hokkaido University Hospital between 23rd June 2016 and 30th April 2021, when two biologics were available in Japan. We compared the characteristics of subjects who continued and switched biologics. The time to switch the biologics was assessed by type 2 inflammatory biomarkers, pulmonary function indices, and the presence of comorbidities, including the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score and aspirin exacerbated respiratory diseases (AERD), using the Kaplan–Meier method and a multivariate Cox proportional hazards model.ResultsEight and five patients were treated by mepolizumab and benralizumab at baseline, respectively among the 31% (13/42) who switched the biologics. Subjects who required switching biologics were characterized by high blood eosinophil counts, younger age, JESREC scores of 11 points or higher, and AERD. The time taken to switch biologics was significantly shorter in the subgroups with high JESREC scores (≥11) or AERD, compared with their counterparts with low JESREC scores or without AERD (both, P < 0.05). JESREC scores of ≥11, but not the presence of AERD, were associated with time to switch biologics.ConclusionThe presence of eosinophilic chronic rhinosinusitis based on JESREC scores of ≥11 and younger age were factors associated with switching biologics in asthma.

Biologicals In Severe asthma – Stopping The Unstoppable

Various society guidelines recommend biologicals (Anti IgE Omalizumab or anti IL5 – Mepolizumab) as an add on therapy for management of severe asthma, but there is no consensus on stoppage of these drugs after obtaining good asthma control. COVID 19 pandemic with lockdowns led to unintentional & unavoidable interruption in administering these drugs and paved way for us to analyze the effects of stoppage of these biologicals in severe asthmatics well controlled on these drugs.

Pathways of Escalation to Asthma Biologics in Real-world Clinical Practice: an Analysis of US Claims Data

Current Global Initiative for Asthma (GINA) guidelines recommend a stepwise approach to asthma treatment. Patients recommended for step-up to biologics include those whose asthma is uncontrolled by high-dose inhaled corticosteroids/long-acting beta-agonists. We examined prior GINA step (GS), exacerbations, and asthma control among patients escalated to biologics during the 12-months prior to escalation.

Development and validation of explainable machine learning prediction model for asthma exacerbations in people who stop asthma biologics

Development and validation of explainable machine learning prediction model for asthma exacerbations in people who stop asthma biologics

Biologics in Severe Eosinophilic Asthma: Three-Year Follow-Up in a SANI Single Center.

Introduction: Biologic drugs have dramatically improved severe eosinophilic asthma (SEA) outcomes. Our aim was to evaluate the long-term efficacy of biological therapy in SEA in a real-life setting and to identify the predictors for switching to another biological drug in patients with poor asthma control. The outcomes for efficacy were decreased annual exacerbations (AE) and improved asthma control test (ACT). Methods: In 90 SEA patients being treated with a biological drug, clinical examination, ACT, blood eosinophils count and spirometry were assessed before (T0) and after 6 (T1), 12 (T2), 24 (T3) and 36 (T4) months from the start of biological therapy. Patients were considered responders (R) or non-responders (NR) to biologics depending on whether or not they had less than two AE and a 20% increase in the ACT after 12 months of treatment. Results: 75% of the patients were R, 25% NR. In R patients, biological therapy add-on was followed by significant improvement in AE and ACT throughout the whole follow-up period. The percentage of patients on oral corticosteroids (OCS) dropped from 40% to 12%. By contrast, the NR patients were shifted to another biological drug after 12 months of therapy, as they still had high AE and nearly unchanged ACT; 40% of them still needed OCS treatment. The predictors of switching to another biological drug were three or more AE, ACT below 17, nasal polyposis and former smoking (p < 0.05). In NR, the shift to another biological drug was followed by a significant decrease in AE and an increase in the ACT. Discussion: This real-life study confirms the long-term efficacy of biologics in most SEA patients and indicates that even in non-responders to a first biological drug, it is worth trying a second one. It is hoped that the availability of additional biologics with different targets will help improve the personalization of SEA therapy.

Utilizing Predictive Inflammatory Markers for Guiding the Use of Biologicals in Severe Asthma.

