Emergence of extrathoracic manifestations of eosinophilic granulomatosis with polyangiitis during benralizumab treatment.
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ABSTRACT:
SUBMITTER: Lim AKH
PROVIDER: S-EPMC8190011 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A 63 years - old woman affected by severe eosinophilic asthma associated with EGPA presented refractory respiratory symptoms, resistant to high dose oral corticosteroid treatment. A significant hyper-eosinophilia was present at the blood test, and the ACT score was steadily low, despite the maximal dose of inhalation therapy. The CT chest scan showed a persistent diffuse bronchial wall thickening, pulmonary infiltration and paranasal sinusitis. We report here the rapid onset of effect of benralizumab 30 mg in a monthly subcutaneous injection in reducing patient's symptom, inducing regression of CT scan abnormalities, determining a steroid sparing effect and improving lung function tests after 3 months of therapy. A fast and stable reduction of peripheral eosinophilia associated with an increase in ACT score were also documented after the first dose of benralizumab.
| S-EPMC7152676 | biostudies-literature
Project description:ObjectiveTo describe clinical manifestations and outcomes in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in North America.MethodsAnalysis of patients aged 18 years or older who fulfilled the 1990 American College of Rheumatology Classification Criteria for EGPA enrolled in the Vasculitis Clinical Research Consortium from 2003 to 2019. Main clinical characteristics, treatments, outcomes, and accumulated damage were studied.ResultsThe cohort included 354 patients; 59% female; age at diagnosis of 50.0 (±14) years; 39% were antineutrophil cytoplasm antibody (ANCA) positive. Time from diagnosis to last follow-up was 7.0 (±6.2) years; 49.4% had one or more relapse. Patients positive for ANCA more commonly had neurological and kidney involvement when compared with patients negative for ANCA, who had more cardiac and lung manifestations. At last study visit, only 35 (12.6%) patients had been off all therapy for more than 2 years during their follow-up. The overall mortality rate was 4.0% and did not differ by ANCA status or cyclophosphamide use. Scores on the Vasculitis Damage Index (VDI) for 134 patients with two or more visits and more than 1 year of follow-up increased from 1.7 (±1.8) at enrollment (3.7 [±5.1] years after diagnosis) to 3.35 (±2.1) at last follow-up (7.5 [±5.8] years after diagnosis), mainly represented by chronic asthma (67.5%), peripheral neuropathy (49.6%), and chronic sinusitis (31.3%). Longer duration of glucocorticoid use and relapse were associated with higher VDI scores.ConclusionThis analysis describes the many clinical manifestations and varied outcomes of EGPA and highlights the ongoing need to attain more sustained, long-term remission to limit the accrual of disease-related damage.
| S-EPMC8207688 | biostudies-literature
Project description: Not available
| S-EPMC7733721 | biostudies-literature
Project description:Vasculitis refers to inflammation of the systemic vessels. Eosinophilic granulomatosis with polyangiitis (EGPA) is a medium and small vessel vasculitis characterized by hypereosinophilia, pulmonary infiltrates, difficult to treat asthma and polyneuropathies. Diagnosis can often be challenging. In this article, we present a case of a young lady who was diagnosed ANCA negative EGPA.
| S-EPMC6446216 | biostudies-literature
Project description:BACKGROUND:Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti-interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis. METHODS:In this multicenter, double-blind, parallel-group, phase 3 trial, we randomly assigned participants with relapsing or refractory eosinophilic granulomatosis with polyangiitis who had received treatment for at least 4 weeks and were taking a stable prednisolone or prednisone dose to receive 300 mg of mepolizumab or placebo, administered subcutaneously every 4 weeks, plus standard care, for 52 weeks. The two primary end points were the accrued weeks of remission over a 52-week period, according to categorical quantification, and the proportion of participants in remission at both week 36 and week 48. Secondary end points included the time to first relapse and the average daily glucocorticoid dose (during weeks 48 through 52). The annualized relapse rate and safety were assessed. RESULTS:A total of 136 participants underwent randomization, with 68 participants assigned to receive mepolizumab and 68 to receive placebo. Mepolizumab treatment led to significantly more accrued weeks of remission than placebo (28% vs. 3% of the participants had ?24 weeks of accrued remission; odds ratio, 5.91; 95% confidence interval [CI], 2.68 to 13.03; P<0.001) and a higher percentage of participants in remission at both week 36 and week 48 (32% vs. 3%; odds ratio, 16.74; 95% CI, 3.61 to 77.56; P<0.001). Remission did not occur in 47% of the participants in the mepolizumab group versus 81% of those in the placebo group. The annualized relapse rate was 1.14 in the mepolizumab group, as compared with 2.27 in the placebo group (rate ratio, 0.50; 95% CI, 0.36 to 0.70; P<0.001). A total of 44% of the participants in the mepolizumab group, as compared with 7% of those in the placebo group, had an average daily dose of prednisolone or prednisone of 4.0 mg or less per day during weeks 48 through 52 (odds ratio, 0.20; 95% CI, 0.09 to 0.41; P<0.001). The safety profile of mepolizumab was similar to that observed in previous studies. CONCLUSIONS:In participants with eosinophilic granulomatosis with polyangiitis, mepolizumab resulted in significantly more weeks in remission and a higher proportion of participants in remission than did placebo, thus allowing for reduced glucocorticoid use. Even so, only approximately half the participants treated with mepolizumab had protocol-defined remission. (Funded by GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT02020889 .).
