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.

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 B-Cell-Depleting Therapy Improves Myocarditis in Seronegative Eosinophilic Granulomatosis with Polyangiitis

2021 ◽  
Vol 10 (19) ◽  
pp. 4577
Author(s):  
Chrong-Reen Wang ◽  
Yi-Shan Tsai ◽  
Hung-Wen Tsai ◽  
Cheng-Han Lee
Keyword(s):  
B Cell ◽  
Clinical Remission ◽  
Granulomatosis With Polyangiitis ◽  
Disease Onset ◽  
Cardiac Insufficiency ◽  
Induction Treatment ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Asthma Attack ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Cardiac involvement is a major mortality cause in eosinophilic granulomatosis with polyangiitis (EGPA), requiring novel therapeutics to spare the use of cyclophosphamide with known cardiotoxicity. Despite the observed efficacy of B-cell-depleting therapy in myocarditis of seropositive microscopic polyangiitis, it remains to be elucidated in seronegative EGPA. A retrospective study was performed in 21 hospitalized active patients aged 20 to 70 years with five-factor score 1 or 2, eosinophil counts 10,034 ± 6641/μL and vasculitis scores 27 ± 6. Overt myocarditis was identified in 10 cases, at disease onset in 6 and relapse in 4, with endomyocarditis in 4 and myopericarditis in 4. Five seronegative and one seropositive patient received rituximab with an induction regimen 375 mg/m2 weekly × 4 for refractory or relapse disease, and the same regimen for annual maintenance therapy. All cases had lower eosinophil counts, improved cardiac dysfunction and clinical remission with a relapse-free follow-up, 48 ± 15 months after the induction treatment. One seronegative endomyocarditis patient had eosinophilia and disease relapse with asthma attack and worsening cardiac insufficiency 24 months after induction, achieving clinical remission under anti-IL-5 therapy. Our findings suggest the suppression of IL-5-mediated eosinophilia as an action mechanism of B-cell-depleting therapy in seronegative EGPA myocarditis.

scholarly journals Longterm Outcomes of 188 Japanese Patients with Eosinophilic Granulomatosis with Polyangiitis

2018 ◽  
Vol 45 (8) ◽  
pp. 1159-1166 ◽  
Author(s):  
Aiko Saku ◽  
Shunsuke Furuta ◽  
Masaki Hiraguri ◽  
Kei Ikeda ◽  
Yoshihisa Kobayashi ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Onset ◽  
Japanese Patients ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Factors Associated ◽  
Hazards Model ◽  
Eosinophilic Granulomatosis ◽  
Eosinophil Counts

Objective.Patients with eosinophilic granulomatosis with polyangiitis (EGPA) frequently experience relapses, which lead to cumulative organ damage. In this retrospective observational study, we aimed to reveal the risk factors for relapse in EGPA.Methods.A total of 188 Japanese patients with EGPA diagnosed between 1996 and 2015 were identified from medical records in 10 hospitals. The diagnosis was based on the American College of Rheumatology 1990 criteria or Lanham’s criteria. Baseline characteristics, treatments, asthma exacerbation, and relapses were evaluated by retrospective chart review.Results.The median followup period was 56 months. The median age at disease onset was 59.7 years. At the disease onset, 95.2% of the patients had a history of bronchial asthma and 44.7% were positive for antineutrophil cytoplasmic antibodies. The cumulative survival and relapse-free survival rates at 5 years were 89.6% and 64.0%, respectively. Multivariate analysis with 2 models, proportional hazards, and competing risk models, was performed to identify the factors associated with relapse. The proportional hazards model identified azathioprine (AZA) maintenance therapy and high eosinophil counts at onset as independent factors with lower relapse risks, and high immunoglobulin E (IgE) levels at onset as a risk factor for relapse. The competing risk model identified no statistically significant factors.Conclusion.Although potential benefit of AZA maintenance therapy in preventing relapse of EGPA was suggested by the proportional hazards model, there was a discrepancy in the results between the models. Eosinophil counts and IgE levels at onset were also identified as candidates of factors associated with relapse in EGPA.

Treatment of ANCA-associated vasculitis

2013 ◽  
Author(s):  
David Jayne
Keyword(s):  
Tissue Damage ◽  
Drug Toxicity ◽  
Granulomatosis With Polyangiitis ◽  
Late Complication ◽  
Response To Therapy ◽  
Remission Induction ◽  
High Dose ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Endstage Renal Disease ◽  
Steroid Dependent

