RARE DISEASE
Eosinophilic granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis
Eosinophilic granulomatosis with polyangiitis
Synonyms: Churg-Strauss syndrome, EGPA, Granulomatous allergic angiitis
Synonyms: Churg-Strauss syndrome, EGPA, Granulomatous allergic angiitis
Synonyms: Churg-Strauss syndrome, EGPA, Granulomatous allergic angiitis
Drug discovery
5
drugs
With orphan designations
Overview
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare ANCA-associated vasculitis characterized by eosinophilic inflammation, necrotizing granulomas, and small-to-medium vessel vasculitis. It typically progresses through three phases: allergic (asthma, sinusitis), eosinophilic (organ infiltration), and vasculitic (neuropathy, purpura). ANCA positivity occurs in 30–40% of cases, often linked to glomerulonephritis. Multisystem involvement includes respiratory (95% asthma), cardiac (leading cause of death), and gastrointestinal systems [1][6][10][11].
Burden
Morbidity: 35% relapse within 5 years; 26% develop new vasculitic manifestations (e.g., mononeuritis multiplex, cardiomyopathy) [5][18].
Healthcare: 19% require EGPA-related hospitalization (median 11 days); 39% receive ≥5 OCS prescriptions/year [2][9][10].
Comorbidities: Asthma (80.6%), nasal polyps (32.1%), and cardiac involvement (up to 50% mortality if untreated) [1][2][15].
Therapies
First-line: High-dose corticosteroids (≥47% OCS dependence post-diagnosis) ± immunosuppressants (cyclophosphamide, azathioprine) [3][9][15].
Biologics: Mepolizumab (anti-IL-5) for refractory/relapsing disease; rituximab (anti-CD20) in ANCA-positive cases [8][13][17].
Relapse management: Chronic low-dose corticosteroids; monitoring for hypogammaglobulinemia with biologics [3][8][13].
Categories: rare cardiac diseases, rare circulatory system diseases, rare neurological diseases, rare renal diseases, rare respiratory diseases, rare systemic and rheumatological diseases, rare systemic or rheumatologic diseases of childhood, rare transplant-related disorders
Research Papers
1,327 drug discovery papers about Eosinophilic granulomatosis with polyangiitis, with 2 first-in-class and 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,327 drug discovery papers about Eosinophilic granulomatosis with polyangiitis, with 2 first-in-class and 11 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-08 | Eosinophilic granulomatosis with polyangiitis complicated by pulmonary aspergillosis and misdiagnosed as allergic bronchopulmonary aspergillosis: a case report.
To enhance the diagnostic and therapeutic awareness of eosinophilic granulomatosis with polyangiitis (EGPA) complicated by pulmonary aspergillosis. We report a case of EGPA initially misdiagnosed as allergic bronchopulmonary aspergillosis (ABPA) in a 52-year-old female patient. The patient presented with intermittent wheezing for more than six months and had a history of sinusitis. An outside hospital diagnosed ABPA based on pulmonary opacities, bronchiectasis, and evidence of Aspergillus infection, but standard therapy proved ineffective. Upon admission, laboratory findings revealed a markedly elevated absolute peripheral blood eosinophil count (5.29 × 109/L) and positivity for MPO-ANCA and p-ANCA. Serum total IgE was 8.85 IU/mL, and specific IgE to Aspergillus fumigatus was <0.10 IU/mL, both of which were inconsistent with ABPA. Chest CT showed multiple bilateral patchy and nodular opacities with bronchiectasis. Bronchoalveolar lavage fluid targeted next-generation sequencing (tNGS) detected Aspergillus at the genus level (23 sequence reads, relative abundance 33.39%). The diagnosis was revised to EGPA complicated by pulmonary aspergillosis. The patient was treated with glucocorticoids combined with mepolizumab, supplemented with voriconazole. Following treatment, the patient's symptoms resolved, with near normalization of imaging findings and pulmonary function. After 10 months of follow-up, methylprednisolone was completely discontinued in December 2025, and at the last follow-up in May 2026, the patient had been off glucocorticoids for 5 months, with sustained remission and successful extension of the mepolizumab dosing interval to 8 weeks. For patients presenting with refractory asthma accompanied by eosinophilia and pulmonary opacities, EGPA should be highly suspected. Glucocorticoids combined with mepolizumab is effective. In patients achieving sustained remission, extending the mepolizumab dosing interval to 8 weeks may be a safe and effective long-term maintenance strategy in carefully selected patients, though this observation requires further validation in prospective studies.
