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[Display omitted] Switching biologics is now common practice in severe eosinophilic asthma. After insufficient response to anti–IL-5 or 5 receptor (anti–IL-5/5R), the optimal switch between an anti–IL-4R mAb (interclass) or another anti–IL-5/5R drug (intraclass) remains unknown. We sought to compare the effectiveness of these 2 strategies in asthma control in patients with severe eosinophilic asthma and insufficient response to an anti–IL-5/5R mAb. We emulated a target randomized trial using observational data from the Recherche sur les AsthMes SEvèreS (RAMSES) cohort. Eligible patients were switched to an anti–IL-4R mAb or another anti–IL-5/5R drug after insufficient response to an anti–IL-5/5R mAb. The primary outcome was the change in Asthma Control Test score at 6 months. Among the 2046 patients in the cohort, 151 were included in the study: 103 switched to an anti–IL-4R mAb and 48 to another anti–IL-5/5R. At 6 months, the difference in Asthma Control Test score improvement was not statistically significant (mean difference groups, 0.82 [−0.47 to 2.10], P =.213). The interclass group exhibited greater cumulative reduction in oral corticosteroid dose (P inter-intra , −1.05 g [−1.76 to −0.34], P =.041). The interclass group had a better effect, although not significantly, on reducing exacerbations (Δ inter-intra , −0.37 [−0.77 to 0.02], P =.124) and increasing lung function (FEV 1) (126.8 mL [−12.7 to 266.4], P =.124). After anti–IL-5/5R mAb insufficient response, switching to dupilumab demonstrated similar improvement in Asthma Control Test scores compared with intraclass switching. However, it appeared more effective in reducing oral corticosteroid use. Larger studies are warranted to confirm these results. [ABSTRACT FROM AUTHOR]

Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. The patients in the PoB group had reduced SARS-CoV-2–specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways. [ABSTRACT FROM AUTHOR]

Although sporadic case reports have demonstrated successful management of eosinophilic granulomatosis with polyangiitis (EGPA) by anti-IL-5 therapy, larger-scale monocentric studies for the efficacy of mepolizumab (MEP), an IL-5 monoclonal antibody, are still lacking in Taiwan. Hospitalized EGPA patients aged at least 18 years were enrolled from November 1998 to October 2023, and analyzed for demographic, clinical, laboratory, medication and outcome data, focusing on the efficacy and safety of biologics use, particularly induction therapy with MEP. Twenty-seven EGPA patients aged 10–70 years (43 ± 15) at disease diagnosis were recruited with 21 under combined corticosteroids/cyclophosphamide induction therapy. Seventeen patients received biologics with 13 under MEP therapy. Ten patients aged 19–71 years (48 ± 15) completed 12-month induction therapy with a 100 mg quadri-weekly subcutaneous injection regimen indicated for active or relapse disease. There were reduced BVAS with complete remission in 6 and partial remission in 4 patients, lower CRP levels, decreased eosinophil counts with an inhibition of 92∼96 %, and tapered prednisolone dosages from 5 to 25 (13.0 ± 6.3) to 0–10 (3.3 ± 3.1) mg/day. Only one patient had an adverse event of injection site reactions. Nine patients received the same regimen for annual maintenance therapy. All had a persistent clinical remission. In these patients, 13–56 injections (41 ± 15) were prescribed with a follow-up period of 12∼52 months (38 ± 14). In this retrospective study, induction therapy with a 12-month 100 mg MEP quadri-weekly subcutaneous injection regimen demonstrates the efficacy and safety for active and relapsing EGPA patients. [ABSTRACT FROM AUTHOR]

This paper aims to review biologies in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in detail. The search is performed in "Pubmed," "Google," Google Scholar" and EBSCO Academic Search Ultimate (EKUAL) database of Kırıkkale University Library from 2021 to 2000, and randomized and/or placebo-controlled studies, review papers, meta-analysis, and reports are taken into consideration. The search was performed with the keywords of "allergic rhinitis," "biologics," "biologic agents," "Omalizumab," "Dupilumab," "Mepolizumab," "Reslizumab," "Benralizumab," "Anti IgE," "Anti-IL-4/IL-13", "Anti IL-5". Search is also performed in the "U.S. Food and Drug Administration" (FDA) and "European Medicines Agency" (EMA) web systems. Biological agents such as monoclonal antibodies (MAb) in treatment are called biological therapy or biotherapy. Omalizumab is a humanized Anti-IgE monoclonal antibody. Omalizumab treatment improved the Daily Nasal Rescue Medication Score (DNSSS) and decreased the use of antiallergic drugs in seasonal and perennial AR and rhino-conjunctivitis. Omalizumab is also used in specific immunotherapy patients with allergic rhinitis and reduced allergic reactions associated with allergen immunotherapy, such as anaphylaxis. Dupilumab is an Anti-IL-4/IL-13 biologic agent. Dupilumab treatment significantly improved sino-nasal Outcome Test (SNOT-22) total scores in perennial allergic rhinitis. Anti-IL-5 monoclonal antibodies of Mepolizumab, Reslizumab Benralizumab reduce the number of eosinophils in the blood and tissue, corticosteroid addiction and asthma attacks are reduced, and their use in the treatment of severe eosinophilic asthma has been approved. Biologics, especially Omalizumab, and Dupilumab, may be used more in allergic rhinitis. [ABSTRACT FROM AUTHOR]

shown improved asthma control and lung function in randomised controlled trials. The aim of this study was to evaluate real-world clinical experience in patients with severe eosinophilic asthma treated with mepolizumab in Slovakia. Methods. A retrospective, non-interventional study based on medical records of all adult asthma patients initiating mepolizumab between November 1, 2017 and January 31, 2019, completing 12 months of treatment. At baseline, general and clinical profile data were recorded 12 months prior to treatment. Primary and secondary endpoints described the results of mepolizumab use at 2, 6, and 12 months after the initiation and compared to baseline. Statistical testing of individual change (in each patient) in selected parameters was performed. Results. The cohort included 17 patients with particularly severe asthma at baseline, with frequent severe exacerbations (SE, median 5 [IQR 4--6]/patient/year), high blood eosinophil counts (median 0.6x109/L), frequent oral corticosteroid (OCS) dependence (82.35%), median dose 15 (IQR 7.5--20) mg/day, impaired lung function, and a spectrum of comorbidities. In a one-year follow-up, the data showed reductions in median SE (0 [IQR 0--1] patient/year, eosinophilia (median 0.175x109/L) and OCS maintenance dose (median 6.25 [IQR 2.5--20] mg/day), all statistically significant after 12 months on mepolizumab. Improved and stabilised lung functions throughout the cohort and a reduced incidence of nasal polyposis were observed. Conclusions. The results provide clinical evidence of mepolizumab efficacy in a real sample of patients with severe asthma when administered in routine care settings in Slovakia. [ABSTRACT FROM AUTHOR]

