Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of antineutrophil cytoplasmic antibody-associated vasculitis characterized by inflammation of small- and medium-sized vessels, causing symptoms in multiple organs. The symptoms and daily life problems reported by patients with EGPA themselves are largely unknown. We conducted a cross-sectional survey to investigate the reality of EGPA-related symptoms in patients with EGPA.

Specialists and specialized facilities with experience in treating patients with EGPA cooperated in the survey; specialists from 28 facilities across Japan participated. Patients diagnosed with EGPA by their physician and treated for ≥ 1 year who agreed to answer the online questions were enrolled and completed the survey between March and June 2024. Patients answered questions about their general symptoms, asthma symptoms, and quality of life.

We analyzed valid responses from 200 patients (61.0% female/38.5% male/0.5% prefer not to answer) with EGPA. The mean age was 57.9 years and 34.5% were ≥ 65 years old. Patients were treated at rheumatology departments (48.0%), respiratory/allergy departments (48.0%), and other departments (4.0%). Basic treatments included oral glucocorticoids (63.0%) and anti-interleukin-5/receptor α biologics (61.0%). Symptoms in > 50.0% of patients (past month) were pain/numbness (73.5%), fatigue/malaise (68.0%), asthmatic symptoms (56.0%), nasal/paranasal symptoms (55.0%), and joint/muscle pain (54.5%). Pain/numbness was considered the most painful symptom (29.5%). Nearly all patients experienced symptoms affecting two or more organs/systems. Patients reported that EGPA symptoms had detrimental impacts on physical and mental health; 67.0% of patients thought they were not understood by others because their disease is invisible, and symptoms frequently affected their daily life (61.5%), work (53.0%), sleep (49.5%), and social life (36.5%).

This is the largest survey of patients with EGPA. We have revealed the reality of patients' perceptions of EGPA-related symptoms. These results are expected to contribute to improvement in patient-centered EGPA management.

jRCT1050230186.

Data on the presentation and management of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in private practice are limited.

We sought to characterize the profiles and disease burden of patients with EGPA in a real-world private practice setting.

This was a retrospective, noninterventional, longitudinal study (GSK ID: 217426) of US Allergy Partners network data. For patients with a diagnosis of EGPA, confirmed by 2 or more EGPA clinical features, index was defined as their first visit with an Allergy Partners physician (January 2007-June 2021); postindex lasted until loss of follow-up or study end (December 2021). Patient characteristics at index, physician characteristics at any time, symptoms, treatment characteristics, and clinical outcomes postindex were assessed.

Of 52 patients (median follow-up, 3.7 years), 75% were diagnosed with EGPA outside the Allergy Partners network. Each patient received care from a median (Q1-Q3) of 4.0 (3.0-5.0) physician specialties. Most had asthma (92%), rhinitis (75%), and sinusitis (62%) and experienced a mean ± SD of 18.1 ± 4.3 distinct self-reported symptoms. Most (85%) used oral corticosteroids, with 73% (32 of 44) on daily doses of more than 12 mg; 60% used mepolizumab. Overall, 75% of patients (39 of 52) achieved a response (improved/controlled symptoms); 46% (24 of 52) achieved controlled status after worsened, unchanged, or active symptoms, and of these 38% (9 of 24) relapsed.

The complex private practice presentation of EGPA, with heterogeneous patient response to standard treatments, highlights a significant disease burden and continued need for optimized treatment strategies within a multidisciplinary team approach.

To provide long-term, real-world safety and effectiveness data for mepolizumab treatment in eosinophilic granulomatosis with polyangiitis in Japan.

MARS (NCT04551989) was a real-world, observational study of patients who had previously completed the PMS study [NCT03557060; ≥96 weeks of mepolizumab treatment before study entry (baseline)] and continued receiving four-weekly mepolizumab 300 mg subcutaneously for a further 96 weeks. Safety outcomes were assessed from baseline to Week 96 (observation period); clinical outcomes were assessed pre-mepolizumab initiation (retrospective period) and during the observation period.

Of 118 patients enrolled in the study, 58% (69/118) experienced adverse events and 22% (26/118) experienced serious adverse events over the observation period; none were mepolizumab-related. Over the study (pre-mepolizumab period, baseline, and end of observation period), the proportion of patients with no clinical symptoms increased (from 6% to 27% to 32%, respectively), median oral glucocorticoid dose decreased (from 6.9 to 3.0 to 2.0 mg/day, respectively), and the proportion of oral glucocorticoid-free patients increased (from 8% to 31% to 36%, respectively).

