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Key Clinical message: A patient with eosinophilic granulomatosis with polyangiitis, who was well‐controlled by pharmacotherapy, developed a psoriasis‐like rash due to a local infection. It represents the consequence of an immunologic imbalance. A 48‐year‐old woman was diagnosed with eosinophilic granulomatosis with polyangiitis and treated with mepolizumab. While on treatment, she developed a psoriasis‐like rash on her lower legs following a local ear infection. The rash promptly disappeared after the ear infection cleared and did not recur. The psoriasis‐like rash that appeared was pathologically similar to psoriasis. Excessive production of inflammatory cytokines by the immune system is believed to be involved in the pathogenesis of psoriasis vulgaris. These cytokines are known to induce inflammatory responses and promote epidermal cell proliferation. It is possible that mepolizumab treatment suppressed Th2‐type cytokines, while the local ear infection temporarily induced a strong Th1‐type immunity. This immunologic imbalance may have led to the development of a psoriasis‐like rash. [ABSTRACT FROM AUTHOR]

Mepolizumab, a humanized anti‐IL‐5 monoclonal antibody used for severe asthma, results in a reduced rate of asthma exacerbation, improved lung function, reduced oral corticosteroid use, and improved quality of life. A 62‐year‐old man using high‐dose inhaled corticosteroid visited our hospital because of poorly‐controlled asthma. He had eosinophilia in peripheral blood and sputum, and high levels of fraction of exhaled nitric oxide. Therefore, he was treated with mepolizumab for severe asthma. Mepolizumab treatment resulted in significantly improved pulmonary function and reduced frequencies of asthma exacerbations. Because of his good asthma control, mepolizumab treatment was discontinued after 3 years. Since discontinuing mepolizumab, his asthma control has remained without exacerbation. Previous studies suggest that mepolizumab should be continued to sustain clinical benefits. However, cases of long‐term controlled asthma have not been reported after mepolizumab withdrawal, and our case may be instructive. [ABSTRACT FROM AUTHOR]

The increasing use of advanced biologic therapies for patients with severe asthma is transforming the standard of care, clinic workflow, and the clinic business model. Expanded patient access to at-home injection treatment possibilities with some biologics has the potential to improve patient adherence and outcomes. Simultaneously, transition to the home setting can address the escalating costs that limit access for certain patients and healthcare facilities. Such moves come with recognized risks. Garnering input from physicians and other healthcare specialists as well as scrutinizing best practice position statements are vital to implementing truly patient-safe and cost-effective strategies in medicine. Mepolizumab is the first anti-IL-5 inhibitor to receive FDA approval in late 2015. We focus on this injectable medication and discuss the specific indications and contraindications for transitioning patients to at-home injection with mepolizumab. In doing so, we review our recent real-world experiences in the University of California, Davis and Loma Linda University severe asthma clinics, which can provide the foundation for building a comprehensive clinic and home-based biologics asthma program. In addition, we offer insight into the barriers to implementing a successful program and strategies for overcoming them.

Little is known about the efficacy and safety of the anti-interleukin 5 monoclonal antibody mepolizumab (MPZ) in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in real-life. We thus evaluated disease activity, damage and disease-related complications in 14 patients with EGPA receiving MPZ for refractory disease for a median time of 16 months in comparison with up to five years before MPZ start. Asthma exacerbation rates, the Birmingham Vasculitis Activity Score and corticosteroid dosage decreased during MPZ (p

Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare interstitial lung disease of unknown cause. It usually responds well to systemic corticosteroid therapy, but relapses are frequent. We describe two cases of 21- and 27-year-old patients, presenting with dyspnea. The diagnosis of steroid-relapsing and steroid-dependent ICEP was made respectively. Mepolizumab was prescribed to both patients. This treatment resulted in successful long-term disease management with much fewer side effects than a traditional corticosteroid therapy.

Amaç: Ağır astımı olan hastalar, viral enfeksiyonların neden olduğu astım alevlenmeleri, hastanelerdeki SARS-CoV-2 viral yükü ve bazı kısıtlamalar nedeniyle sağlık tesislerine erişimdeki zorluklar nedeniyle özellikle SARS-CoV-2 enfeksiyonu için daha yüksek risk altındadır. Bundan dolayı monoklonal antikor (MAb) tedavisi alan hastalarda SARS-CoV-2 pandemisinin astım tedavisi ve kontrolü üzerindeki etkisini araştırılması amaçlandı. Materyel-Metod: Ağır persistan astım tedavisi için MAb kullanan hastalar çalışmaya dahil edildi. Her hastadan onaylanmış bir Coronavirüs kaygı ölçeği ve mini bir anket doldurması istendi. Bulgular:Ağır Astım nedeniyle MAb tedavisi alan 62 hasta (Kadın: 44; Erkek: 18) çalışmaya alındı. Mart-Nisan-Mayıs 2020'de hastaların tedaviye uyumu %56.5 idi. Sokağa çıkma yasağı, hastaların tedaviye uyumunu (%35.5) etkileyen en yaygın hükümetle ilgili faktörolarak saptandı. En yaygın bireysel faktör, SARS-CoV-2 kapma korkusuydu (%40.3). Tedaviye uyum sağlamayan hastalarda, MAb tedavisine uyan hastalara göre, semptomlarda artış ve astım için ek tedavi gereksinimi anlamlı olarak daha fazlaydı (p:0.034 ve p:0.013) Sonuç: MAb tedavisi alan hastalarda hem resmi hem de bireysel nedenlerle tedaviye uyum azalmıştır. Bu durum acil servise astım şikayetleri ve ek tedavi ihtiyacı ile daha sık başvurulara neden olmuştur. Tüm bu bulgular, hastaların pandemiye rağmen MAb tedavilerini sürdürmeleri gerektiğini ve kılavuzlarda yayınlanan tavsiyelere uyarak SARS-CoV-2 enfeksiyon riskini en aza indirmeleri gerektiğini göstermektedir.