2026-08-05 | Advances in the treatment of eosinophilic granulomatosis with polyangiitis.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies and characterized by blood and tissue eosinophilia, severe respiratory manifestations, and multiorgan involvement. The management of newly diagnosed EGPA still relies on therapeutic strategies that were initially validated for other forms of anti-neutrophil cytoplasmic antibody-associated vasculitis, including microscopic polyangiitis and granulomatosis with polyangiitis. Whereas the long-term prognosis of microscopic polyangiitis and granulomatosis with polyangiitis depends primarily on controlling initial organ involvement and preventing relapses, EGPA is distinguished by chronic involvement of both upper and lower respiratory airways, which often necessitates prolonged glucocorticoid therapy. Data from clinical trials suggest that targeting the IL-5 pathway with mepolizumab or benralizumab can effectively control persistent respiratory symptoms and reduce the need for glucocorticoids, yet the role of these agents in the management of EGPA at the time of diagnosis and in the long term remains to be defined. Emerging retrospective data on therapies targeting other type 2 cytokines (such as IL-4, IL-13 and thymic stromal lymphopoietin) suggest potential benefits for relapsing respiratory symptoms; however, prospective evidence remains limited and safety has yet to be established. This Review discusses the role of these new targeted therapies in the management of EGPA, alongside historical treatments.
2026-08-04 | The Past, the Present, and the Future of Periostin in Allergy.
Periostin is a matricellular protein that binds to its receptors, which include several integrin molecules but mainly αvβ3 integrin on cell surfaces, thereby transducing its signals into cells. Almost 20 years have passed since we found that periostin is involved in the pathogenesis of asthma, which marked the first evidence of its involvement in allergic diseases. Over the past 2 decades, cumulative evidence has demonstrated that periostin plays important roles in the onset or progress of many allergic diseases such as chronic rhinitis with nasal polyp, atopic dermatitis (AD), allergic conjunctivitis, eosinophilic esophagitis, eosinophilic otitis media, allergic rhinitis, and eosinophilic granulomatosis with polyangiitis. Starting from the observation of highly expressed periostin in the lesions of these diseases, periostin studies have expanded to include how periostin contributes to the generation of allergic phenotypes, how measurement of periostin is useful as a biomarker for allergic diseases, and recently how periostin inhibitors can improve allergic diseases. Periostin contributes to the generation of allergic phenotypes by acting as a matricellular protein on many cells, including both non-immune and immune cells. Based on the characteristics of periostin as a surrogate biomarker of interleukin-13, a signature cytokine of type 2 inflammation, serum periostin has been used as a biomarker for stratifying endotypes, estimating disease severity, predicting or monitoring the efficacy of therapeutic drugs, and predicting disease relapse or recurrence. Moreover, a lot of attention is now being paid to periostin in body fluids such as tears and sputum as a biomarker directly reflecting type 2 inflammation. Since it has been shown that periostin evokes itch in AD, we hope to see the development of a novel therapeutic agent for AD targeting periostin/αvβ3 integrin. Here we summarize the discovery and characteristics of periostin, as well as questions and/or problems regarding periostin that remain to be resolved.
2026-08-04 | Clinical outcomes after switching from mepolizumab to benralizumab in eosinophilic granulomatosis with polyangiitis: A single-centre retrospective cohort study.
