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Eosinophilic asthma is characterized by frequent exacerbations, poor symptom control and accelerated lung function decline. It is now recognized that the immune response underlying eosinophilic asthma involves a complex network of interconnected pathways from both the adaptive and innate immune systems. Within this response, interleukin‐5 (IL‐5) plays a central role in eosinophil differentiation, activation and survival and has emerged as a key target for therapies treating severe asthma. The monoclonal antibodies mepolizumab and reslizumab target the ligand IL‐5, preventing its interaction with eosinophils; in contrast, benralizumab binds to the IL‐5 receptor (IL‐5R), preventing IL‐5 from binding and leading to substantially greater eosinophil reduction by enhanced antibody‐dependent cell‐mediated cytotoxicity. Although no direct head‐to‐head clinical trials of asthma have been published to formally evaluate the clinical significance of these different therapeutic approaches, the potential benefits of partial versus complete eosinophil depletion continue to remain an important area of study and debate. Here, we review the existing real‐world and clinical study data of anti‐IL‐5/anti‐IL‐5R therapies in severe eosinophilic asthma. [ABSTRACT FROM AUTHOR]

Background: Eosinophils are key therapeutic targets in severe asthma that are suppressed by IL5 (mepolizumab) and IL5 receptor (benralizumab) blockade. The effect of IL5 pathway biologics on recently described homeostatic (hEOs) and inflammatory (iEOs) eosinophil subsets is unknown. We aimed to determine the relative impact of mepolizumab and benralizumab treatment on eosinophil subset and phenotype, and explore clinical associations of eosinophil subsets with severe asthma characteristics and treatment response. Methods: We performed a cross‐sectional observational study of severe asthma (eosinophilic n = 32, non‐eosinophilic n = 23, mepolizumab‐treated n = 25), with longitudinal follow‐up of 30 eosinophilic participants at two timepoints (4–24 weeks, >24 weeks) post‐commencement of mepolizumab (n = 20) or benralizumab (n = 10). Blood hEOs and iEOs were measured by flow cytometry assessment of surface CD62L protein. Results: iEO proportion was significantly lower in mepolizumab‐treated participants in both the cross‐sectional and longitudinal study. Mepolizumab and benralizumab depleted iEOs to a similar extent, however a significantly greater number of hEOs remained in mepolizumab participants at follow‐up. Greater iEO proportion correlated with poorer asthma control in eosinophilic but not non‐eosinophilic asthma. Higher residual iEO proportion correlated with poorer asthma control in mepolizumab‐treated individuals. Reduced blood eosinophil viability was observed in around half of mepolizumab‐treated participants, which was associated with significantly better asthma control and spirometry. Conclusions: Mepolizumab depletes iEOs and reduces circulating eosinophil viability in severe asthma but preserves a residual population of circulatory hEOs. In contrast benralizumab depleted both iEOs and hEOs. Higher iEO abundance and eosinophil viability are associated with poorer clinical outcomes following mepolizumab‐treatment. Monitoring circulating eosinophil phenotype and viability may be useful to predict biologic treatment response in severe asthma. [ABSTRACT FROM AUTHOR]

We present three cases of eosinophilic granulomatosis with polyangiitis (EGPA) where patients experienced relapse of eosinophilic sinusitis without peripheral eosinophilia while on remission maintenance therapy with mepolizumab (MPZ), an anti-interleukin (IL)-5 monoclonal antibody. Despite the initial control of symptoms with high-dose prednisolone (PSL) and MPZ, patients experienced a relapse of nasal obstruction and eosinophilic infiltration in nasal mucosal biopsies. Notably, relapses occurred despite normal peripheral eosinophil counts, indicating the localized nature of eosinophilic inflammation. While IL-5 inhibitors effectively reduce peripheral blood eosinophils, eosinophilic sinusitis may persist due to local factors such as IL-4-mediated inflammation. IL-4 has been implicated in promoting eosinophil migration into nasal tissues, suggesting that IL-5 inhibitors alone may not sufficiently suppress eosinophilic infiltration in such cases. These findings highlight the importance of considering the possibility of eosinophilic sinusitis relapse in EGPA patients treated with IL-5 inhibitors and reduced glucocorticoid doses. Further research is warranted to elucidate the mechanisms underlying local eosinophilic inflammation and optimize treatment strategies for EGPA patients. [ABSTRACT FROM AUTHOR]

Mepolizumab, an anti-interleukin-5 antibody, has been proven a safe and effective glucocorticoid (GC)-sparing drug for many patients with nonclonal hypereosinophilic syndrome (HES) and is now approved in many countries. It remains unclear, however, which patients are most likely to benefit from therapy and whether the currently approved dosing regimen is appropriate for all. This observational retrospective study included all patients with HES who were enrolled in the MHE104317 compassionate use program (CUP) in our center. Patient and disease characteristics, mepolizumab dosing, and both clinical and hematological responses to treatment were collected from medical files. Treatment responses and mepolizumab dosing requirements were analyzed according to disease characteristics. Eighteen patients with HES were enrolled in the CUP, of whom nine are still on treatment. The median duration of exposure to mepolizumab was 45 mo (maximum 18 yr). A lower number of affected organs, requirement for GC dosing ≤10 mg prednisone-equivalent, and single-organ HES were associated with a higher likelihood of complete response. Lymphocytic variant HES (L-HES) was less treatment-responsive, leading to withdrawal and/or requiring higher mepolizumab dosing to achieve some degree of disease control. In contrast, all patients with single-organ disease had a complete response that could often be maintained despite increasing between-dose intervals. Few potentially treatment-related adverse events were observed despite prolonged exposure. This study confirms the efficacy and safety of mepolizumab in HES, although patients with L-HES rarely experience a complete response. In contrast, patients with single-organ disease affecting the lungs are often super-responders, and decreasing mepolizumab dosing may be attempted. [ABSTRACT FROM AUTHOR]

