ABSTRACT
CONTEXTO: Pacientes portadores de vasculites associadas aos anticorpos (VAA) anticitoplasma de neutrófilos (ANCA) possuem maior risco de hemorragia alveolar, erupção purpúrica, infarto em tecidos irrigados. O tratamento destas vasculites é imprescindível para prevenção de dano potencialmente irreversível, secundário ao processo inflamatório de capilares, arteríolas e vênulas. O rituximabe (RTX) pode ser indicado como opção terapêutica na fase de indução para pacientes com GPA ou MPA que não apresentaram remissão completa com ciclofosfamida ou que apresentam doença recidivante com manifestações graves, principalmente entre os que já utilizaram ciclofosfamida previamente. Além disso, o RTX pode ser utilizado como primeira escolha na indução de pacientes com manifestações graves da VAA, mas que estejam em fase reprodutiva e possuam desejo gestacional futuro, pois a ciclofosfamida possui a infertilidade como efeito colateral, tanto em homens quanto em mulheres. Ademais, o RTX pode ser utilizado como terapia de manutenção dos pacientes com VAA. Pergunta: Qual é a efetividade e segurança do uso de RTX comparado a ciclofosfamida para o tratamento de indução de remissão de pacientes com VAA ativa e grave, com diagnóstico confirmado de GPA ou MPA e para os casos de recidiva
Subject(s)
Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Rituximab/therapeutic use , Recurrence , Unified Health System , Brazil , Efficacy , Cost-Benefit Analysis/economicsABSTRACT
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.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Rheumatology , Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antibodies, Antineutrophil Cytoplasmic , Glucocorticoids/therapeutic use , Plasma Exchange , PlasmapheresisABSTRACT
This article reviews the pulmonary manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Its frequency in the different phenotypes of the disease, clinical manifestations and updated therapeutic recommendations are reviewed, aiming to alert the medical community about the existence of these diseases. We pretend to stimulate a timely suspicion, diagnostic precision, and the implementation of effective therapies, to reduce the eventual sequelae derived from a diagnostic omission or an inappropriate treatment for the different clinical scenarios in which these diseases appear.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Antibodies, Antineutrophil Cytoplasmic , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Humans , LungABSTRACT
This article reviews the pulmonary manifestations of anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Its frequency in the different phenotypes of the disease, clinical manifestations and updated therapeutic recommendations are reviewed, aiming to alert the medical community about the existence of these diseases. We pretend to stimulate a timely suspicion, diagnostic precision, and the implementation of effective therapies, to reduce the eventual sequelae derived from a diagnostic omission or an inappropriate treatment for the different clinical scenarios in which these diseases appear.
Subject(s)
Humans , Antibodies, Antineutrophil Cytoplasmic , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , LungABSTRACT
OBJECTIVES: Azathioprine has been the therapy of choice for the maintenance of remission in patients with antineutrophil cytoplasm antibody (ANCA)-associated systemic vasculitis, but recent studies show that rituximab could be more effective. To evaluate the cost-effectiveness of azathioprine, fixed-schedule rituximab, and tailored-dose rituximab for ANCA-associated systemic vasculitis. METHODS: A Markov model from the perspective of the Colombian healthcare system was designed with annual cycles and a 5-year time horizon, charting the following states: remission, minor relapse, major relapse, and death. The discount rate was 5%. Transition probabilities were obtained from a systematic literature review. The costs (1 US dollar = 2956 Colombian pesos in 2018) were estimated based on national drug registries and official fee manuals for procedures, along with other resources. The main outcomes were quality-adjusted life-years (QALYs) taken from the Tufts registry. Univariate and multivariate sensitivity analyses were performed. RESULTS: Final costs were $1446 for azathioprine, $4898 for tailored-dose rituximab, and $6311 for fixed-schedule rituximab. QALYs gained were 3.18, 4.08, and 3.98, respectively. Rituximab was cost-effective (cost per incremental QALY gained: $4919, and $6865), and tailored-dose administration had a lower cost. Sensitivity analyses did not affect the results. CONCLUSIONS: Tailored-dose rituximab was the most cost-effective treatment for ANCA-associated vasculitis. Azathioprine presented worse effectiveness and lower cost, and fixed-schedule rituximab was dominated by tailored-dose rituximab.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Azathioprine , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Azathioprine/therapeutic use , Colombia , Cost-Benefit Analysis , Cytoplasm , Humans , Rituximab/therapeutic useABSTRACT