To investigate the impact of switching to benralizumab on flare risk in patients with eosinophilic granulomatosis with polyangiitis (EGPA) previously treated with mepolizumab. We conducted a single-centre retrospective cohort study including 26 patients with EGPA who received mepolizumab. A landmark analysis was performed at 910 days after mepolizumab initiation (median time to switching), and patients were grouped according to treatment. The primary outcome was disease flares requiring treatment intensification. We used a Cox model with treatment switching as a time-dependent covariate. In the landmark analysis, the benralizumab group (n=4) had a higher flare rate than the mepolizumab group (n=10) (log-rank test, P = 0.002). However, the Cox model did not converge and the time-dependent analysis yielded an imprecise estimate (hazard ratio 3.14, 95% confidence interval 0.31-32.02). The 1-year flare-free rate after switching to benralizumab (n=19) was 94.1%, and no severe flares occurred. Most patients had low disease activity at switching, and switching was primarily driven by patient preference. Short-term flare-free survival after switching to benralizumab was high despite a small number of minor flares. Further evidence is warranted to assess long-term outcomes.
2026-08-03 | Clinical spectrum and outcomes of mononeuritis multiplex in rheumatic diseases: evidence from a nationwide multicenter study.
Mononeuritis multiplex (MM) is a severe and clinically heterogeneous form of peripheral neuropathy, most commonly arising in the context of systemic vasculitis in rheumatology practice. Despite its potential to cause substantial functional impairment, data on its clinical spectrum, management, and outcomes remain limited. This study aimed to comprehensively evaluate the clinical characteristics, underlying etiologies, treatment approaches, and outcomes of MM in a nationwide multicenter rheumatology cohort. Retrospective, multicenter observational study. Adult patients diagnosed with MM by rheumatologists across 27 tertiary referral centers were included. Data were collected using a standardized case report form, encompassing demographic features, clinical presentation, electrophysiological findings, laboratory parameters, treatment modalities, and outcomes. Neurological status was assessed at the final follow-up visit. A total of 72 patients were analyzed (mean age 53.5 ± 14.9 years; 61.1% male). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was the most common underlying etiology (68%), with eosinophilic granulomatosis with polyangiitis being the predominant subtype. The typical clinical presentation consisted of acute-onset, asymmetric, distal involvement of the lower extremities, with foot drop as the most frequent manifestation (69.4%). Electrophysiological findings were consistent with a classical MM pattern in the majority of patients. Most patients received high-dose glucocorticoids combined with immunosuppressive therapy. Over a median follow-up of 29 months, 81.9% of patients achieved complete or partial neurological improvement. Outcomes were similar between ANCA-associated and non-ANCA-related diseases. MM represents a clinically diverse but potentially manageable neurological complication of rheumatic diseases. Early recognition supported by electrophysiological assessment, together with timely immunosuppressive treatment, may improve clinical outcomes. A multidisciplinary approach is essential to optimize long-term recovery and functional status.
2026-08-08 | Eosinophilic granulomatosis with polyangiitis complicated by pulmonary aspergillosis and misdiagnosed as allergic bronchopulmonary aspergillosis: a case report.
To enhance the diagnostic and therapeutic awareness of eosinophilic granulomatosis with polyangiitis (EGPA) complicated by pulmonary aspergillosis. We report a case of EGPA initially misdiagnosed as allergic bronchopulmonary aspergillosis (ABPA) in a 52-year-old female patient. The patient presented with intermittent wheezing for more than six months and had a history of sinusitis. An outside hospital diagnosed ABPA based on pulmonary opacities, bronchiectasis, and evidence of Aspergillus infection, but standard therapy proved ineffective. Upon admission, laboratory findings revealed a markedly elevated absolute peripheral blood eosinophil count (5.29 × 109/L) and positivity for MPO-ANCA and p-ANCA. Serum total IgE was 8.85 IU/mL, and specific IgE to Aspergillus fumigatus was <0.10 IU/mL, both of which were inconsistent with ABPA. Chest CT showed multiple bilateral patchy and nodular opacities with bronchiectasis. Bronchoalveolar lavage fluid targeted next-generation sequencing (tNGS) detected Aspergillus at the genus level (23 sequence reads, relative abundance 33.39%). The diagnosis was revised to EGPA complicated by pulmonary aspergillosis. The patient was treated with glucocorticoids combined with mepolizumab, supplemented with voriconazole. Following treatment, the patient's symptoms resolved, with near normalization of imaging findings and pulmonary function. After 10 months of follow-up, methylprednisolone was completely discontinued in December 2025, and at the last follow-up in May 2026, the patient had been off glucocorticoids for 5 months, with sustained remission and successful extension of the mepolizumab dosing interval to 8 weeks. For patients presenting with refractory asthma accompanied by eosinophilia and pulmonary opacities, EGPA should be highly suspected. Glucocorticoids combined with mepolizumab is effective. In patients achieving sustained remission, extending the mepolizumab dosing interval to 8 weeks may be a safe and effective long-term maintenance strategy in carefully selected patients, though this observation requires further validation in prospective studies.