Long-term MARS study data are consistent with the known safety profile of mepolizumab. Over 192 weeks (pre-mepolizumab observation), mepolizumab was well tolerated, with improvements in eosinophilic granulomatosis with polyangiitis disease control and reductions in oral glucocorticoid use.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis associated with varying clinical presentations and overlapping multiorgan involvement. Asthma is a predominant feature of EGPA, typically in its prodromal phase, often severe, and precedes vasculitic complications. However, there is paucity of studies describing the prevalence and characteristics of EGPA in the asthma population.

To describe the clinical and serological characteristics and longitudinal therapeutic outcomes of patients with EGPA in the severe asthma (SA) cohort.

A retrospective study of patients with EGPA attending the multidisciplinary SA clinic in a tertiary hospital from 2011 to 2023 was conducted. Baseline demographics, organ manifestations, biological markers, lung function, and therapeutic outcomes were assessed.

Twenty-three of 596 patients in the SA registry were identified to have EGPA. Median time interval between asthma and EGPA diagnosis was 10 years (range, 2.5-32 years). Almost all patients (95.7%) had peak blood eosinophil count of more than 1.0 × 109/L (range, 0.47-14.08 × 109/L). Upper airway involvement was the most detected manifestation in addition to asthma, followed by neuropathy and renal involvement. Patients who were treated with biologic therapy were significantly younger and had more upper airway, renal, and pulmonary involvement and lower Five Factor Score.

The prevalence of EGPA in the SA population was 3.9% in our cohort. Its diagnosis requires high clinical suspicion in patients with SA and blood eosinophilia, prompting stringent evaluation for extrapulmonary manifestations and multidisciplinary involvement.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of autoimmune vasculitis. The involvement of IgG4 and HBsAg in EGPA is less common but can occur and may present unique challenges in management.

We present a case study of a 70-year-old female diagnosed with EGPA confirmed via renal biopsy. She initially presented with recurrent purpura, diarrhea and progressive numbness in the hands and feet, accompanied by general weakness. Complete remission was achieved with a one-year course of prednisone acetate and cyclophosphamide treatment. However, upon discontinuation of self-medication, the disease relapsed, manifesting as a generalized rash and weakness in the extremities.Skin biopsy revealed eosinophil infiltration, with inflammatory cells predominantly surrounding blood vessels. Notably, during treatment, the patient's hepatitis B markers transitioned from negative to positive for HBsAg. Subsequent administration of entecavir, along with monitoring for a decrease in HBV DNA levels, preceded the initiation of steroids and rituximab to attain remission once more. Among the remaining 15 patients analyzed, all exhibited elevated serum IgG4 levels, with none testing positive for hepatitis B. Notably, only one patient was diagnosed with immunoglobulin G4-related disease (IgG4-RD), suggesting that elevated IgG4 levels alone may not necessarily indicate IgG4-RD.

Our case report highlights the first instance of recurrent EGPA accompanied by elevated IgG4 and positivity for hepatitis B, which was successfully treated with rituximab. In cases of concurrent hepatitis B, rituximab treatment may be considered once viral replication is under control. However, emphasis on maintenance therapy is crucial following the induction of disease remission.

The objective of the study is to assess real-world, long-term safety/effectiveness of mepolizumab for eosinophilic granulomatosis with polyangiitis (EGPA) in Japan.

The Mepolizumab long-term study to Assess Real-world Safety and effectiveness of EGPA in Japan (MARS) (GSK ID: 213684/NCT04551989) is an ongoing 96-week study of patients with EGPA who received four-weekly mepolizumab 300 mg subcutaneously for ≥96 weeks before study entry (baseline) and continued treatment. This interim analysis included safety from baseline to Week 48 (observation period) and clinical outcomes before mepolizumab and during the observation period.

Of 118 patients enrolled, 29% (34/118) experienced adverse events (AEs), of which 13% (15/118) experienced serious AEs; none were considered mepolizumab related. The median oral corticosteroid (OCS) dose decreased from 6.9 (pre-mepolizumab) to 3.0 (baseline) and 2.0 mg/day (Weeks 45-48); the proportion of patients receiving no OCS increased from 8% to 32% and 38%, respectively. Patients experiencing clinical symptoms decreased from 94% (pre-mepolizumab) to 73% (baseline) and 67% (Week 48). During the observation period, 5% of patients experienced EGPA relapse; the rates of EGPA-related hospitalisations, EGPA-related emergency room/unscheduled visits, and asthma exacerbations were 0.05, 0.09, and 0.08 event/person-year, respectively.