AIM: To validate the new classification criteria for antineutrophil cytoplasmic antibody-associated vasculitis in a real-life Peruvian cohort of antineutrophil cytoplasmic antibody-associated vasculitis patients. METHODS: We reviewed medical records from a Peruvian tertiary care center from January 1990 to December 2019. Antineutrophil cytoplasmic antibody-associated vasculitis was diagnosed based on the 1990 American College of Rheumatology (ACR) criteria, the 2012 Chapel Hill Consensus Conference definitions, the European Medicines Agency (EMEA) algorithm, and the clinical acumen of the treating rheumatologists. We classified all patients using the "former criteria" (the 1990 ACR criteria for granulomatosis with polyangiitis [GPA] and eosinophilic GPA [EGPA] and the 1994 Chapel Hill Consensus Conference definition for microscopic polyangiitis [MPA]), the EMEA algorithm, and the "new criteria" (the 2017 ACR/European League Against Rheumatism Provisional Criteria). The level of agreement (using Cohen κ) was calculated using the clinical diagnosis as the criterion standard. RESULTS: We identified 212 patients, 12 of whom were excluded. One hundred fifty-four (77%) had MPA, 41 (20.5%) GPA, and 5 (2.5%) EGPA. The new criteria performed well for MPA (κ = 0.713) and EGPA (κ = 0.659), whereas the EMEA algorithm performed well for GPA (κ = 0.938). In the overall population, the new criteria showed better agreement (κ = 0.653) than the EMEA algorithm (κ = 0.506) and the former criteria (κ = 0.305). CONCLUSIONS: The 2017 ACR/European League Against Rheumatism Provisional Criteria showed better agreement for the clinical diagnosis of all the patients overall and had the best performance for MPA and EGPA. The EMEA algorithm had the best performance for GPA.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Rheumatic Diseases , Rheumatology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology , Antibodies, Antineutrophil Cytoplasmic , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/epidemiology , Humans , Peru/epidemiology , Rheumatic Diseases/complications , Rheumatic Diseases/diagnosis , Rheumatic Diseases/epidemiology , Tertiary Care Centers , United States/epidemiologyABSTRACT
Abstract ANCA-associated vasculitis is a heterogeneous group of rare autoimmune conditions of unknown cause. Clinical characteristics and prognostic factors were analyzed in 47 patients: 20 (42.5%) with granulomatosis with polyangiitis, 17 (36.2%) with microscopic polyangiitis, 6 (12.8%) with renal-limited vasculitis, and 4 (8.5%) with eosinophilic granulomatosis with polyangiitis. Mean age at diagnosis was 53.5 ± 16.5 years and the median of BVAS (Birmingham Vasculitis Activity Score) was 14 (4-42). The most frequent clinical manifesta tions were: general in 44 (93.6%), renal in 30 (63.8%) and respiratory in 28 (59.6%). All received corticosteroids at the beginning of treatment. Intravenous cyclophosphamide was associated in 20 (42.5%) and oral route in 14 (29.8%); azathioprine in 3 (6.4%) and rituximab in 2 (4.2%). At a median follow-up of 35.5 months (range 0.14- 234), 21 relapses were recorded in 14 patients. Overall mortality was 3.5 deaths per 100 patient-year in the whole group. Those over 55 years old, the presence of alveolar hemorrhage, those with FFS (Five Factor Score) of 2, and patients with MPA had poor prognosis. Renal involvement, ANCA pattern and BVAS were not associated to a poorer prognosis.
Resumen Las vasculitis asociadas a ANCA son un grupo heterogéneo de entidades autoinmunes, poco frecuentes, de etiología desconocida. Analizamos las características clínicas y factores pronóstico en 47 pacientes: 20 (42.5%) granulomatosis con poliangeítis, 17 (36.2%) poliangeítis microscópica, 6 (12.8%) vasculitis limitada al riñón y 4 (8.5%) granulomatosis eosinofílica con poliangeítis. La edad promedio al diagnóstico fue 53.5 ± 16.5 años y la mediana de BVAS (Birmingham Vasculitis Activity Score) 14 (4-42). Las manifestaciones clínicas más frecuentes fueron: generales en 44 (93.6%), renales 30 (63.8%) y respiratorias en 28 (59.6%). Todos recibieron corticoides al inicio del tratamiento. Se asoció ciclofosfamida endovenosa en 20 (42.5%) y oral en 14 (29.8%); azatioprina en 3 (6.4%) y rituximab en 2 (4.2%). En una mediana de seguimiento de 35.5 meses (rango 0.14-234), se registraron 21 recaídas en 14 pacientes. La mortalidad fue 3.5 por cien pacientes-año en todo el grupo. Los mayores de 55 años, con presencia de hemorragia alveolar, FFS (Five Factor Score) de 2, y los casos con poliangeítis microscópica tuvieron peor pronóstico. El compromiso renal, el patrón de ANCA y el BVAS no se asociaron a peor pronóstico.
