scholarly journals Effectiveness and Safety of Mepolizumab in Combination with Corticosteroids in Patients with Eosinophilic Granulomatosis with Polyangiitis

2020 ◽  
Author(s):  
Masanobu Ueno ◽  
Ippei Miyagawa ◽  
Kazuhisa Nakano ◽  
Shigeru Iwata ◽  
Kentaro Hanami ◽  
...  
Keyword(s):  
Real World ◽  
Eosinophil Count ◽  
Granulomatosis With Polyangiitis ◽  
Remission Rate ◽  
Retention Rate ◽  
Damage Index ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Interleukin 5 ◽  
Number Of Patients ◽  
Eosinophilic Granulomatosis

Abstract Objectives: Mepolizumab (MPZ), an anti-interleukin-5 antibody, is effective for treating eosinophilic granulomatosis with polyangiitis (EGPA). However, its effectiveness has not been adequately evaluated in real-world clinical practice. In this study, we assessed the effectiveness and safety of 300 mg MPZ for relapsing/refractory EGPA resistant to corticosteroids (CS) for 1 year in real-world settings. Methods: We administered MPZ (300 mg) to 16 patients with relapsing/refractory EGPA resistant to CS (with-MPZ). We also retrospectively collected data from the same patients for 12 months before administering MPZ (without-MPZ). The primary endpoint was the 12-month remission rate after MPZ administration, and the secondary endpoints were the Birmingham vasculitis activity score (BVAS), vasculitis damage index (VDI), eosinophil count, changes in concomitant CS doses/concomitant immunosuppressant use, MPZ retention rate, and incidence of adverse events. The clinical course was compared between Without-MPZ and With MPZ.Results: The 12-month remission rate after initiating MPZ was 75%. No change was observed in BVAS, eosinophil count, or concomitant CS dose in the without-MPZ, whereas all these parameters were significantly decreased in the with-MPZ. The number of patients on concomitant immunosuppressants also decreased in the with-MPZ. VDI did not increase in both groups. The MPZ retention rate was 100%, and only three patients (18.8%) had infections.Conclusion: This study demonstrated that MPZ is effective and safe for EGPA, furthermore, compared to Without-MPZ, MPZ improves disease activity and possesses a higher remission rate and CS sparing effect.

scholarly journals Effectiveness and safety of mepolizumab in combination with corticosteroids in patients with eosinophilic granulomatosis with polyangiitis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Masanobu Ueno ◽  
Ippei Miyagawa ◽  
Kazuhisa Nakano ◽  
Shigeru Iwata ◽  
Kentaro Hanami ◽  
...  
Keyword(s):  
Real World ◽  
Eosinophil Count ◽  
Granulomatosis With Polyangiitis ◽  
Remission Rate ◽  
Retention Rate ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Number Of Patients ◽  
Significant Difference ◽  
Eosinophilic Granulomatosis ◽  
Over Time

Abstract Background Mepolizumab (MPZ), an anti-interleukin-5 antibody, is effective for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). However, its effectiveness has not been adequately evaluated in real-world clinical practice. In this study, we assessed the effectiveness and safety of MPZ (300 mg) for relapsing/refractory EGPA resistant to corticosteroids (CS) for 1 year in real-world settings. Methods We administered MPZ (300 mg) to 16 patients with relapsing/refractory EGPA resistant to CS (Post-MPZ). We also retrospectively collected data from the same patients for the 12 months before the administration of MPZ (Pre-MPZ). The primary endpoint was the 12-month remission rate after MPZ administration and the secondary endpoints were the Birmingham vasculitis activity score (BVAS), vasculitis damage index (VDI), eosinophil counts, changes in concomitant CS doses/concomitant immunosuppressant use, MPZ retention rate, and incidence of adverse events. The clinical course was compared between Pre-MPZ and Post-MPZ. Results The 12-month remission rate after the initiation of MPZ was 75%. No change was observed in BVAS, eosinophil count, or concomitant CS dose over time in the Pre-MPZ group, whereas all these parameters were significantly decreased over time in the Post-MPZ group. The number of patients using concomitant immunosuppressant also decreased over time in the Post-MPZ group. VDI did not increase in either group. The MPZ retention rate was 100% and only three patients (18.8%) had infections. Changes in BVAS, eosinophil count, and cumulative concomitant CS dose were significantly lower in the Post-MPZ group than in the Pre-MPZ group. There was no significant difference in the changes in VDI between the groups. Conclusion This study demonstrated that MPZ is effective and safe for EGPA. Furthermore, MPZ decreases disease activity, increases remission rate, and has a CS-sparing effect.