2026-08-05 | Advances in the treatment of eosinophilic granulomatosis with polyangiitis.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies and characterized by blood and tissue eosinophilia, severe respiratory manifestations, and multiorgan involvement. The management of newly diagnosed EGPA still relies on therapeutic strategies that were initially validated for other forms of anti-neutrophil cytoplasmic antibody-associated vasculitis, including microscopic polyangiitis and granulomatosis with polyangiitis. Whereas the long-term prognosis of microscopic polyangiitis and granulomatosis with polyangiitis depends primarily on controlling initial organ involvement and preventing relapses, EGPA is distinguished by chronic involvement of both upper and lower respiratory airways, which often necessitates prolonged glucocorticoid therapy. Data from clinical trials suggest that targeting the IL-5 pathway with mepolizumab or benralizumab can effectively control persistent respiratory symptoms and reduce the need for glucocorticoids, yet the role of these agents in the management of EGPA at the time of diagnosis and in the long term remains to be defined. Emerging retrospective data on therapies targeting other type 2 cytokines (such as IL-4, IL-13 and thymic stromal lymphopoietin) suggest potential benefits for relapsing respiratory symptoms; however, prospective evidence remains limited and safety has yet to be established. This Review discusses the role of these new targeted therapies in the management of EGPA, alongside historical treatments.
2026-08-04 | The Past, the Present, and the Future of Periostin in Allergy.
Periostin is a matricellular protein that binds to its receptors, which include several integrin molecules but mainly αvβ3 integrin on cell surfaces, thereby transducing its signals into cells. Almost 20 years have passed since we found that periostin is involved in the pathogenesis of asthma, which marked the first evidence of its involvement in allergic diseases. Over the past 2 decades, cumulative evidence has demonstrated that periostin plays important roles in the onset or progress of many allergic diseases such as chronic rhinitis with nasal polyp, atopic dermatitis (AD), allergic conjunctivitis, eosinophilic esophagitis, eosinophilic otitis media, allergic rhinitis, and eosinophilic granulomatosis with polyangiitis. Starting from the observation of highly expressed periostin in the lesions of these diseases, periostin studies have expanded to include how periostin contributes to the generation of allergic phenotypes, how measurement of periostin is useful as a biomarker for allergic diseases, and recently how periostin inhibitors can improve allergic diseases. Periostin contributes to the generation of allergic phenotypes by acting as a matricellular protein on many cells, including both non-immune and immune cells. Based on the characteristics of periostin as a surrogate biomarker of interleukin-13, a signature cytokine of type 2 inflammation, serum periostin has been used as a biomarker for stratifying endotypes, estimating disease severity, predicting or monitoring the efficacy of therapeutic drugs, and predicting disease relapse or recurrence. Moreover, a lot of attention is now being paid to periostin in body fluids such as tears and sputum as a biomarker directly reflecting type 2 inflammation. Since it has been shown that periostin evokes itch in AD, we hope to see the development of a novel therapeutic agent for AD targeting periostin/αvβ3 integrin. Here we summarize the discovery and characteristics of periostin, as well as questions and/or problems regarding periostin that remain to be resolved.
2026-08-04 | Clinical outcomes after switching from mepolizumab to benralizumab in eosinophilic granulomatosis with polyangiitis: A single-centre retrospective cohort study.