Asthma is one of the 4 leading causes of death worldwide. Severe asthma is associated with poor quality of life, decreased life expectancy, and higher health resources consumption such as the use of oral corticosteroids (OCSs). This study aimed to assess the cost-effectiveness of mepolizumab as an add-on compared with the standard care of the Chilean public health system (combined inhaled corticosteroid therapy and a long-acting beta-agonist, short-acting beta-agonist, and OCS). A Markov model was adapted to represent the day-to-day of patients with severe asthma over a lifetime horizon. Deterministic and probabilistic sensitivity analyses were performed to account for the second-order uncertainty of the model. In addition, a risk subgroup analysis was conducted to evaluate the cost-effectiveness of mepolizumab across different risk populations. Mepolizumab produces more benefits than standard of care alone (1 additional quality-adjusted life-year, a decrease of OCS usage, an approximated 11 avoided exacerbations) but it cannot be considered cost-effective in the light of the Chilean threshold (incremental cost-effectiveness ratio: US dollars [USD] 105 967/quality-adjusted life-year vs USD 14 896). Despite this, cost-effectiveness increases in specific subgroups, with an incremental cost-effectiveness ratio of USD 44 819 in patients with eosinophil count ≥ 300 cell/mcL and exacerbation history of at least 4 exacerbations in the past year. Mepolizumab cannot be considered a cost-effective strategy for the Chilean health system. Nevertheless, price discount in specific subgroups improves its cost-effectiveness profile significantly and may offer opportunities for access to specific subgroups. • Severe eosinophilic asthma affects patients, their families, and the health system. Regarding treatments, studies have reported no cost-effectiveness for mepolizumab. Incremental cost-effectiveness ratio and quality-adjusted life-year reported on the literature study, the asthma population in general, were not different in subgroups. • Our study provides robust evidence in the cost-effectiveness of mepolizumab as an add-on to standard care. The model included 5 stages of asthma and death and provided a subgroup analysis. • Compared with the Chilean threshold, this treatment is not cost-effective, although the results and model used in this study can be used as a reference for other low- and middle-income countries seeking comparisons with their local standard of care. [ABSTRACT FROM AUTHOR]

Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma. We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/μL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV 1 value over 12 months of follow-up. In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV 1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI = –0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI –0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI –0.083 to 0.140 L) for omalizumab versus mepolizumab. Among patients with asthma and eosinophil counts of at least 150 cells/μL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV 1 value than omalizumab and mepolizumab. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has been traditionally managed with a combination of topical and systemic medical therapy as well as endoscopic sinus surgery. The emergence of biologic therapies that target specific aspects of the inflammatory cascade has ushered in a potentially new paradigm in the management options available for CRSwNP. Purpose: To summarize the current literature and recommendations supporting the use of available biologic therapies for CRSwNP and to develop an algorithm to aid clinical decision-making regarding treatment selection. Methods: A review of available literature and studies that demonstrated the clinical efficacy of biologic agents for the treatment of CRSwNP informing current CRSwNP consensus algorithms. Results: Current biologic medications target immunoglobulin E, interleukins, or interleukin receptors implicated in the Th2 inflammatory cascade. Institution of biologic therapy is now an option for patients who have disease refractory to topical medical therapy and endoscopic sinus surgery, those who cannot tolerate surgery, or patients with other comorbid Th2 diseases. Response to treatment should be monitored at 4–6 months and 1 year after initiating therapy. Across multiple indirect comparisons, dupilumab appears to have the largest therapeutic benefit across multiple subjective and objective outcomes. The choice of therapeutic agent also depends on drug availability, patient tolerance, presence of comorbid illnesses, and cost. Conclusions: Biologics are emerging as an important option in the management of patients with CRSwNP. While more data is required to fully inform indications, treatment selection, and health economics related to their use, biologics may offer robust symptom relief to patients who have failed other interventions. [ABSTRACT FROM AUTHOR]

[Display omitted] It is unclear how the efficacy of tezepelumab, approved for the treatment of type 2 high and low asthma, compares to the efficacy of other biologics for type 2–high asthma. We sought to conduct an indirect comparison of tezepelumab to dupilumab, benralizumab, and mepolizumab in the treatment of eosinophilic asthma. The investigators conducted a systematic review and Bayesian network meta-analyses. They identified randomized controlled trials indexed in PubMed, Embase, or Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 2000, and August 12, 2022. Outcomes included exacerbation rates, prebronchodilator FEV 1 , and the Asthma Control Questionnaire. Ten randomized controlled trials (n = 9201) met eligibility. Tezepelumab (relative risk: 0.63; 95% credible interval [CI]: 0.46-0.86) was associated with significantly lower exacerbation rates than benralizumab and larger improvements in FEV 1 compared to mepolizumab (mean difference [MD]: 66; 95% CI: −33 to 170) and benralizumab (MD: 62; 95% CI: −22 to 150), though the 95% CI crossed the null value of 0. Mepolizumab improved the Asthma Control Questionnaire score the most, but this improvement was not significantly different from that of tezepelumab (tezepelumab vs mepolizumab; MD: 0.14; 95% CI: −0.10 to 0.38). For efficacy by clinically important thresholds, tezepelumab, mepolizumab, and dupilumab achieved a >99% probability of reducing exacerbation rates by ≥50% compared to placebo, but benralizumab had only a 66% probability of doing so. Tezepelumab and dupilumab had a probability of 1.00 of improving prebronchodilator FEV 1 by ≥100 mL above placebo. Compared to mepolizumab, dupilumab had >90% chance for improving FEV 1 by ≥50 mL, but none of the differences between biologics exceeded 100 mL. In individuals with eosinophilic asthma, tezepelumab and dupilumab were associated with greater improvements (although below clinical thresholds) in exacerbation rates and lung function than benralizumab or mepolizumab. [ABSTRACT FROM AUTHOR]