scholarly journals Multiple hepatic aneurysms and dry gangrene of fingertips in eosinophilic granulomatosis with polyangiitis: a case report

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Eunsil Koh ◽  
Noeul Kang ◽  
Jin-Young Lee ◽  
Duk-Kyung Kim ◽  
Young Soo Do ◽  
...  
Keyword(s):  
Eosinophil Count ◽  
Granulomatosis With Polyangiitis ◽  
Stable State ◽  
Clinical Situation ◽  
High Dose ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Case Presentation ◽  
The Right ◽  
Small Aneurysms ◽  
Eosinophilic Granulomatosis

Abstract Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis mainly affecting small-sized arteries. Involvement of medium-sized vessels is very rare in EGPA. Here we present the case of a patient with EGPA who showed multiple hepatic aneurysms and distal gangrene. Case presentation A known EGPA patient visited to the emergency room (ER) with abrupt squeezing abdominal pain. She had suffered from gangrene in the fingertips of both hands for 1 year because of arterial thrombosis associated with hypereosinophilia. However, her absolute eosinophil count in the ER was 1120 cells/µL. An abdomen-pelvis CT demonstrated subcapsular hematoma in the right hepatic lobe. A celiac angiogram demonstrated multiple sized aneurysms in both hepatic lobes and some aneurysms in S7 and S8 were huge, more than 1 cm in size. The shape of the small aneurysms resembled a string of beads, as in polyarteritis nodosa. Given the clinical situation, emergency embolization was performed. Before this patient visited to the ER, she had been treated with a high dose of systemic corticosteroid, azathioprine, and cyclophosphamide. After addition of mepolizumab, the eosinophil count remained stable state with a near zero percentage of total white blood cell count. Conclusions Aneurysm and gangrene resulting from the involvement of medium-sized vessels can occur in EGPA. Destruction of vessels might occur even if eosinophil count is below 1500 cells/µL. If involvement of medium-sized arteries is suspected, thorough investigation to identify the involved organs and prompt management are needed to prevent fatal complications.

scholarly journals Cardiac manifestations of eosinophilic granulomatosis with polyangiitis from a single-center cohort in China: clinical features and associated factors

2021 ◽  
Vol 12 ◽  
pp. 204062232098705
Author(s):  
Suying Liu ◽  
Ling Guo ◽  
Zhaocui Zhang ◽  
Mengtao Li ◽  
Xiaofeng Zeng ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pericardial Effusion ◽  
Eosinophil Count ◽  
Associated Factors ◽  
Granulomatosis With Polyangiitis ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Single Center ◽  
Myocardial Involvement ◽  
Cardiac Manifestations ◽  
Eosinophilic Granulomatosis

Background: Cardiac 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. Methods: We 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. Results: Cardiac 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. Conclusion: In 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.

scholarly journals A real-world assessment of mycophenolate mofetil for remission induction in eosinophilic granulomatosis with polyangiitis

2021 ◽  
Author(s):  
Mariana Philobos ◽  
Amy Perkins ◽  
Maira Karabayas ◽  
Paula Dospinescu ◽  
Nick Fluck ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Real World ◽  
Granulomatosis With Polyangiitis ◽  
Controlled Trial ◽  
Remission Induction ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Newly Diagnosed ◽  
Real World Data ◽  
Disease Remission ◽  
Eosinophilic Granulomatosis

AbstractEosinophilic granulomatosis with polyangiitis (EGPA) is a form of ANCA-associated vasculitis (AAV). Clinical trials demonstrating the efficacy of mycophenolate mofetil (MMF) for remission induction in AAV excluded patients with EGPA. Despite this, MMF is commonly used in these patients. The objective of this study was to evaluate, for the first time, the effectiveness and tolerance of MMF in EGPA remission induction. A retrospective, two-center, real-world study was conducted in patients with EGPA who received MMF in addition to prednisolone for newly diagnosed or relapsing disease between 2009 and 2019. Baseline, 3-, 6- and 12-month outcome data were extracted from electronic health records. The primary outcome was disease remission, defined as a Birmingham Vasculitis Activity Score of 0 at 6 months. Secondary outcomes included disease relapse, median prednisolone dose at 12 months and drug tolerance. In total, 15 patients (73% male, median age 57) with EGPA (11 newly diagnosed/4 relapsing) were identified. At 6 months, 67% had achieved disease remission. At 12 months, this was maintained (66.7%) and 4 patients had relapsed. All but one patient remained on MMF at study completion and all patients tolerated MMF. Our real-world data suggest that MMF is an effective and well-tolerated agent for achieving disease remission in EGPA. A future randomized controlled trial of MMF in this neglected orphan disease is now warranted.