The results of mepolizumab treatment for ≥144 weeks (before baseline plus observation) were consistent with the known safety profile and allowed OCS dose reduction while improving disease control versus pre-treatment among patients with EGPA.

We report the prevalence of eosinophilic granulomatosis with polyangiitis (EGPA) and describe oral corticosteroid (OCS) use and disease burden before and after the mepolizumab approval in 2018 for EGPA in Japan.

Two retrospective studies (GSK IDs: 218083 and 218084) used two databases: (1) the JMDC insurer database (Japanese health insurer claims) was used to report annual EGPA prevalence and OCS use in mepolizumab-treated patients and (2) Medical Data Vision database was used to report annual treatment use, OCS dose, relapses, and healthcare resource utilization in patients with EGPA.

EGPA prevalence (95% confidence interval) increased from 4.2 (0.1, 23.4) in 2005 to 58.6 (53.2, 64.5) per 1,000,000 in 2020. Median OCS dose (mg/day) decreased from a range of 4.8-7.7 during 2010-2017 to 4.5-4.8 during 2018-2020 (lowest dose in 2020). The proportion of patients with prednisolone-equivalent daily OCS dose >10 mg decreased from 2017 (11.9%) to 2020 (10.3%), while the median dose halved. The proportion of patients with EGPA relapses (64.3% to 41.6%) and hospitalization (27.8% to 23.6%) decreased from 2010 to 2020.

EGPA prevalence increased between 2005 and 2020. With the introduction of mepolizumab for EGPA in 2018, real-world OCS use, relapses, and healthcare resource utilization decreased.

Although the high disease burden associated with eosinophilic granulomatosis with polyangiitis (EGPA) has been established, the disease burden in patients initiating mepolizumab in real-world practice is poorly understood. This study aimed to assess characteristics and burden of real-world patients with EGPA initiating mepolizumab.

This was a database study (GSK study ID: 214156) of US patients (≥12 years old) with EGPA and ≥1 mepolizumab claim (index date) identified from the Merative MarketScan Commercial and Medicare Supplemental Databases (November 1, 2015, to March 31, 2020). Outcomes assessed in the 12-month baseline period before index (inclusive) included patient characteristics, treatment use, EGPA relapses, asthma exacerbations, health care resource utilization, and costs.

In the 103 patients included (mean age, 51.1 years; 63.1% female), the most common manifestations were asthma (89.3%), chronic sinusitis (57.3%), and allergic rhinitis (43.7%). In total, 91.3% of patients had ≥1 oral corticosteroid (OCS) claim (median dose, 7.4 mg/d prednisone-equivalent), 45.6% were chronic OCS users (≥10 mg/d during the 90 days preindex), 99.0% had ≥1 EGPA-related relapse, and 62.1% ≥1 asthma exacerbation. During the baseline period, 26.2% and 97.1% of patients had EGPA-related inpatient admissions and office visits, respectively. Median all-cause total health care costs per patient were $33,298, with total outpatient costs ($16,452) representing the largest driver.

Before initiating mepolizumab, a substantial real-world EGPA disease burden is evident for patients, with resulting impact on health care systems, and indicative of unmet medical needs. Mepolizumab treatment, with a demonstrated positive clinical benefit-risk profile may represent a useful treatment option for reducing EGPA disease burden.

This report describes a hitherto unique case of eosinophilic granulomatosis with polyangiitis (EGPA), a subtype of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The patient was an 81-year-old man whose clinical course involved notable changes in the ANCA profile, specifically a transition from positive proteinase 3 (PR3)-ANCA to myeloperoxidase (MPO)-ANCA, followed by simultaneous positivity for both. The patient's medical history included bronchial asthma, allergic rhinitis, sinusitis, and multiple comorbidities. Despite being initially PR3-ANCA-positive, subsequent admissions demonstrated MPO-ANCA positivity along with eosinophilic manifestations, highlighting the complexity of diagnosis of EGPA. Diagnostic evaluation included imaging, serological markers, and clinical symptoms, which collectively supported the classification of EGPA. Notably, this case challenges the conventional diagnostic paradigms and emphasizes the evolving nature of ANCA profiles in vasculitis. The shift in ANCA profile prompted a reevaluation of the patient's diagnosis and treatment strategy. This case underscores the importance of considering fluctuations in ANCA in patients with a diagnosis of EGPA, management decisions, and potential implications for disease progression. Further research is warranted to elucidate the mechanisms underlying changes in ANCA and their clinical significance in vasculitis.