Abstract Small airway dysfunction (SAD) in asthma is characterized by the inflammation and narrowing of airways with less of 2 mm in diameter between generations 8 and 23 of the bronchial tree. It is now widely accepted that small airways are involved in the pathogenesis of asthma and are a major determinant of airflow obstruction in this disease. In recent years, specialized tests have been developed, such as Impulse Oscillometry (IOS) and Multiple Breath Nitrogen Washout (MBNW) tests, which have been deemed more accurate in detecting SAD than conventional spirometry. Clinical studies show that SAD is associated with more severe bronchial hyperresponsiveness, worse asthma control, and a higher risk of exacerbations. Recent data from a large cohort study showed that the prevalence of SAD in asthma patients increases with asthma severity. Overall, SAD seems to represent a treatable trait, which makes it appealing for asthma control optimization and exacerbation rate reduction, especially in moderate-to-severe asthma. Biologic agents are now available for the treatment of different severe asthma phenotypes and endotypes. However, the effect of these therapies on SAD remains poorly characterized. Literature showing that biologic agents can also favorably improve small airway function is accumulating. In particular, anti-IL5 agents (mepolizumab and benralizumab) seems to have a greater impact on SAD as compared to other biological agents, but direct comparisons in prospective randomized controlled trials are lacking. In this mini-review article, we address the latest evidence on the effect of biological therapies on SAD in patients with severe asthma.

Aim: This study aimed to evaluate the effects of the COVID-19 pandemic on treatment adherence in patients with severe asthma who were receiving omalizumab and mepolizumab treatment in our clinic. Material and Method: A total of 53 patients with severe asthma, 45 of whom were using omalizumab and 8 of whom were using mepolizumab, were included in the study. The medical records of the patients were recorded anonymously and retrospectively. Results: It was seen that the rate of patients using omalizumab in the study population decreased during the pandemic period compared to the 1-year period before the pandemic. It was observed that approximately 51% of the patients using omalizumab missed routine treatment doses. The major factor in skipping treatment doses was the fear of contracting COVID-19 upon admission to the hospital. In the mepolizumab group, the rate of using biologic agents during the pandemic period increased compared to 1 year before the pandemic. Dose skipping was observed among 37.5% of the patients in this group and it was found that the major risk factor for skipping a dose was the fear of contracting COVID-19 upon admission to the hospital. Conclusion: In this study, it was found that there was a decrease in the duration and rate of use of biologic agent therapies administered in a health institution under the supervision of a healthcare professional among patients with severe asthma during the pandemic.

Oral corticosteroids (OCS) are commonly used for the acute management of severe asthma exacerbations or as maintenance therapy; however, chronic use is associated with significant toxicities, e.g., osteoporosis. In the REal worlD Effectiveness and Safety (REDES) study of mepolizumab in a multicentric Spanish cohort of asthma patients, mepolizumab effectively reduced clinically severe asthma exacerbations and decreased OCS dependence. This post-hoc analysis further evaluates mepolizumab's de-escalation effect on OCS dose. Patients enrolled in REDES who had OCS consumption data available for 12 months pre- and post-mepolizumab treatment were included in this analysis. Primary outcomes were to determine the change in the proportion of patients eligible for anti-osteoporotic treatment due to the changes in OCS consumption before and after 1 year of mepolizumab treatment. All analyses are descriptive. Approximately one-third (98/318; 30.8%) of patients in REDES were on maintenance OCS at the time of mepolizumab treatment initiation. In REDES, mean cumulative OCS exposure decreased by 54.3% after 1 year of treatment. The proportion of patients on high-dose OCS (≥7.5 mg/day) fell from 57.1% at baseline to 28.9% after 12 months of mepolizumab treatment. Thus, 53.6% of OCS-dependent asthma patients treated with mepolizumab would cease to be candidates for anti-osteoporotic treatment according to guidelines thresholds. [ABSTRACT FROM AUTHOR]

Background: The mainstay of treatment for eosinophilic granulomatosis with polyangiitis (EGPA) is systemic corticosteroid therapy; some patients also receive intravenous immunoglobulins, other immunosuppressive agents, and biologics. Mepolizumab, an anti-interleukin-5 monoclonal antibody, induces remission and decreases the daily corticosteroid dose; however, the clinical efficacy of mepolizumab in EGPA and the prognosis with long-term treatment with this drug are unknown. Methods: Seventy-one EGPA patients were treated at Hiratsuka City Hospital, Japan, between April 2018 and March 2022. We administered mepolizumab for a mean of 2.8 ± 1.7 years to 43 patients in whom remission could not be induced by conventional treatment. After excluding 18 patients who had received mepolizumab for less than 3 years, we classified 15 patients into a "super-responder group" (the daily dose of corticosteroids or other immunosuppressant could be decreased, or the interval between IVIG treatments could be prolonged) and 10 patients into a "responder group" (neither of these changes was achievable). Eosinophil numbers, serum IgG levels, daily doses of corticosteroids and other immunosuppressants, Birmingham Vasculitis Activity Score (BVAS), and relapse frequency before and after mepolizumab initiation were determined. Results: Blood eosinophil count at diagnosis and the lowest serum IgG level before mepolizumab treatment were significantly higher in super-responders than in responders (p < 0.05). In super-responders, the prednisolone dose at last visit on mepolizumab treatment was lower than that before treatment (p < 0.01) and lower than that at last visit in the responders (p < 0.01). In both groups, peripheral blood eosinophil numbers and BVAS were lower after starting mepolizumab than before (p < 0.01). BVAS before mepolizumab (p < 0.05) and at last visit (p < 0.01) were lower in super-responders than in responders. Relapse rates every year after the start of mepolizumab were lower in super-responders than in responder groups (p < 0.01). In super-responders, relapse rates were lower during the 3 years following mepolizumab initiation (p < 0.01) and at last visit (p < 0.01) were significantly lower than after 1 year of treatment. Conclusion: Mepolizumab treatment of super-responders sustainably reduced the relapse rate. [ABSTRACT FROM AUTHOR]