Subject(s)
Humans , Middle Aged , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/drug therapy , Churg-Strauss Syndrome/epidemiology , Granulomatosis with Polyangiitis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Prognosis , Antibodies, Antineutrophil Cytoplasmic , Microscopic PolyangiitisABSTRACT
ANCA-associated vasculitis is a heterogeneous group of rare autoimmune conditions of unknown cause. Clinical characteristics and prognostic factors were analyzed in 47 patients: 20 (42.5%) with granulomatosis with polyangiitis, 17 (36.2%) with microscopic polyangiitis, 6 (12.8%) with renal-limited vasculitis, and 4 (8.5%) with eosinophilic granulomatosis with polyangiitis. Mean age at diagnosis was 53.5 ± 16.5 years and the median of BVAS (Birmingham Vasculitis Activity Score) was 14 (4-42). The most frequent clinical manifestations were: general in 44 (93.6%), renal in 30 (63.8%) and respiratory in 28 (59.6%). All received corticosteroids at the beginning of treatment. Intravenous cyclophosphamide was associated in 20 (42.5%) and oral route in 14 (29.8%); azathioprine in 3 (6.4%) and rituximab in 2 (4.2%). At a median follow-up of 35.5 months (range 0.14-234), 21 relapses were recorded in 14 patients. Overall mortality was 3.5 deaths per 100 patient-year in the whole group. Those over 55 years old, the presence of alveolar hemorrhage, those with FFS (Five Factor Score) of 2, and patients with MPA had poor prognosis. Renal involvement, ANCA pattern and BVAS were not associated to a poorer prognosis.
Las vasculitis asociadas a ANCA son un grupo heterogéneo de entidades autoinmunes, poco frecuentes, de etiología desconocida. Analizamos las características clínicas y factores pronóstico en 47 pacientes: 20 (42.5%) granulomatosis con poliangeítis, 17 (36.2%) poliangeítis microscópica, 6 (12.8%) vasculitis limitada al riñón y 4 (8.5%) granulomatosis eosinofílica con poliangeítis. La edad promedio al diagnóstico fue 53.5 ± 16.5 años y la mediana de BVAS (Birmingham Vasculitis Activity Score) 14 (4-42). Las manifestaciones clínicas más frecuentes fueron: generales en 44 (93.6%), renales 30 (63.8%) y respiratorias en 28 (59.6%). Todos recibieron corticoides al inicio del tratamiento. Se asoció ciclofosfamida endovenosa en 20 (42.5%) y oral en 14 (29.8%); azatioprina en 3 (6.4%) y rituximab en 2 (4.2%). En una mediana de seguimiento de 35.5 meses (rango 0.14-234), se registraron 21 recaídas en 14 pacientes. La mortalidad fue 3.5 por cien pacientes-año en todo el grupo. Los mayores de 55 años, con presencia de hemorragia alveolar, FFS (Five Factor Score) de 2, y los casos con poliangeítis microscópica tuvieron peor pronóstico. El compromiso renal, el patrón de ANCA y el BVAS no se asociaron a peor pronóstico.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Churg-Strauss Syndrome , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antibodies, Antineutrophil Cytoplasmic , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/drug therapy , Churg-Strauss Syndrome/epidemiology , Humans , Middle Aged , PrognosisABSTRACT
INTRODUCTION: ANCA-associated vasculitis (AAV) is an infrequent disease in childhood. International literature about pediatric vasculitis is scarce, and it mainly refers to other systemic vasculitides with a higher incidence in childhood, such as IgA vasculitis and Kawasaki disease. OBJECTIVE: To describe the clini cal and laboratory characteristics of a series of pediatric cases with AAV. PATIENTS AND METHOD: Re trospective, descriptive study of patients with diagnosis of AAV treated at a tertiary health center from Santiago, Chile, between 2000 and 2020. Electronic medical records were reviewed collecting epidemiological, laboratory, images, and biopsies data. RESULTS: There were five cases of pediatric pa tients with AAV, with varying degrees of severity, and the age range at the onset was 5.5 to 13.5 years. We observed frequent renal involvement in microscopic polyangiitis (MPA) and eye involvement due to orbital pseudotumor in patients with granulomatosis with polyangiitis (GPA), an infrequent manifestation in the international pediatric literature. Patients were treated according to recommen dations extrapolated from clinical trials in adult populations, showing excellent clinical response to induction therapy with systemic corticosteroids and cyclophosphamide or rituximab. During main tenance therapy, most of the patients were stable on rituximab, azathioprine, or methotrexate. No patient developed organ damage and all cases achieved discontinuation of the corticosteroid therapy. CONCLUSION: This report describes the clinical characteristics of AAV in a series of pediatric patients. In this series, renal involvement was common in MPA and eye involvement due to orbital pseudotu mor in GPA. The clinical response with treatment according to recommendations extrapolated from the adult population was favorable.