To investigate the impact of switching to benralizumab on flare risk in patients with eosinophilic granulomatosis with polyangiitis (EGPA) previously treated with mepolizumab. We conducted a single-centre retrospective cohort study including 26 patients with EGPA who received mepolizumab. A landmark analysis was performed at 910 days after mepolizumab initiation (median time to switching), and patients were grouped according to treatment. The primary outcome was disease flares requiring treatment intensification. We used a Cox model with treatment switching as a time-dependent covariate. In the landmark analysis, the benralizumab group (n=4) had a higher flare rate than the mepolizumab group (n=10) (log-rank test, P = 0.002). However, the Cox model did not converge and the time-dependent analysis yielded an imprecise estimate (hazard ratio 3.14, 95% confidence interval 0.31-32.02). The 1-year flare-free rate after switching to benralizumab (n=19) was 94.1%, and no severe flares occurred. Most patients had low disease activity at switching, and switching was primarily driven by patient preference. Short-term flare-free survival after switching to benralizumab was high despite a small number of minor flares. Further evidence is warranted to assess long-term outcomes.
2026-08-03 | Clinical spectrum and outcomes of mononeuritis multiplex in rheumatic diseases: evidence from a nationwide multicenter study.
Mononeuritis multiplex (MM) is a severe and clinically heterogeneous form of peripheral neuropathy, most commonly arising in the context of systemic vasculitis in rheumatology practice. Despite its potential to cause substantial functional impairment, data on its clinical spectrum, management, and outcomes remain limited. This study aimed to comprehensively evaluate the clinical characteristics, underlying etiologies, treatment approaches, and outcomes of MM in a nationwide multicenter rheumatology cohort. Retrospective, multicenter observational study. Adult patients diagnosed with MM by rheumatologists across 27 tertiary referral centers were included. Data were collected using a standardized case report form, encompassing demographic features, clinical presentation, electrophysiological findings, laboratory parameters, treatment modalities, and outcomes. Neurological status was assessed at the final follow-up visit. A total of 72 patients were analyzed (mean age 53.5 ± 14.9 years; 61.1% male). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was the most common underlying etiology (68%), with eosinophilic granulomatosis with polyangiitis being the predominant subtype. The typical clinical presentation consisted of acute-onset, asymmetric, distal involvement of the lower extremities, with foot drop as the most frequent manifestation (69.4%). Electrophysiological findings were consistent with a classical MM pattern in the majority of patients. Most patients received high-dose glucocorticoids combined with immunosuppressive therapy. Over a median follow-up of 29 months, 81.9% of patients achieved complete or partial neurological improvement. Outcomes were similar between ANCA-associated and non-ANCA-related diseases. MM represents a clinically diverse but potentially manageable neurological complication of rheumatic diseases. Early recognition supported by electrophysiological assessment, together with timely immunosuppressive treatment, may improve clinical outcomes. A multidisciplinary approach is essential to optimize long-term recovery and functional status.
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Drug Discovery Landscape
5 orphan drug designations for Eosinophilic granulomatosis with polyangiitis, including 2 approved therapies.
5 orphan drug designations for Eosinophilic granulomatosis with polyangiitis, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
small molecule, selective Janus kinase (JAK) 1 inhibitor | small molecules | FDA | 2025-04-14 | — | NS Pharma, Inc. |
Methyl-(1-{[6-{[(1S)-1-cyclopropylethyl]amino}-2-(pyrazolo[5,1-b][1,3]thiazol-7-yl)-pyrimidin-4-yl]carbonyl}piperidin-4-yl)carbamate mono(4-methylbenzenesulfonate) | antibodies | EMA | 2024-01-12 | — | Syneos Health Netherlands B.V. |
benralizumab [Fasenra] | antibodies | FDA | 2018-11-21 | 2024-09-17 | AstraZeneca Pharmaceuticals LP |
Mepolizumab | antibodies | EMA | 2013-03-12 | — | Glaxosmithkline (Ireland) Limited |
mepolizumab [NUCALA] | antibodies | FDA | 2011-07-14 | 2017-12-12 | GlaxoSmithKline LLC |
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