Background: Individualized prediction of treatment response may improve the value proposition of advanced treatment options in severe asthma. This study aimed to investigate the combined capacity of patient characteristics in predicting treatment response to mepolizumab in patients with severe asthma. Methods: Patient-level data were pooled from two multinational phase 3 trials of mepolizumab in severe eosinophilic asthma. We fitted penalized regression models to quantify reductions in the rate of severe exacerbations and the 5-item Asthma Control Questionnaire (ACQ5) score. The capacity of 15 covariates towards predicting treatment response was quantified by the Gini index (measuring disparities in treatment benefit) as well as observed treatment benefit within the quintiles of predicted treatment benefit. Results: There was marked variability in the ability of patient characteristics to predict treatment response; covariates explained greater heterogeneity in predicting treatment response to asthma control than to exacerbation frequency (Gini index 0.35 v. 0.24). Key predictors for treatment benefit for severe exacerbations included exacerbation history, blood eosinophil count, baseline ACQ5 score and age, and those for symptom control included blood eosinophil count and presence of nasal polyps. Overall, the average reduction in exacerbations was 0.90/year (95%CI, 0.87‒0.92) and average reduction in ACQ5 score was 0.18 (95% CI, 0.02‒0.35). Among the top 20% of patients for predicted treatment benefit, exacerbations were reduced by 2.23/year (95% CI, 2.03‒2.43) and ACQ5 score were reduced by 0.59 (95% CI, 0.19‒0.98). Among the bottom 20% of patients for predicted treatment benefit, exacerbations were reduced by 0.25/year (95% CI, 0.16‒0.34) and ACQ5 by -0.20 (95% CI, -0.51 to 0.11). Conclusion: A precision medicine approach based on multiple patient characteristics can guide biologic therapy in severe asthma, especially in identifying patients who will not benefit as much from therapy. Patient characteristics had a greater capacity to predict treatment response to asthma control than to exacerbation. Trial registration: ClinicalTrials.gov number, NCT01691521 (registered September 24, 2012) and NCT01000506 (registered October 23, 2009). [ABSTRACT FROM AUTHOR]

Background: Mepolizumab 300 mg is an approved treatment option for patients with eosinophilic granulomatosis with polyangiitis (EGPA), yet, the adequacy of 100 mg of mepolizumab in disease control is controversial. Objective: To evaluate the sinonasal and respiratory outcomes of EGPA patients treated with 100 mg mepolizumab for one year. Methods: Evaluations of 11 patients were made of the sinonasal outcome test (SNOT-22) (nasal, otologic, sleep, and emotional domains), asthma control test (ACT), forced expiratory volume in 1 s (FEV1), blood eosinophil counts and oral steroid doses before mepolizumab treatment (T0) and at the 6th (T6) and 12th (T12) months. Results: A significant decrease was observed in the total SNOT-22 scores in the 6th month, after which the scores continued to be stable until the 12th month. (SNOT-22 median (IQR); T0: 70(53-82); T6: 19(4-35); T12: 11(6-40); T0-T6, p = 0.02; T6-T12, p = 0.85). In the subdomains of SNOT-22, nasal and sleep-related domains improved significantly in the first 6 months, and the otologic and emotional domains only improved from baseline in the 12th month. There was a significant decrease in blood eosinophil counts in the 6th month and oral steroid dose in the 12th month (eosinophils, median(IQR), T0: 1000(700-1800), T6: 100(0-200), p = 0.02; OCS dose, median(IQR), T0: 16(8-16); T6: 4(0-4); T12: 0(0-4); T0-T12, p = 0.002). A significant improvement was observed in ACT values in the 6th month (ACT median (IQR); T0:16(8-18); T6: 22(21-25); p = 0.01). Conclusion: Mepolizumab 100 mg provided a significant decrease in SNOT-22 values, especially in nasal and sleep domains, eosinophil counts and OCS dose in the 6th month. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically. [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]

Introduction: Clinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment. Methods: The real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission. Results: 37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not. Discussion: Clinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression. [ABSTRACT FROM AUTHOR]

Objective: The effect of biological agents used in severe allergic diseases on the risk of coronavirus disease 2019 (COVID-19) and the course of the disease still remains unclear. The aim of the study was to evaluate retrospectively the frequency and severity of COVID-19 to determine risk factors and to present real-life data in patients using biological agents. Materials and Methods: Patients who have used omalizumab or mepolizumab for at least six months were questioned retrospectively in terms of a history of COVID-19. Patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) or serological IgG positivity, symptoms, lung involvement, the need for supplemental oxygen, hospital and intensive care admission, and mortality were queried. Results: Of the 71 patients (omalizumab/mepolizumab: 51/20) included in the study, the average age was 37.2±12.9, and the female/male ratio was 46/25. Of the 11 patients (omalizumab/mepolizumab: 6/5) with SARS-CoV-2 positivity, two were hospitalized for pneumonia and needed oxygen. However, intensive care was not required and they survived. There was no significant difference between mepolizumab users who had COVID-19 and those who did not in terms of baseline and post-treatment 6th-month eosinophil values (p= 0.7, p= 0.59, respectively). It was established that eosinopenia developing after treatment did not increase the risk of COVID-19 in patients using mepolizumab [RR (95% Cl) 0.99 (0.97-1.02), p=0.88]. Conclusion: According to our single center data, we found the risk of severe COVID-19 in patients using biological agents to be quite low. Especially, eosinopenia that developed after mepolizumab treatment did not constitute a risk factor for the severity of COVID-19. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic eosinophilic vasculitis has been described in previous case series as a possible manifestation of hypereosinophilic syndrome (HES) in asthma-free patients. A rare disease, it can be classified as an eosinophilic-rich, necrotizing, systemic form of vasculitis that affects vessels of various sizes in these patients. This report shares our experience with the treatment of a patient with eosinophilic vasculitis. Case Presentation: We present the case of a 45-year-old man who suffered from idiopathic HES manifesting as digital ulcers and peripheral ischemia of both the upper and lower limbs without the involvement of other systems. Diagnosis was made after excluding the primary and secondary causes of eosinophilia. The patient responded well to both corticosteroids and mepolizumab, an interleukin-5 inhibitor, as a corticosteroid-sparing therapy. Conclusion: Our case of HES-associated vasculitis in an asthma-free patient supports previous reports describing this rare diagnosis of idiopathic eosinophilic vasculitis in recent years. We describe a good response to mepolizumab (interleukin-5 inhibitor) in our patient. [ABSTRACT FROM AUTHOR]