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Adolescent , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antibodies, Antineutrophil Cytoplasmic/therapeutic use , Child , Child, Preschool , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/drug therapy , Humans , Microscopic Polyangiitis/complications , Microscopic Polyangiitis/diagnosis , Microscopic Polyangiitis/therapy , Rituximab/therapeutic useABSTRACT
Objetivo: descrever as evidências disponíveis na literatura científica sobre eficácia e segurança do rituximabe comparado a diferentes tratamentos. Materiais e métodos: é uma revisão rápida de evidências científicas para tomada de decisão informada por evidências em políticas e práticas de saúde. Conclusão: o Rituximabe tem eficácia e segurança similares à da Ciclofosfamida, para terapia de indução de remissão e para manutenção da remissão e, para pacientes com doença recidivante, o Rituximabe é mais eficaz que a Ciclofosfamida para manter a remissão. Para terapia de manutenção, Rituximabe é mais eficaz que Azatioprina, com perfil de segurança similar. Diferentes regimes de dosagem do Rituximabe tem eficácia e segurança similar para terapia de manutenção. O Infliximabe parece ser superior ao Rituximabe nos desfechos de eficácia (indução e manutenção da remissão).
Objective: to describe the evidence available in the scientific literature on the efficacy and safety of rituximab compared to different treatments. Materials and Methods: is a rapid review of scientific evidence for evidence-informed decision making in health policy and practice. Conclusion: Rituximab has similar efficacy and safety to Cyclophosphamide, for remission induction therapy and for maintenance of remission, and for patients with relapsing disease, Rituximab is more effective than Cyclophosphamide in maintaining remission. For maintenance therapy, Rituximab is more effective than Azathioprine, with a similar safety profile. Different dosing regimens of Rituximab have similar efficacy and safety for maintenance therapy. Infliximab appears to be superior to Rituximab in efficacy outcomes (induction and maintenance of remission).
Subject(s)
Humans , Granulomatosis with Polyangiitis/drug therapy , Systemic Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Microscopic Polyangiitis/drug therapy , Rituximab/drug effects , Azathioprine , Cyclophosphamide , Infliximab , GlucocorticoidsABSTRACT
Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.
Resumo As glomerulopatias figuram entre as principais causas de doença renal terminal. Nos últimos anos, a pesquisa clínica efetuou contribuições significativas para a compreensão desse grupo de patologias. Recentemente, o rituximabe (RTX) surgiu como um tratamento razoavelmente seguro. As diretrizes do Kidney Disease: Improving Global Outcomes (KDIGO) recomendam o RTX apenas como tratamento inicial na vasculite associada ao ANCA (VAA) e em pacientes não respondedores com nefrite lúpica (NL), embora não sejam atualizadas desde 2012. Atualmente, o RTX parece ser pelo menos tão eficaz quanto outros esquemas imunossupressores na nefropatia membranosa idiopática (NMI). Na doença por lesão mínima (DLM), o medicamento pode proporcionar um período de remissão duradouro em pacientes córtico-dependentes ou com recidivas frequentes. Resultados preliminares corroboram o uso de RTX em pacientes com NL membranosa pura e glomerulonefrite membranoproliferativa (GNMP) mediada por imunoglobulina, mas não em pacientes com NL classe III/IV ou GNMP mediada por complemento. Os achados a respeito de glomeruloesclerose segmentar e focal (GESF) idiopática e doença por anticorpo antimembrana basal glomerular (anti-MBG) não são conclusivos em função do pequeno número, porte e heterogeneidade dos estudos publicados até o presente momento. Por fim, a imunossupressão com RTX não é particularmente útil na nefropatia por IgA. A presente revisão apresenta o racional da prescrição de RTX nas diferentes glomerulopatias, desfechos e segurança. Nesse sentido, foram incluídos ensaios clínicos randomizados (ECRs) realizados em adultos, sempre que possível. Pesquisas bibliográficas foram realizadas nas bases de dados do clinictrials.gov e no PubMed.