The goals of treatment in anti-neutrophil cytoplasm antibody (ANCA) vasculitis are to stop vasculitic activity, to prevent vasculitis returning, and to address longer-term comorbidities caused by tissue damage, drug toxicity, and increased cardiovascular and malignancy risk. Cyclophosphamide and high-dose glucocorticoids remain the standard induction therapy with alternative immunosuppressives, such as methotrexate or azathioprine, to prevent relapse. Refractory disease resulting from a failure of induction or remission maintenance therapy requires alternative agents and rituximab has been particularly effective. Replacement of cyclophosphamide by rituximab for remission induction is supported by recent evidence. Additional therapy with intravenous methylprednisolone and plasma exchange is employed in severe presentations with failing vital organ function. Drug toxicity contributes to comorbidity and mortality and has led to newer regimens with reduced cyclophosphamide exposure. Glucocorticoid toxicity remains a major problem, with controversy over the rapidity with which glucocorticoids can be reduced or withdrawn. Disease relapse occurs in 50% and requires early detection at a stage when it will not adversely affect outcomes. Rates of cardiovascular disease and malignancy are higher than in control populations but strategies to reduce their risk, apart from cyclophosphamide-sparing regimens, have not been developed. Thromboembolic events occur in 10% and may be linked to the recently identified autoantibodies to plasminogen and tissue plasminogen activator. Outcomes of vasculitis depend heavily on the level of tissue damage at diagnosis, especially renal dysfunction, but are also influenced by patient age, ANCA subtype, disease extent, and response to therapy. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)is treated along similar principles to granulomatosis with polyangiitis (GPA) and microscopic polyangiitis but the persistence of steroid-dependent asthma in over one-third and differences in pathogenesis has suggested alternative treatment approaches. Chronic morbidity results from tissue damage and is especially common in the upper and lower respiratory tract and kidneys. Tracheobronchial disease is a severe late complication of GPA, while deafness, nasal obstruction, and chronic sinusitis are sequelae of nasal and ear vasculitis. Chronic infection of damaged epithelial surfaces acts as a drive for vasculitic activity and adequate infection control is necessary for stable remission. Chronic kidney disease can stabilize for many years but the risks of endstage renal disease (ESRD) are increased by acute kidney injury at presentation or renal relapse. Renal transplantation is successful, with similar outcomes to other causes of ESRD.

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.

Non-severe eosinophilic granulomatosis with polyangiitis: long-term outcomes after remission-induction trial

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2107-2116 ◽  
Author(s):  
Xavier Puéchal ◽  
Christian Pagnoux ◽  
Gabriel Baron ◽  
François Lifermann ◽  
Loïk Geffray ◽  
...  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Task Force ◽  
Controlled Trial ◽  
Remission Induction ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Long Term Outcomes ◽  
First Relapse ◽  
Eosinophilic Granulomatosis

Abstract Objective In a previous controlled trial, 1-year adjunction of AZA to glucocorticoids (GC) for patients with non-severe, newly diagnosed eosinophilic granulomatosis with polyangiitis (EGPA) failed to lower remission failure, vasculitis relapse and isolated asthma/rhinosinus exacerbation rates, or cumulative GC use at month (M) 24. The aim of this study was to analyse longer-term outcomes to determine whether subsequent vasculitis relapse or isolated asthma/rhinosinus exacerbation (IARE) rates differed. Methods After M24, patients were followed prospectively, being treated based on physicians’ best judgment. Flares and reasons for increased GC dose or immunosuppressant use were recorded, and reviewed according to randomization group to distinguish vasculitis relapses from IAREs according to EGPA Task Force recommendations. Results Fifty EGPA trial participants were followed for a median (interquartile range) of 6.3 (5.4–7.6) years; two (4%) died 11 months post-inclusion. By M24, vasculitis had relapsed in 21/49 (43%) patients and 14/50 (28%) had IAREs. Another patient died 4.8 years post-inclusion (infection). Among nine patients with subsequent vasculitis relapses, three had a major relapse and three had their first relapse after M24; among 25 patients with later IAREs, 17 occurred after M24. At 5 years, respective vasculitis relapse and IARE rates were 48% (95% CI 34.0, 62.6) and 56% (95% CI 41.7, 70.8), with no between-arm differences (P = 0.32 and 0.13). No entry clinical or biological parameter was associated with these outcomes during follow-up. Conclusion These results confirmed that 1-year AZA and GC induction obtained good overall survival but no long-term benefit for non-severe EGPA patients. Vasculitis relapses, occurring mostly during the first 2 years, and IAREs, occurring throughout follow-up, require other preventive treatments. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT00647166.

scholarly journals Safety and Efficacy of Mepolizumab in Patients with Eosinophilic Granulomatosis with Polyangiitis

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Ravi Ranjan Pradhan ◽  
Gaurav Nepal ◽  
Shobha Mandal
Keyword(s):  
Side Effects ◽  
Granulomatosis With Polyangiitis ◽  
Multiple Organ ◽  
High Dose ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Sustained Remission ◽  
Organ Systems ◽  
Frequent Relapses ◽  
Systemic Glucocorticoids ◽  
Eosinophilic Granulomatosis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis disorder which involves multiple organ systems and is characterized by asthma, pulmonary infiltrates, sinusitis, neuropathy, and peripheral eosinophilia. It also has an effect on the heart, skin, kidneys, and gastrointestinal tract. Interlukin-5 (IL-5) is involved in maturation and activation of eosinophil, the production of which is increased in the EGPA. Treatments of EGPA are limited to systemic corticosteroids and immunomodulators. These drugs are associated with significant side effects. Besides this, the response of patients to these drugs may be disappointing. Frequent relapses, the need for long-term medium-to-high-dose glucocorticoid therapy, and failure to achieve remission are not uncommon findings. There is a need for noble agents that could reduce frequent relapses and the dose of systemic glucocorticoids and maintain a sustained remission without significant side effects. Mepolizumab is IL-5 antagonist and may have value in treating patients with EGPA. Therefore, we did a systematic review to evaluate the efficacy and safety of mepolizumab in patients with EGPA.

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