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Manifestations driving relapse during rituximab treatment Manifestations driving relapse, mean relapses/person (% persons who suffered at least one relapse)
Source publication
Introduction:
Eosinophilic granulomatosis with polyangiitis (EGPA) is a subset of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis with distinct pathophysiological mechanisms, clinical features and treatment responses. Rituximab is a licensed therapy for granulomatosis with polyangiitis and microscopic polyangiitis but there is l...
Contexts in source publication
Context 1
... mean number of relapses per patient was 0.9±1.27. Relapses were mainly driven by asthma, with 43.5% of the patients suffering at least one asthma relapse (table 3). ENT relapses were the second most frequent, followed by joint and skin manifestations. ...Similar publications
Rituximab (RTM), a monoclonal antibody against CD20+ receptors on the membrane of B-cells, is becoming increasingly important for the induction and maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (ANCA-SV). The challenge facing us is to optimize its efficacy, while limiting adverse events (AEs).
Ob...
Objective
To assess through systematic review and meta-analysis whether plasma exchange (PE) is associated with prognosis in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients.
Methods
A systematic search of PubMed, MEDLINE, Embase, and CENTRAL databases from inception to 17 June 2020 was conducted. Ongoing or unpublis...
Purpose
Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) overlap with systemic sclerosis (SSc) is uncommon. We aimed to determine the incidence of AAV and define clinical outcomes relevant to asymptomatic screening positive for ANCA in SSc after 2 years of follow-up.
Patients and Methods
The study was a cohort study of 185...
Objective
Eosinophilic granulomatosis with polyangiitis (EGPA) is part of a group of vasculitides commonly referred to as antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), in addition to granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal‐limited vasculitis. Patients with EGPA characteristically h...
Objective Treatment-refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition without evidence-based treatment options. One emerging treatment option for several antibody-mediated autoimmune diseases is the anti-CD38 antibody daratumumab, which depletes autoantibody-secreting plasma cells.
Met...
Citations
... Kolejne badanie (n = 69) prowadzone w latach 2003-2017 z zastosowaniem RTX wykazało poprawę odpowiedzi całkowitej po 24 miesiącach u 77,3% chorych. Ponadto, zmniejszono też stosowaną dawkę prednizolonu, a pacjenci z przeciwciałami ANCA mieli znacząco wydłużony czas do kolejnego nawrotu choroby i krótszy czas uzyskania remisji [53]. ...
Rituximab (RTX) is a monoclonal antibody anti-CD20, primarily registered in 1997 for treating patients with Non-Hodgkin lymphoma. Off-label use of this drug applies primarily to patients with kidney diseases and saves the lives of these patients. This study aims to review the existing knowledge about off-label use of RTX in kidney diseases. Rituximab has been shown to be effective in membranous nephropathy, minimal lesion disease, focal segmental glomerulosclerosis, membrano-proliferative glomerulonephritis, as well as in IgG4 nephropathy, throm- botic thrombocytopenic purpura, lupus nephritis, Schönlein-Henoch purpura and eosinophilic granulomatosis with polyangiitis and mixed cryoglobulinemia. The use of RTX makes it possible to reduce proteinuria, reduce serum creatinine levels, and, above all, prolong the time to the subsequent relapse of the disease (remission). Many applications confirm the great potential of RTX not only in nephrology but also in other fields, indicating the need for further research. (Farm Współ 2024; 17: 3-12) doi: 10.53139/FW.20241702
... Rituximab, an anti-CD20 monoclonal antibody that targets B cells, is approved for the treatment of related AAVs, microscopic polyangiitis and granulomatosis with polyangiitis [18]. However, evidence that rituximab may also offer treatment benefit for patients with EGPA is limited to observational studies [19,20]. Biologics such as the anti-interleukin (IL)-5 monoclonal antibodies mepolizumab and reslizumab, or those targeting the IL-5 receptor (benralizumab), are also potential treatments in EGPA, owing to their mechanism of action in depleting eosinophil levels [21]; each is approved for the treatment of severe eosinophilic asthma [22][23][24]. ...
Background
Real-world evidence characterising the burden of eosinophilic granulomatosis with polyangiitis (EGPA) in Europe is limited.
