Efficacy and Safety of Mepolizumab in Patients With Eosinophilic Granulomatosis With Polyangiitis: A Single-Center Experience.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic vasculitis characterized by eosinophil-rich, necrotizing granulomatous inflammation primarily affecting the respiratory tract with necrotizing vasculitis of small- to medium-sized arteries. In this case series, we retrospectively evaluated the efficacy and safety of mepolizumab in seven patients diagnosed with EGPA who presented to the Department of Allergy and Clinical Immunology at Cleveland Clinic Abu Dhabi. The variables assessed before and after mepolizumab treatment included Birmingham Vasculitis Activity Score (BVAS), prednisolone dose, Asthma Control Test (ACT) score, and blood eosinophil count (BEC). We found a significant reduction in BVAS and prednisolone dosage with clinical improvements in asthma symptoms after treatment with mepolizumab. Our case series, the first from the Middle East on the use of mepolizumab in EGPA, demonstrates that mepolizumab is a safe and effective treatment for patients with EGPA.

Real-World Studies of Biologics for the Treatment of Moderate-to-Severe Asthma.

Presently, there are 6 biologic agents available for treatment of asthma. Each of these agents has undergone robust clinical trials in their approval programs. Such studies rely upon very rigid entry criteria that may not translate to real-world efficacy. Thus, exploring the efficacy of these agents in a larger, more heterogeneous, population brings a sense of comfort regarding their efficacy in the real-world. This review explores the available literature regarding the use of biologics in the real world, with a focus on markers of likely response to therapy.

Biologics in Asthma: Potential to Achieve Clinical Remission.

Establishing a universal definition for asthma remission has the potential to improve asthma outcomes and advance research. However, there is still no consensus definition despite broad multidisciplinary efforts to achieve this goal. This study explores the evolving concept of asthma remission, emphasizing the potential of biologics to achieve this state. We will discuss various proposed definitions of asthma remission, international guidelines, and studies evaluating the effectiveness of biologics at achieving clinical remission. We highlight the need for a consensus definition of asthma remission to standardize treatment goals and improve patient outcomes.

Reduced Sense of Smell in Patients with Severe Chronic Rhinosinusitis and its Implications for Diagnosis and Management: A Narrative Review.

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.

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. Supplementary file1 (MP4 60193 kb).

Successful Treatment of Refractory Asthma Clinically Diagnosed As Eosinophilic Granulomatosis With Polyangiitis in a Hairdresser Using Tezepelumab.

We report a case of a 53-year-old male hairdresser with refractory asthma clinically diagnosed as eosinophilic granulomatosis with polyangiitis (EGPA) who showed remarkable improvement with tezepelumab after failing mepolizumab therapy. The patient presented with a three-year history of progressive multisystem involvement, including anosmia, asthma, hearing loss, and skin rash. The patient was clinically diagnosed as EGPA based on asthma, sinusitis with nasal polyps, eosinophilia, and purpura. Despite initial improvement with oral corticosteroids and mepolizumab, he experienced recurrent exacerbations of asthma. Tezepelumab was initiated, resulting in significant symptom improvement, successful corticosteroid tapering, and marked enhancement in pulmonary function tests. This case suggests that tezepelumab may be an effective treatment option for patients with refractory asthma, particularly those with suspected occupational exposure. Further research is needed to identify factors that predict response to different biologic therapies in refractory EGPA-related asthma and to explore the potential role of occupational exposures in treatment outcomes.

Peak nasal inspiratory flow assessment of polyp size and response from SYNAPSE.

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 <1 point or worsening). Results: Patients with improvements in NPS had greater improvements in PNIF (a median of 50 L per minute [interquartile range (IQR) = 10.5-87.5] with mepolizumab vs a median of 40 L per minute [IQR = 0-85.0] with placebo) than did those patients without improvements in NPS (a median of 0.0 L per minute [IQR = -10.0 to 45.0] with mepolizumab vs a median of 0.0 L per minute [IQR = -30.0 to 30.0] with placebo). Similar results were seen for the following: change from baseline in overall symptoms (a median of -5.8 [IQR = -8.1 to -3.80] with mepolizumab and a median of -4.1 [IQR = -7.0 to -1.2] with placebo with improvement in NPS vs a median of -1.3 [IQR = -6.3 to 0.0] with mepolizumab and a median of -0.1 [IQR = -3.4 to 0.0] with placebo without improvement in NPS); change in nasal obstruction (a median of -5.7 [IQR = -8.2 to -3.5] with mepolizumab and a median of -4.5 [IQR = -7.3 to -1.2] with placebo with improvement in NPS vs a median of -1.3 [IQR = -6.6 to 0.0] with mepolizumab and a median of 0.0 [IQR = -3.6 to 0.0] with placebo without improvement in NPS); change in loss of smell (a median of -2.8 [IQR = -7.9 to 0.0] with mepolizumab and a median of -0.7 [IQR = -4.0 to 0.0] with placebo with improvement in NPS vs a median of 0.0 [IQR = -2.4 to 0.0] with mepolizumab and a median of 0.0 [IQR = -0.3 to 0.0]) with placebo without improvement in NPS); and change in visual analog scale score and 22-Item Sino-Nasal Outcome Test total score (a median of -37.0 [IQR = -52.0 to -24.0] with mepolizumab and a median of -29.0 [IQR = -43.0 to -9.0] with placebo with improvement in NPS vs a median of -16.0 [IQR = -42.0 to 0.0] with mepolizumab and a median of 0.0 [IQR = -27.0 to 0.0] with placebo without improvement in NPS). Conclusion: Improvement in NPS was associated with improvements in PNIF and patient-reported outcomes irrespective of treatment. PNIF could be a useful noninvasive tool for monitoring nasal polyp size.