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[Display omitted] The relative utility of eosinophil peroxidase (EPX) and blood and sputum eosinophil counts as disease biomarkers in asthma is uncertain. We sought to determine the utility of EPX as a biomarker of systemic and airway eosinophilic inflammation in asthma. EPX protein was measured by immunoassay in serum and sputum in 110 healthy controls to establish a normal reference range and in repeated samples of serum and sputum collected during 3 years of observation in 480 participants in the Severe Asthma Research Program 3. Over 3 years, EPX levels in patients with asthma were higher than normal in 27% to 31% of serum samples and 36% to 53% of sputum samples. Eosinophils and EPX correlated better in blood than in sputum (r s values of 0.74 and 0.43, respectively), and high sputum EPX levels occurred in 27% of participants with blood eosinophil counts less than 150 cells/μL and 42% of participants with blood eosinophil counts between 150 and 299 cells/μL. Patients with persistently high sputum EPX values for 3 years were characterized by severe airflow obstruction, frequent exacerbations, and high mucus plug scores. In 59 patients with asthma who started mepolizumab during observation, serum EPX levels normalized in 96% but sputum EPX normalized in only 49%. Lung function remained abnormal even when sputum EPX normalized. Serum EPX is a valid protein biomarker of systemic eosinophilic inflammation in asthma, and sputum EPX levels are a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts. Eosinophil measures in blood frequently miss airway eosinophilic inflammation, and mepolizumab frequently fails to normalize airway eosinophilic inflammation even though it invariably normalizes systemic eosinophilic inflammation. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory condition of the upper airways. Optimal management is unclear. We compared the effects of mAbs and aspirin desensitization (ASA-D) for treatment of CRSwNP. We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, US Food and Drug Administration, and the European Medicines Agency databases from inception to August 4, 2021, for randomized controlled trials comparing the effects of mAbs and ASA-D for CRSwNP. We conducted network meta-analysis of sinusitis symptoms, heath-related quality of life, rescue oral corticosteroids and surgery, endoscopic and radiologic scores, and adverse events. We used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach to assess certainty of evidence. PROSPERO CRD42020177334. Twenty-nine randomized controlled trials evaluating 8 treatments (n = 3461) were included in the network meta-analysis. Compared to placebo, moderate to high certainty evidence showed that health-related quality of life (SNOT-22) improved with dupilumab (mean difference [MD] −19.91 [95% confidence interval (CI) −22.50, −17.32]), omalizumab (MD −16.09 [95% CI −19.88, −12.30]), mepolizumab (MD −12.89 [95% CI −16.58, −9.19], ASA-D (MD −10.61 [95% CI −14.51, −6.71]), and benralizumab (MD −7.68 [95% CI −12.09, −3.27]). The risk of rescue nasal polyp surgery likely decreased with dupilumab (risk difference [RD] −16.35% [95% CI −18.13, −13.48]), omalizumab (RD −7.40% [95% CI −11.04, −2.43]), mepolizumab (RD −12.33% [95% CI −15.56, −7.22]), and ASA-D (RD −16.00% [95% CI −19.79, 0.21]; all moderate certainty). Comparisons among agents show with moderate to high certainty that dupilumab ranks among the most beneficial for 7 of 7 outcomes, omalizumab for 2 of 7, mepolizumab for 1 of 7, and ASA-D for 1 of 7. Multiple biologics and ASA-D credibly improve patient-important outcomes, with clinically important differences in effects among agents; dupilumab uniquely ranks among the most beneficial for all outcomes studied. [Display omitted] [ABSTRACT FROM AUTHOR]

Eosinophilic asthma and nasal polyposis are hallmarks of aspirin-exacerbated respiratory disease (AERD), and IL-5 inhibition has been shown to provide therapeutic benefit. However, IL-5Rα is expressed on many cells in addition to eosinophils, and the mechanisms by which IL-5 inhibition leads to clinical benefit in eosinophilic asthma and nasal polyposis are unlikely to be due exclusively to antieosinophil effects. We sought to identify the mechanisms by which anti–IL-5 treatment with mepolizumab improves respiratory inflammation in AERD. The clinical characteristics, circulating granulocytes, nasal scraping transcripts, eosinophilic cationic protein, tryptase, and antibody levels, and urinary and nasal eicosanoid levels were measured for 18 subjects with AERD who were taking mepolizumab and compared with those of 18 matched subjects with AERD who were not taking mepolizumab. Subjects taking mepolizumab had significantly fewer peripheral blood eosinophils and basophils, and those cells that remained had higher surface CRTH2 expression than did the cells from subjects not taking mepolizumab. Nasal prostaglandin F 2α , prostaglandin D 2 metabolites, leukotriene B 4 , and thromboxane levels were lower in subjects taking mepolizumab, as were urinary levels of tetranor–prostaglandin D 2 and leukotriene E 4. The nasal epithelial cell transcripts that were overexpressed among subjects with AERD who were taking mepolizumab were enriched for genes involved in tight junction formation and cilium organization. Nasal and urinary prostaglandin E 2 , tryptase, and antibody levels were not different between the 2 groups. IL-5 inhibition in AERD decreases production of inflammatory eicosanoids and upregulates tight junction–associated nasal epithelial cell transcripts, likely due to decreased IL-5 signaling on tissue mast cells, eosinophils, and epithelial cells. These direct effects on multiple relevant immune cells contribute to the mechanism of benefit afforded by mepolizumab. [Display omitted] [ABSTRACT FROM AUTHOR]

Episodic angioedema with eosinophilia (EAE) is a rare multilineage cyclic syndrome of unknown etiology characterized by episodes of angioedema, myalgia, fatigue, and fever that occur every 3 to 8 weeks and resolve between episodes without therapy. Cyclic elevations in serum IL-5 levels and neutrophils precede the increase in absolute eosinophil count (AEC) in most patients. We sought to assess the role of IL-5–driven eosinophilia in the clinical manifestations of EAE. An open-label pilot study of mepolizumab (700 mg intravenously monthly for 3 months followed by sequential dose reduction to the Food and Drug Administration–approved dose of 300 mg subcutaneously monthly) was conducted. The primary end point was reduction in the number and severity of clinical symptoms as assessed by patient-reported symptom questionnaires. Secondary end points were greater than or equal to 75% reduction in peak AEC after 1 dose of mepolizumab and sustained reduction in AEC after 3 doses of mepolizumab. Exploratory end points included effects of mepolizumab treatment on other cell lineages (numbers and surface marker expression), levels of plasma mediators, and biomarkers of eosinophil activation. Four female and 1 male (median age, 45 years) participants with EAE were enrolled. None of the 5 participants experienced a reduction in the number of symptomatic flares on mepolizumab therapy, and 1 participant withdrew before study completion because of lack of improvement. Peak AEC was reduced by 75% or more in 3 participants after the first dose of mepolizumab and in 4 participants after 3 doses. In a small cohort of participants with EAE, mepolizumab was unsuccessful in substantially reducing clinical symptoms despite reduction in AEC. [ABSTRACT FROM AUTHOR]

Background: Allergic Fungal Rhinosinusitis (AFRS) is a non-invasive fungal disease that results from chronic allergic inflammation of the sinonasal mucosa. Failure to respond to mainstay medical therapies and sinus surgery leaves AFRS patients with limited alternatives and a decreased quality of life. Mepolizumab is a known IL-5 antagonist for patients with severe eosinophilic asthma. Objective: To identify the efficacy of mepolizumab on improving Modified Lund-Kennedy (MLK) endoscopic scores in recalcitrant AFRS patients with asthma. Methods: Retrospective chart review of 27 recalcitrant AFRS patients with asthma receiving a monthly mepolizumab injection between January 2017 and July 2019. Patients were evaluated endoscopically at baseline and at each follow-up visit every 6–8 weeks until their third visit. Secondary outcomes included SNOT-22 scores, serum eosinophil counts and the rate of prednisone rescues required in patients receiving mepolizumab compared to a retrospective control arm. Results: Total median MLK scores improved significantly for all patients over three follow-up visits (6[4,7], 4[2,6], 5[2,6], 3.5[2.25,5]; p = 0.04). Amongst patients with a baseline polyposis score of 1 or more, combined MLK edema and polyposis sub-scores significantly improved (6[5.25,6], 3.5[2.25,5,75], 4[2.75,5.25], 4[3,4]; p = 0.02) versus patients with no polyposis (4[3,4], 3[1,4], 4[2,4], 3[0,4]; p = 0.90). Total SNOT-22 scores (56 vs 43; p = 0.04) and eosinophil counts (0.40 × 109/L vs 0.00 × 109/L; p < 0.01) decreased significantly when comparing baseline to last follow up. There was no significant difference in rate of prednisone rescues per 1000 person-days when comparing control to Mepolizumab population (1.19 vs 1.23; p = 1). Conclusion: Mepolizumab injections administered once monthly as an adjunctive treatment for recalcitrant AFRS patients with asthma appear to significantly reduce endoscopic signs of inflammation, patient-reported symptomatology and serum eosinophil levels. Patients with evidence of more severe endoscopic inflammation appear to benefit the most. Adjunctive treatment with mepolizumab does not reduce the need for prednisone rescues. [ABSTRACT FROM AUTHOR]

