Prognosis of microscopic polyangiitis is well predictable in the first 2 weeks of treatment.

BACKGROUND: Kidney and life outcomes remain unsatisfactory in patients with microscopic polyangiitis (MPA). Appropriate treatment intensity must be provided to the appropriate patients. To identify severe cases early, we investigated the factors related to kidney and life outcomes. METHODS: We included patients diagnosed with MPA based on myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positivity and kidney histopathology results after kidney biopsies between January 1, 2021, and May 11, 2023, at 10 affiliated centers, including our hospital. Death, maintenance dialysis, and estimated glomerular filtration rate (eGFR) < 15 after 6 months of treatment were defined as poor prognosis groups, and factors associated with these conditions were investigated. RESULTS: We included 84 (36 men and 48 women) patients in this study. Median age was 73.8 (interquartile range: 71-81) years. After 6 months of treatment, the proportion of patients in the poor prognosis group was 16.7 %, with a mortality of 7.1 % and a poor kidney prognosis rate of 9.5 %. Area under the receiver operating characteristic curve showed that eGFR at 2 weeks had a comparable prognostic performance equal as eGFR at 4 weeks (area under the curve: 0.875 and 0.896, respectively). After adjustment by various factors, eGFR at 2 weeks was related with prognosis significantly (p = 0.031). CONCLUSION: Kidney function 2 weeks after the start of treatment for MPA can predict prognosis.

First-year cumulative myeloperoxidase-ANCA titres are associated with all-cause mortality in patients with microscopic polyangiitis.

OBJECTIVES: We investigated whether first-year cumulative myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3 (PR3)-ANCA titres were associated with all-cause mortality and relapse during follow-up in patients with microscopic polyangiitis (MPA) and granMETHODS: Altogether, 74 patients with MPA and 40 with GPA were included in this study. Their clinical data at diagnosis were collected. First-year cumulative ANCA titres were defined as the area under the curve (AUC) of ANCA titres during the first year after MPA or GPA diagnosis, which was obtained using the trapezoidal rule. All-cause mortality and relapse were considered poor outcomes of MPA and GPA. RESULTS: The median ages of patients with MPA and GPA were 65.5 and 60.5 years, respectively. No significant correlation was observed between ANCA titres at diagnosis and concurrent MPA and GPA activity or the inflammatory burden. First-year cumulative MPO-ANCA titres exhibited a significant AUC for all-cause mortality during follow-up in patients with MPA. The optimal cut-off of first-year cumulative MPO-ANCA titres for all-cause mortality was determined as 720.8 IU/mL using receiver operating characteristic curve analysis. MPA patients with first-year cumulative MPO-ANCA titres ≥720.8 IU/mL exhibited a significantly higher risk for all-cause mortality than those without (relative risk 13.250). Additionally, MPA patients with first-year cumulative MPO-ANCA titres ≥720.8 IU/mL exhibited a significantly lower cumulative patients' survival rate than those without. CONCLUSIONS: This is the first study to demonstrate the association between first-year cumulative MPO-ANCA titres and all-cause mortality during follow-up in patients with MPA.

Epidemiology and treatment outcome of ANCA-associated vasculitis in South Korea: a nationwide, population-based cohort study.

OBJECTIVES: To investigate the epidemiological features of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in South Korea. METHODS: We identified the index cases of GPA and MPA using the 2010-2018 Korean National Health Insurance Service database and the Rare Intractable Disease registry for the entire Korean population. Each disease's incidence and prevalence rates and trends over time were analysed. To assess the impact of disease on morbidity and mortality, a comparator group comprising the general population was established using nearest-neighbour matching by age, sex, income, and comorbidity index, at a 5:1 ratio. Morbidity outcomes included the initiation of renal replacement therapy and admission to the intensive care unit. RESULTS: We identified 546 and 795 patients with GPA and MPA, respectively. The incidence rates of both diseases increased with age, with peak incidence rates observed among patients aged ≥70 years. The incidence of MPA increased continuously over time, whereas that of GPA showed no significant changes. During the observation period, 132 (28.7%) and 277 (41.1%) patients in the GPA and MPA groups, respectively, died, which were significantly higher than that in the general population (standardised mortality ratio: 3.53 and 5.58, respectively) and comparator group (hazard ratio: 4.02 and 5.64, respectively). Higher mortality and morbidity rates were observed among patients with MPA than among those with GPA. CONCLUSIONS: In South Korea, the incidence of MPA has increased over time. Although both GPA and MPA had high rates of mortality and morbidity, MPA has a poorer prognosis than GPA.

Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis.

BACKGROUND AND OBJECTIVES: Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. RESULTS: In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation (P=0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. CONCLUSIONS: The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3.

Clinical Significance of Interstitial Lung Disease and Its Acute Exacerbation in Microscopic Polyangiitis.

BACKGROUND: Presence of interstitial lung disease (ILD) is thought to be associated with mortality in microscopic polyangiitis (MPA); however, evidence on MPA-ILD remains lacking. Acute exacerbation (AE) refers to rapidly progressive, fatal respiratory deterioration that may develop in patients with various ILDs. No study has investigated the clinical significance of AE in MPA-ILD. RESEARCH QUESTION: We aimed to determine the clinical picture and prognostic factors, the incidence of AE, and the risk factors in patients with MPA-ILD. STUDY DESIGN AND METHODS: Eighty-four consecutive patients with MPA-ILD and 95 patients with MPA-non-ILD were analyzed. We also compared 80 patients with MPA-ILD and 80 patients with idiopathic interstitial pneumonia without myeloperoxidase-antineutrophil cytoplasmic antibody positivity (ILD alone), who were matched for age, sex, and chest high-resolution CT scan pattern. RESULTS: The MPA-ILD group had a higher frequency of men and smokers and was associated with higher mortality than the MPA-non-ILD group. The matched MPA-ILD group had a higher mortality rate than the matched ILD alone group. There was no significant difference in AE incidence between the matched MPA-ILD and ILD alone groups (1-year AE cumulative incidence rate, 7.5% and 5.2%, respectively; P = .75). In the MPA-ILD group, a lower percent predicted FVC (%FVC) was independently associated with a higher mortality rate (hazard ratio [HR], 0.96 per 1% increase; P < .01) and a higher AE incidence rate (HR, 0.96 per 1% increase; P = .01). On multivariable Cox regression analysis with time-dependent covariates, developing AE during their clinical course was strongly associated with shorter survival (HR, 17.1; P < .001). INTERPRETATION: MPA-ILD represented a distinct phenotype with poor prognosis. Lower %FVC was an independent prognostic factor. Patients with lower %FVC had a risk of developing AE, which was a strong prognostic determinant. The specific management for MPA-ILD and AE should be established.

Fibrosis-5 predicts end-stage renal disease in patients with microscopic polyangiitis and granulomatosis with polyangiitis without substantial liver diseases.

We previously reported that fibrosis-4 (FIB-4) was associated with poor outcomes of microscopic polyangiitis (MPA) and granuloma with polyangiitis (GPA). We also investigated the potential of FIB-5, a novel index, in predicting all-cause mortality and end-stage renal disease (ESRD) during follow-up in patients with MPA and GPA without substantial liver diseases. Clinical and laboratory data at diagnosis were collected by reviewing the medical records of 180 patients with MPA and GPA. FIB-5 was obtained by a following equation: FIB-5 = (serum albumin (g/L) × 0.3 + platelet count (109/L) × 0.05) - (alkaline phosphatase (IU/L) × 0.014 + aspartate aminotransferase/alanine aminotransferase ratio × 6 + 14). The median age of the patients at diagnosis was 61.0 years. FIB-5 at diagnosis could not reflect the cross-sectional vasculitis activity. The cutoffs of FIB-5 for poor outcomes was set as 0.82 (the lowest tertile) and -0.42 (the lowest quartile) at diagnosis. In Kaplan-Meier survival analysis, patients with FIB-5 < 0.82 and those with FIB-5 < -0.42 exhibited lower ESRD-free survival rates than those without. However, it could not predict all-cause mortality. In multivariable Cox hazards analysis, both FFS (Hazard ratio (HR) 1.554) and FIB-5 < 0.82 (HR 2.096) as well as both FFS (HR 1.534) and FIB-5 < -0.42 (HR 2.073) at diagnosis independently predicted ESRD during follow-up. In conclusion, FIB-5 < 0.82 and FIB-5 < -0.42 at diagnosis could predict the occurrence of ESRD, but not all-cause mortality, during follow-up in patients with MPA and GPA without substantial liver diseases.

Evaluation of poor prognostic factors of respiratory related death in microscopic polyangiitis complicated by interstitial lung disease.