Although an increasing number of real-life data confirm large-scale clinical trial findings on the efficacy and safety of SARS-CoV-2 vaccines, rare but severe adverse reactions have begun to emerge. Here, we report a full-blown hypereosinophilic syndrome (HES) following a BNT162b2 (BioNTech/Pfizer) vaccine. A 48-year-old man developed, 5 days after the first shot of the SARS-CoV-2 vaccine, erythematous and painful nodular lesions in the lower and upper limbs accompanied by widespread itching, acrocyanosis with gangrenous lesions at the tips of the first and fourth fingers of the right hand, as well as paresthesia in the right hand and foot. Investigations revealed isolated eosinophilia, occlusion of the right ulnar artery, and electromyography alteration compatible with multifocal sensory neuropathy, as well as minimal accentuation of the interstitial texture with some ground glass appearance. Despite treatment with prednisone in combination with warfarin, he developed thrombosis of the left ulnar artery. Therefore, therapy with an IL-5 inhibitor and acetylsalicylic was successfully added. Given the time interval between the onset of clinical manifestations and the vaccine shot, we believe that the mRNA vaccine triggered the eosinophilic response. This case evidences a possible link between HES and the SARS-CoV-2 vaccination. Mepolizumab, an IL-5 inhibitor, might be considered in steroid refractory cases. [ABSTRACT FROM AUTHOR]

Overlapping eligibility to different biologics for severe asthma is still challenging, especially when addressing the same target. We aimed to characterize severe eosinophilic asthma patients according to their maintained or reduced response to mepolizumab over time and to explore baseline variables significantly associated with the occurrence of switching to benralizumab. We performed a multicentre retrospective observational study evaluating OCS reduction, exacerbation rate, lung function, exhaled nitric oxide levels (FeNO), Asthma control test (ACT), and blood eosinophil concentrations at baseline and before and after switching occurrence among 43 female and 25 male patients with severe asthma aged 23 to 84 years. Younger age, higher OCS daily dose and lower blood eosinophils at baseline were associated with a significantly higher risk (odds) for switching occurrence. All the patients showed an optimal response to mepolizumab, up to six months. The need for switching, according to the above-mentioned criterion, occurred for 30 out of 68 patients after a median time of 21 months (Q1–Q3: 12–24) from mepolizumab initiation. At the follow-up time-point after the switch (median time: 31 months, Q–Q3: 22–35), all the outcomes substantially improved and no cases of poor clinical response to benralizumab were detected. Although the small sample size and the retrospective design represent major limitations, to our knowledge, our study provides the first real-word focus on clinical variables potentially predicting a better response to anti IL-5r in patients fully eligible for both mepolizumab and benralizumab and suggests that in late non responder patients to mepolizumab, more robustly targeting the IL-5 axis may be effective. [ABSTRACT FROM AUTHOR]

Background: Patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) often require repeat sinus surgery. Mepolizumab reduced the need for sinus surgery in the SYNAPSE trial; this analysis sought to provide a more in‐depth assessment of surgery endpoints in SYNAPSE. Methods: SYNAPSE was a double‐blind Phase III trial (NCT03085797) in adults with recurrent, refractory, severe, CRSwNP eligible for repeat sinus surgery despite standard of care treatments and previous surgery. Patients were randomized (1:1) to mepolizumab 100 mg subcutaneously or placebo, plus standard of care, every 4 weeks for 52 weeks. Time to first inclusion on a waiting list for sinus surgery and time to first actual sinus surgery (both up to week 52) were assessed; the latter endpoint was also analyzed post hoc according to time since last sinus surgery before study screening and baseline blood eosinophil count. Results: Among 407 patients (mepolizumab: 206; placebo: 201), mepolizumab versus placebo reduced the risk of being included on a waiting list for sinus surgery (week 52 Kaplan–Meier probability estimate [95% confidence interval]: 13.9% [9.8%, 19.5%] vs. 28.5% [22.7%, 35.4%]). Mepolizumab versus placebo reduced the risk of sinus surgery irrespective of time (<3 vs ≥3 years) since patients' last sinus surgery prior to study screening (hazard ratios [95% confidence intervals] 0.28 [0.09, 0.84] and 0.50 [0.26, 0.98], respectively) and baseline blood eosinophil count. Conclusions: Mepolizumab reduced the risk of further sinus surgery in patients with recurrent, refractory, severe CRSwNP, irrespective of the patient baseline characteristics assessed. [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]

Antecedentes: El manejo del asma grave eosinofílica incluye tipificación para identificar fenotipos alérgicos, eosinofílicos y no TH2. Niveles elevados de eosinófilos se asocia a mayor nivel de IL-5. Los eosinófilos durante su migración a los tejidos diana, secretan proteínas que dañan el epitelio bronquial activado y se correlacionan con la gravedad del asma. Mepolizumab, anticuerpo monoclonal humanizado que se une y neutraliza la IL-5. Objetivos: Describir experiencia con el uso de biológico anti-interleucina 5 Mepolizumab. Métodos: Reporte de casos, estudio descriptivo. Se incluyeron pacientes con asma grave descontrolada, antecedente de Rinosinusitis con poliposis nasal y/o EREA. Eosinófilos ≥150 células/μL, FeNO ≥25 ppb y espirometría con patrón obstructivo. Resultados: Se incluyeron 6 pacientes mujeres con diagnóstico de Asma grave. Valores iniciales de eosinófilos de 180 – 630 cél/μL, IgE 176 – 2500 Ui/ml, FENO 23 -39, ACT a los 2, 4 y 6 meses de uso, mínima de 9 y final máxima de 25. Mejoría considerable en la prueba ACT desde los primeros dos meses de uso, disminucion de esteroide inhalado y 0 a 2 exacerbaciones en 6 meses. Conclusión: Existen múltiples estudios, no se cuenta con reportes estadísticamente significativos para demostrar superioridad con el uso de algún biológico en específico, aunado a las diferentes limitantes económicas que existen en el país. Es necesario identificar poblaciones objetivo con los fenotipos que responderán a una terapia específica y dirigir el tratamiento. En México hay pocos centros hospitalarios con estas terapias, es necesario continuar con la evaluación constante y aporte de información para poder encontrar el tratamiento idóneo para la población mexicana.

BackgroundEosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis characterized by asthma, systemic manifestations, and blood and tissue eosinophilia.ObjectiveTo assess the effectiveness and safety of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in EGPA for 24 months.MethodsWe conducted a multicenter observational study, including patients with EGPA treated with anti-IL-5/Rα biologics in 9 Italian specialized facilities. Systemic disease activity, remission and relapse rate were evaluated from 3 to 24 months after treatment initiation. Respiratory outcomes, hematological parameters, corticosteroid (OCS) and immunosuppressants consumption were also assessed.Results49 patients with relapsing-refractory EGPA were included [26 (53.1%) benralizumab 30mg, 20 (40.8%) mepolizumab 100mg, 3 (6.1%) mepolizumab 300mg]. Overall, 38.8% and 57.1% achieved remission after 12 and 24 months, respectively (69.2% benralizumab and 43.5% mepolizumab). Lower OCS intake and higher blood eosinophil count at baseline were associated with remission at 24 months. Both biologics exerted beneficial effects on severe asthma outcomes. Indeed, 61.2% (61.5% benralizumab and 60.8% mepolizumab) remained exacerbation-free during treatment. Lung function parameters showed improvements in the overall cohort (all p

Key Clinical message A patient with eosinophilic granulomatosis with polyangiitis, who was well‐controlled by pharmacotherapy, developed a psoriasis‐like rash due to a local infection. It represents the consequence of an immunologic imbalance. Abstract A 48‐year‐old woman was diagnosed with eosinophilic granulomatosis with polyangiitis and treated with mepolizumab. While on treatment, she developed a psoriasis‐like rash on her lower legs following a local ear infection. The rash promptly disappeared after the ear infection cleared and did not recur. The psoriasis‐like rash that appeared was pathologically similar to psoriasis. Excessive production of inflammatory cytokines by the immune system is believed to be involved in the pathogenesis of psoriasis vulgaris. These cytokines are known to induce inflammatory responses and promote epidermal cell proliferation. It is possible that mepolizumab treatment suppressed Th2‐type cytokines, while the local ear infection temporarily induced a strong Th1‐type immunity. This immunologic imbalance may have led to the development of a psoriasis‐like rash.

Abstract Mepolizumab, a humanized anti‐IL‐5 monoclonal antibody used for severe asthma, results in a reduced rate of asthma exacerbation, improved lung function, reduced oral corticosteroid use, and improved quality of life. A 62‐year‐old man using high‐dose inhaled corticosteroid visited our hospital because of poorly‐controlled asthma. He had eosinophilia in peripheral blood and sputum, and high levels of fraction of exhaled nitric oxide. Therefore, he was treated with mepolizumab for severe asthma. Mepolizumab treatment resulted in significantly improved pulmonary function and reduced frequencies of asthma exacerbations. Because of his good asthma control, mepolizumab treatment was discontinued after 3 years. Since discontinuing mepolizumab, his asthma control has remained without exacerbation. Previous studies suggest that mepolizumab should be continued to sustain clinical benefits. However, cases of long‐term controlled asthma have not been reported after mepolizumab withdrawal, and our case may be instructive.

Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare interstitial lung disease of unknown cause. It usually responds well to systemic corticosteroid therapy, but relapses are frequent. We describe two cases of 21- and 27-year-old patients, presenting with dyspnea. The diagnosis of steroid-relapsing and steroid-dependent ICEP was made respectively. Mepolizumab was prescribed to both patients. This treatment resulted in successful long-term disease management with much fewer side effects than a traditional corticosteroid therapy.

Abstract Background Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic state characterized by seizures, headache, vision change, paresis, and altered mental status. PRES has an important place in medicine due to the wide variety of causative diseases, infections, and medications that precipitate its mysterious onset. Although exposure to medications, particularly immunosuppressants, cancer chemotherapy, and biologic drugs, is a common occurrence in patients who develop PRES, Mepolizumab has never before been associated. Case presentation This report of a 67-year-old male patient outlines the first reported case of Mepolizumab-induced PRES in the literature. Conclusions Treatment of severe asthma, asthma-exacerbations, and diseases such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss) with Mepolizumab is rapidly gaining popularity ever since the drug’s recent FDA-approval. This report aims to raise awareness of this potentially life-threatening and previously unreported side effect of Mepolizumab since early identification of the causative agent is the key to preventing the severe neurologic disability and possible death that may occur from the delayed treatment of PRES.

Introduction: Pediatric asthma affects 5.5 million US children and is the leading cause of pediatric chronic illness globally. Those with severe asthma have significantly higher healthcare costs compared to those with non-severe disease. Biologics are the newest class of anti-asthma therapy approved for use in patients with severe asthma > 6 years with the eosinophilic phenotype. Objective: The goals of this study were to (1) describe the baseline characteristics of new US pediatric mepolizumab users between 2015 and end dates that varied by data partner (6/30/19–5/31/21), (2) describe asthma medication use in the 12 months preceding and following mepolizumab initiation in this group and (3) assess adherence and persistence to mepolizumab in the 12 months following initiation. Methods: Through an observational cohort study using insurance claim databases, we studied children with a diagnosis of asthma in the preceding 12 months who started mepolizumab and had 12 months of follow-up data. Results: Baseline characteristics of the 72 children who initiated mepolizumab showed variable comorbidities, the most common being allergic rhinitis (88%) and recurrent respiratory infections (71%), as well as varied medication dispensings and patterns of healthcare utilization prior to initiating mepolizumab. Half met the criteria for severe asthma per the GINA guidelines. Comparing weighted averages of treatments dispensed in the 12 months prior to versus following mepolizumab initiation, we observed no significant change in asthma treatments dispensed. Conclusion: This study demonstrates that pediatric patients prescribed mepolizumab have variable previous treatment history and severity of disease, and we found no evidence that mepolizumab alters other asthma medications dispensed in the first 12 months following initiation.