Background and aim Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder associated with the presence of blood and tissue eosinophilia, extravascular granulomas, and asthma. Currently, the burden of EGPA on the patient and the healthcare system is not well characterized. This study aimed to assess the real-world clinical and economic burden of disease in adult patients with EGPA compared with matched patients with asthma without EGPA. Methods This retrospective cohort study used medical, pharmacy, enrolment, and demographic data from a US administrative claims database (PharMetrics Plus). Patients ≥18 years old, with ≥six months of continuous health plan enrolment in the baseline period, and ≥12 months of continuous health plan enrolment in the follow-up period were eligible for this analysis. Patients with EGPA and patients with asthma without EGPA were identified using diagnosis codes and were subsequently matched 1:5 (e.g., one patient with EGPA matched with five patients with asthma, without EGPA) based on baseline characteristics. The primary outcome measure was all-cause healthcare costs; secondary outcomes included healthcare resource utilization, medication usage, and clinical characteristics. Results In the final matched cohorts, there were 7183 patients with EGPA and 35,915 patients with asthma without EGPA. During the follow-up period, mean total all-cause healthcare costs were significantly higher in patients with EGPA than in those with asthma without EGPA (mean {standard deviation}: $44,405 {$82,060} vs $24,487 {$54,691}; p<0.0001). Patients with EGPA had mean total all-cause healthcare costs that were 73.9% greater than those in patients with asthma without EGPA, even after applying a multivariable analysis to adjust for differences in demographic and clinical characteristics. Medication usage was consistently higher in the EGPA population than in the asthma population (excepting short-acting β2-agonists). The majority of patients in the EGPA population (83.1%) also experienced ≥one relapse during the study period, with 26.3% of patients in the EGPA population experiencing a major relapse. Conclusions There is a significantly greater economic and clinical burden associated with EGPA compared with asthma without EGPA in adults. These results underscore the unmet need in this patient population for improved disease control strategies that will reduce the burden of EGPA on patients and the healthcare system.

The recent publication of the American College of Rheumatology (ACR)-European Alliance of Associations for Rheumatology (EULAR) classification criteria for large vessel vasculitis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) has provided modern criteria for the classification of these conditions, which incorporate contemporary methods of investigation and diagnosis. Further validation is required in independent cohorts, especially from populations that were not well represented in the development cohort. Studies of the occurrence of large vessel vasculitis report that Takayasu arteritis is a rare disease in most populations, and giant cell arteritis is the most common vasculitis in older populations. The incidence of AAV appears to have plateaued, but the prevalence is increasing as a result of lower mortality. The new classification criteria may affect the reported incidence and prevalence, and studies will be needed to confirm this. The impact of COVID-19 on the occurrence of the vasculitides is not completely known, but there is evidence of reduced occurrence of Kawasaki disease and IgA-associated vasculitis following lockdowns with reduced transmission of possible trigger infectious agents.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, is a systemic disorder characterized by asthma, eosinophilia, and vasculitis primarily affecting small vessels. Although this disease is classified as an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis along with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), observations suggest that eosinophils play a vital role in the pathophysiology of EGPA. Therefore, biopsy specimens derived from patients with EGPA demonstrated an increase in eosinophils within the vascular lumen and extravascular interstitium, especially in patients negative for ANCA. In addition, active secretion of eosinophil intracellular components by cytolysis and piecemeal degranulation occurs in the extravascular interstitium and bloodstream. Although the treatment for EGPA is described in the context of ANCA-associated vasculitis along with MPA and GPA, a therapeutic approach to suppress eosinophils is also considered. Monoclonal antibodies directed against interleukin-5 (IL-5) or its receptors are good therapeutic agents because IL-5 plays an important role in eosinophil growth, activation, and survival. Currently, mepolizumab (Nucala), reslizumab (Cinqair), and benralizumab (Fasenra) have been studied for use in patients with EGPA. These monoclonal antibodies were initially approved for use in patients with severe eosinophilic asthma. Mepolizumab is now approved for treating EGPA following the success of phase 3 randomized controlled trial. Therefore, further studies are needed to clarify long-term safety and efficacy of anti-IL-5 agents and establish indications of individual therapeutic agents tailored to individual conditions of patients with EGPA.