The prognosis of microscopic polyangiitis (MPA) with interstitial lung disease (ILD) is significantly worse than that of MPA without ILD. However, the clinical characteristics in MPA-ILD, especially poor prognostic factors, are not elucidated. We evaluated demographic, clinical, laboratory, and radiological findings, treatments, and outcomes of 80 patients with MPA, and investigated prognostic factors of respiratory-related death in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positive MPA-ILD. Ground-glass opacity and fibrosis were evaluated as scores on high-resolution computed tomography (HRCT). The presence of ILD was consistent with a high risk of respiratory-related death (hazard ratio, 4.8; P = 0.04). Multivariable logistic regression analyses using propensity scoring showed right or left lower lobe fibrosis score to be significantly associated with respiratory-related death (P = 0.0005 and 0.0045, respectively). A right or left lower lobe fibrosis score ≥ 2, indicating the presence of honeycombing at 1 cm above the diaphragm, was determined to be the best cut-off value indicating a poor prognosis. The 5-year survival rate was significantly lower in patients with right or left lower lobe fibrosis score ≥ 2 (survival rates: 37% and 19%, respectively) than those with a score < 2 (71% and 68%, respectively) (P = 0.002 and 0.0007, respectively). These findings suggest that the presence of honeycomb lesions in bilateral lower lobes on chest HRCT was associated with respiratory-related death in patients with MPO-ANCA positive MPA-ILD.

Rituximab Biosimilar Prevents Poor Outcomes of Microscopic Polyangiitis and Granulomatosis with Polyangiitis as Effectively as Rituximab Originator.

PURPOSE: There has been no extensive study to compare the efficacy between rituximab originator (Mabthera®) and its biosimilar (Truxima®) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Here, we investigated the clinical effects of rituximab on poor outcomes of MPA and GPA in Korean patients, and compared those between Mabthera® and Truxima®. MATERIALS AND METHODS: We retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®. RESULTS: The median age at diagnosis was 60.1 years and 46 patients were men (97 MPA and 42 GPA patients). Among poor outcomes, patients receiving rituximab exhibited a significantly lower cumulative relapse-free survival rate compared to those not receiving rituximab (p=0.002). Nevertheless, rituximab use did not make any difference in other poor outcomes of MPA and GPA except for relapse, which might be a rebuttal to the fact that rituximab use after relapse eventually led to better prognosis. There were no significant differences in variables at diagnosis and during follow-up between patients receiving Mabthera® and those receiving Truxima®. Patients receiving Truxima® exhibited a similar pattern of the cumulative survival rates of each poor outcome to those receiving Mabthera®. CONCLUSION: Truxima® prevents poor outcomes of MPA and GPA as effectively as does Mabthera®.

Microscopic polyangiitis: Clinical characteristics and long-term outcomes of 378 patients from the French Vasculitis Study Group Registry.

OBJECTIVE: To describe characteristics and long-term outcomes of patients with microscopic polyangiitis (MPA), an antineutrophil cytoplasm antibody (ANCA)-associated small-vessel necrotizing vasculitis. METHODS: MPA patients from the French Vasculitis Study Group Registry satisfying the European Medicines Agency algorithm were analyzed retrospectively. Characteristics at diagnosis, treatments, relapses and deaths were analyzed to identify factors predictive of death or relapse. RESULTS: Between 1966 and 2017, 378 MPA patients (median age 63.7 years) were diagnosed and followed for a mean of 5.5 years. At diagnosis, the main clinical manifestations included renal involvement (74%), arthralgias (45%), skin (41%), lung (40%) and mononeuritis multiplex (32%), with less frequent alveolar hemorrhage (16%), cardiomyopathy (5%) and severe gastrointestinal signs (4%); mean serum creatinine was 217 µmol/L. ANCA were detected in 298/347 (86%) patients by immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA). Among the 293 patients with available ELISA specificities, 272 (92.8%) recognized myeloperoxidase and 13 (4.4%) proteinase-3. During follow-up, 131 (34.7%) patients relapsed and 78 (20.6%) died, mainly from infections. Respective 5-year overall and relapse-free survival rates were 84.2% and 60.4%. Multivariable analyses retained age >65 years, creatinine >130 µmol/L, severe gastrointestinal involvement and mononeuritis multiplex as independent risk factors for death. Renal impairment was associated with a lower risk of relapse. CONCLUSION: Non-renal manifestations and several risk factors for death or relapse were frequent in this nationwide cohort. While mortality was low, and mainly due to treatment-related complications, relapses remained frequent, suggesting that MPA management can be further improved.

Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis.

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double-center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non-disease-specific mortality. The 1-year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five-Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.