Objective
To characterise patients in a large European EGPA cohort.
Methods
This retrospective, non-interventional, longitudinal study recruited cross-specialty physicians from France, Germany, Italy, Spain, and the United Kingdom to conduct medical chart reviews for patients with a physician-confirmed diagnosis of EGPA. Patients were ≥12 years of age at diagnosis with ≥1 year of follow-up data from the first clinical visit with the physician (index date). Outcome measures collected from index date to end of follow-up included clinical manifestations and healthcare resource utilisation (HCRU).
Results
In total, 407 patient medical charts were reviewed by 204 physicians; median (interquartile range) duration of follow-up from index date was 2.2 (1.7, 3.5) years. Most patients (73.5%) had asthma. Patients underwent multiple diagnostic assessments, and 74.9% received ≥3 different therapies between diagnosis and end of follow-up (98.8% oral corticosteroids, 63.9% immunosuppressive therapies, 45.5% biologics). During follow-up, 84.5% of patients experienced EGPA clinical manifestations; most were considered moderate or severe and commonly affected the lungs (55.8%; including lung infiltrates: 25.8% and severe asthma: 24.8%), ear, nose, and throat (53.3%), and skin (41.8%). HCRU was substantial: 26.0% of patients made emergency department visits, 36.6% were hospitalised and 84.8% had outpatient visits.
Conclusions
These real-world data show that EGPA presents a substantial burden to patients and the healthcare system. Earlier and better differential diagnosis and appropriate treatment may help reduce incidence of clinical manifestations and HCRU.
... RTX is an effective alternative for remission induction in EGPA. Together with data from observational studies [135][136][137][138], the RCT REOVAS, presented as abstract at the 2021 American College of Rheumatology convergence, demonstrated a similar efficacy of RTX in inducing remission in patients with FFS ≥ 1 [139]. Achieving a Birmingham Vasculitis Activity Score (BVAS) of zero and attaining a prednisone dose ≤7.5 mg per day were comparable between patients treated with RTX (two 1-gram pulses on day 1 and 15) and those treated with CYC (nine intravenous pulses over 13 weeks) [139]. ...
... Achieving a Birmingham Vasculitis Activity Score (BVAS) of zero and attaining a prednisone dose ≤7.5 mg per day were comparable between patients treated with RTX (two 1-gram pulses on day 1 and 15) and those treated with CYC (nine intravenous pulses over 13 weeks) [139]. In contrast to prior observational studies [135,138], the response to RTX in this RCT seems to be comparable in both ANCA-positive and ANCA-negative patients [139]. Adverse events, cumulative prednisone doses, and quality of life were also similar between the two groups. ...
Introduction:
ANCA-associated vasculitides (AAV), classified into granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis represent a group of disorders characterized by necrotizing vasculitis of small vessels, endothelial injury and tissue damage. The outcomes and prognosis of AAV have undergone significant changes with the introduction of glucocorticoids (GCs) and other immunosuppressants (cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil). The enhanced understanding of pathogenesis has subsequently led to the incorporation into clinical practice of drugs targeting specific therapeutic targets.
Areas covered:
After an extensive literature search of Pubmed, Medline, Embase of the most recent evidence, we provide an overview of available treatments, highlighting how newer drugs have integrated into standard protocols. Our review also explores potential new therapeutic targets, including B cell depletion and inhibition, T cell inhibition, complement inhibition, and IL-5 and IgE inhibition.
Expert opinion:
There is hope that the new treatment targets currently under study in AAV may enable a faster and more lasting clinical response, ensuring the reduction of possible side effects from therapies. Moreover, numerous aspects necessitate further exploration in the future, such as tailoring of GCs, integration of GCs-sparing agents, efficacy of combination therapy, optimal maintenance therapy, to reduce organ-damage and improve quality of life.
... Experience in EGPA is scant but growing, with the recent publication of several series in EGPA patients in which rituximab demonstrated efficacy in controlling disease activity and possibly reducing maintenance doses of corticosteroids. 2,3 In our patient, refractory vasculitis and mononeuritis multiplex improved partially with rituximab treatment. However, persistent neurological symptoms and poor asthma control prompted the initiation of mepolizumab associated with corticosteroids as an alternative to other treatments (methotrexate, azathioprine and mycophenolate mofetil, etc.). ...