Subject(s)
Humans , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Rituximab/adverse effects , Glomerulonephritis/drug therapy , Immunosuppressive Agents/adverse effects , Nephrosis, Lipoid/drug therapy , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Glomerulonephritis/drug therapy , Immunosuppressive Agents/adverse effects , Nephrosis, Lipoid/drug therapy , Rituximab/adverse effects , Adult , Humans , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
OBJECTIVE: To determine the incidence of positive CMV antigenemia (CMV-Ag) in patients with autoimmune rheumatic diseases (AIRD) and to describe the outcomes of these patients. METHODS: From January 2011 to December 2014, a total of 443 patients with AIRD were enrolled in this retrospective analysis. Demographic, clinical and laboratory data, current clinical manifestations, organs affected by CMV infection, therapeutic management and outcomes were evaluated. The CMV-Ag was considered positive when one cell was detected at least. RESULTS: CMV-Ag was requested in 70 (15.8%) patients with suspicious CMV infection and was positive in 24 (34.3%). The incidence rate of positive CMV-Ag was 4.97% (95% CI 3.1-7.4%). Systemic lupus erythematosus (SLE) (59%), followed by ANCA-related vasculitis (18.2%) and rheumatoid arthritis (9%) were the diseases more associated with positive CMV-Ag. At the time of CMV infection, SLE patients had moderate to severe disease activity, with high frequency of positive anti-dsDNA antibody (69.2%) and complement consumption (61.5%), as well as high doses of corticosteroids and use of immunosuppressants. The main CMV sites involved were lung (45.5%), bone marrow (40.9%) and gut (27.3%). Mortality rate was 45.5%, especially in those with higher doses of daily oral corticosteroids (107 ± 55.4 mg vs. 71.7 ± 46.3 mg; p = 0.07) and lower number of lymphocytes (309 ± 368.2/mm3 vs. 821 ± 692.9/mm3; p = 0.06). CONCLUSIONS: Our data showed high incidence of CMV-Ag in AIRD patients, particularly those with SLE and greater disease severity. In addition, it was observed high mortality in these patients, highlighting the CMV infection should be included in differential diagnosis.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Antigens, Viral/blood , Arthritis, Rheumatoid/immunology , Cytomegalovirus Infections/immunology , Cytomegalovirus/immunology , Lupus Erythematosus, Systemic/immunology , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/mortality , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/virology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/mortality , Arthritis, Rheumatoid/virology , Bone Marrow/immunology , Bone Marrow/virology , Brazil/epidemiology , Female , Granulomatosis with Polyangiitis/immunology , Granulomatosis with Polyangiitis/virology , Humans , Immunosuppressive Agents/therapeutic use , Intestines/immunology , Intestines/virology , Lung/immunology , Lung/virology , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/mortality , Lupus Erythematosus, Systemic/virology , Male , Middle Aged , Retrospective Studies , Rheumatic Fever/immunology , Rheumatic Fever/virology , Time Factors , Young AdultSubject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Adolescent , Adult , Aged , Clinical Protocols , Female , Humans , Male , Middle Aged , Recurrence , Treatment Outcome , Young AdultSubject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Recurrence , Clinical Protocols , Treatment OutcomeABSTRACT
The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed), EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Brazil , Consensus , Humans , Rheumatology , Societies, MedicalABSTRACT
Rituximab is a plausible alternative first-line treatment of ANCA-associated vasculitis. Adverse effects related to its infusion are common and usually have a benign course. However, there have been reports of refractory cardiogenic shock simulating septic shock. We report an 81-year-old male with the diagnosis of ANCA associated vasculitis. Rituximab 500 mg was administered intravenously for a relapse. The infusion proceeded without incident. However, 24 hours after its administration the patient began with fever, chills, coughing and strong malaise. The patient was transferred to the critical patient unit where a septic shock was suspected and resuscitative measures were started. However, the fast response to moderate doses of vasoactive drugs and complementary tests did not support an infectious etiology for the shock. Antimicrobials were discontinued and systemic corticosteroids were maintained, achieving remission of the symptoms. Shock as an unusual adverse reaction to Rituximab was suspected.