scholarly journals Cardiac Involvement in Eosinophilic Granulomatosis With Polyangiitis: A Retrospective Study in the Chinese Population

2020 ◽  
Vol 7 ◽  
Author(s):  
Yingying Chen ◽  
Xiaoxiao Guo ◽  
Jiaxin Zhou ◽  
Jing Li ◽  
Qingjun Wu ◽  
...  
Keyword(s):  
Disease Activity ◽  
Eosinophil Count ◽  
Chinese Population ◽  
Cardiac Involvement ◽  
Granulomatosis With Polyangiitis ◽  
Age At Onset ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Appropriate Treatment ◽  
Younger Age ◽  
Eosinophilic Granulomatosis

Introduction: Cardiac involvement in eosinophilic granulomatosis with polyangiitis (EGPA) is associated with a poor prognosis and high mortality; however, few studies about cardiac involvement in EGPA in the Chinese population are available. We conducted this study to determine the clinical characteristics and overall outcomes of Chinese EGPA patients with cardiac involvement.Materials and Methods: We retrospectively collected the clinical data of 83 patients diagnosed with EGPA and analyzed the differences between the patients with and without cardiac involvement.Results: The prevalence of cardiac involvement in EGPA in this cohort was 27.7%. Compared with those without cardiac involvement, EGPA patients with cardiac involvement tended to have a younger age at onset (mean ± SD: 38.4 ± 10.5 vs. 42.1 ± 15.9 years, respectively, p = 0.039), higher eosinophil count (median [IQR]: 5810 [4020–11090] vs. 2880 [1530–6570] n/μL, respectively, p = 0.004), higher disease activity assessed using the Birmingham vasculitis activity score (BVAS) (median [IQR]: 20 [16–28] vs. 15 [12–18], respectively, p = 0.001), and poorer prognosis (Five Factor Score [FFS] ≥ 1: 100% vs. 38.3%, respectively, p = 0.001). In the cardiac involvement group, 43.5% of patients were asymptomatic, but cardiac abnormalities could be detected by cardiac examinations. With appropriate treatment, the overall outcomes of EGPA patients with cardiac involvement in our cohort were good, with only 3 (13.0%) patients dying in the acute phase and no patients dying during follow-up.Conclusions: Cardiac involvement in EGPA was associated with a younger age at onset, higher eosinophil count, higher disease activity, and a poorer prognosis. Comprehensive cardiac examinations and appropriate treatment are essential to improve the prognosis of those with cardiac involvement.

INTERLEUKIN-5 IS A NEW TARGET IN THE TREATMENT OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS

2020 ◽  
Vol 58 (3) ◽  
pp. 321-329
Author(s):  
T. V. Beketova ◽  
E. V. Arseniev
Keyword(s):  
Adverse Reactions ◽  
Granulomatosis With Polyangiitis ◽  
Standard Treatment ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Rare Form ◽  
Double Blind ◽  
Interleukin 5 ◽  
Treatment Regimens ◽  
Multiple Organs ◽  
Eosinophilic Granulomatosis

Interleukin-5 (IL-5) is involved in the maturation and activation of eosinophils, its production is increased in patients with eosinophilic granulomatosis with polyangiitis (EGPA). This rare form of systemic vasculitides (SV) is characterized by peripheral eosinophilia and involves multiple organs and systems. The clinical introduction of glucocorticoids (GCs) and immunosuppressants has considerably improved the prognosis of EGPA, but their use is associated with significant adverse reactions and cannot be effective enough. The use of standard treatment regimens cannot always allow to achieve remission; the rate of EGPA relapses remains high. Mepolizumab is an IL-5 antagonist and a promising drug for the treatment of patients with EGPA. The presented literature review considers arguments in favor of using mepolizumab in EGPA patients and discusses its efficacy and safety. The currently accumulated data suggest that mepolizumab is effective and safe in treating patients with EGPA, what has been demonstrated in the registration double-blind, randomized, placebo-controlled MIRRA study. Treatment with the IL-5 antagonist allows one to control both the symptoms of asthma and the manifestations of SV, enhances the probability of achieving remission of EGPA, can help reduce the risk of relapse and minimize the dose of GS.

