The maintenance treatment of ANCA-associated vasculitides (AAVs) has benefited from the results of several prospective clinical trials focusing on the evaluation of new drugs, therapeutic strategies, ...and adjuvant treatments. They also showed that rituximab was the most effective agent to maintain remission. However, because treatments can induce adverse events, including facilitating infections, therapeutic strategies should be adapted to find the optimal dose(s) and their administration duration(s) and to make them commensurate to the expected severity of relapse. That task is not easy to achieve because we have not yet been able to identify the clinical or biological parameters that can predict when a relapse will occur and its severity. Among AAVs, eosinophilic granulomatosis with polyangiitis (EGPA) has pathogenic and clinical specificities, and new drugs directly address those features. If rituximab could have a place such as in other AAVs, anti-IL5 biotherapies could also be prescribed successfully for maintenance. Another aim of vasculitis maintenance therapy is to control the disease with less prednisone than in the past. Herein, we emphasize the importance of individually devising a maintenance regimen adapted to the objectives of keeping the patient in remission without the adverse events related to the prescribed treatment(s).
Treatment of vasculitides has benefited from the results of several prospective clinical trials focusing on the evaluation of new drugs, therapeutic strategies and adjuvant treatments. In the field ...of autoimmunity, vasculitides are the group of diseases for which the most important medical progress has been made, combining advances in understanding the pathogenetic mechanisms, classification of the various entities and willingness to evaluate treatments. Several international groups have been actively involved in these tasks. The French Vasculitis Study Group was the first to design and organize prospective trials in the field and to contribute to these medical advances. In this review, we analyze the different treatments and therapeutic strategies evaluated over the last few decades and, more precisely, the last 39 years by the French Vasculitis Study Group.
Infections in vasculitis Guillevin, Loïc
Best practice & research. Clinical rheumatology,
02/2013, Volume:
27, Issue:
1
Journal Article
Peer reviewed
Infections, mainly viral, are the cause of some vasculitides, like polyarteritis nodosa (hepatitis B virus) or mixed cryoglobulinemia (hepatitis C virus), and it has been hypothesized that others ...might be due to infectious agents (HIV, EBV, parvovirus...). Among etiologies of vasculitis, the responsibility of a Burkholderia-like strain has been recently demonstrated as the cause of giant-cell arteritis. On the other hand, patients frequently develop infections, mainly as a consequence of steroids, immunosuppressants and most immunomodulating treatments prescribed to treat vasculitides. Infections occur when patients receive steroids and immunosuppressants, especially in the long term. They are more frequently observed in elderly patients or in patients with poor general condition. Infection risk is not reduced when biotherapies are prescribed to induce or maintain remission. Patients, considered at higher risk for infections, should be followed closely and their immunological status monitored periodically. We recommend especially to monitor neutrophiles, lymphocytes and if needed CD3-, CD4- and CD8-cell counts in patients receiving steroids and cyclophosphamide or other cytotoxic agents. In patients treated with rituximab, CD19 and gammaglobulins should be monitored regularly. Prophylaxis are needed in patients at risk to develop infections.
A new challenge for La Presse Médicale Guillevin, Loïc
La Presse médicale (1983),
April 2020, 2020-04-00, 20200401, Volume:
49, Issue:
1
Journal Article
Abstract Recently, a group of experts in the field suggested to rename Churg–Strauss syndrome as eosinophilic granulomatosis with polyangiitis (EGPA). This condition, first described in 1951, is a ...rare small- and medium-sized–vessel vasculitis characterized by an almost constant association with asthma and eosinophilia, and, by the presence of anti-myeloperoxidase (MPO) antineutrophil cytoplasm antibodies (ANCA) in 30–38% of the patients. Vasculitis typically develops in a previously asthmatic and eosinophilic middle-aged patient. Asthma is severe, associated with eosinophilia and extrapulmonary symptoms. Most frequently EGPA involves the peripheral nerves and skin. Other organs, however, may be affected and must be screened for vasculitis, especially those associated with a poorer prognosis, such as the heart, kidney and gastrointestinal tract, as assessed by the recently revised Five-Factor Score (FFS). Recent insights, particularly concerning clinical differences associated with ANCA status, showed that EGPA patients might constitute a heterogeneous group. Thus, EGPA patients with anti-MPO ANCA suffered more, albeit not exclusively, from vasculitis symptoms, such as glomerulonephritis, mononeuritis multiplex and alveolar hemorrhage, whereas ANCA-negative patients more frequently develop heart involvement. This observation led to the hypothesis that EGPA might be divided into different clinical and pathophysiological subtypes, which could be managed better with more specifically adapted therapies. For now, EGPA treatment still relies mainly on corticosteroids and, when necessary for patients with poorer prognoses, combined immunosuppressant drugs, especially cyclophosphamide. Overall survival of EGPA patients is good, despite not uncommon relapses.
Abstract Immunoglobulin A (IgA) vasculitis, formerly called Henoch–Schönlein purpura, is an immune complex vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations ...mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. IgA vasculitis is more common among children than adults, with more severe disease in adults. Gastrointestinal and renal involvements represent the principal causes of morbidity and mortality in adults. Factors associated with long-term end-stage renal disease (ESRD) include baseline renal function impairment and baseline proteinuria > 1 or 1.5 g/day, and on renal biopsy degree of interstitial fibrosis, sclerotic glomeruli and fibrinoid necrosis. Management of IgA vasculitis in adults is rendered difficult for clinicians because of the absence of correlation between initial presentation and long-term renal outcome, and the possible occurrence of spontaneous remission in patients with severe presentation or, in contrast, possible evolution to ESRD in patients with mild symptoms. Treatment is often symptomatic because disease course is usually benign. Treatment of severe involvement, including severe gastrointestinal complications or proliferative glomerulonephritis, remains controversial, with no evidence that corticosteroids or immunosuppressive agents improved long-term outcome. Prospective, randomized, controlled trials are thus needed to analyze the benefit–risk ratio of such treatments.
Eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome) is a rare type of anti-neutrophil cytoplasm antibody-associated vasculitis. Nevertheless, eosinophilic granulomatosis ...with polyangiitis stands apart because it has features of vasculitis and eosinophilic disorders that require targeted therapies somewhat different from those used for other anti-neutrophil cytoplasm antibody-associated vasculitides. Considerable advances have been made in understanding the underlying pathophysiology of eosinophilic granulomatosis with polyangiitis that have highlighted the key role of eosinophils and opened new therapeutic opportunities. Its conventional treatment relies mainly on agents that decrease inflammation: corticosteroids and immunosuppressant adjunction for severe manifestations. New therapeutic approaches are needed for refractory disease, relapses and issues associated with corticosteroid dependence, especially for asthma manifestations. Drugs under evaluation mostly target eosinophils and B cells. Results of low-evidence-based trials suggested possible efficacies of biologicals: B-cell-blocking rituximab and anti-immunoglobulin E omalizumab. Recently, the first large-scale randomised controlled trial on eosinophilic granulomatosis with polyangiitis proved the efficacy of anti-interleukin-5 mepolizumab. That finding opens a new era in eosinophilic granulomatosis with polyangiitis management, with mepolizumab approval but also in future drug evaluations and trial designs for eosinophilic granulomatosis with polyangiitis. Additional studies are needed to determine which patients would benefit most from targeted therapies and achieve personalised treatment for patients with eosinophilic granulomatosis with polyangiitis. Herein, we review eosinophilic granulomatosis with polyangiitis characteristics and provide an overview of established and novel pharmacological agents.
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