Introduction: The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies. Methods: A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation. Primary endpoint: incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores). Results: Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19–0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of − 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation. Conclusion: Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article. Plain Language Summary: Severe asthma occurs when asthma symptoms remain uncontrolled despite optimised treatment. In many low-middle income countries, and in some countries in the Middle East, Asia, Latin America and the Arab Gulf, the management and treatment of patients with severe asthma remain poor, with many patients having unscheduled hospital visits or admission, and use of steroids for a prolonged period. Mepolizumab is an injectable monoclonal antibody approved as an add-on treatment for severe asthma in patients ≥ 6 years of age. In clinical trials, mepolizumab has demonstrated reductions in the risk of clinically significant exacerbations (CSE; an asthma exacerbation that requires systemic corticosteroids and/or an emergency room visit and/or hospitalisation) and the need for oral corticosteroid (OCS) treatment in patients with severe asthma by reducing inflammation caused by eosinophil (a type of white blood cell) production. The Nucala Effectiveness Study (NEST) was performed to observe the effectiveness of mepolizumab in people with severe asthma in Colombia, Chile, India, Turkey, Saudi Arabia, United Arab Emirates, Kuwait, Oman and Qatar. The frequency of CSEs and other outcomes was compared 12 months pre- and post-mepolizumab initiation. Post-initiation, the risk of CSEs was significantly reduced by 76% (p < 0.001), and 72% of patients had no CSEs. Fewer patients were dependent on OCS, with 36.1% of patients not using OCS at all, and fewer patients were hospitalised. Lung function and asthma control also improved. NEST shows that mepolizumab could benefit people with severe asthma living in countries where disease-related burden and OCS use remain high. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings. Objectives: This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM). Results: After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012). Conclusion: Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodResultConclusionMepolizumab, an anti-IL-5 monoclonal antibody, has shown promise in reducing exacerbations and steroid dependency in severe eosinophilic asthma. This study aims to evaluate the effectiveness of mepolizumab in achieving clinical remission in asthma over 12 months and explore Vitamin D levels as a predictor of response.We assessed Asthma Control Questionnaire (ACQ) scores, spirometry, number of exacerbations, oral corticosteroid (OCS) use, and inhaled corticosteroid (ICS) use in 32 patients, observing significant clinical improvements. Data were collected 1 year prior to starting mepolizumab and one year after starting mepolizumab. Nasal polyps were not seen in all the patients, and computed tomography of para-nasal sinuses are not available for all the patients, so nasal polyps status are not evaluated to avoid any bias.Our results indicate that 12 patients achieved clinical remission after starting mepolizumab, with a strong correlation between higher Vitamin D levels and positive treatment outcomes. This suggests that optimizing Vitamin D levels could enhance the response to mepolizumab in asthma patients, and help in achieving better asthma control.Mepolizumab is an effective treatment for severe eosinophilic asthma, significantly improving clinical outcomes and reducing corticosteroid use. This study highlights the importance of Vitamin D as a predictor of response to mepolizumab, suggesting that higher Vitamin D levels may enhance treatment efficacy. [ABSTRACT FROM AUTHOR]

Key points: CRSwNP‐specific mean total annual spending ranged from $5,837 (EDS‐FLU) to $28,058 (dupilumab).Most CRSwNP patients receiving biologics had comorbid asthma and did not undergo sinus surgery.While biologics were covered by most Medicare Part D plans, only 37% of plans covered EDS‐FLU. [ABSTRACT FROM AUTHOR]

Introduction: Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is heterogeneous in both phenotypes and endotypes. Due to insufficient head-to-head comparison studies, it is hard to decide which biological to initiate. This study aimed to compare the efficacy of omalizumab and mepolizumab which can be used in the treatment of patients with severe eosinophilic asthma diagnosed with N-ERD. Methods: The population of this observational, cross-sectional study comprised of N-ERD patients who received omalizumab or mepolizumab for at least 6 months for severe asthma. Outcomes included the asthma control test (ACT), and sino-nasal outcome test scores (SNOT-22), blood eosinophil counts at initiation of biological treatment (T0, baseline) and at the end of 6th months (T6). Adverse effects related to biological treatment and changes of oral corticosteroids dose was recorded. Results: The study included a total of 22 patients, of whom 11 received mepolizumab and 11 received omalizumab. The change in ACT, SNOT-22, eosinophil counts, and adverse effects related to biologicals were similar at T6 (p = 0.606, p = 0.168, p = 0.05, p = 0.053, respectively). However, when examining the SNOT-22 and ACT based on the cumulative distribution curve (SUCRA), mepolizumab (SUCRA value: 0.61, 0.72, respectively) demonstrated greater efficacy compared to omalizumab (SUCRA value: 0.19, 0.35, respectively). The oral corticosteroids discontinuation rate was similar between the two groups (p = 0.05). Conclusion: We found both omalizumab and mepolizumab to be effective in treatment; however, we determined that mepolizumab may have a potential superiority in efficacy. [ABSTRACT FROM AUTHOR]

[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]

AbstractObjectiveMethodsResultsConclusionsThis study aimed to compare the clinical characteristics and treatment outcomes of allergic patients (AP) and non-allergic patients (NAP) with severe eosinophilic asthma (SEA) treated with anti-IL5/IL5R biologic agents (mepolizumab, benralizumab, or reslizumab) over one year. Sub-analyses assessed treatment response variations between AP and NAP based on the biological used and compared outcomes among AP with and without fungal allergy.Observational retrospective analysis. Clinical characteristics, laboratory findings, pulmonary function tests, Asthma Control Test (ACT) scores, oral corticosteroid (OCS) usage, and exacerbation frequency were assessed at the initiation of biological treatment and after one year.Sixty-five patients with SEA were included, 41 AP and 24 NAP. 55.4% were treated with mepolizumab, 33.8% with benralizumab, and 10.8% with reslizumab. Before anti-IL5/5R treatment, AP had worse baseline outcomes but there were no differences in pulmonary function. Mean annual exacerbation rate and percentage of patients requiring OCS and dose of prednisone were higher in AP than NAP. AP had significantly higher total IgE values. After one year of treatment, more AP discontinued OCS than NAP (p = 0.025). Both experienced a significant reduction in exacerbation frequency (p = 0.001) and improved respiratory function. 70.7% of AP and 60% of NAP improved ACT ≥3 points. There was no significant difference between AP and NAP using mepolizumab (p = 0.145) or benralizumab (p = 0.174) in reducing OCS.Anti-IL5/IL5R reduced the need for OCS and improved asthma control, regardless of allergic status. Fungal allergy led to lower ACT scores and higher exacerbations than other allergens; both groups improved with anti-IL5/ILR. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common chronic inflammatory diseases of childhood with a heterogeneous impact on health and quality of life. Mepolizumab is an antagonist of interleukin-5, indicated as an adjunct therapy for severe refractory eosinophilic asthma in adolescents and children aged >6 years old. We present the case of a 9 year-old boy with severe asthma who experienced several asthmatic exacerbations following a SARS-CoV-2 infection, necessitating therapy with short-acting bronchodilators, oral corticosteroids, and hospitalization. We follow the patient using validated questionnaires for the evaluation of asthma control: Children Asthma Control Test, Asthma Control Questionnaire, respiratory function tests, and evaluation of exhaled nitric oxide fraction. After 12 weeks from the start of therapy with mepolizumab, we found significant improvements in lung function, a reduction in the degree of bronchial inflammation, and improvements in quality of life. No asthmatic exacerbations have been reported since the initiation of treatment with mepolizumab. Respiratory infections, such as those related to SARS-CoV-2, represent a significant risk factor for exacerbations in patients with moderate to severe forms of asthma. In our experience, following new episodes of exacerbation, the initiation of treatment with mepolizumab has allowed us to improve asthma control and enhance the quality of life of patients from the first doses. Although mepolizumab showed promise in this child with severe asthma during SARS-CoV-2 infection, the results from this single case cannot be generalized. Further studies are needed to confirm its safety and effectiveness. [ABSTRACT FROM AUTHOR]