scholarly journals New Insights Into Novel Therapeutic Targets in ANCA-Associated Vasculitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuji Nozaki
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Granulomatosis With Polyangiitis ◽  
New Drugs ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Interleukin 5 ◽  
Anca Associated Vasculitis ◽  
New Findings ◽  
Eosinophilic Granulomatosis ◽  
Novel Therapeutic

Biologics targeting inflammation-related molecules in the immune system have been developed to treat rheumatoid arthritis (RA), and these RA treatments have provided revolutionary advances. Biologics may also be an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, particularly in patients with resistance to standard treatments. Despite the accumulation of clinical experience and the increasing understanding of the pathogenesis of vasculitis, it is becoming more difficult to cure vasculitis. The treatment of vasculitis with biologics has been examined in clinical trials, and this has also enhanced our understanding of the pathogenesis of vasculitis. A humanized anti-interleukin-5 monoclonal antibody known as mepolizumab was recently demonstrated to provide clinical benefit in the management of eosinophilic granulomatosis with polyangiitis in refractory and relapsing disease, and additional new drugs for vasculitis are being tested in clinical trials, while others are in abeyance. This review presents the new findings regarding biologics in addition to the conventional immunosuppressive therapy for ANCA-associated vasculitis.

scholarly journals Improvement of Chronic Rhinosinusitis and Reduction of the Myeloperoxidase-Antineutrophil Cytoplasmic Antibody Titer in a Patient with Eosinophilic Granulomatosis with Polyangiitis by Additional Mepolizumab

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Shin-ya Tamechika ◽  
Shuntaro Isogai ◽  
Shinji Maeda ◽  
Taio Naniwa ◽  
Akio Niimi
Keyword(s):  
Side Effects ◽  
Chronic Rhinosinusitis ◽  
Eosinophil Count ◽  
Granulomatosis With Polyangiitis ◽  
Clinical Course ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Inflammatory Cascade ◽  
Myeloperoxidase Antineutrophil Cytoplasmic Antibody ◽  
Eosinophilic Granulomatosis

A case of eosinophilic granulomatosis with polyangiitis (EGPA) in which chronic rhinosinusitis (CRS) was improved with a reduction in the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titer after the addition of mepolizumab is reported. A 55-year-old woman with EGPA receiving prednisolone 5 mg/day developed CRS with increases in the eosinophil count and the MPO-ANCA titer. Although it improved with prednisolone 15 mg/day in addition to mizoribine 150 mg/day, because azathioprine could not be taken orally due to side effects, it relapsed after prednisolone was tapered to 5 mg/day. There was no exacerbation of other vasculitis symptoms such as mononeuropathy multiplex. The patient was treated with additional mepolizumab 300 mg every 4 weeks, which resulted in the improvement of CRS and marked reductions of the eosinophil count and MPO-ANCA titer, and the reduction of prednisolone to 2 mg/day. Furthermore, even after tapering mepolizumab to 200 mg every 4 weeks, her condition remained stable without relapse of EGPA and without increases in the eosinophil count and MPO-ANCA titer. The clinical course of mepolizumab treatment in this patient suggests that the IL5-dependent inflammatory cascade is one of the factors contributing to the increase in MPO-ANCA in EGPA.

scholarly journals Safety and Effectiveness of Mepolizumab Therapy in Remission Induction Therapy for Eosinophilic Granulomatosis with Polyangiitis: A Retrospective Study

2021 ◽  
Author(s):  
Masanobu Ueno ◽  
Ippei Miyagawa ◽  
Takafumi Aritomi ◽  
Koichi Kimura ◽  
Shigeru Iwata ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Granulomatosis With Polyangiitis ◽  
Retention Rate ◽  
Remission Induction ◽  
High Dose ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Primary Endpoints ◽  
Secondary Endpoints ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

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.

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