Asthma is a chronic respiratory disease characterized by chronic airway inflammation and airflow obstruction. Up to ten percent of asthmatics have severe asthma, and many remain uncontrolled despite optimal medical management. With our increased understanding of the heterogeneity of asthma and its complex pathophysiology, several biomarkers have been developed and in the recent past, several biologic therapies for severe asthma have been developed and are now in widespread use. Although these biological agents have shown great benefit in treating severe asthma, not all patients respond equally well, and some do not derive any benefit. As much of the current literature of these medications have not assessed biomarkers or have used different cutoffs, it is often challenging to decide the best medication for an individual patient. Here, we review common asthma subtypes, current available biologic therapies for asthma, the clinical application of currently available type 2 biomarkers, as well as summarizing the evidence on how patient characteristics and biomarkers can help with choosing the optimal biologic for a patient that has the highest likelihood of success.

Barrier Impairment and Type 2 Inflammation in Allergic Diseases: The Pediatric Perspective.

Allergic diseases represent a global burden. Although the patho-physiological mechanisms are still poorly understood, epithelial barrier dysfunction and Th2 inflammatory response play a pivotal role. Barrier dysfunction, characterized by a loss of differentiation, reduced junctional integrity, and altered innate defence, underpins the pathogenesis of allergic diseases. Epithelial barrier impairment may be a potential therapeutic target for new treatment strategies Up now, monoclonal antibodies and new molecules targeting specific pathways of the immune response have been developed, and others are under investigation, both for adult and paediatric populations, which are affected by atopic dermatitis (AD), asthma, allergic rhinitis (AR), chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic esophagitis (EoE). In children affected by severe asthma biologics targeting IgE, IL-5 and against IL-4 and IL-13 receptors are already available, and they have also been applied in CRSwNP. In severe AD Dupilumab, a biologic which inhibits both IL-4 and IL-13, the most important cytokines involved in inflammation response, has been approved for treatment of patients over 12 years. While a biological approach has already shown great efficacy on the treatment of severe atopic conditions, early intervention to restore epithelial barrier integrity, and function may prevent the inflammatory response and the development of the atopic march.

Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach.

In severe asthma with type 2 (T2) inflammation, biologics targeting key mediators of T2 inflammation, including interleukin (IL)-5, IL-4/IL-13, and immunoglobulin (Ig)E, remarkably improve the management of severe asthma, providing new insights into the clinical course of asthma such as disease modification and broad modulation of T2 inflammation. Once severe asthma has become a “controllable” condition, the question of discontinuation of biologics arises due to cost and side effects. The studies on discontinuing biologics in asthma demonstrate that some of patients successfully discontinue biologics, indicating that it is a feasible option in a subset of patients. Incorporating the evidence of discontinuation, we propose the criteria for the discontinuation of biologics. Our proposed criteria for the discontinuation of biologics consist of an absence of asthma symptoms (asthma control questionnaire [ACQ] score < 1.5 or asthma control test [ACT] score > 19), no asthma exacerbations, no use of oral corticosteroids, normalized spirometry (forced exhaled volume in 1 second [FEV1] ≥ 80%), suppressed T2 inflammation (blood eosinophil counts < 300 μL and fractional exhaled nitric oxide [FeNO] < 50 ppb), and control of asthma comorbidities. Real-world evidence verified a subset of patients achieving highly well-controlled conditions after use of biologics, namely super-responders, who are candidates for the discontinuation of biologics. If super-responders meet all of the criteria, they are allowed to discontinue biological therapies. Our proposed algorithm may support physicians’ treatment decisions for patients receiving biologics.