Few reports have described the treatment of eosinophilic pneumonia (EP) complicated by refractory pneumothorax. A 62‐year‐old man with a medical history of ulcerative colitis who was undergoing maintenance treatment presented with fever, cough, and diffuse bilateral consolidation on chest radiography. Laboratory findings showed peripheral eosinophilia, and he was hospitalized with a diagnosis of drug‐induced EP and started on corticosteroid therapy. During the course, he developed refractory pneumothorax, and it was difficult to control the air leakage. As it was necessary to control the eosinophilic inflammation and air leakage, mepolizumab, a humanized anti‐interleukin‐5 monoclonal antibody, and an endobronchial Watanabe spigot (EWS), were introduced. After EWS insertion, the leakage of the refractory pneumothorax disappeared. The patient continued to have no recurrence of EP or pneumothorax after the removal of the EWS. The combination of mepolizumab and an EWS may be effective in cases of EP complicated by refractory pneumothorax. [ABSTRACT FROM AUTHOR]

Objectives: We report the prevalence of eosinophilic granulomatosis with polyangiitis (EGPA) and describe oral corticosteroid (OCS) use and disease burden before and after the mepolizumab approval in 2018 for EGPA in Japan. Methods: Two retrospective studies (GSK IDs: 218083 and 218084) used two databases: (1) the JMDC insurer database (Japanese health insurer claims) was used to report annual EGPA prevalence and OCS use in mepolizumab-treated patients and (2) Medical Data Vision database was used to report annual treatment use, OCS dose, relapses, and healthcare resource utilization in patients with EGPA. Results: EGPA prevalence (95% confidence interval) increased from 4.2 (0.1, 23.4) in 2005 to 58.6 (53.2, 64.5) per 1,000,000 in 2020. Median OCS dose (mg/day) decreased from a range of 4.8–7.7 during 2010–2017 to 4.5–4.8 during 2018–2020 (lowest dose in 2020). The proportion of patients with prednisolone-equivalent daily OCS dose >10 mg decreased from 2017 (11.9%) to 2020 (10.3%), while the median dose halved. The proportion of patients with EGPA relapses (64.3% to 41.6%) and hospitalization (27.8% to 23.6%) decreased from 2010 to 2020. Conclusions: EGPA prevalence increased between 2005 and 2020. With the introduction of mepolizumab for EGPA in 2018, real-world OCS use, relapses, and healthcare resource utilization decreased. [ABSTRACT FROM AUTHOR]

Introduction: Severe asthma is a chronic respiratory condition that affects a significant number of individuals, causing persistent inflammation of the airways and leading to recurrent symptoms such as wheezing, coughing, and shortness of breath. While conventional asthma treatments, including inhaled corticosteroids and bronchodilators, are generally effective for most asthma patients, they may not always provide sufficient relief for individuals with severe asthma. In such cases, the use of biologic agents licensed specifically for severe asthma can be a valuable treatment option. Aim of the study: This article aims to explore the different biologic agents licensed for severe asthma and delve into their effectiveness in managing this complex and challenging condition. Material and methods: Literature available in the PubMed database was reviewed using the following keywords: biologic agents for asthma; omalizumab; mepolizumab; bernalizumab; tezepelumab; monoclonal antibodies. Conclusions: These medications are designed to target the underlying mechanisms of severe asthma, addressing the root causes of the condition rather than just managing the symptoms. As a result, they have shown promising results in improving symptoms and reducing exacerbations in individuals with severe asthma. By understanding the potential benefits of these medications, healthcare professionals can make informed decisions when it comes to treating patients with severe asthma. [ABSTRACT FROM AUTHOR]

Background: Specific biomarkers, such as eosinophilia in peripheral blood or fractional exhaled nitric oxide (FeNO), can guide us in the choice of biologic therapy, allowing a more personalized approach. Although there are multiple evidences in the literature about the role of FeNO as a predictor of response to different biologic treatments, there are no data on the relationship between FeNO changes and clinical response to the four biologic drugs currently in use. Objective: To evaluate and to compare the expression of multiple-flows FeNO parameters in a cohort of patients with severe asthma (SA) before and during the treatment with biologics to evaluate the performance of these biomarkers in predicting the achievement of clinical remission. Methods: We prospectively enrolled 50 patients with severe asthma eligible for biologic therapy. Patients underwent clinical and functional monitoring at baseline (T0) and after 1, 6, and 12 months of treatment (T1, T6, T12), including multiple flows FeNO assessment. Results: A statistically significant reduction of FeNO50 values and J'awNO was observed only in benralizumab and dupilumab subgroups. Among biomarkers, the reduction of FeNO 50 values at T1 was associated with a higher probability of achieving clinical remission at T12 (p = 0.003), which was also confirmed by ROC curve analysis (AUC 0.758, p = 0.002; sensitivity 60% and specificity 74% for a reduction of 16 ppb). Conclusion: These data confirm the potential of this biomarker in predicting clinical response to biologic treatment in patients with severe asthma in order to guide clinical decisions and evaluate a shift to other biologic therapy. [ABSTRACT FROM AUTHOR]

Reduced sense of smell is a common symptom in patients with chronic rhinosinusitis (CRS). Although it is often under-diagnosed by healthcare providers, reduced sense of smell can have a substantial negative impact on patient's quality of life as measured by health-related quality of life (HRQoL) assessments and patient-reported outcomes. This narrative review describes current smell loss diagnosis and management guidelines in CRS, and the relationship between smell loss and CRS. Reduced sense of smell can be an indication of CRS disease severity in patients with (CRSwNP) and without nasal polyps (CRSsNP), and recovery of smell can be an indicator of successful CRS treatment. The current first-line therapeutic options for smell loss are intranasal corticosteroids and nasal irrigation, and second-line therapeutic options include systemic steroids and surgery. Shared decision-making between patient, caregiver, and healthcare provider is important when choosing the most appropriate CRS treatment option. Emerging biologic therapies that target type 2 inflammation signaling pathways, such as dupilumab, omalizumab, and mepolizumab, have been shown to improve smell and taste in randomized controlled trials of patients with CRSwNP. A graphical abstract and video abstract are available with this article. Plain Language Summary: Chronic rhinosinusitis (CRS) is an inflammatory condition often associated with a loss of smell and taste. Patients with CRS and a loss of smell often rate their quality of life as poor and are more likely to also suffer from depression and anxiety than patients without smell loss. Patients with severe smell loss are also more likely to have increased severity of CRS disease by other measures. Standard treatments for smell loss include topical steroids, corticosteroids absorbed into the whole body system (systemic), and/or sinonasal surgery, but the effects may not last, and patients may experience side effects when they use repeated short bursts or long-term treatment with systemic corticosteroids. A newer treatment option for CRS is biologic therapy, which targets the immunologic pathways associated with inflammation. Biologic therapies have been shown to be effective in the treatment of CRS with nasal polyps including improvement in sense of smell. Here, we review the most common diagnostic tests and treatment options for CRS-associated smell loss and show how severity of smell loss is linked to severity of CRS. -o4AhrHG7BfpfqMBka8hwD Supplementary file1 (MP4 60193 kb) [ABSTRACT FROM AUTHOR]