... Given the concomitant presence of refractory ITP, the choice of rituximab over cyclophosphamide was made. Rituximab, associated with corticoids as a second-line treatment or as an induction therapy in ITP, is reported efficacious [20]; moreover, rituximab has shown efficacy in retrospective studies among patients with EGPA refractory to standard therapy [21]. A controlled trial to evaluate rituximab as an induction treatment in EGPA showed no significant difference in achieving remission comparing to standard treatment [22]. ...
During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a second dose of the mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involvement, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1,000,000 inhabitants, and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lymphocyte activation with hypereosinophilia; nevertheless, cases of inflammatory diseases (IMIDs) emerging in the context of vaccination remain rare and the benefits of preventing severe COVID presentations with SARS-CoV-2 mRNA vaccines remain unquestionable.
... Rituximab associated to corticoids as second line treatment or as induction therapy in ITP is reported efficacious [15]. Moreover, rituximab has shown efficacy in retrospective studies among patients with EGPA refractory to standard therapy [16]. A controlled trial to evaluated rituximab as induction treatment in EGPA is currently ongoing [17]. ...
During one of the worst global health crises, millions of people were vaccinated against SARS-CoV-2. In rare cases, new onset systemic inflammatory diseases were reported with temporal coincidence to the vaccination. We describe a case of severe Eosinophilic Granulomatosis with Polyangiitis (EGPA) in a young asthmatic woman, occurring after a 2nd dose of mRNA-1273 vaccine. She presented with multisystem EGPA with cardiac and central nervous system involve-ment, complicated by secondary immune thrombocytopenia (ITP). We review the reported cases of EGPA coinciding with SARS-CoV-2 mRNA vaccination. All potentially vaccine-related EGPA cases reported so far occurred within 14 days from immunization. EGPA is very rare with an incidence of 1:1’000’000 inhabitants and the number of reported post-vaccination EGPA cases lies within the expected incidence rate for the period. While we cannot prove a causal relationship between the vaccine and EGPA onset, the temporal relationship with the vaccine immune stimulation is intriguing, in a disease occurring almost always in adults with asthma and/or chronic rhinosinusitis and driven by an aberrant Th2 lym-phocyte activation with hypereosinophilia. Nevertheless, cases of inflammatory diseases emerging in the context of vaccination remain rare and the benefits of preventing severe Covid presentations with SARS-CoV-2 mRNA vaccines remains unquestionable.
... Available evidence-mostly of low and very low quality-suggests that patients with severe forms of EGPA (severe ANCA-associated vasculitis manifestations are reported in the appendix [p 3]) might benefit from remission induction with high-dose glucocorticoids plus cyclophosphamide or rituximab. [42][43][44][45] Thus, for patients with newly diagnosed or relapsing EGPA with active, severe disease, we conditionally recommend cyclophosphamide or rituximab plus glucocorticoids over glucocorticoids alone (recommendation 14). We particularly recommend this treatment for patients with severe disease presenting with vasculitic manifestations (eg, rapidly progressive glomerulonephritis), and those with positive ANCA results. ...
... Observational retrospective studies suggest that nontargeted immunosuppressants and rituximab might also offer some benefits in this patient population. 43,44,52 In the absence of randomised controlled studies comparing nontargeted immunosuppressants, rituximab, and mepolizumab for patients with non-severe relapse while on glucocorticoids and non-targeted immuno suppressants, we recommend switching from one non-targeted immunosuppressant to another, or adding mepolizumab if accessible. Rituximab might also be considered in this clinical scenario, particularly for patients with positive ANCA results at the time of relapse. ...
