RESUMO
OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Consenso , Canadá , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Citoplasma , Anticorpos Anticitoplasma de NeutrófilosRESUMO
OBJECTIVE: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence. METHODS: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation. RESULTS: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations. CONCLUSION: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Canadá , Consenso , Citoplasma , HumanosRESUMO
To present an unrecognized vascular complication of bacillus Calmette-Guérin (BCG) therapy administered for superficial bladder carcinoma. We also review the potential mimickers for primary angiitis of the central nervous system (PACNS) as well as complications of intravesical BCG therapy. An 89-year-old Caucasian man with a history of relapsing high-grade bladder carcinoma treated with intravesical BCG presented with recurring episodes of right upper limb paresthesia with clumsiness and dysarthria. Magnetic resonance imaging of the head revealed multiple predominantly left-sided frontotemporal micronodular peri-vascular lesions. Left frontal lobe biopsy showed non-necrotizing granulomatous vasculitis. Ziehl staining was negative. Initially, he was treated for PACNS but his symptoms relapsed during every attempt to taper the corticosteroids. Six months later, he developed bilateral mycobacterial endophthalmitis, caused by Mycobacterium bovis. Brain biopsy was reviewed and confirmed the presence of perivascular mycobacteria. A retrospective diagnosis of BCG-induced central nervous system vasculitis was made and he was treated with high-dose corticosteroids, moxifloxacin, isoniazid, ethambutol, and rifampicin. BCG is a live attenuated form of Mycobacterium bovis widely used as tuberculosis vaccination and intravesical therapy for superficial forms of bladder cancer. Systemic complications affect roughly 5% of patients and can manifest months or years after the last instillation. Cases of endophthalmitis, meningitis, aortitis, or mycotic aneurysms have been described, but no reports of CNS vasculitis have been found. In disseminated forms of BCG infections, referred to as BCGitis, histopathology usually reveals granulomatous inflammation. Mycobacterial cultures are often negative, making this a diagnostic challenge. This is the first documented case of BCG-induced small-vessel CNS vasculitis. Mycobacterium bovis infection is rare and findings are often nonspecific, making the diagnosis very difficult. Other infectious and non-infectious causes must be ruled out appropriately before considering this entity.
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Vacina BCG/efeitos adversos , Encéfalo/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Vasculite do Sistema Nervoso Central/induzido quimicamente , Vasculite do Sistema Nervoso Central/patologia , Administração Intravesical , Corticosteroides/uso terapêutico , Idoso de 80 Anos ou mais , Vacina BCG/administração & dosagem , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Moxifloxacina/uso terapêutico , Vasculite do Sistema Nervoso Central/tratamento farmacológicoRESUMO
PURPOSE OF REVIEW: Takayasu arteritis remains a therapeutic challenge. In spite of current treatments, progression of vascular lesions is observed frequently. The purpose of this article is to describe advances in therapeutic strategies for Takayasu arteritis. RECENT FINDINGS: Immunosuppressive agents including methotrexate, mycophenolate mofetil, and azathioprine added to corticosteroids can bring Takayasu arteritis into remission in many patients. Unfortunately, relapse is common when prednisone is tapered to dosages of 15 mg/day or less. A better understanding of pathogenesis has lead to trials with anti-tumor necrosis factor-alpha agents in patients with refractory disease. Preliminary results are encouraging. For patients who require revascularization intervention, both surgical and endovascular procedures can be performed that are safe, with low morbidity and mortality. The best long-term outcomes are achieved with conventional bypass grafts. Percutaneous transluminal angioplasty provides good results for short lesions. In contrast to the results in treating atherosclerosis, the use of conventional stents may not yield long-term vessel patency in Takayasu arteritis. Persistent inflammation and endothelial dysfunction may put patients with Takayasu arteritis at risk for premature atherosclerosis. SUMMARY: In the future, greater therapeutic success may be achieved by addressing both the inflammatory and the myointimal proliferative components of Takayasu arteritis. New drugs that target intimal hyperplasia, as well as drug-eluting stents, deserve to be studied for possible utility as adjuncts to present treatments.
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Reumatologia/métodos , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/cirurgia , Terapia Combinada , Quimioterapia Combinada , HumanosRESUMO
OBJECTIVE: Granulomatous inflammation is a typical feature of Takayasu arteritis (TA), and tumor necrosis factor (TNF) is important in the formation of granulomas. In this study, we assessed therapy with anti-TNF agents in patients with TA that was not controlled by glucocorticoid therapy or other immunosuppressants. METHODS: We conducted an open-label trial of anti-TNF therapy at 3 academic medical centers over a period of 4.25 years. Fifteen patients with active, relapsing TA (median 6 years) were selected. Seven received etanercept (later changed to infliximab in 3 patients), and 8 received infliximab. Relapses had occurred in all patients while they were receiving glucocorticoids and, in 13 patients, additional immunosuppressive drugs. No other agents were added to the treatment regimen concurrently with anti-TNF. If patients were receiving cytotoxic agents, the dosage was not increased. Clinical symptoms were recorded, and physical examinations, laboratory studies, and serial magnetic resonance imaging were performed. RESULTS: The median daily dose of prednisone required to maintain remission prior to anti-TNF therapy was 20 mg. Ten of the 15 patients achieved complete remission that was sustained for 1-3.3 years without glucocorticoid therapy. Four patients achieved partial remission, with a >50% reduction in the glucocorticoid requirement. At a median of 12 months of followup, the median dose of prednisone was 0. Therapy failed in 1 patient. In 9 of the 14 responders, an increase in the anti-TNF dosage was required to sustain remission. Two relapses occurred during periods when anti-TNF therapy (etanercept) was interrupted, but remission was reestablished upon reinstitution of therapy. CONCLUSION: In this pilot study of relapsing TA, addition of anti-TNF therapy resulted in improvement in 14 of 15 patients and sustained remission in 10 of 15 patients, who were able to discontinue glucocorticoid therapy. Anti-TNF may be a useful adjunct to glucocorticoids in the treatment of TA. Our results justify a randomized, controlled clinical trial of anti-TNF therapy for TA.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Etanercepte , Feminino , Glucocorticoides/administração & dosagem , Humanos , Imunoglobulina G/efeitos adversos , Infliximab , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prednisona/administração & dosagem , Recidiva , Indução de RemissãoRESUMO
OBJECTIVE: To provide an analysis of outcomes of vascular interventions in 20 patients with Takayasu's arteritis (TA) who received care at the Cleveland Clinic Foundation between 1979 and 2001. METHODS: We performed a retrospective chart review. The primary outcome measure of our review was patency of vessels as assessed by repeat invasive angiography or magnetic resonance angiography. The secondary outcome measures included periprocedural complications, morbidity, and mortality. Interventions included bypass grafts, patch angioplasty, endarterectomy, percutaneous transluminal angioplasty (PTA), or stent placement. RESULTS: Sixty-two revascularization procedures were performed in 20 patients. Followup evaluations were available for 52 procedures. Eleven of 31 bypass grafts restenosed or occluded between one day to 168 months after surgery. Three of 7 PTA and 5 of 7 stents restenosed or became occluded after 1-72 months and 2-45 months of followup, respectively. There were no deaths associated with revascularization procedures. CONCLUSION: Despite providing short term benefit, endovascular revascularization procedures are associated with a high failure rate in patients with TA.