Background: Some patients with severe asthma may benefit from treatment with biologics, but evidence has been mostly collected from randomized controlled trials (RCTs), in which patients' characteristics are different from those encountered in asthma patients in the real-world setting. The aim of this study was to describe the clinical features of complete responders versus non-complete responders to long-term treatment with biologics in patients with severe asthma attended in routine daily practice. Methods: Data of a cohort of 90 patients with severe asthma who were treated with biologics (omalizumab, benralizumab, and mepolizumab) for at least 12 months and were followed up to March 2022. Data recorded included clinical characteristics and effectiveness of treatment (exacerbation, Asthma Control Test [ACT] score, lung function, use of maintenance oral corticosteroids [mOCS]), FeNO, and blood eosinophils at baseline, at 12months, and at the end of follow-up. Complete response is considered if, in addition to not presenting exacerbations or the use of mOCS, the ACT score was >20 and, the FEV1 >80% predicted. Results: An improvement in all asthma control parameters was observed after 12months of treatment and a mean follow-up of 55months. After 12months of treatment 27.2% of patients met the criteria of complete response and this percentage even increased to 35.3% at the end of follow-up. Long-term complete response was associated to better lung function with mepolizumab and omalizumab treatment and to less previous exacerbations in the benralizumab group. The main cause of not achieving a complete response was the persistence of an airflow obstructive pattern. Conclusions: This study shows that omalizumab, benralizumab, and mepolizumab improved the clinical outcomes of patients with severe asthma in a clinic environment with similar effect sizes to RCTs in the long term follow-up. Airflow obstruction, however, was a predictor of a non-complete response to biologics. [ABSTRACT FROM AUTHOR]

Background: Patients with severe asthma are often dependent on oral corticosteroids (OCS) and have frequent exacerbations. This article aims to report very long-term data of patients with severe eosinophilic asthma assessing asthma control, lung function, inhaled corticosteroid (ICS) dose reduction, and clinical and biological parameters of patients treated with mepolizumab. Methods: Four cases of adult patients with severe eosinophilic asthma who were treated for 60 months or more with mepolizumab 100 mg/4 weeks, leading to the stable discontinuation of OCS, are presented. ICS dose, OCS dose and withdrawal date, lung function, eosinophil count, fractional exhaled nitric oxide, and asthma control test were recorded as well as exacerbations in the 12 months before commencing mepolizumab and in the 12 months before the last follow-up visit. Results: Three of the patients were men, median age was 52.5 years (range 79–53), median length of asthma before mepolizumab start was 67.5 months (range 24–240), three had chronic rhinosinusitis without nasal polyposis and two were atopic. All had eosinophil counts >300 cells/μL at baseline. The median follow-up was 73.5 months (range 71–74), and OCS withdrawal from baseline occurred after a median of 13 months of mepolizumab treatment (range 12–39). A substantial reduction of ICS treatment was registered as well as improvement in asthma control test, fractional exhaled nitric oxide and functional parameters, and a significant reduction of exacerbations in the last 12 months before last visit was observed as compared to the 12 months before baseline (from a median of 4 (range 3–6) to 0; p=0.0286). Conclusions: Mepolizumab could be a ‘disease-modifying’ agent, with high tolerability and a good efficacy profile in the long term.

Objective: 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. Methods: 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. Results: 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). Conclusion: 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.

Background: Severe eosinophilic asthma (SEA) is often linked to a dysregulation in the Interleukin-(IL)-5 axis. Mepolizumab, a humanized monoclonal antibody, reduces eosinophils by directly binging to IL-5, potentially restoring homeostatic eosinophil biology, with a significant impact on quality of life, acute exacerbations and oral corticosteroids (OCS) elimination in SEA patients. While its short-and middle-term effects are well described, no study has so far investigated its longlasting effects in SEA patients. The aim of our study was therefore to explore the effects of a long-term, six-year continuous treatment with mepolizumab on clinical control and clinical remission in a cohort of SEA patients. Methods: We conducted a retrospective review of clinical records of patients who were prescribed mepolizumab between June 2017 and April 2018. We collected demographical, functional, and clinical data from visits performed at baseline and then at the specified timepoints and checked if patients had reached clinical remission after 6 years. We assessed asthma control test (ACT), exacerbation rate, and OCS elimination dose at 6 years. Clinical Remission (CR) was defined on the basis of the elimination of OCS and the contemporary presence of all the following: 1) stable lung function; 2) no exacerbation in the previous 12 months; 3) acceptable symptom control (ACT ≥ 20). Results: Of 86 patients screened, 62 were included in the final analysis. Our study suggests that mepolizumab is effective and well tolerated after a six-year course of continuous treatment in patients with SEA. We reported a prevalence of 28 (46.8%) patients who reached complete CR at 72 months from the treatment start. 75% of patients eliminated the maintenance OCS already after 1 year of treatment; this proportion reached the 87% within the sixth year of treatment. Conclusion: Mepolizumab proved to be effective in real-life after 6 years of treatment, inducing a complete clinical remission in the 46.8% of patients, with sustained improvements in quality of life, exacerbation rate, OCS intake and lung function. [ABSTRACT FROM AUTHOR]

Summary The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading to the production of allergen‐specific immunoglobulin E (IgE), a key driver of many allergic conditions. At a high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL‐25, IL‐33, and TSLP, which activate type 2 innate lymphoid cells as well as other immune cells to secrete type 2 cytokines IL‐4, IL‐5 and IL‐13, promoting Th2 cell development and eosinophil recruitment. Th2 cell dependent B cell activation promotes the production of allergen‐specific IgE, which stably binds to basophils and mast cells. Rapid degranulation of these cells upon allergen re‐exposure leads to allergic symptoms. Recent advances in our understanding of the molecular and cellular mechanisms underlying allergic pathophysiology have significantly shaped the development of therapeutic intervention strategies. In this review, we highlight key therapeutic targets within the allergic cascade with a particular focus on past, current and future treatment approaches using monoclonal antibodies. Specific targeting of alarmins, type 2 cytokines and IgE has shown varying degrees of clinical benefit in different allergic indications including asthma, chronic spontaneous urticaria, atopic dermatitis, chronic rhinosinusitis with nasal polyps, food allergies and eosinophilic esophagitis. While multiple therapeutic antibodies have been approved for clinical use, scientists are still working on ways to improve on current treatment approaches. Here, we provide context to understand therapeutic targeting strategies and their limitations, discussing both knowledge gaps and promising future directions to enhancing clinical efficacy in allergic disease management. [ABSTRACT FROM AUTHOR]

Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians in real life. The aim of the study is to define characteristics of a biologic-treated T2-driven-SA population and to evaluate the effectiveness of biologic treatments in a real-world setting by variation in intra/inter-biologic parameters in an up to 4-year follow-up. Methods: Demographic, clinical, functional, and biological characteristics were evaluated retrospectively in 104 patients recruited until July 2022 at baseline (T0) and over a maximum of 4 years (T4) of biologic therapy (omalizumab/OmaG = 41, from T0 to T4, mepolizumab/MepoG = 26, from T0 to T4, benralizumab/BenraG = 18, from T0 to T2, and dupilumab/DupiG = 19, from T0 to T1). Variations of parameters using means of paired Delta were assessed. Results: At baseline, patients had high prevalence of T2-driven comorbidities, low asthma control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV1 65 ± 18 %pred), frequent exacerbations/year (AEs 3.5 ± 3), and OCS dependence (60%). DupiG had lower T2 biomarkers/comorbidities and AEs, and worse FEV1 (57 ± 19 %pred) compared to other biologics (p < 0.05). All biologics improved ACT, FEV1%, FVC%, AEs rate, and OCS use. FEV1% improved in MepoG and BenraG over the minimal clinically important difference and was sustained over 4 years in OmaG and MepoG. A significant RV reduction in OmaG (T4) and DupiG (T1), and BenraG normalization (T2) of airflow limitation were found. We observed through inter-biologic parameters pair delta variation comparison a significant nocturnal awakenings reduction in BenraG vs. OmaG/MepoG, and neutrophils reduction in BenraG/DupiG vs. OmaG. Conclusions: Indirect comparison among biologics unveils clinical and functional improvements that may mark a different effectiveness. These results may highlight the preference of a single biologic compared to another with regard to specific treatable traits. [ABSTRACT FROM AUTHOR]

The aim of this retrospective multicentre study is to describe the clinical characteristics of patients diagnosed with severe eosinophilic asthma receiving anti-IL-5/anti-IL-5Rα therapies and to compare their effectiveness. We collected and analysed results separately for anti-IL-5 and anti-IL-5Rα therapies from January 2016 until December 2021 in multidisciplinary severe asthma units. We collected demographic and clinical data, treatment with previous anti-IgE and/or anti-IL-5 agents, and comorbidities. We compared the number of exacerbations and admissions to the hospital, daily oral corticosteroid intake, pulmonary function tests, and Asthma Control Test scores before and after 12 months of therapy. 261 patients were included: 176 patients in the anti-IL-5 group and 85 in the anti-IL-5Rα group. Both groups led to statistically significant reductions in asthma exacerbations, hospital admissions, and visits to the Emergency Room. Although both groups showed a significant reduction in blood eosinophiliccount, we found a difference, although not significant, in the magnitude of reduction as benralizumab was able to decrease eosinophil counts to zero. Patients in the anti-IL-5 group achieved higher ACT scores after treatment, although this improvement was seen in both treatment groups. The anti-IL-5 and anti-IL-5Rα biologics have shown similar effectiveness despite having different mechanisms of action. The anti-IL-5 group appeared to be better than benralizumab at improving ACT scores and FEV1/FVC and at reducing the number of inhalers. Although these differences were not statistically significant, it is not clear whether they may have clinical relevance and they might highlight the need for further head-to-head studies comparing these treatments. [ABSTRACT FROM AUTHOR]

Mepolizumab is an anti-interleukin-5 monoclonal antibody shown to reduce asthma exacerbations in adults and adolescents with severe eosinophilic asthma. To assess the impact of mepolizumab on children and adolescents over 12 months by examining steroid usage, asthma-related hospitalizations, Asthma Control Test (ACT) scores, fractional exhaled nitric oxide concentration (FeNO), forced expiratory volume in 1 s (FEV1), mid expiratory flow (FEF25–75%), and blood eosinophil count. Retrospective analysis performed between October 2015 and December 2022. Data was reviewed 12 months before and after commencing mepolizumab. Mepolizumab was offered if the patient had severe eosinophilic asthma and were unresponsive to or ineligible for omalizumab. Sixteen participants (age 7–17, 8 males, 8 females) received subcutaneous mepolizumab monthly with no serious adverse reactions. Incidence of hospital admissions fell significantly (IRR 0.33, p = 0.007). Among the 11 patients receiving daily oral corticosteroids, 3 were weaned off daily oral steroids and 3 patients' daily dose was significantly reduced (mean Δ-0.095 ± 0.071 mg/kg, p = 0.0012). Eosinophil count was decreased (mean Δ-0.85 x 109/L, p < 0.001). There was no significant change in mean overall steroid burden per patient (mean Δ-1445.63 ± 1603.18 mg, p = 0.10), ACT scores (mean Δ2.88 ± 6.71, p = 0.17), FEV1 z-scores (mean Δ-0.99 ± 1.88, p = 0.053), FEF25–75% z-scores (mean Δ-0.65 ± 1.61, p = 0.13), FeNO (mean Δ-20.09 ± 80.86, p = 0.34), or number of courses of oral steroids given for asthma attacks (IRR 0.71, p = 0.09). Among children and adolescents with severe eosinophilic asthma ineligible for or not responsive to omalizumab, mepolizumab therapy exhibited significant reduction in rate of asthma-related hospitalizations and significant decrease in daily steroid dosage. [ABSTRACT FROM AUTHOR]

The most promising treatment options for severe uncontrolled asthma (SUA) have emerged in recent years with the development of monoclonal antibodies for blocking selective targets responsible for the underlying inflammation, such as mepolizumab and benralizumab. However, there is variability in treatment response that is not fully controlled. The variability of the response to mepolizumab and benralizumab could be influenced by single-nucleotide polymorphisms (SNPs), and it would be useful to detect these and use them as predictive biomarkers of response. We conducted a retrospective observational cohort study of 72 Caucasian patients recruited from a tertiary hospital with severe uncontrolled eosinophilic asthma treated with mepolizumab and benralizumab. Polymorphisms in the IL5 (rs4143832, rs17690122), RAD50 (rs11739623, rs4705959), IL1RL1 (rs1420101, rs17026974, rs1921622), GATA2 (rs4857855), IKZF2 (rs12619285), FCGR2A (rs1801274), FCGR2B (rs3219018, rs1050501), FCGR3A (rs10127939, rs396991), FCER1A (rs2251746, rs2427837), FCER1B (rs1441586, rs573790, rs569108), and ZNF415 (rs1054485) genes were analyzed by real-time polymerase chain reaction (PCR) using Taqman probes. The response was analyzed after 12 months of treatment. In patients under mepolizumab treatment, a treatment response defined as a reduction in exacerbations was associated with ZNF415 rs1054485-T (p = 0.042; OR = 5.33; 95% CI = 1.06–30.02), treatment response defined as a reduction in oral corticosteroids use was associated with the number of exacerbations in the previous year (p = 0.029; OR = 3.89; 95% CI = 1.24–14.92), and treatment response defined as improvement in lung function was associated with the age at the beginning of biological therapy (p = 0.002; OR = 1.10; 95% CI = 1.04–1.18), FCER1B rs569108-AA (p < 0.001; OR = 171.06; 95% CI = 12.94–6264.11), and FCER1A rs2427837-A (p = 0.021; OR = 8.61; 95% CI = 1.71–76.62). On the other hand, in patients under benralizumab treatment, treatment response, defined as a reduction in exacerbations, was associated with ZNF415 rs1054485-T (p = 0.073; OR = 1.3 × 108; 95% CI = 1.8 × 10−19–NA), FCER1B rs569108-AA (p = 0.050; OR = 11.51; 95% CI = 1.19–269.78), allergies (p = 0.045; OR = 4.02; 95% CI = 1.05–16.74), and sex (p = 0.028; OR = 4.78; 95% CI = 1.22–20.63); and treatment response defined as improvement in lung function was associated with polyposis (p = 0.027; OR = 9.16; 95% CI = 1.58–91.4), IKZF2 rs12619285-AA (p = 0.019; OR = 9.1; 95% CI = 1.7–75.78), IL5 rs4143832-T (p = 0.017; OR = 11.1; 95% CI = 1.9–112.17), and FCER1B rs1441586-C (p = 0.045; OR = 7.81; 95% CI = 1.16–73.45). The results of this study show the potential influence of the studied polymorphisms on the response to mepolizumab and benralizumab and the clinical benefit that could be obtained by defining predictive biomarkers of treatment response. [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]