A Case of Refractory Vasospastic Angina Complicated by Bronchial Asthma with Eosinophilia1.

A 48-year-old woman with a history of bronchial asthma and allergic rhinitis presented with cardiac arrest due to ventricular fibrillation and was resuscitated by defibrillation. Coronary angiography revealed coronary vasospasm. Various antispastic agents were unable to control recurrent coronary spasms. We searched for other points of intervention and found a significant increase in the eosinophil count. The patient received mepolizumab for bronchial asthma with eosinophilia, which normalized the eosinophil count. Since then, the patient has remained free from coronary vasospasm, suggesting that mepolizumab may be a viable option for treating refractory coronary angina associated with bronchial asthma and eosinophilia.

Effects of Mepolizumab in the treatment of type 2 CRSwNP: a real-life clinical study.

PURPOSE: Mepolizumab was recently approved for treating Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) unresponsive to standard treatment or recurring after endoscopic sinus surgery (ESS). To date, few studies have assessed Mepolizumab's efficacy in severe type-2 CRSwNP. Our study aimed to analyze sinonasal outcomes in type-2 CRSwNP patients treated with 100 mg Mepolizumab administered subcutaneously every four weeks. METHODS: We conducted a retrospective study of patients with severe, recalcitrant CRSwNP treated with Mepolizumab. Demographic and clinical characteristics were collected, including age, sex, and comorbidities such as asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD), and allergic rhinitis (AR), as well as the number of previous ESS procedures and the interval since the last one. Patients were evaluated at baseline and after one year for blood eosinophil count, nasal polyp score (NPS), modified Lund-Kennedy score (mLKS), olfactory function (using a VAS scale and a 16-item Sniffin' identification test), SNOT-22, and sinus opacification on CT scans. The need for rescue ESS or systemic corticosteroids (SCS), response to treatment, and side effects were also recorded. RESULTS: Data from 27 patients were collected. After one year, all scores showed significant improvement. NERD was the only factor associated with a less favorable improvement in olfactory function. There were no side effects reported, although 2 patients discontinued Mepolizumab as they were considered "non-responders." CONCLUSIONS: Mepolizumab is safe and effective in reducing the clinical, endoscopic, and radiological burden of disease, as well as in decreasing the need for salvage ESS or systemic steroids.

Targeting the IL-5 pathway in eosinophilic asthma: A comparison of anti-IL-5 versus anti-IL-5 receptor agents.

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.

Biologics in Hypereosinophilic Syndrome and Eosinophilic Granulomatosis with Polyangiitis.

Hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) are complex disorders defined by blood and tissue eosinophilia and heterogeneous clinical manifestations. Historically, the mainstay of therapy for both conditions has been systemic glucocorticoids. However, recent availability of biologics that directly or indirectly target eosinophils has provided new avenues to pursue improved outcomes with decreased toxicity. In this article, we summarize the evidence supporting the use of specific biologics in HES and/or EGPA and provide a framework for their clinical use in patients.

Solo Addition of Mepolizumab Turned Antineutrophil Cytoplasmic Antibody Negative and Achieved Glucocorticoid Discontinuation in a Patient with Eosinophilic Granulomatosis with Polyangiitis: A Case Report.

The IL-5 inhibitor mepolizumab is beneficial in eosinophilic granulomatosis with polyangiitis (EGPA), and the inhibition of antineutrophil cytoplasmic antibody (ANCA) production has been suggested as a possible mechanism. We herein report a 78-year-old Japanese man with EGPA who received solo mepolizumab 300 mg twice for elevated ANCA levels, which led to subsequent GC discontinuation after achieving remission. The patient was able to be freed from the adverse events associated with long-term GC treatment, and the sole addition of mepolizumab also proved that mildly elevated ANCA could be converted to a negative result, thus leading to GC discontinuation.

Cluster Analysis Identifies Patients With Severe Eosinophilic Asthma Who Achieve Super-Response and Remission With Mepolizumab.

This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies.

Treatment of Severe Asthma: Case Report of Fast Action of Mepolizumab in a Patient with Recent SARS-CoV-2 Infection.

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.

Current Goals of NSAID-ERD Management: Patient-Centered Approaches Involving NSAID Desensitization With and Without Biologics.