Anti–IL-5 therapy is a potential treatment for patients with hypereosinophilic syndrome (HES), although its clinical efficacy is unclear. We sought to investigate the clinical efficacy and safety of mepolizumab versus placebo in patients with HES. This randomized, multicenter, double-blind, placebo-controlled, phase III trial was conducted across 39 centers in 13 countries. Eligible patients had FIP1L1-PDGFRA -negative HES, experienced 2 or more flares (worsening of HES-related symptoms or blood eosinophil count requiring therapeutic escalation) in the previous 12 months, and had a screening blood eosinophil count greater than or equal to 1000 cells/μL. Patients were randomized (1:1) to subcutaneous mepolizumab (300 mg) or placebo every 4 weeks for 32 weeks, plus existing HES therapy. The primary outcome was the proportion of patients with 1 or more flares (worsening of HES-related symptoms necessitating therapy escalation or ≥2 courses of blinded rescue oral corticosteroids) during the study; in addition, patients who withdrew early from the study were counted as having a flare. Safety end points were also assessed. The proportion of patients experiencing 1 or more flares/withdrawing from the study was 50% lower with mepolizumab versus placebo (15 of 54 [28%] vs 30 of 54 [56%]; P =.002). Logistic regression analysis was consistent with the primary analysis (odds ratio, 0.28; 95% CI, 0.12-0.64; P =.003). Similar proportions of patients in the mepolizumab and placebo groups experienced on-treatment adverse events (48 of 54 [89%] vs 47 of 54 [87%]). Compared with placebo, mepolizumab significantly reduced the occurrence of flares in patients with HES, with no new safety signals identified. [ABSTRACT FROM AUTHOR]

A 67-year-old woman with a history of poorly controlled asthma was admitted to our hospital with a persistent cough and abnormal chest radiographic findings. Her diagnosis was allergic bronchopulmonary aspergillosis (ABPA). Following treatment with mepolizumab, her symptoms and imaging findings improved initially. However, after approximately 2 years, the patient experienced a recurrent cough with elevated non-specific immunoglobulin E levels and worsening chest imaging findings, thereby changing her diagnosis to recurrent ABPA. Mepolizumab was substituted with dupilumab, and her subjective symptoms and imaging findings improved. Our findings suggest that dupilumab may be effective in ABPA cases following the failure of another antibody therapy. • Humanized monoclonal antibodies are effective in patients with ABPA and may serve as a viable substitute for prednisolone. • Humanized monoclonal antibodies exhibit initial efficacy against ABPA; however, their effectiveness may attenuate over time. • Dupilumab may be effective in ABPA cases following the failure of another antibody therapy. [ABSTRACT FROM AUTHOR]

Severe Asthma (SA) is characterized by inadequate disease control despite maximal inhalation therapy. In November 2021, a 68-years old female patient presented at our facility referring a worsening in her asthma-related symptoms and a high exacerbations rate. She reported a liver transplantation in 2015 and was in treatment with tacrolimus. We started treatment with Mepolizumab 100 mg once every 28 days and monitored her lung function as well as her lymphocytes subsets. After one year follow-up, the patient had a substantial improvement in lung function, exacerbation rate, daily OCS intake dose and no variation in the blood concentration of tacrolimus. [ABSTRACT FROM AUTHOR]

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction caused by the fungus Aspergillus , and it is often treated with steroids or antifungal agents. However, long-term use of these medications can lead to infections and drug interactions. We present the case of a 71-year-old woman with ABPA who was diagnosed with hepatitis B and active hepatitis C, and sputum analysis revealed the presence of bacteria. Oral steroids were initially administered, but the patient was switched to mepolizumab because of numerous infectious complications. The early introduction of mepolizumab is effective in patients with ABPA complicated by infectious diseases. [ABSTRACT FROM AUTHOR]

In a recent phase III trial (NCT02020889) 53% of mepolizumab-treated versus 19% of placebo-treated patients with eosinophilic granulomatosis with polyangiitis (EGPA) achieved protocol-defined remission. We sought to investigate post hoc the clinical benefit of mepolizumab in patients with EGPA using a comprehensive definition of benefit encompassing remission, oral glucocorticoid (OGC) dose reduction, and EGPA relapses. The randomized, placebo-controlled, double-blind, parallel-group trial recruited patients with relapsing/refractory EGPA receiving stable OGCs (prednisolone/prednisone, ≥7.5–50 mg/d) for 4 or more weeks. Patients received 300 mg of subcutaneous mepolizumab or placebo every 4 weeks for 52 weeks. Clinical benefit was defined post hoc as follows: remission at any time (2 definitions used), 50% or greater OGC dose reduction during weeks 48 to 52, or no EGPA relapses. The 2 remission definitions were Birmingham Vasculitis Activity Score of 0 plus OGC dose of 4 mg/d or less (remission 1/clinical benefit 1) or 7.5 mg/d or less (remission 2/clinical benefit 2). Clinical benefit was assessed in all patients and among subgroups with a baseline blood eosinophil count of less than 150 cells/μL, baseline OGC dosage of greater than 20 mg/d, or weight of greater than 85 kg. With mepolizumab versus placebo, 78% versus 32% of patients experienced clinical benefit 1, and 87% versus 53% of patients experienced clinical benefit 2 (both P <.001). Significantly more patients experienced clinical benefit 1 with mepolizumab versus placebo in the blood eosinophil count less than 150 cells/μL subgroup (72% vs 43%, P =.033) and weight greater than 85 kg subgroup (68% vs 23%, P =.005); in the OGC greater than 20 mg/d subgroup, results were not significant but favored mepolizumab (60% vs 36%, P =.395). When a comprehensive definition of clinical benefit was applied to data from a randomized controlled trial, 78% to 87% of patients with EGPA experienced benefit with mepolizumab. [ABSTRACT FROM AUTHOR]

Background Chronic rhinosinusitis with nasal polyposis is a complex inflammatory disorder, which is often recalcitrant to medical and surgical management. Recently, biologic agents have been studied as an adjunct treatment for this patient population. Objective The purpose of this study is to examine the role of biologic agents for chronic rhinosinusitis patients by reviewing literature and clinical trials. Methods A comprehensive review of literature and clinical trials—both recently completed and ongoing—was undertaken to examine up-to-date evidence of current biologic therapy and its role in chronic rhinosinusitis patients—including anti-IgE, anti-IL-4, anti-IL-5, anti-IL-13, and GATA-3 DNAzyme. Results Specific biologic agents discussed include omalizumab, reslizumab, mepolizumab, benralizumab, dupilumab, and Hgd40/SB010. Risks, side effects, and administration information are also reviewed. An algorithm for the use of biologics in patients with chronic rhinosinusitis with nasal polyposis is proposed. Conclusion These treatments have promising results and may prove to be an important adjunct for patients with recalcitrant sinus disease. [ABSTRACT FROM AUTHOR]