Abstract Objectives To investigate the safety and effectiveness of mepolizumab (MPZ), an anti-interleukin-5 antibody, as remission induction therapy for severe eosinophilic granulomatosis with polyangiitis (EGPA). Methods The clinical courses of patients with severe EGPA over 6 months were retrospectively investigated and compared between patients treated with high-dose corticosteroid (CS) plus MPZ therapy (MPZ group, n = 7) and those treated with high-dose CS plus intravenous cyclophosphamide (IVCY) pulse therapy (IVCY group, n = 13). The primary endpoints were the MPZ retention rate and the IVCY completion rate. The secondary endpoints were adverse events and changes in the Birmingham Vasculitis Activity Score (BVAS), Vascular Damage Index (VDI), eosinophil counts, and concomitant CS doses, and the extent and rates of these changes were compared between the MPZ and IVCY groups. Results Regarding the primary endpoints, the MPZ retention rate was 100%, and the IVCY completion rate was 61.5%. Regarding the secondary endpoints, adverse events were detected in 2/7 patients (28.6%) in the MPZ group and 7/13 patients (53.8%) in the IVCY group. BVAS and eosinophil counts significantly decreased in both groups at and after month 1, but there was no significant difference in the magnitude of changes between the two groups. VDI scores did not significantly increase in either group, and the degree of changes did not significantly differ between the two groups. Although concomitant CS doses significantly decreased at and after month 1 in both groups, the rates of decrease in CS doses at and after month 3 were significantly higher in the MPZ group. Conclusions This study suggested that the use of MPZ as remission induction therapy for severe EGPA might be safe and effective for controlling disease activity and reducing CS doses.

Oral corticosteroids (OCS) are commonly used for the acute management of severe asthma exacerbations or as maintenance therapy; however, chronic use is associated with significant toxicities, e.g., osteoporosis. In the REal worlD Effectiveness and Safety (REDES) study of mepolizumab in a multicentric Spanish cohort of asthma patients, mepolizumab effectively reduced clinically severe asthma exacerbations and decreased OCS dependence. This post-hoc analysis further evaluates mepolizumab’s de-escalation effect on OCS dose. Patients enrolled in REDES who had OCS consumption data available for 12 months pre- and post-mepolizumab treatment were included in this analysis. Primary outcomes were to determine the change in the proportion of patients eligible for anti-osteoporotic treatment due to the changes in OCS consumption before and after 1 year of mepolizumab treatment. All analyses are descriptive. Approximately one-third (98/318; 30.8%) of patients in REDES were on maintenance OCS at the time of mepolizumab treatment initiation. In REDES, mean cumulative OCS exposure decreased by 54.3% after 1 year of treatment. The proportion of patients on high-dose OCS (≥7.5 mg/day) fell from 57.1% at baseline to 28.9% after 12 months of mepolizumab treatment. Thus, 53.6% of OCS-dependent asthma patients treated with mepolizumab would cease to be candidates for anti-osteoporotic treatment according to guidelines thresholds.

Background: mAbs (biologics) are indicated in patients with poorly controlled moderate-to-severe asthma. The process of prior authorization and administration of a biologic requires exceptional commitment from clinical teams. Objective: Our aim was to evaluate the process of approval and administration of biologics for asthma and determine the most common reasons associated with denials of biologics and delays in administration. Methods: We examined the records of patients with asthma who were prescribed biologics from January 2018 to January 2020 at 2 centers, Montefiore Medical Center (Bronx, NY) and Scripps Clinics (San Diego, Calif). Demographics, insurance information, and details on the approval process were collected. Results: After querying of electronic health records, the records of 352 and 70 patients with moderate-to-severe asthma were included from Montefiore and Scripps, respectively. Most patients at Montefiore (58.2%) were insured under Managed Care Medicaid (MC Medicaid), whereas most patients at Scripps (61.4%) had commercial insurance. The median times from prescription to administration of a biologic were similar: 34 days (interquartile range [IQR] = 18-63 days) and 34 days (IQR = 22.5-56.0 days) (P = .97) for Montefiore and Scripps, respectively. However, the median approval time for Montefiore was 6 days (IQR = 1-20 days) and that for Scripps was 22 days (IQR = 10-36 days) (P < .001). Approval times for prescriptions requiring appeals were significantly longer than for prescriptions approved after the initial submission: 23 days versus 2.5 days and 40.5 days versus 15.5 days (for Montefiore and Scripps, respectively [P < .001 for both]). Conclusions: Lengthy appeals contribute to delays between prescribing and administering a biologic. Site-specific practices and insurance coverage influence approval timing of the biologics for asthma.

Abstract An 82‐year‐old man had been diagnosed with asthma. He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high‐dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated. The patient had been free from exacerbations for 15 months; however, he suffered from post‐obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain. In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was established. The patient underwent treatment with tezepelumab. Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms. Tezepelumab might provide a novel steroid‐sparing strategy for the management of ABPA, although further studies are required.

Objective: Idiopathic eosinophilic vasculitis has been described in previous case series as a possible manifestation of hypereosinophilic syndrome (HES) in asthma-free patients. A rare disease, it can be classified as an eosinophilic-rich, necrotizing, systemic form of vasculitis that affects vessels of various sizes in these patients. This report shares our experience with the treatment of a patient with eosinophilic vasculitis. Case Presentation: We present the case of a 45-year-old man who suffered from idiopathic HES manifesting as digital ulcers and peripheral ischemia of both the upper and lower limbs without the involvement of other systems. Diagnosis was made after excluding the primary and secondary causes of eosinophilia. The patient responded well to both corticosteroids and mepolizumab, an interleukin-5 inhibitor, as a corticosteroid-sparing therapy. Conclusion: Our case of HES-associated vasculitis in an asthma-free patient supports previous reports describing this rare diagnosis of idiopathic eosinophilic vasculitis in recent years. We describe a good response to mepolizumab (interleukin-5 inhibitor) in our patient.