The classic approach of nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NSAID-ERD) includes pharmaceutical and surgical treatments, as well as avoidance of cyclooxygenase 1-inhibitor NSAIDs. The introduction of biologics in the treatment of severe asthma and chronic rhinosinusitis with nasal polyps represents an alternative therapeutic approach to the classical aspirin therapy after desensitization (ATAD) in some regions, and with convincing results. However, their use is limited due to approval and/or high-cost restrictions. NSAID-ERD is a mainly type 2 and highly eosinophilic disease, and mAbs targeting IgE or IL-5, IL-4, and IL-13 have been shown to be effective for both severe asthma and severe chronic rhinosinusitis with nasal polyps. So far, dupilumab demonstrated greater efficacy in patients with NSAID-ERD than in aspirin-tolerant patients with regard to several clinical outcomes. Patients with NSAID-ERD respond very rapidly to omalizumab also, with reduction in the release of prostaglandin D2 and cysteinyl leukotrienes. Patients favored biologic treatment over ATAD in multiple retrospective analyses, which must be acknowledged when choosing one or the other option. Although this review will summarize ATAD in general, it will more prominently focus on when ATAD should be considered, even when type 2 biologics are available. In addition, there are conflicting studies as to whether patients on a type 2 biologic become desensitized to NSAIDs, because omalizumab proved to restore tolerance to aspirin in only two-third of patients. This goal of NSAID tolerance should be considered as part of disease control future approaches, representing one of many aspects in a patient-centered care approach.

Three cases of relapsed eosinophilic sinusitis without eosinophilia during mepolizumab maintenance therapy for eosinophilic granulomatosis with polyangiitis.

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.

'Efficacy of biologics in NSAID-ERD: United airways from the nose to the bronchi'.

NSAID-exacerbated respiratory disease (NSAID-ERD), the clinical triad of severe chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and respiratory reactions to cyclooxygenase 1 inhibitors, is often challenging to manage, with many patients failing first line therapies for CRSwNP and asthma. There are now six biologic mediations approved for asthma and/or severe CRSwNP: omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab and tezepelumab. With the availability of respiratory biologic treatment for both asthma and CRSwNP, clinicians now have a multitude of additional management options for patients with NSAID-ERD. Herein we will review the currently available clinical trial and real-world evidence for biologic efficacy and safety patients with NSAID-ERD, discuss the mechanisms of biologic therapy specific to NSAID-ERD, and review evidence regarding the use of biologic therapy versus endoscopic sinus surgery therapy for CRSwNP and NSAID-ERD. We will propose a management approach for choosing biologic therapy or endoscopic sinus surgery with aspirin therapy after desensitization for patients with NSAID-ERD.

Efficient use of mepolizumab in children: An analysis of the economically justifiable price in Colombia.

INTRODUCTION: Asthma imposes a crucial economic burden on health systems, especially with the incorporation of new drugs. Recently, mepolizumab has been approved to prevent exacerbations in patients with eosinophilic asthma. This study explores the economically justifiable price of mepolizumab for preventing exacerbations in children with severe asthma. MATERIALS AND METHODS: A model was developed using the microsimulation to estimate the quality-adjusted costs and life years of two interventions: mepolizumab versus not applying standard treatment without mepolizumab. This analysis was made during a time horizon of 50 years and from a third-payer perspective. RESULTS: Mepolizumab was cost-effective using a WTP of U$ 19,992 per QALY, but not at a WTP of U$ 4828, U$ 5128 per QALY. The economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of U$ 4828, and U$ 5128 respectively. At the current price of Mepolizumab, U$ 780 per dose, only using a WTP higher than U$ 10,300 per QALY mepolizumab will be the best alternative to no mepolizumab. CONCLUSION: Our study shows that the economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of 4828 and 5180 respectively. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.

A comparison of the impact of anti-IL5/5r therapies in allergic versus non-allergic patients with severe eosinophilic asthma in a real-life setting.

OBJECTIVE: This 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Superiority of Avacopan and Mepolizumab to Glucocorticoid Tapering in the Treatment of Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Systematic Review.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a spectrum of autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies have shown that avacopan and mepolizumab are promising therapeutics for partial or complete replacement of glucocorticoids (GC), with sustained remission while completely weaning off GC. Avacopan inhibits C5aR in the complement pathway, preventing neutrophil migration, while mepolizumab targets IL-5R, reducing eosinophil activity. Additionally, complement inhibition has not only contributed to the recovery of renal function and alleviation of physical symptoms but has also enhanced patients' overall quality of life and mental well-being. This systematic review explores the pathogenesis of AAV, traditional treatments, and the potential of emerging complement and interleukin antagonist therapies such as avacopan and mepolizumab in revolutionizing AAV management.

Combination effect of Mepolizumab and Endobronchial Watanabe Spigot (EWS) in drug-induced eosinophilic pneumonia complicated by refractory pneumothorax.

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.