Background: Although, in most children with asthma, good symptom control is achieved with a low to moderate dose of inhaled corticosteroids, a small group of patients still experiences frequent symptoms, and even severe exacerbations, impairment of lung function, and reduced quality of life. Some of these subjects with severe asthma require biologic drugs as add-on therapy. In the past decade, numerous monoclonal antibodies have been approved for children or adolescents with severe asthma, in addition to their increasing use in adult asthma. However, the available evidence on how to select the most appropriate biologic based on a single patient's clinical, functional, and laboratory characteristics is still scant, and is insufficient to guide clinicians in the decision-making process of a personalized treatment. Materials and Methods: We report a case series of four patients with severe eosinophilic asthma treated with mepolizumab, an anti-interleukin-5 monoclonal antibody, and review the existing literature on this treatment in children and adolescents. Results: Our patients, all with blood eosinophilia and elevated fractional exhaled nitric oxide levels, developed poor symptom control despite prolonged treatment with high-dose inhaled corticosteroids plus a second controller, addressing the addition of a biologic drug. In all of them, a 12-month treatment with subcutaneous mepolizumab showed a reduction in the blood eosinophil count and in asthma exacerbations, as well as an improvement on the Asthma Control Test. The results of the literature search focused on the strengths and limitations of the pediatric use of mepolizumab and highlighted the areas worthy of further research. Conclusions: Mepolizumab has proven effective in improving symptom control in pediatric patients with severe asthma. Additional well-powered clinical trials will be helpful in developing evidence-based guidelines regarding biologic drugs in the pediatric population. [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES—Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches. [ABSTRACT FROM AUTHOR]

This article discusses a case of subarachnoid hemorrhage (SAH) associated with eosinophilic granulomatosis with polyangiitis (EGPA), a rare autoimmune disease. The patient experienced SAH along with other symptoms such as purpura, peripheral neuropathy, lung lesions, and rapidly progressive glomerulonephritis. Treatment included immunosuppressive therapy and the use of mepolizumab, a monoclonal antibody. The article highlights the importance of recognizing SAH as a potentially fatal complication of EGPA and the need for prompt treatment. Further research is needed to evaluate the effectiveness of mepolizumab for CNS involvement in EGPA. [Extracted from the article]

Anti-interleukin (IL) 5 is an effective treatment modality for inhibiting eosinophilic inflammation in patients with T2-high severe asthma. The aim of this study was to determine the clinical efficacy and serum levels of type 2 inflammatory mediators during 24 weeks of mepolizumab treatment in patients with T2-high severe asthma. Eighteen patients with T2-high severe asthma were enrolled in this study. All patients received 100 mg of mepolizumab subcutaneously every 4 weeks and were retested at 4, 12, and 24 weeks. A clinical examination, asthma control test (ACT), and spirometry were performed; fractional exhaled nitric oxide (FeNO) levels were evaluated; and blood samples were drawn at every visit. Type 2 inflammation mediator levels were measured using enzyme-linked immunosorbent assay (ELISA). The blood eosinophil level significantly decreased, the ACT score and FEV1 increased after 4 weeks of mepolizumab treatment with the same tendency after 12 and 24 weeks (p < 0.05), and the FeNO level did not change (p > 0.05). A total of 27.8% of patients reached clinical remission criteria after 24 weeks of mepolizumab treatment. IL-33 and eotaxin significantly increased (p < 0.05) while IL-5, IL-13, thymic stromal lymphopoietin (TSLP), soluble IL-5 receptor subunit alpha (sIL-5Rα), and soluble high-affinity immunoglobulin E receptor (sFcεRI) decreased, with the same tendency after 12 and 24 weeks (p < 0.05). The serum levels of immunoglobulin (Ig) E and IL-4 and IL-25 levels did not change during mepolizumab treatment compared to baseline (p > 0.05). In conclusion, treatment with mepolizumab over 24 weeks improved lung function and asthma control in T2-high severe asthma patients, with nearly one-third achieving clinical remission criteria, and affected the balance of type 2 inflammatory mediators. [ABSTRACT FROM AUTHOR]

Key points: In 2021, Medicare spending on biologics was $926 million in Part B (FFS) and $1.3 billion in Part D (FFS/MA).Between 2017 and 2021, annual Medicare spending on biologics increased by approximately 200%.Between 2023 and 2025, Medicare Part D OOP costs for biologics will decrease by an estimated 50%–60%. [ABSTRACT FROM AUTHOR]

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare autoimmune disorder characterized by necrotizing vasculitis, asthma, and eosinophilia. We report a case of EGPA that developed during benralizumab treatment for severe asthma and provide a literature review. A 79‐year‐old Japanese male with severe asthma presented with generalized purpura 4 months after initiating benralizumab treatment. He had reduced his oral prednisolone dose from 7.5 to 2 mg/day. Laboratory tests revealed eosinophilia, and skin biopsy showed vasculitis with eosinophilic infiltration. He was diagnosed with EGPA and treated with corticosteroids, azathioprine, and mepolizumab, which led to rapid improvement and sustained remission. Five cases of EGPA developing during benralizumab treatment have been reported, with onset ranging from 14 to 36 weeks after initiation. Clinicians should monitor for EGPA development in patients receiving benralizumab, particularly during oral corticosteroid reduction. [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]