IntroductionClinical remission as a multicomponent treatment goal in severe asthma is being explored in clinical practice. This post hoc analysis used data from the REDES study to assess the proportion of patients with severe eosinophilic asthma achieving our multicomponent definitions of clinical remission after 1 year of mepolizumab treatment.MethodsThe real-world, retrospective observational REDES study enrolled patients with severe eosinophilic asthma who were newly prescribed mepolizumab and with ≥12 months of medical records pre-enrolment. Multicomponent clinical remission was defined as: oral corticosteroid (OCS)-free; exacerbation-free; asthma control test (ACT) score ≥20; and with or without post-bronchodilator forced expiratory volume in 1 second ≥80%. Baseline characteristics were also assessed in those who did/did not achieve clinical remission.Results37% and 30% of patients with severe eosinophilic asthma met our proposed three- and four-component on-treatment clinical remission definitions; an increase from 2% and 3% at baseline. Most frequently achieved individual components of clinical remission were: OCS-free; ACT score ≥20. For patients fulfilling the multicomponent clinical remission definitions, at baseline we observed higher blood eosinophil counts, better ACT scores and lung function, lower maintenance OCS use, and a slightly lower rate of prior exacerbations versus those who did not.DiscussionClinical remission is a realistic target in clinical practice for a subset of patients with severe eosinophilic asthma receiving mepolizumab. Further studies are required to elucidate whether features linked to the underlying endotype can help predict treatment outcomes, increase rates of clinical remission, and potentially modify disease progression.

BackgroundHypereosinophilic syndrome (HES) is characterized by persistent elevated blood and/or tissue eosinophil levels and eosinophil-mediated organ damage. Presentation is highly heterogenous; patients may experience symptoms affecting multiple organ systems.ObjectivesTo assess the effects of mepolizumab, which targets interleukin-5, on HES-related symptom burden, based on HES daily symptoms (HES-DS) questionnaire data collected during the Phase III (ClinicalTrials.gov ID: NCT02836496) study of mepolizumab in patients with HES.MethodsEach of the six HES-related symptoms were rated (0–10) daily by patients, recalling worst symptom experience in the prior 24 hours; change from baseline at Week 32 was also calculated for mepolizumab versus placebo.ResultsMepolizumab versus placebo reduced HES-related symptom burden severity in patients with HES at Week 32. Improvements in the median change from baseline scores were seen across all symptom groups except skin for patients treated with mepolizumab; greatest improvement from baseline was observed for breathing symptoms.ConclusionThese data highlight the considerable symptom burden associated with HES and further support the clinical benefits of mepolizumab treatment for these patients.

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained with mepolizumab and benralizumab in severe asthmatics treated for 12 months in a real-life setting. In these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, and symptom control were evaluated during the observation period, to understand which patients met all the criteria in order to be considered in disease remission. The percentage of remittent patients was 30.12% in the mepolizumab-treated subgroup, while in the benralizumab-treated subgroup, patients in complete disease remission were 40%, after 12 months. The results of this study confirm the efficacy of anti-IL-5 biologic drugs in the treatment of severe eosinophilic asthma in a real-life setting. [ABSTRACT FROM AUTHOR]

Severe Uncontrolled Asthma (SUA) counts for more than 25% of cases of severe asthma. The main factors that impair the quality of life of these patients are high doses of oral corticosteroids, the presence of exacerbations, and reduced lung function. The objective of this study was to evaluate, in real life, the clinical improvement of patients with SUA treated with anti-interleukin 5 (IL5) therapies: mepolizumab and benralizumab, together with the search for biomarkers associated with the response. We conducted a retrospective observational cohort study that included patients with severe uncontrolled eosinophilic asthma in a tertiary hospital receiving biological therapies. Three types of response were evaluated: improvement in lung function, reduction in exacerbations, and decrease in the use of oral corticosteroids. After 12 months of treatment, significant reductions were found in the number of exacerbations, the use of oral corticosteroids, and blood eosinophil levels for both biological therapies (p < 0.001). Lung function improved, achieving a significant improvement in %FEV1 (p < 0.001), as well as asthma control, with a significant increase in asthma control test (ACT) scores in both therapies. The markers associated with the corticosteroid-saving effect were the low doses of oral corticosteroids and absence of exacerbations for mepolizumab, and higher blood eosinophilia, absence of chronic obstructive pulmonary disease (COPD), and reduction in oral corticosteroid cycles for benralizumab. The greatest improvement in lung function in both therapies was linked to lower previous FEV1 levels and absence of other respiratory diseases. The reduction in exacerbations was associated with absence of exacerbations the previous year for mepolizumab and never smokers for benralizumab. The results of this real-life study confirm the clinical benefit obtained after the introduction of an anti-IL5 biological therapy and the possible predictive biomarkers of response to treatment. [ABSTRACT FROM AUTHOR]