| S-EPMC5548295 | biostudies-literature
Project description:BackgroundEosinophilic myocarditis (EM) is a rare and potentially life-threatening form of myocarditis, frequently (but not always) associated with eosinophilia, and presents with acute chest pain, or signs and symptoms of acute or chronic heart failure. Eosinophilic myocarditis has various aetiologies, including eosinophilic granulomatosis with polyangiitis (EGPA).Case summaryA 52-year-old female with a long-standing history of asthma, acral paraesthesia, subcutaneous nodules, and recurrent chest pain treated with anti-inflammatory drugs was admitted to our hospital with chest pain, repolarization disturbances, eosinophilia, and increased troponin levels. After an initial evaluation by coronary angiography, echocardiography and cardiac magnetic resonance, a definitive diagnosis of EM was made with the help of an endomyocardial biopsy. The aetiological diagnosis of EM as a manifestation of tissue involvement in EGPA was concluded after ruling out other possible causes of eosinophilia and with the help of other diagnostic criteria for EGPA (asthma, eosinophilia, and neuropathy). Therefore, we started with a high dosage of glucocorticoids, and attained relief of symptoms and normalization of eosinophilic count after a few days.DiscussionIn cases of myocarditis (particularly if associated with eosinophilia), EM is a manifestation of EGPA and should be considered for a prompt differential diagnosis. Endomyocardial biopsy represents the gold standard for the diagnosis of EM. The mainstay of therapy for EM is immunosuppressive drugs to help prevent its evolution to a fulminant form and chronic progression towards restrictive cardiomyopathy.
| S-EPMC8564711 | biostudies-literature
Project description:Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare autoimmune disease characterized by medium and small vessels inflammation. Cardiac vasculitic involvement is one of the most severe manifestations with a significant impact on patients' long-term prognosis: anyway, a specific therapeutic approach for heart involvement in EGPA has not been explored yet. Current regimen consists of a long-term therapy with high dose of glucocorticoids, causing the well-known related-adverse events; immunosuppressive drugs are used in patients with severe manifestations, with some limitations. New therapeutic approaches are needed for patients with refractory disease or contraindications to conventional therapies. The quest for the ideal therapy is going toward a more and more personalized approach: on the one hand, efforts are made to use already existing therapies in the most appropriate way; on the other hand, new insights into EGPA pathogenesis allow the discovery of new targets, as demonstrated by mepolizumab and rituximab, targeting eosinophils, and B-cell compartments. This review summarizes the emerging therapies used in EGPA, focusing on the most recent studies on biologics and analyzing their efficacy and safety.
| S-EPMC8593004 | biostudies-literature
Project description:ObjectiveIdentification of a biomarker for disease activity in eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss) remains an unmet need. This study examined the value of serum periostin, a marker of type 2 inflammation, as a measure of disease activity in patients with EGPA.MethodsParticipants enrolled in a multicenter, prospective cohort of patients with EGPA were included in this study if they had disease activity (defined as Birmingham Vasculitis Activity Score [BVAS] > 0) during follow-up. Serum levels of periostin were measured at flare visit as well as two pre- and two post-flare visits, if available. The outcome of disease activity was assessed either with BVAS or Physician Global Assessment (PGA). Mixed-effect models were used to examine the association between periostin levels and disease activity. Comparisons were made with a historical cohort of healthy individuals and patients with asthma.ResultsIn the 49 patients included in the study, the median periostin level was 60 ng/ml (IQR 50 to 73) in all visits and did not significantly change across visits. Multivariate analyses found no association between periostin level and presence or absence of flare according to the BVAS (adjusted OR 1.00 [95% CI 0.98 to 1.02], p = 0.98) but an increase in periostin level was significantly associated with greater disease severity during a flare according to the PGA (adjusted beta-coefficient 0.02 [95% CI 0.004 to 0.03], p = 0.01). Periostin levels in EGPA were significantly higher than previously studied healthy controls and patients with asthma.ConclusionIn EGPA serum periostin level is modestly associated with greater disease severity during a flare but does not discriminate active from inactive disease. Periostin levels in EGPA are higher than in other previously studied cohorts, including healthy populations and patients with asthma, and are relatively stable over time.