Abstract A 56-year-old woman was referred to our hospital for recurrent asthma of 20 years duration. She was diagnosed as having allergic bronchopulmonary aspergillosis on the basis of clinical symptoms, peripheral blood eosinophilia, elevated total serum immunoglobulin E value, positive results of specific IgE and precipitating antibodies against Aspergillus sp., central bronchiectasis, and mucoid impaction. Systemic corticosteroids and anti-fungal therapy improved her symptoms, but the cessation of these treatments led to frequent exacerbations. Omalizumab improved her asthmatic symptoms to the point that corticosteroids could be stopped; however, radiological findings were not improved, and coexisting eosinophilic sinusitis and otitis media worsened. After her treatment was changed from omalizumab to mepolizumab, not only her asthmatic symptoms but also her sinusitis and otitis media became well controlled, and chest radiological findings improved. [ABSTRACT FROM AUTHOR]

Résumé Après les rhumatismes inflammatoires chroniques, la granulomatose éosinophilique avec polyangéite (GEPA, Churg-Strauss) illustre parfaitement le bouleversement qui est en train de s’opérer avec l’avènement des biomédicaments dans la prise en charge des vascularites nécrosantes associées aux ANCA. Pour améliorer la prise en charge des patients, ces médicaments biologiques devront montrer qu’ils permettent des rémissions prolongées, une épargne cortisonique, une réduction de la toxicité médicamenteuse et des séquelles cumulatives, une amélioration de la qualité de vie des patients avec un impact médico-économique acceptable. L’utilisation du rituximab dans le traitement de la GEPA reste actuellement non validée mais de larges essais thérapeutiques sont en cours en France, en traitement d’induction mais aussi de maintien de la rémission. Ils sont rendus possibles grâce à l’émergence de définition consensuelle de critères d’évaluation de cette vascularite et la structuration de réseaux d’investigateurs comme celui du Groupe français d’étude des vascularites (GFEV). L’interleukine-5 est une autre cible thérapeutique prometteuse au cours de la GEPA, dont le blocage fait l’objet d’un essai thérapeutique international avec le mépolizumab en traitement d’entretien, après son autorisation de mise sur le marché dans l’asthme éosinophilique. Les résultats préliminaires de cette étude sont encourageants. D’autres essais thérapeutiques testeront de nouvelles cibles dans cette maladie rare, comme l’interleukine-4 et -13. Gageons que cette nouvelle ère des médicaments biologiques au cours de la GEPA permette de voir émerger de nouvelles thérapeutiques qui amélioreront la qualité de vie des patients. After the inflammatory rheumatic diseases, eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) perfectly illustrates the breakthrough of the advent of biologics in the management of ANCA-associated vasculitides. To improve the management of patients, biologics will have to demonstrate that they allow sustained remission, steroid sparing, and reduction of side effects and accrual damage, improvement of the quality of life of patients with an acceptable medico-economic ratio. Anti-CD20 rituximab treatment of EGPA remains at present not validated but large randomized trials are ongoing in France, both as induction and maintenance therapy. They are made possible thanks to the emergence of consensual definition of assessment criteria for this vasculitis and the structuring of investigators’ networks such as the French Vasculitis Study Group (FVSG). Interleukine-5 is another promising therapeutic target in EGPA, the blocking of which is the objective of an international pivotal mepolizumab trial, after its marketing authorization in eosinophilic asthma. Preliminary results are encouraging as maintenance therapy. Further trials will evaluate other targets in this rare disease, such as interleukin-4 and -13. Let us hope that this new era of biological response modifiers for EGPA allow the emergence of new therapies, which will improve patients’ quality of life. [ABSTRACT FROM AUTHOR]

Résumé La présence d’une inflammation éosinophilique est le phénotype le plus fréquemment rencontré dans l’asthme sévère. L’interleukine-5 (IL-5) est une cytokine pro-inflammatoire qui joue un rôle crucial dans la maturation, le recrutement, la prolifération et la migration vers les tissus de l’éosinophile et est également impliquée dans la survie cellulaire et la prévention de l’apoptose des éosinophiles. Plusieurs anticorps monoclonaux dirigés contre l’IL-5 ou contre son récepteur cellulaire sont actuellement en cours d’évaluation à différentes phases de développement clinique dans la prise en charge de l’asthme sévère. Leur mode d’action respectif et les résultats obtenus dans les essais cliniques récemment publiés sont discutés. Il apparaît que, d’une manière générale, le traitement ciblé par les anti-IL-5 permet une réduction de la fréquence des exacerbations et l’amélioration de paramètres cliniques et fonctionnels chez les patents asthmatiques sévères avec phénotype « éosinophile ». Il s’agit donc d’une nouvelle classe thérapeutique qui devrait indiscutablement présenter un progrès pour le traitement des patients asthmatiques sévères ayant des critères d’inflammation éosinophilique persistante malgré les traitements jusqu’à présent disponibles. The presence of eosinophilic inflammation is the most frequent clinical phenotype encountered in patients with severe asthma. Interleukin-5 (IL-5) is a pro-inflammatory cytokine that plays a pivotal pathogenic role in eosinophilic asthma; it is involved in eosinophil differentiation, activation and tissue migration, and it is equally involved in eosinophil survival and the prevention of apoptosis. Several monoclonal antibodies (MABs) targeting IL-5 or its cellular receptor are currently being developed for the treatment of severe asthma. We discuss their mode of action and the results observed in recently published clinical trials. It seems that, generally, anti-IL-5 therapies have as their target a reduction of the frequency of asthma exacerbations and improvement of clinical and lung function parameters in selected patients with severe asthma and an eosinophilic phenotype. This new therapeutic class of drugs should certainly lead to improvement in the management of patients with persistent severe eosinophilic asthma who have not responded to currently available anti-asthmatic treatment. [ABSTRACT FROM AUTHOR]

Abstract Here we report on a 61-year-old man with refractory eosinophilic granulomatosis with polyangiitis (EGPA) who presented with dyspnea. Despite treatment with glucocorticoids, intravenous cyclophosphamide, and plasma exchange, his symptoms worsened despite his eosinophil count and myeloperoxidase antineutrophil cytoplasmic antibody titer trending downwards. EGPA with diffuse alveolar hemorrhage was diagnosed on analysis of bronchoalveolar lavage fluid. The patient was treated with rituximab and methylprednisolone pulse therapy and a remission was achieved. He has been receiving mepolizumab since then and remains in remission. It should be recognized that refractory diffuse alveolar hemorrhage can occur in patients with EGPA without elevation of biomarkers if they are receiving systemic corticosteroids. [ABSTRACT FROM AUTHOR]

A 26-year-old female with steroid dependent eosinophilic asthma and nasal polyps who had successfully been treated with mepolizumab for 17 consecutive months with complete steroid withdrawal and symptoms control, stopped biologic treatment due to pregnancy efforts. Mepolizumab discontinuation resulted in frequent exacerbations and daily symptoms despite high dose ICS/LABA and re-initiation of oral steroids. Mepolizumab was initiated again, followed by improvement of asthma control and gradual withdrawal of steroids within 2 months. The patient became pregnant during the fourth month of mepolizumab re-initiation. The patient presented two asthma exacerbations during pregnancy treated with short course (3 days) oral steroids and delivery was uneventful (female, Apgar 9, weight 2750 g, length 59 cm) in week 40 by caesarean section. [ABSTRACT FROM AUTHOR]