Paediatric Severe Asthma Biologics Service: From Hospital to Home

To assess whether biologics could be given safely at home in children with severe asthma, including measuring spirometry and quality of life.Children with severe asthma who had received omalizumab or mepolizumab and were willing to administer medication by supervised video calls in London, England, during the coronavirus disease 2019 pandemic from April to July 2020.In the study, children were identified who previously received at least 3 doses of biologics in the clinic or hospital setting safely with no reactions, were deemed suitable by a multidisciplinary team, and had no previous experience with home medication administration. Patients and their caretakers were trained for 1 to 2 hours, after which clinical nurse specialists virtually observed them during home medication administration. Patients and their families were given a home spirometer that measured forced expiratory volume in 1 second and forced vital capacity (FVC) to track asthma status. They were then managed every 2 to 4 weeks, with video calls to assist with medication dosing, assess asthma control, determine if oral corticosteroids (OCSs) were required or unscheduled health care visits, and determine general well-being the preceding 4 weeks.A total of 16 of 23 patients with a median age of 14.5 years (6 to 18 years) fulfilled the criteria for homecare and consented. A total of 14 adolescents independently completed home administration, and 2 required community nursing to administer the medication. Seven patients who did not participate in home administration served as the control group. Video calls with medication dosing were completed on 75 occasions. The drug was administered improperly on 2 of 75 occasions. Spirometry was used before each virtual appointment to assess asthma control. Patients and parents felt confident with video monitoring at the time of injection and felt relieved that they did not have to travel to the hospital for drug administration. Overall, patients felt monitoring devices were easy to use. Both Asthma Control Test and mini Pediatric Asthma Quality of Life Questionnaire scores improved within the first 3 months during home administration.Home administration of biologics with virtual monitoring is feasible and acceptable for patients and their families.Mepolizumab and omalizumab are available for home infusion for children ≥12. There is concern over which patients will be the “right” patient for this treatment method. Indeed, during the height of the coronavirus disease 2019 pandemic, home infusion options would have been beneficial. Although the number of patients with home infusions is small in this study, it does suggest a valuable combination of parameters to follow at home with a portable forced expiratory volume in 1 second meter and asthma control tests. Video supervision and telehealth is a practical option, ensures safety and support for families, and reinforces asthma medication adherence. Telehealth administration of biologics could reduce severe asthma attacks, increase patient satisfaction and convenience, and decrease the burden of coming to the hospital/clinic for the severe child with asthma.

Real-world Omalizumab and Mepolizumab Treated Difficult Asthma Phenotypes and Their Clinical Outcomes

To examine the real-world effectiveness of omalizumab and mepolizumab and better understand the clinical characteristics of real-world populations treated with these biologics.In the study, researchers included 478 patients from the Wessex Asthma Cohort recruited from a difficult to control asthma clinic in the United Kingdom. Patients were seen between June 2006 and May 2019. Inclusion criteria included patients on “high dose therapies” and/or “continuous or frequent use of oral corticosteroids.”This was a retrospective study of biological naïve patients with severe asthma. In the study, researchers compared 182 patients who started either omalizumab or mepolizumab and 178 patients who did not start biological therapy. Data concerning asthma control were collected at the baseline visit and each injection visit. The effectiveness of biologics was determined by using biological specific standard criteria.Omalizumab treated subjects were found to be younger and more ethnically diverse and had higher prevalence of rhinitis, allergic bronchopulmonary aspergillosis, and nasal polyps, compared with that of the mepolizumab or no biological treatment groups. Mepolizumab-treated subjects had greater eosinophilia and were diagnosed later in life. They also had more nasal polyps than the control group did. Both biological therapies significantly improved asthma control and reduced asthma exacerbations, acute health care encounters, and maintenance oral steroid dose. Patients in the nonresponder groups were evaluated and found to have worse baseline asthma control and greater prevalence of anxiety, when compared with biological responders.Omalizumab and mepolizumab both showed significant clinical benefit in real-world populations. Omalizumab patients were younger and more atopic. Mepolizumab patients were older with a less atopic phenotype. Nonresponders had more severe asthma at that baseline and more psychological comorbidities.It has been widely discussed that populations in clinical trials of asthma biologics are not representative of the full population that needs these therapies. In this cohort study, the authors evaluate the efficacy of these 2 biologics in real-world populations. There is no information on how the biological was selected, but, with this cohort, the authors still gives valuable information about the population characteristics and potential exacerbating factors in biological nonresponders. The authors also highlight that both omalizumab and mepolizumab were highly efficacious.

Asthma biologic trial eligibility and real-world outcomes in the United States

Objective To compare the outcomes of real-world patients who would have been eligible for asthma biologics to those who would not have been eligible. Methods We used data from the OptumLabs Data Warehouse (OLDW) to categorize patients into eligible and ineligible groups based on clinical trials (n = 19 trials) used for Food and Drug Administration (FDA) approval. We then compared the change in the number of asthma exacerbations before and after biological initiation between the two groups. Results The percentage of people who would have been eligible for asthma biologic clinical trials ranged from 0–10.2%. The eligible group had a greater reduction in number of asthma exacerbations compared to the ineligible group based on eligibility criteria from 1 omalizumab trial (1.52, 95% CI 1.25, 1.8 in eligible vs. 0.47, 95% CI 0.43, 0.52 in ineligible) and from 1 dupilumab trial (1.6, 95% CI 0.92, 2.28 in eligible vs. 0.52, 95% CI 0.38, 0.65 ineligible). Notably, 15 of the 19 trials had fewer than 11 eligible people, limiting additional comparisons. Conclusions Fewer than 1 in 10 people in the United States treated with asthma biologics would have been eligible to participate in the trial for the biologic they used. Where comparisons could be made, trial eligible people have a greater reduction in exacerbations. Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2010749 .