| S-EPMC6181402 | biostudies-literature
Project description:BackgroundCardiac manifestations are common and life-threatening in eosinophilic granulomatosis with polyangiitis (EGPA), which remains poorly studied in China. We aim to investigate its clinical features, associated factors, treatment, and outcomes.MethodsWe reviewed the clinical records of 110 EGPA patients and examined the independent factors associated with cardiac manifestations using multivariate logistic regression. Receiver operating characteristic curves determined the cut-off values, and survival was calculated via Kaplan-Meier curves.ResultsCardiac involvement was present in 36.4% (40/110) of EGPA patients, which mainly manifested as pericardial effusion (16.4%, 18/110), myocardial involvement (13.6%, 15/110), and heart failure (8.2%, 9/110). The mean age was 42.1 ± 14.23 years with no female/male predominance. Compared with the cardiac-unaffected group, the cardiac-affected group showed a lower rate of biopsy-proved vasculitis (0% versus 20%, p = 0.002). The eosinophil count [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.029-1.267] was independently associated with cardiac manifestations in EGPA, with a cut-off value of 3.66 × 109/L [area under the curve (AUC) = 0.692, p = 0.001]. Regarding treatment, the cardiac-affected group displayed a higher ratio of glucocorticoid pulse combined with intravenous cyclophosphamide (CYC-IV) (40% versus 21.4%, p = 0.037), and intravenous immunoglobulin combined with glucocorticoid plus CYC-IV (17.5% versus 4.3%, p = 0.035) than the control group. Outcomes (p = 0.131) and survival (p = 0.1972) were not significantly different between the groups.ConclusionIn this single-center Chinese EGPA cohort, cardiac manifestations are observed in 36.4% of patients, which primarily presents as myocardial involvement, pericardial effusion, and heart failure, independently associated with eosinophil count. Glucocorticoid combined with cyclophosphamide is the treatment cornerstone for EGPA patients with cardiac manifestations.
| S-EPMC7841702 | biostudies-literature
Project description:BackgroundIn a recent phase III trial (NCT02020889) 53% of mepolizumab-treated versus 19% of placebo-treated patients with eosinophilic granulomatosis with polyangiitis (EGPA) achieved protocol-defined remission.ObjectiveWe sought to investigate post hoc the clinical benefit of mepolizumab in patients with EGPA using a comprehensive definition of benefit encompassing remission, oral glucocorticoid (OGC) dose reduction, and EGPA relapses.MethodsThe randomized, placebo-controlled, double-blind, parallel-group trial recruited patients with relapsing/refractory EGPA receiving stable OGCs (prednisolone/prednisone, ≥7.5-50 mg/d) for 4 or more weeks. Patients received 300 mg of subcutaneous mepolizumab or placebo every 4 weeks for 52 weeks. Clinical benefit was defined post hoc as follows: remission at any time (2 definitions used), 50% or greater OGC dose reduction during weeks 48 to 52, or no EGPA relapses. The 2 remission definitions were Birmingham Vasculitis Activity Score of 0 plus OGC dose of 4 mg/d or less (remission 1/clinical benefit 1) or 7.5 mg/d or less (remission 2/clinical benefit 2). Clinical benefit was assessed in all patients and among subgroups with a baseline blood eosinophil count of less than 150 cells/μL, baseline OGC dosage of greater than 20 mg/d, or weight of greater than 85 kg.ResultsWith mepolizumab versus placebo, 78% versus 32% of patients experienced clinical benefit 1, and 87% versus 53% of patients experienced clinical benefit 2 (both P < .001). Significantly more patients experienced clinical benefit 1 with mepolizumab versus placebo in the blood eosinophil count less than 150 cells/μL subgroup (72% vs 43%, P = .033) and weight greater than 85 kg subgroup (68% vs 23%, P = .005); in the OGC greater than 20 mg/d subgroup, results were not significant but favored mepolizumab (60% vs 36%, P = .395).ConclusionWhen a comprehensive definition of clinical benefit was applied to data from a randomized controlled trial, 78% to 87% of patients with EGPA experienced benefit with mepolizumab.
| S-EPMC7254609 | biostudies-literature