Objective: To investigate the frequency and nature of adverse events related to type 2 biologic use in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including dupilumab and mepolizumab. Methods: This is a single‐institution retrospective study of real‐world patient data. Patients were included if they have a diagnosis of CRSwNP, have undergone at least one endoscopic sinus surgery, and have taken at least two doses of dupilumab or mepolizumab between January 1, 2016, and July 1, 2023. Data collected include clinicodemographic information and past medical/surgical history. The primary outcomes are the incidence and types of adverse events. Adjusted odds ratio was calculated to compare the biologics using logistic regression. Risk factors for developing adverse events were investigated. Results: Eighty‐seven patients on dupilumab and 51 patients on mepolizumab were included. Thirty‐nine (45%) and 10 (20%) patients respectively encountered adverse events, which differed from phase 3 trial data. The adjusted odds ratio for adverse event rates between these two treatment groups was 3.8 (95% CI, 1.5–10.5). The most common adverse events for dupilumab were arthralgia (16%), rash (14%), and conjunctivitis or xerophthalmia (10%). The main adverse events for mepolizumab were headache (6%) and fatigue (6%). Seven dupilumab and three mepolizumab patients discontinued therapy due to adverse events. The average duration of treatment was 22.5 (range: 1–77) months for mepolizumab and 15.9 (range: 1–35) months for dupilumab. Conclusion: Dupilumab and mepolizumab have distinct adverse event profiles. This study contributes to informing clinicians' decisions regarding the use of type 2 biologics in CRSwNP patients. Level of Evidence: 3 Laryngoscope, 134:3054–3059, 2024 [ABSTRACT FROM AUTHOR]

Interleukin-5 functions as a B-cell differentiation factor, but more importantly, in the context of this review, it plays a variety of roles in eosinophil biology, including eosinophil differentiation and maturation in the bone marrow, and facilitates eosinophil migration to tissue sites, usually in the context of an allergic reaction. Given the availability of selective anti-IL-5 drugs such as mepolizumab and reslizumab, as well as the IL-5 receptor antagonist benralizumab, it is worth investigating whether they could be used in some cases of allergic disease. Asthma has a well-documented involvement of IL-5 in its pathophysiology and has clear benefits in the case of anti-IL-5 therapy; therefore, current knowledge is presented to provide a reference point for the study of less-described diseases such as atopic dermatitis, chronic rhinosinusitis, chronic spontaneous urticaria, and its association with both IL-5 and anti-IL-5 treatment options. We then review the current literature on these diseases, explain where appropriate potential reasons why anti-IL-5 treatments are ineffective, and then point out possible future directions for further research. [ABSTRACT FROM AUTHOR]

Background: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. Methods: A retrospective data analysis was jointly conducted at the Otolaryngology–Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow–up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. Results: Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. Conclusions: Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients' response to biological treatment in CRSwNP. [ABSTRACT FROM AUTHOR]

Mepolizumab is a therapy for severe asthma. We have little knowledge of the characteristics of people in the US that discontinue mepolizumab in clinical care. To investigate the real-world efficacy and time to clinical discontinuation of mepolizumab, we evaluated individuals with asthma started on mepolizumab at the Cleveland Clinic. We hypothesized that individuals that discontinue mepolizumab have more severe and uncontrolled asthma at baseline. Between 2016 and 2022, patients who started on mepolizumab consented to be assessed over 18 months. At baseline, a questionnaire including demographic and medical history was collected. Laboratory findings such as ACT score, FENO (Fractional Excretion of Nitric Oxide), and spirometry were recorded. At the conclusion of the observation period, the participants were divided into two categories: Group A and Group B. Group B [N = 28] discontinued mepolizumab (p < 0.05) at an average of 5.8 months (SD 4.2 months). Group A [N = 129] stayed on the therapy for at least 1 year. A participant with an ACT score less than 13 has an odds ratio of 6.64 (95% CI, 2.1 − 26.0) of discontinuing mepolizumab therapy. For a male, the odds of discontinuing mepolizumab therapy is 3.39 (95% CI, 1.1–11.2). In this real-world study, we find that high eosinophil count may not be adequate in screening which individuals will benefit from mepolizumab. Up to 17% of patients fail therapy within 6 months, with male sex and low ACT score increasing risk of mepolizumab discontinuation at Cleveland Clinic. [ABSTRACT FROM AUTHOR]

Biologic drugs have been shown to reduce asthma exacerbations, improve lung function and quality of life, reduce oral corticosteroid use in appropriately selected patients. Mepolizumab has been demonstrated to have a safety profile that is similar to placebo, however, when present side effects may lead to treatment discontinuation. Among these, headache is one of the most common. We hereby describe the case of a never-smoking male patient with an eosinophilic corticosteroid-dependent severe asthma. He displayed well controlled comorbidities and good adherence to the inhaled therapy. Mepolizumab was started in 2017 with an initial remarkable clinical improvement. After three doses of biologic therapy, he reported a severe orthostatic headache associated with vomiting, unresponsive to analgesic drugs, that required hospitalization. No other cause than treatment with Mepolizumab was found to be plausibly associated with this new-onset headache. The therapeutic regimen was modified by administering Mepolizumab for two consecutive months alternated with a one-month break. The patient did not experience any further episodes of headache, while maintaining a good and stable control of his asthma. We were able to taper oral corticosteroids, and no flares-ups occurred in the following 5 years. Our experience indicates that a tailored strategy for managing severe asthmatic patients, who have experienced side effects from biologic drugs, can be effective in maintaining drug efficacy while minimizing side effects. Further studies on a larger number of patients are required to demonstrate whether the positive outcomes here described are replicable on a larger scale. [ABSTRACT FROM AUTHOR]

Clinical trials and real world studies demonstrated benefit of mepolizumab treatment in severe asthma but data on its effectiveness beyond 2 years remain limited. Herein, we provide mepolizumab treatment evaluation up to 4 years. we studied all patients initiated on mepolizumab in our center from June 2017 to August 2018. Clinical outcomes data were retrieved from the local dendrite systems registry. Comparison analyses and logistic regression were conducted to explore longevity and predictors of response to mepolizumab treatment. a total of 66 patients initiated on mepolizumab with a median follow-up of 45.8 (42.4,48.1) months were included in the study [mean age 50.3 years (range 18-79), females 50 (73%) ]. At 20.7 months of treatment, 42 patients (63.6%) had positive response, 13 (19.7%) negative response, and 11 (16.7%) discontinued due to other factors. At 45.8 months, 35 (53%) patients were still on mepolizumab, 21 (31.8%) switched to a different biologic, and 10 (15.2%) discontinued biologics. Two deaths were recorded during the study period. The median blood eosinophil was reduced from 0.43x109/L (0.27, 0.75) to 0.04 (0.0, 0.1) (p < 0.00001)]. The median annual exacerbations were reduced from 6.0 (4,8) to 1.0 (0.0,3.0) (p < 0.00001), and mOCS use was reduced from59% to 29%, p = 0.001. The mean asthma control questionnaire-6 (ACQ6) improved from 3.1 ± 1.7 to 2.1 ± 1.3 (p < 0.00001). mepolizumab clinical benefit was sustained over 4 years. However, approximately half of the cohort discontinued the treatment prompting the need for further research into the treatment response longevity. [ABSTRACT FROM AUTHOR]