The comparative safety and efficacy of the biologics currently approved for asthma are unclear. We compared the safety and efficacy of mepolizumab, benralizumab, and dupilumab in individuals with severe eosinophilic asthma. We performed a systematic review of peer-reviewed literature published 2000 to 2021. We studied Bayesian network meta-analyses of exacerbation rates, prebronchodilator FEV 1 , the Asthma Control Questionnaire, and serious adverse events in individuals with eosinophilic asthma. Eight randomized clinical trials (n = 6461) were identified. We found in individuals with eosinophils ≥300 cells/μL the following: in reducing exacerbation rates compared to placebo: dupilumab (risk ratio [RR], 0.32; 95% credible interval [CI], 0.23 to 0.45), mepolizumab (RR, 0.37; 95% CI, 0.30 to 0.45), and benralizumab (RR, 0.49; 95% CI, 0.43 to 0.55); in improving FEV 1 : dupilumab (mean difference in milliliters [MD] 230; 95% CI, 160 to 300), benralizumab (MD, 150; 95% CI, 100 to 200), and mepolizumab (MD, 150; 95% CI, 66 to 220); and in reducing Asthma Control Questionnaire scores: mepolizumab (MD, −0.63; 95% CI, −0.81 to −0.45), dupilumab (MD, −0.48; 95% CI, −0.83 to −0.14), and benralizumab (MD, −0.32; 95% CI, −0.43 to −0.21). In individuals with eosinophils 150-299 cells/μL, benralizumab (RR, 0.62; 95% CI, 0.52 to 0.73) and dupilumab (RR, 0.60; 95% CI, 0.38 to 0.95) were associated with lower exacerbation rates; and only benralizumab (MD, 81; 95% CI, 8 to 150) significantly improved FEV 1. These differences were minimal compared to clinically important thresholds. For serious adverse events in the overall population, mepolizumab (odds ratio, 0.67; 95% CI, 0.48 to 0.92) and benralizumab (odds ratio, 0.74; 95% CI, 0.59 to 0.93) were associated with lower odds of a serious adverse event, while dupilumab was not different from placebo (odds ratio, 1.0; 95% CI, 0.74 to 1.4). There are minimal differences in the efficacy and safety of mepolizumab, benralizumab, and dupilumab in eosinophilic asthma. [ABSTRACT FROM AUTHOR]

An 81-year-old woman presented to our hospital due to an abnormal shadow on a chest X-ray and a 4-week-old persistent cough. Laboratory examination revealed increased serum eosinophils and immunoglobulin E. The Asthma Control Test (ACT) score and forced expiratory volume in 1 sec indicated airway obstruction. Chest computed tomography (CT) revealed mucoid impaction in the dilated left-lingular lobar bronchus. She was diagnosed with bronchial asthma and treated with a high-dose inhaled corticosteroid/long-acting β2 agonist. Two months later, her mucoid impaction in the CT image worsened; moreover, bronchoscopy revealed the white mucus plug with Charcot–Leyden crystals and filamentous fungi. The patient was diagnosed with Allergic bronchopulmonary aspergillosis (ABPA) and treatment with 30 mg/day prednisolone was started. Both the blood eosinophil count and the chest image improved almost substantially, and the steroid was discontinued after a year. Sixteen months after cessation of prednisolone treatment, peripheral eosinophilia and mucoid impaction in the left B3b recurred. For the treatment of bronchial asthma and recurrent ABPA, administration of mepolizumab was initiated. Subsequently, although her peripheral eosinophils count decreased, chest CT showed expansion of the mucoid impaction and IgE increased despite mepolizumab treatment. Alternative subcutaneous injection therapy with dupilumab improved chest image, serum IgE level, and her ACT score. After changing from mepolizumab to dupilumab, her ABPA, asthma, and pulmonary function improved remarkably. This case illustrates the potential utility of dupilumab for ABPA without re-administration of oral prednisolone. Additional research is needed to identify an effective therapy for ABPA with asthma. • Systemic corticosteroids are the standard treatment for ABPA. • ABPA often recurs and requires prolonged courses of corticosteroids. • We successfully treated a recurrent ABPA case by changing mepolizumab to dupilumab. • Dupilumab can be used as an alternative for prednisolone for treating ABPA. [ABSTRACT FROM AUTHOR]

Symptomatic asthma in childhood has lifelong effects on lung function and disease severity, emphasizing the need for improved pediatric asthma control. Control of pediatric risk and impairment domains can be achieved through increased medication adherence or new therapeutic strategies. Developing electronic monitoring device technology with reminders might be a key noninvasive resource to address poor adherence in children and adolescents in a clinical setting. In patients who have persistently poor control despite optimal medication compliance, newly emerging pharmaceuticals, including inhaled therapies and biologics, might be key to their treatment. However, barriers exist to their development in the pediatric population, and insights must be drawn from adult studies, which has its own unique limitations. Biomarkers to direct the use of such potentially expensive therapies to those patients most likely to benefit are imperative. In this review the current literature regarding strategies to improve pediatric asthma control is addressed with the goal of exploring the potential and pitfalls of strategies that might be available in the near future. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a heterogeneous disease with clinical manifestations that are influenced by the presence or absence of nasal polyposis. Understanding of the current and future treatment modalities for CRS is essential in preventing exacerbation and morbidity associated with this chronic condition. Objective: The aim of this article is to review the evidence behind current medical therapies and potential new treatments for CRS. Methods: Scientific literature regarding intranasal and systemic antibiotics, intranasal systemic corticosteroids, and monoclonal antibodies as interventions for CRS with and without nasal polyps was reviewed. Results: The literature supports the use of topical or systemic glucocorticoids in patients with nasal polyps, and there appears to be a role for systemic antibiotics in the treatment of acute exacerbations of CRS with nasal polyps. The response to corticosteroids or antibiotics in the treatment of exacerbations of CRS without nasal polyps is variable. Due to the lack of appropriately designed trials, there is weak evidence for the adjunctive use of immunotherapy at this time. Monoclonal antibodies that target Immunoglobulin E and T helper cell 2 cytokines have been clinically effective in symptom reduction for some patients with CRS with nasal polyps although further studies are needed. Conclusion: Current therapies used in the treatment of CRS are discussed. [ABSTRACT FROM AUTHOR]