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Cardiac manifestations are the major cause of mortality in patients with eosinophilic granulomatosis with polyangiitis (EGPA). Among these manifestations in EGPA patients, in the literature, there are fewer reports describing bradycardia in EGPA patients than those describing tachycardia. A 50-year-old woman with a history of childhood-onset asthma. At age 28, she was diagnosed with eosinophilic gastroenteritis without the diagnosis of EGPA and was started on a systemic steroid and had maintenance daily dose of 2.5 mg after gradually tapered. She had experiencing dizziness and palpitations 2 weeks after discontinuation of the steroid treatment. At emergency visit, electrocardiography revealed an advanced atrioventricular block of 3:1 or less. Forty-eight minutes after the start of electrocardiography, only a P wave was observed and cardiac arrest occurred for 9 s and temporary emergency pacing was performed immediately. She was diagnosed as EGPA presenting leukocyte count, 16,500/μL, 42.8% of which were eosinophils and sinusitis in computed-tomography. She could be survival by treatment of steroid, following the patient to withdraw from an external pacemaker. She received prednisolone of 60 mg, intravenous cyclophosphamide and intravenous immunoglobulin. She had relapsed presenting peripheral eosinophilia, abdominal and numbness in the toes of the left leg pain, but not arrythmia after tapered of prednisolone. Following additional steroid pulse, she had an increase of prednisolone and continued by intravenous cyclophosphamide, intravenous immunoglobulin and started mepolizumab. We presented a severe case of EGPA presenting an advanced atrioventricular block into cardiac arrest. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the efficacy of mepolizumab in patients affected by chronic rhinosinusitis with nasal polyps (CRSwNP) in real-life. A single-center retrospective observational study was conducted on severe CRSwNP patients treated with mepolizumab. Nasal endoscopic polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), asthma control test (ACT) score, fractional exhaled nitric oxide (FeNO), eosinophils blood cells and prednisone intake were assessed at baseline and after 6 months. A total of 55 patients were included; 49 patients (89%) presented with asthma; aspirin exacerbated respiratory disease (AERD) in 28 patients (51%). A statistically significant decrease in the SNOT-22 score was observed (median difference −63; 95% CI: −68; −58; p < 0.001) with median t0 76 and IQR (61;90) to t6 10 (5;15). A reduction in NPS, median t0 NPS 4; (IQR:4;6), median t6 NPS 1; (IQR:0;1) p < 0.001, was greater in patients with AERD. The median baseline VAS score was 6 (IQR:6;7) and the differences between t0 and t6 were statistically significant p < 0.001. Significant changes in blood eosinophils cells, median t0 500 cell/mcl (IQR:340;830), median t6 97 cell/mcl (IQR:60;160) p < 0.001, were greater in patients with AERD. Mepolizumab treatment effects have been demonstrated with significantly reduced symptoms, polyp scores, blood eosinophils and systemic corticosteroid use, resulting in an increased health-related quality of life in patients with severe CRSwNP, regardless of the presence or absence of asthma or AERD. [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndrome (HES) represents a group of blood disorders characterized by an absolute eosinophil count (AEC) > 1.5 × 103/μl in the peripheral blood, which eventually extravasate and cause organ damage. It can be primary or secondary to infections or tumors. The infiltration of eosinophils in tissue and organs is associated with different disorders and, in some cases, with life-threatening manifestations. Albeit the pathogenesis of HES in patients with solid tumo\rs is not yet clarified; recently, HES has also been described as an immune-related adverse event in patients with solid tumors receiving immune checkpoint inhibitors. Treatment of HES is still debated, especially in patients with concomitant solid tumors, and different drugs including imatinib, hydroxyurea, interferon-ɑ, glucocorticoids, and the monoclonal antibody targeting circulating IL-5 mepolizumab have been proposed according to the underlying cause and the severity of HES. Herein, we describe, for the first time, the successful use of mepolizumab for the treatment of immune checkpoint–induced HES in two patients with metastatic solid tumor. [ABSTRACT FROM AUTHOR]

Background: Although the psychometric properties of patient-reported outcome measures (e.g. the 22-item Sino-nasal Outcomes Test [SNOT-22]) in chronic rhinosinusitis with nasal polyps (CRSwNP) have been defined, these definitions have not been extensively studied in patients with very severe CRSwNP, as defined by recurrent disease despite ≥ 1 previous surgery and a current need for further surgery. Therefore, the psychometric properties of the symptoms visual analogue scales (VAS) were evaluated, and meaningful within-patient change thresholds were calculated for VAS and SNOT-22. Methods: SYNAPSE (NCT03085797), a randomized, double-blind, placebo-controlled, 52-week trial, assessed the efficacy and safety of 4-weekly mepolizumab 100 mg subcutaneously added to standard of care in very severe CRSwNP. Enrolled patients (n = 407) completed symptom VAS (six items) daily and SNOT-22 every 4 weeks from baseline until Week 52. Blinded psychometric assessment of individual and composite VAS was performed post hoc, including anchor-based thresholds for meaningful within-patient changes for VAS and SNOT-22, supported by cumulative distribution function and probability density function plots. The effect of mepolizumab versus placebo for 52 weeks on VAS and SNOT-22 scores was then determined using these thresholds using unblinded data. Results: Internal consistency was acceptable for VAS and SNOT-22 scores (Cronbach's α-coefficients ≥ 0.70). Test–retest reliability was demonstrated for all symptom VAS (Intra-Class Correlation coefficients > 0.75). Construct validity was acceptable between individual and composite VAS and SNOT-22 total score (r = 0.461–0.598) and between individual symptom VAS and corresponding SNOT-22 items (r = 0.560–0.780), based upon pre-specified ranges. Known-groups validity assessment demonstrated generally acceptable validity based on factors associated with respiratory health, with all VAS responsive to change. Mepolizumab treatment was associated with significantly increased odds of meeting or exceeding meaningful within-patient change thresholds, derived for this very severe cohort using six anchor groups for individual VAS (odds ratio [OR] 2.19–2.68) at Weeks 49–52, and SNOT-22 (OR 1.61–2.96) throughout the study. Conclusions: Symptoms VAS and SNOT-22 had acceptable psychometric properties for use in very severe CRSwNP. Mepolizumab provided meaningful within-patient improvements in symptom severity and health-related quality of life versus placebo, indicating mepolizumab provides substantial clinical benefits in very severe CRSwNP. Plain English summary: Patients with chronic rhinosinusitis (CRS) often have blocked or runny noses, and loss of sense of smell. They can also have sac-like growths in their nose called nasal polyps, which often require surgical removement. The symptoms of CRS with nasal polyps can affect quality of life. In a clinical study named SYNAPSE, a new treatment option called mepolizumab reduced the size and severity of nasal polyps in patients suffering from very severe CRS with nasal polyps, compared with placebo. Mepolizumab also reduced the need for nasal polyp surgery. The SYNAPSE study also measured if 1 year of mepolizumab treatment improved patients' symptoms and quality of life. This was evaluated by asking patients to complete two separate tasks. These tasks were rating symptoms on a visual analogue scale (VAS) and completing a quality of life questionnaire called SNOT-22. The objective of this analysis was to see if these questionnaires accurately assessed a patient's quality of life. The analysis also assessed how many patients had major improvements in their symptoms with mepolizumab. Overall, data from 407 patients in the SYNAPSE study was analyzed. Results showed that both the VAS and SNOT-22 questionnaires accurately captured CRS symptoms and quality of life. In addition, patients treated with mepolizumab for 1 year had improvements in quality of life compared with placebo. In conclusion, these findings suggest that the VAS and SNOT-22 questionnaires are appropriate evaluation tools for patients with very severe CRS with nasal polyps. The findings also show that mepolizumab treatment is beneficial for these patients. [ABSTRACT FROM AUTHOR]