Subject(s)
Antirheumatic Agents/adverse effects , Rituximab/adverse effects , Shock, Cardiogenic/chemically induced , Aged, 80 and over , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Antirheumatic Agents/therapeutic use , Humans , Male , Rituximab/therapeutic use , Shock, Cardiogenic/diagnosisABSTRACT
PURPOSE OF REVIEW: The purpose of this review is to describe the efficacy and safety of rituximab (RTX) as a remission induction and maintenance therapy in ANCA-associated vasculitis (AAV). RECENT FINDINGS: A PubMed search was carried out to track down articles published between February 2006 and February 2016. Randomized controlled trials (RCTs) that encompassed patients with AAV were included. The American College of Rheumatology (ACR) and the European League against Rheumatism (EULAR) 2014-2015 online abstracts were also reviewed whether they were RTCs or not. Ten PubMed RCTs were analyzed along with eight ACR and four EULAR abstracts. RTX was not inferior to cyclophosphamide (CYC) for remission induction in AAV; it was superior to CYC in patients with relapsing disease and superior for remission maintenance in comparison with azathioprine (AZA). Rituximab is a therapeutic option to induce and maintain remission in patients with AAV.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Immunosuppressive Agents/therapeutic use , Rituximab/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Remission Induction , Rituximab/adverse effects , Treatment OutcomeABSTRACT
Rituximab is a plausible alternative first-line treatment of ANCA-associated vasculitis. Adverse effects related to its infusion are common and usually have a benign course. However, there have been reports of refractory cardiogenic shock simulating septic shock. We report an 81-year-old male with the diagnosis of ANCA associated vasculitis. Rituximab 500 mg was administered intravenously for a relapse. The infusion proceeded without incident. However, 24 hours after its administration the patient began with fever, chills, coughing and strong malaise. The patient was transferred to the critical patient unit where a septic shock was suspected and resuscitative measures were started. However, the fast response to moderate doses of vasoactive drugs and complementary tests did not support an infectious etiology for the shock. Antimicrobials were discontinued and systemic corticosteroids were maintained, achieving remission of the symptoms. Shock as an unusual adverse reaction to Rituximab was suspected.
Subject(s)
Humans , Male , Aged, 80 and over , Shock, Cardiogenic/chemically induced , Antirheumatic Agents/adverse effects , Rituximab/adverse effects , Shock, Cardiogenic/diagnosis , Antirheumatic Agents/therapeutic use , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Rituximab/therapeutic useABSTRACT
Abstract The purpose of these recommendations is to guide the appropriate induction treatment of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with active disease. The recommendations proposed by the Vasculopathies Committee of the Brazilian Society Rheumatology for induction therapy of AAV, including granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited vasculitis, were based on systematic literature review and expert opinion. Literature review was performed using Medline (PubMed), EMBASE and Cochrane database to retrieve articles until October 2016. PRISMA guidelines were used for the systematic review and articles were assessed according to the Oxford levels of evidence. Sixteen recommendations were made regarding different aspects of induction therapy for AAV. The purpose of these recommendations is to serve as a guide for therapeutic decisions by health care professionals in the management of AAV patients presenting active disease.
Resumo O objetivo destas recomendações é orientar o tratamento apropriado de indução em pacientes com vasculite associada a anticorpos anticitoplasma de neutrófilos (VAA) ativa. As recomendações propostas pelo Comitê de Vasculopatias da Sociedade Brasileira de Reumatologia para a terapia de indução para vasculites associadas aos anticorpos anticitoplasma de neutrófilos (VAA), inclusive granulomatose com poliangiite, poliangiite microscópica e vasculite limitada ao rim, foram baseadas em uma revisão sistemática da literatura e na opinião de especialistas. A revisão da literatura foi feita com as bases de dados Medline (PubMed), Embase e Cochrane para consultar artigos até outubro de 2016. As diretrizes Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Principais itens para reportar revisões sistemáticas e metanálises) foram usadas para a revisão sistemática e os artigos foram avaliados de acordo com os níveis de evidência Oxford. Dezesseis recomendações foram feitas em relação a diferentes aspectos da terapia de indução para VAA. O objetivo dessas recomendações é servir como um guia para decisões terapêuticas por profissionais da saúde no tratamento de pacientes com VAA que apresentem a doença ativa.