In the phase III SYNAPSE study, mepolizumab reduced nasal polyp (NP) size and nasal obstruction in chronic rhinosinusitis with NP. We sought to assess the efficacy of mepolizumab in patients from SYNAPSE grouped by comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and baseline blood eosinophil count (BEC). SYNAPSE, a randomized, double-blind, 52-week study (NCT03085797), included patients with severe bilateral chronic rhinosinusitis with NP eligible for surgery despite intranasal corticosteroid treatment. Patients received 4-weekly subcutaneous mepolizumab 100 mg or placebo plus standard of care for 52 weeks. Coprimary end points were change in total endoscopic NP score (week 52) and nasal obstruction visual analog scale score (weeks 49-52). Subgroup analyses by comorbid asthma and AERD status, and post hoc by BEC, were exploratory. Analyses included 407 patients (289 with asthma; 108 with AERD; 371 and 278 with BEC counts ≥150 or ≥300 cells/μL, respectively). The proportion of patients with greater than or equal to 1-point improvement from baseline in NP score was higher with mepolizumab versus placebo across comorbid diseases (asthma: 52.9% vs 29.5%; AERD: 51.1% vs 20.6%) and baseline BEC subgroups (<150 cells/μL: 55.0% vs 31.3%; ≥150 cells/μL: 49.5% vs 28.1%; <300 cells/μL: 50.7% vs 29.0%; ≥300 cells/μL: 50.4% vs 28.1%). A similar trend was observed in patients without comorbid asthma or AERD. More patients had more than 3-point improvement in nasal obstruction VAS score with mepolizumab versus placebo across comorbid subgroups. Mepolizumab reduced polyp size and nasal obstruction in chronic rhinosinusitis with NP regardless of the presence of comorbid asthma or AERD. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders. [Copyright &y& Elsevier]

Airway remodeling, or structural changes of the airway wall arising from injury and repair, plays an important role in the pathophysiology of asthma. Remodeling is characterized as structural changes involving the composition, content, and organization of many of the cellular and molecular constituents of the bronchial wall. These structural changes can include epithelial injury, subepithelial thickening/fibrosis, airway smooth muscle hyperplasia, goblet cell hypertrophy and hyperplasia, and angiogenesis. Historically, these changes are considered a consequence of long-standing airway inflammation. Recent infant and child studies, however, suggest that remodeling occurs in parallel with inflammation in asthmatic subjects. Despite advancements in the recognition of key cellular and molecular mechanisms involved in remodeling, there remains a paucity of information about which treatments or interactions are most likely to regulate these processes. Furthermore, it is unclear as to when is the best time to initiate treatments to modify remodeling, which components to target, and how best to monitor interventions on remodeling. Indeed, inhaled corticosteroids, which are generally considered to have limited influence on remodeling, have been shown to be beneficial in studies in which the dose and duration of treatment were increased and prolonged, respectively. Moreover, several studies have identified the need to identify novel asthma indices and phenotypes that correlate with remodeling and, as a consequence, might specifically respond to new therapies, such as anti-IgE, anti–IL-5, and anti–TNF-α mAbs. Our review will evaluate the development of remodeling in asthmatic subjects and the effects of treatment on these processes. [ABSTRACT FROM AUTHOR]

Background: Treatments for Churg-Strauss syndrome (CSS), a rare eosinophilic vasculitis characterized by asthma, sinusitis, peripheral eosinophilia, pulmonary infiltrates, and tissue infiltration, are limited by toxicity or poor efficacy. Levels of IL-5, a cytokine regulating eosinophils, can be increased in patients with CSS. Mepolizumab, a humanized monoclonal anti–IL-5 antibody, decreases steroid requirements in patients with non-CSS hypereosinophilic syndromes. Objective: The purpose of this study was to assess whether mepolizumab would safely allow corticosteroid tapering in patients with steroid-dependent CSS while decreasing serum markers of disease activity. Methods: This open-label pilot study treated 7 patients with 4 monthly doses of mepolizumab to assess whether it safely decreased CSS disease activity and permitted tapering of systemic corticosteroids. Results: Mepolizumab was safe and well tolerated in patients with CSS. Mepolizumab reduced eosinophil counts and allowed for safe corticosteroid reduction in all 7 subjects. On cessation of mepolizumab, CSS manifestations recurred, necessitating corticosteroid bursts. Conclusion: Mepolizumab is a safe and well-tolerated therapy in patients with CSS, offering clinical benefit by enabling corticosteroid tapering while maintaining clinical stability. [Copyright &y& Elsevier]

The hypereosinophilic syndromes (HESs) are a heterogeneous group of diseases characterized by peripheral blood eosinophilia with end-organ damage and varying in severity from nonspecific symptoms to life-threatening. Treatment objectives are a safe reduction of blood and tissue eosinophil levels and prevention of eosinophil-mediated tissue damage. Current treatment of patients with HESs, who lack the FIP-1–like 1-platelet-derived growth factor receptor α (FIP1L1-PDGFRA) fusion gene, is mainly systemic corticosteroid therapy. Eosinophil development from hematopoietic progenitor cells is regulated by IL-5, which influences maturation, differentiation, mobilization, activation, and survival. Consequently, inhibiting IL-5 is a logical therapeutic objective for patients with HESs or selected patients with asthma. Mepolizumab is a fully humanized anti–IL-5 monoclonal IgG1 antibody that binds to free IL-5 with high affinity and specificity to prevent IL-5 from associating with the IL-5 receptor complex α-chain on the surface of eosinophils. In clinical trials with patients with HESs, mepolizumab reduced blood eosinophil counts and the maintenance corticosteroid dose and had no major safety concerns. Mepolizumab reduced airway and blood eosinophils and prevented asthma exacerbations. Thus, mepolizumab may be effective for long-term treatment of patients with selected eosinophilic disorders. [Copyright &y& Elsevier]

Background: Anti–IL-5 might be a useful therapeutic agent for eosinophilic disorders, yet its immunologic consequences have not been well characterized. Objective: We sought to characterize the hematologic and immunologic effects of anti-IL-5 in human subjects. Methods: The effects of 3-month infusions of mepolizumab were assessed in 25 patients with a variety of eosinophilic syndromes. Samples with increased IL-5 levels after therapy were analyzed by using size exclusion filtration. Immunoreactive IL-5 fraction and plasma samples were subsequently precipitated with saturating concentrations of protein A/G. Results: Twenty-three patients responded to anti–IL-5 therapy with a decrease in blood eosinophil counts and a reduced percentage of CCR3+ cells by 20- and 13-fold, respectively (P < .0001). Responsiveness was not related to the levels of baseline plasma IL-5 or the presence of FIP1L1-PDGFRA fusion gene. Persistently decreased blood eosinophilia remained for 3 months after final infusion in 76% of subjects. Therapy was associated with a large increase in blood IL-5 levels, likely because of a circulating IL-5/mepolizumab complex precipitated with protein A/G, a significant increase in eosinophil IL-5 receptor α expression, and increased percentage of CD4+ and CD8+ cells producing intracellular IL-5 (P < .05). Additionally, anti-IL-5 therapy decreased eotaxin-stimulated eosinophil shape change ex vivo. Conclusions: Anti–IL-5 therapy induces a dramatic and sustained decrease in blood eosinophilia (including CCR3+ cells), decreased eosinophil activation, and increased circulating levels of IL-5 in a variety of eosinophilic disorders. Increased levels of IL-5 receptor α and lymphocyte IL-5 production after anti–IL-5 therapy suggest an endogenous IL-5 autoregulatory pathway. [Copyright &y& Elsevier]