Difficult-to-Treat Asthma Management in School-Age Children

The World Health Organization divides severe asthma into three categories: untreated severe asthma; difficult-to-treat severe asthma; and severe, therapy-resistant asthma. The apparent frequency of severe asthma in the general population of asthmatic children is probably around 5%. Upon referral of these children, it is important to evaluate the diagnosis of asthma carefully before modifying management and applying a long-term monitoring plan. Identification of pathophysiologic phenotypes using objective biomarkers is essential in our routine assessments of severe asthma. Although conventional pharmacologic approaches should be attempted first, there is growing recognition that children with difficult-to-treat asthma may have unique clinical phenotypes that may necessitate alternative treatment approaches including asthma biologics. These new medications, especially those with effects on multiple pathologic features of asthma, raise the hope that new treatment strategies could induce remission. Besides introducing new medications, the opportunity for closer monitoring is feasible with advances in digital health. Therefore, we have the opportunity to improve response to medications, individualize treatment, and monitor response along with potential steps to prevent severe asthma.

Biologics for Asthma and Allergic Skin Diseases in Children.

An estimated 7 million children in the United States have asthma, which causes a significant health care burden and affects quality of life. The minority of these children have asthma that does not respond to Global Initiative for Asthma steps 4 and 5 care, and biological medications are recommended at this level in the 2019 Global Initiative for Asthma recommendations. In addition, biologics have been introduced into the care of children with allergic skin diseases. Omalizumab and mepolizumab are approved for children as young as 6 years, and benralizumab and dupilumab are approved for people aged ≥12 years. Reslizumab is approved only for people aged ≥18 years. These monoclonal antibodies may be added for appropriate patients when asthma or allergic skin diseases are not well controlled. Pediatricians and pediatric subspecialists should work together and be aware of the benefits and risks of these medications for their patients, as well as the practical implications of providing these options for their patients. This clinical report serves as an evaluation of the current literature on these types of medications in the treatment of children with asthma and allergic skin disease.

P9‐29: Bone mineral density can be one of the predictors of response to biologics in severe asthma

P9‐29: Bone mineral density can be one of the predictors of response to biologics in severe asthma

Real-world benefits of biologics for asthma: Exacerbation events and systemic corticosteroid use

BackgroundStudies have shown the efficacy of asthma biologics in real-world settings, confirming the generalizability of randomized controlled trial (RCT) results, but studies on more than one biologic are scarce. Accordingly, little is known about the different background characteristics in users of asthma biologics. This study aimed to describe the backgrounds of asthma patients using biologics (omalizumab, mepolizumab, benralizumab, and dupilumab) and examine the effectiveness of these biologics for reducing asthma exacerbations and total systemic corticosteroid doses. MethodsWe conducted a retrospective cohort study using self-controlled methods to evaluate the association between the use of biologics and reduction in exacerbations and hospitalizations using a large-scale health insurance claims database in Japan. ResultsOf 355 continuously treated asthma patients using biologics, 119, 82, 69, and 85 patients were assigned to the omalizumab, mepolizumab, benralizumab, and dupilumab groups, respectively. The baseline characteristics differed among users of biologics. The incidence ratios of exacerbations and hospitalizations during biologics use were 0.68 (95% confidence interval, 0.62–0.74) and 0.65 (0.55–0.77) compared with the period before biologics use. The total systemic corticosteroid dose equivalent to prednisolone per person-year was reduced from a median of 600 [interquartile range, 90–1713] mg to 164 [0–1010] mg (P < .001). Similar results were obtained for individual biologics with a few exceptions. ConclusionsThe background characteristics of biologics users differed in a real-world setting. Our results confirmed findings from RCTs demonstrating that each biologic (omalizumab, mepolizumab, benralizumab, and dupilumab) is associated with decreased exacerbation numbers and corticosteroid-sparing effects, even outside of the controlled settings of RCTs.

Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma.

Anti-interleukin-13 and anti-interleukin-4 agents versus placebo, anti-interleukin-5 or anti-immunoglobulin-E agents, for people with asthma.