Purpose: Nowadays, several efficacious biologic drugs are used for severe asthma with or without chronic rhinosinusitis with nasal polyps (CRSwNP). However, it has been observed that not all comorbid patients (asthma/CRSwNP) receiving biologic treatment for asthma experience satisfactory control of both conditions equally. Methods: We selected 20 patients who had both severe asthma and comorbid CRSwNP under biological treatment with benralizumab, omalizumab or mepolizumab with adequate control of asthma but inadequate control of nasal symptoms. Patients were switched to dupilumab and outcomes were evaluated at baseline (T0), at 3 months (T1), at 6 months (T2), at 12 months (T3) and finally at 18 months (T4). Data were collected at each time point including blood tests measuring eosinophil levels and total IgE, SNOT22, ACT, NPS score, rhinomanometry, olfactory testing, and nasal cytology. Results: The results showed an overall improvement in all the outcomes. Peripheral eosinophilia was observed consistently with existing literature. All patients registered an improvement in sinonasal outcomes, while only one patient had a worsening of asthma. Three patients interrupted the therapy due to various causes: poor asthma control, onset of psoriasis and thrombocytopenia. Conclusions: The response to a biologic treatment for CRSwNP control may be heterogenous and it seems that patients may benefit from switching improving control in equal measure in the upper and lower airway. Further studies to explore the endotype/phenotype which best fits with each biologic are mandatory to personalize the therapy. [ABSTRACT FROM AUTHOR]

Background: In the phase III SYNAPSE study, mepolizumab plus standard of care reduced total endoscopic nasal polyp score (NPS) versus that with placebo in patients with chronic rhinosinusitis with nasal polyps. Objective: Our aim was to investigate relationships between NPS and (1) peak nasal inspiratory flow (PNIF) and (2) patient-reported outcomes. Methods: In this post hoc analysis, patients randomized 1:1 received mepolizumab, 100 mg, or placebo subcutaneously every 4 weeks (plus standard of care). Changes from baseline in PNIF (week 52), visual analog scale scores (overall symptoms, nasal obstruction, and loss of smell [weeks 49-52]), and total 22-Item Sino-Nasal Outcome Test score (week 52) were assessed in patients with or without improvements in NPS (improvement of ≥1 point) or without (improvement of

ContextRecent insights into type 2 inflammation have led to the development of monoclonal antibody therapies for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite add-on therapy with a monoclonal antibody, some individuals remain uncontrolled in terms of upper and/or lower airway symptoms, prompting an exploration of the efficacy of combining biological therapies and their impact on inflammatory pathways.ObjectivesIn this article, we present a distinctive case of a patient with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, who experienced substantial clinical and local inflammatory improvements through dual monoclonal antibody therapy.MethodsWe provide a detailed case description and analysis of the patient's nasal tissue and secretions to gain insights into the local nasal inflammation under this unique therapeutic approach.ResultsThe addition of an anti-IL-4Rα antibody led to an improvement in upper airway symptoms and a reduction in both eosinophilic and neutrophilic inflammation, despite prior anti-IL-5 therapy. These effects were consistently observed in both polyp tissue and nasal secretions.ConclusionOur patient, with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, experienced substantial improvement with dual monoclonal antibody therapy, without major complications or side effects.

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is used to treat severe eosinophilic asthma and other eosinophilia-related conditions. Given its growing use, there is a pressing need for the latest data to improve the understanding and management of its adverse events (AEs). This study aimed to investigate the safety of mepolizumab by analyzing the pharmacovigilance database of the US Food and Drug Administration.MethodsThe AE signals associated with mepolizumab from 2015 to 2024 were analyzed and the correlations using reporting ratios (RORs) quantified. Subgroup analyses were conducted to understand AEs in individuals ≤ 18 years of age. We also used time-to-onset (TTO) analysis to examine AE occurrence patterns.ResultsIn total, 82,478 AE reports linked to mepolizumab therapy were included. Our analysis, involving 24,156 patients, revealed a predominance of female patients, with the highest incidence of AEs occurring in those aged 18–65 years. Disproportionality analyses revealed significant signals across various system organ classifications (SOCs), most prominently respiratory, thoracic, and mediastinal disorders (ROR = 5.12, 95% confidence intervals [CI] 5.03–5.21), infections and infestations (ROR = 1.86, 95% CI 1.81–1.90), and immune system disorders (ROR = 1.14, 95% CI 1.08–1.21). The highest ROR was found for asthma crisis (ROR = 104.90, 95% CI 95.31–115.44) at the preferred term (PT) level, and the other notables were coronavirus infection (ROR = 7.33, 95% CI 6.05–8.88) and coronavirus disease 2019 (COVID-19) (ROR = 1.34, 95% CI 1.23–1.47). A subgroup analysis of patients ≤ 18 years old identified four significant SOC signals, with the highest ROR in respiratory, thoracic, and mediastinal disorders (ROR = 5.28, 95% CI 4.17–6.68). PT analysis revealed significant AEs, such as wheezing, bronchospasm, and chest discomfort. TTO analysis revealed that 18.5% of AEs occurred within the first 30 days of treatment. The Weibull shape parameter indicated an “early failure-type” pattern for mepolizumab-associated AEs, underscoring the need for vigilant monitoring during the initial stages of therapy.ConclusionOur study highlights the importance of post-market surveillance for monitoring the safety of mepolizumab, which revealed significant AE signals, particularly for respiratory diseases, infections, and immune system complications. The association with opportunistic infections, including COVID-19, highlights the need for vigilant surveillance and further research.

Abstract Few reports have described the treatment of eosinophilic pneumonia (EP) complicated by refractory pneumothorax. A 62‐year‐old man with a medical history of ulcerative colitis who was undergoing maintenance treatment presented with fever, cough, and diffuse bilateral consolidation on chest radiography. Laboratory findings showed peripheral eosinophilia, and he was hospitalized with a diagnosis of drug‐induced EP and started on corticosteroid therapy. During the course, he developed refractory pneumothorax, and it was difficult to control the air leakage. As it was necessary to control the eosinophilic inflammation and air leakage, mepolizumab, a humanized anti‐interleukin‐5 monoclonal antibody, and an endobronchial Watanabe spigot (EWS), were introduced. After EWS insertion, the leakage of the refractory pneumothorax disappeared. The patient continued to have no recurrence of EP or pneumothorax after the removal of the EWS. The combination of mepolizumab and an EWS may be effective in cases of EP complicated by refractory pneumothorax.

This article discusses a study that examined the effectiveness of the drug mepolizumab in treating severe eosinophilic asthma (SEA). The study used cluster analysis to identify two subgroups of patients with SEA, with Cluster 2 (C2) showing higher rates of response to the medication compared to Cluster 1 (C1). The study also found that family history of asthma was a predictor of treatment response. The research suggests that personalized treatment strategies based on subgroup identification could be beneficial for patients with SEA. Further validation studies are needed to confirm these findings. [Extracted from the article]