Considerable variability exists in the way health-care providers treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in Latin America. The most frequently used treatments for ANCA-associated vasculitis are cyclophosphamide and prolonged glucocorticoid tapers; however, randomised controlled trials conducted over the past 30 years have led to the development of several evidence-based treatment alternatives for these patients. Latin America faces socioeconomic challenges that affect access to care, and the use of certain costly medications with proven efficacy ANCA-associated vasculitis is often restricted. For these reasons, the Pan American League of Associations for Rheumatology developed the first ANCA-associated vasculitis treatment guidelines tailored for Latin America. A panel of local vasculitis experts generated clinically meaningful questions related to the treatment of ANCA-associated vasculitis using the Population, Intervention, Comparator, and Outcome (PICO) format. Following the Grading of Recommendations Assessment, Development, and Evaluation methodology, a team of methodologists conducted a systematic literature review. The panel of vasculitis experts voted on each PICO question and made recommendations, which required at least 70% agreement among the voting members. 21 recommendations and two expert opinion statements for the treatment of ANCA-associated vasculitis were developed, considering the current evidence and the socioeconomic characteristics of the region. These recommendations include guidance for the use of glucocorticoids, non-glucocorticoid immunosuppressants, and plasma exchange.
... The evidence of RTX benefits in patients with EGPA is limited to case series and small-sized [83][84][85][86][87][88], open-label studies on refractory/relapsing EGPA [9,89]. ...
Eosinophilic granulomatosis with polyangiitis (EGPA) is a multiorganic syndrome that affects the cardiovascular, neurologic, renal, and gastrointestinal systems with an incidence ranging from 0 case to 67 cases per one million person-years, and its pathophysiology remains unknown. It is believed that genetic factors, the environment, and changes in immune system function contribute to the development of EGPA, overlapping the immune mechanisms of vasculitides and the pathologic mechanisms in eosinophilic syndromes. This disease is commonly divided into two phenotypes depending on the presence of antineutrophil cytoplasmic antibodies (ANCA). ANCA-positive patients usually have more vasculitic manifestations like peripheral neuropathy, purpura, renal involvement, and biopsy-proven vasculitis. The keystone of EGPA therapy is systemic corticosteroids (CS) as monotherapy or in combination with other immunosuppressive treatments, and recently the efficacy of eosinophil-targeted biotherapy, anti-interleukin-5 (IL-5), has been shown to be efficacious in EGPA. Although this phenotype/phase distinction has not yet had an impact on the current treatment strategies, emerging targeted biotherapies under evaluation could lead to a phenotype-based approach and personalised treatment regimens for EGPA patients. The present review describes the new therapeutical approaches with biological drugs for EGPA.
... Patients with EGPA can be subclassified according to the ANCA status (ANCA-positive versus ANCA-negative). Preliminary evidence, mainly from observational studies, has suggested that ANCA-positive and ANCA-negative patients have different sensitivity to treatments; in particular, ANCA-positive patients seemed to be more responsive to rituximab therapy than ANCA-negative patients 26,97 . This view has been challenged by the results of the REOVAS trial, which did not reveal significant differences in the rates of response to rituximab between ANCA-positive and ANCA-negative patients 56 . ...
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis,
characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA
that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA.
These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.
... Patients with EGPA can be subclassified according to the ANCA status (ANCA-positive versus ANCA-negative). Preliminary evidence, mainly from observational studies, has suggested that ANCA-positive and ANCA-negative patients have different sensitivity to treatments; in particular, ANCA-positive patients seemed to be more responsive to rituximab therapy than ANCA-negative patients 26,97 . This view has been challenged by the results of the REOVAS trial, which did not reveal significant differences in the rates of response to rituximab between ANCA-positive and ANCA-negative patients 56 . ...
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, characterized by asthma, eosinophilia and granulomatous or vasculitic involvement of several organs. The diagnosis and management of EGPA are often challenging and require an integrated, multidisciplinary approach. Current practice relies on recommendations and guidelines addressing the management of ANCA-associated vasculitis and not specifically developed for EGPA. Here, we present evidence-based, cross-discipline guidelines for the diagnosis and management of EGPA that reflect the substantial advances that have been made in the past few years in understanding the pathogenesis, clinical subphenotypes and differential diagnosis of the disease, as well as the availability of new treatment options. Developed by a panel of European experts on the basis of literature reviews and, where appropriate, expert opinion, the 16 statements and five overarching principles cover the diagnosis and staging, treatment, outcome and follow-up of EGPA. These recommendations are primarily intended to be used by healthcare professionals, pharmaceutical industries and drug regulatory authorities, to guide clinical practice and decision-making in EGPA. These guidelines are not intended to limit access to medications by healthcare agencies, nor to impose a fixed order on medication use.