Background: Eosinophilic esophagitis (EE) is characterized by high numbers of eosinophils in the esophagus and epithelial hyperplasia, and is being increasingly recognized. IL-5 promotes eosinophil trafficking to the esophagus, and positively regulates eosinophil growth, activation, survival, and tissue recruitment. Objective: We hypothesized that the humanized monoclonal IgG1 antibody against human IL-5 (mepolizumab) may be useful in the control of EE. Methods: An open-label phase I/II safety and efficacy study of anti–IL-5 in 4 adult patients with EE and longstanding dysphagia and esophageal strictures was conducted. Patients received 3 infusions of anti–IL-5 (750 mg intravenously monthly) without change in their current therapy. The levels of plasma IL-5, peripheral blood eosinophils, and CCR3+ cells in blood, quality of life measurements, and histological analysis of esophageal biopsies were determined before and 1 month after treatment. Results: Peripheral blood eosinophilia and percent of CCR3+ cells decreased by 6.4-fold and 7.9-fold (P < .05), respectively, after anti–IL-5 treatment. Notably, mean and maximal esophageal eosinophilia decreased from 46 to 6 and from 153 to 28 eosinophils/high-power field (×400; average, 8.9-fold, P < .001, and 6-fold, P < .05), respectively. Patients reported a better clinical outcome and improved quality of life (P = .03). Therapy was generally well tolerated, and responsiveness to anti–IL-5 therapy did not correlate with plasma IL-5 levels. Conclusion: Anti–IL-5 therapy is associated with marked decreases in peripheral blood and esophageal eosinophilia (including the number of CCR3+ blood cells) in patients with EE and improved clinical outcomes. Clinical implications: Anti–IL-5 is a promising therapeutic intervention for EE. [Copyright &y& Elsevier]

We report the case of a 50-year-old man with allergic bronchopulmonary mycosis (ABPM) complicated with bilateral septic arthritis of the knees caused by Methicillin-resistant Staphylococcus aureus (MRSA). He had a background of bronchial asthma and end-stage renal failure on maintenance dialysis. He was treated with 30 mg/day of prednisolone for 14 days for ABPM. He developed bilateral septic arthritis of the knees, caused by MRSA during prednisolone treatment. He underwent bilateral arthroscopic washout with a 2-week course of intra-articular arbekacin, concomitantly treated with a 6-week course of intravenous teicoplanin and oral rifampicin, subsequently followed by oral linezolid treatment. However, he suffered exacerbation of ABPM during treatment of septic arthritis. Because of these serious infectious complications, he was treated with mepolizumab instead of corticosteroids for the ABPM, which resolved all symptoms and clinical features. This case highlights mepolizumab treatment as an alternative to corticosteroid therapy for treatment of ABPM in patients with comorbidities such as infection. [ABSTRACT FROM AUTHOR]

Asthma is a complex condition that affects 14% of the world's children and the approach to management includes both pharmacologic as well as non-pharmacologic strategies including attention to complex socioeconomic status phenomena. After an historical consideration of asthma, allergic and immunologic aspects of asthma in children and adolescents are presented. Concepts of socioeconomic aspects of asthma are considered along with environmental features and complications of asthma disparities. Also reviewed are links of asthma with mental health disorders, sleep disturbances and other comorbidities. A stepwise approach to asthma management is discussed that includes pharmacologic and non-pharmacologic strategies in the pediatric population. The role of immunotherapy and use of various immunomodulators are considered as well. [ABSTRACT FROM AUTHOR]

Mepolizumab is approved for patients with severe asthma with an eosinophilic phenotype aged 12 or more (United States) or 6 or more (European Union) years, but its long-term use in children aged 6 to 11 years has not yet been assessed. We sought to assess the long-term safety, efficacy, and pharmacodynamics of mepolizumab in children aged 6 to 11 years with severe asthma with an eosinophilic phenotype. In this open-label, uncontrolled, repeat-dose extension study (NCT02377427), children aged 6 to 11 years with severe asthma with an eosinophilic phenotype (blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL in the previous year) received a body weight–dependent dose of subcutaneous mepolizumab of 40 mg (<40 kg) or 100 mg (≥40 kg) over 52 weeks. End points included the incidence of adverse events (AEs) and immunogenicity (primary), absolute blood eosinophil counts (cells per microliter; secondary), and annualized exacerbation rates and asthma control questionnaire/childhood asthma control test scores (exploratory). Over 52 weeks, 30 children received mepolizumab; 27 (90%) and 7 (23%) experienced on-treatment AEs and serious AEs, respectively. No serious AEs were treatment related. There were no fatal AEs. No specific patterns of AEs were evident, and no anti-drug antibody or neutralizing antibody responses were reported. Compared with baseline values, mepolizumab treatment reduced blood eosinophil counts and asthma exacerbations and improved asthma control across all treatment groups. Long-term safety, pharmacodynamic, and efficacy data from this study support a positive benefit-risk profile for mepolizumab in children with severe asthma with an eosinophilic phenotype and were similar to data in studies in adults and adolescents. [ABSTRACT FROM AUTHOR]

Severe asthma affects between 5 and 10% of patients with asthma worldwide and requires best standard therapies at maximal doses. A subgroup of patients remains refractory to all treatments. We describe two case reports with severe allergic asthma who progressively worsened over the years despite the best therapy. The patients were first treated with omalizumab, which was completely ineffective, and then with bronchial thermoplasty (BT), again without clinical benefit. Since our patients met the AIFA criteria for inclusion in mepolizumab treatment, a therapy with this anti-IL5 biological agent was initiated. In the first case (a 53-year-old female), after the second mepolizumab administration, symptoms improved progressively, with a reduction in the number and severity of exacerbations, so the patient could finally be discharged from hospital. At follow-up, it was possible to reduce oral corticosteroids and continuing with inhaled corticosteroids/long-acting beta-agonists and montelukast. The patient had only one exacerbation/year. Symptom control and quality of life improved significantly. In the second case report (a 55-year-old male), after the sixth mepolizumab administration, symptoms improved progressively, with a reduction in the number and severity of exacerbations. At follow-up, it was possible to reduce and stop oral corticosteroids, continuing with inhaled therapy and montelukast. Symptom control and quality of life improved significantly.These are the first cases of patients unresponsive to sequential omalizumab and BT but with good and prolonged clinical response to mepolizumab. Both cases suggest that also after the failure of two consecutive third-line treatments, a third treatment (mepolizumab) should be attempted. [ABSTRACT FROM AUTHOR]

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction that is associated with an allergic immunological response to Aspergillus species via Th2-related inflammation. The long-term use of a systemic corticosteroid is often needed for the treatment of ABPA. However, systemic corticosteroid treatment imposes a risk of the onset of a nontuberculous mycobacterial infection. Here we report the case of a patient with ABPA who required the long-term use of an oral corticosteroid because her repeated asthmatic attacks were successfully treated with mepolizumab, an anti-interleukin-5 monoclonal antibody. The patient, a 60-year-old Japanese female, had been treated with an oral corticoid and itraconazole. Despite the success of the initial treatment for ABPA, it was difficult to discontinue the use of the oral corticosteroid. In addition, Mycobacterium avium was detected from her bronchial lavage. We initiated mepolizumab treatment to taper the amount of corticosteroid and control the asthma condition. The patient's number of blood eosinophils, serum IgE level, fractional exhaled nitric oxide level, dosage of oral prednisolone, and need for inhaled budesonide/formoterol all improved, without an exacerbation of her asthma attacks. Although further research regarding mepolizumab treatment is needed, we believe that mepolizumab could be considered one of the agents for treating refractory ABPA. [ABSTRACT FROM AUTHOR]