Vasculitis asociada a anticuerpos anticitoplasma de neutrófilos: poliangeítis microscópica / Antineutrophil Cytoplasmic Antibody Associated Vasculitis: Microscopic Polyangiitis

La poliangeítis microscópica se define como una enfermedad autoinmune, multisistémica, de rara incidencia, asociada a anticuerpos anticitoplasma de neutrófilos. Se caracteriza por presentar vasculitis necrotizante de pequeños vasos, no granulomatosa y ausencia de depósito de inmunocomplejos, que afecta predominantemente el tejido renal, pulmonar y cutáneo. Se presenta un paciente masculino, 49 años, sin antecedentes patológicos. Presenta cuadro clínico de 30 días de evolución con tos seca de tipo irritativa, que evoluciona a tos productiva, hemoptisis, disnea de moderado esfuerzo, astenia y edema con fóvea en zonas en declive. Tenía anemia grave y los estudios imagenológicos de tórax evidenciaron infiltrados difusos con aspecto de vidrio deslustrado. Se inició terapia inmunosupresora con metilprednisolona y ciclofosfamida y profilaxis antibiótica. Se obtuvo una disminución en el puntaje de la escala de actividad vasculítica y la posterior remisión; sin embargo, debido al daño tisular renal, no hubo mejoría en la tasa de filtrado glomerular, por lo que el paciente se mantiene en terapia de sustitución renal permanente. Es trascendental el conocimiento de las manifestaciones clínicas, procedimiento diagnóstico y tratamiento de esta enfermedad, ya que, a pesar de su rara incidencia, posee una llamativa morbimortalidad que puede modificarse significativamente con un diagnóstico y tratamiento oportunos(AU)

Microscopic Polyangiitis is defined as an autoimmune, multisystemic, low prevalence disease, associated to antineutrophil cytoplasmic antibody. Characterized by necrotizing vasculitis of small vessels, with no granulomatous inflammation and absence of immune complex deposits, predominantly affecting renal, pulmonary and cutaneous tissue. 49-year old male patient with no past medical history. Refers symptomatology that started thirty days ago, characterized by dry cough, that evolves to productive cough, hemoptysis, exertional dyspnea, asthenia and pitting edema. Laboratory tests show severe anemia, glomerular filtration rate of 6.9 ml/min/1.73m2, hematuria, proteinuria, positive presence of antineutrophil cytoplasmic antibodies and anti-myeloperoxidase antibodies, additional thoracic imaging shows ground glass opacities consolidations. Immunosuppressive therapy is started with Methylprednisolone and Cyclophosphamide along with antibiotic prophylaxis, resulting in a decrease in the vasculitis activity score with subsequent remission; however due to renal tissue damage, there is no improvement in the glomerular filtration rate and the patient continues receiving renal replacement therapy. Due to its striking morbidity and mortality, we consider of great importance the knowledge of its clinical presentation, diagnostic procedures and treatment, in order to obtain a positive impact on the patient's quality of life and survival rate(AU)

Clinical characteristics and outcomes in microscopic polyangiitis patients with renal involvement: a study of 124 Chinese patients.

BACKGROUND: Microscopic polyangiitis (MPA) is a systemic autoimmune disease, and renal involvement is frequently present in MPA. MPA patients with renal involvement may have a worse prognosis. In this study, we aimed to evaluate the prognostic factors associated with all-cause death and renal survival in MPA patients with renal involvement. METHODS: A retrospective observational cohort study was performed. One hundred twenty-four patients newly diagnosed with MPA with renal involvement excluding end-stage renal disease (ESRD) who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from January 2012 to July 2017 were included. All the survivors were followed up with until July 2018. The clinical and laboratory data at the time of the initial MPA diagnosis were collected, and the predictive values of the variables for mortality and renal outcome were analysed. RESULTS: Among the 124 patients, 52 were men (41.9%) and 72 were women (58.1%), and the age range was from 25 to 85 years (63.9±10.6 years). Seventy-six patients (61.3%) had pulmonary involvement. Multivariate Cox analysis revealed that age≥65 years (HR: 2.437; P=0.021), serum creatinine≥500 µmol/L (HR=2.207; P=0.009) and interstitial lung disease (ILD) (HR=2.366; P=0.013) were associated with mortality. Cox multivariate analysis identified that serum creatinine≥500 µmol/L (HR=8.236; P<0.001) and ILD (HR=2.649; P=0.001) were independent detrimental factors for renal survival, and immunosuppressive treatment was a protective factor for renal survival (HR=0.349; P=0.001). The area under the ROC curve (AUC) of the serum creatinine level at diagnosis was 0.705 for mortality and 0.870 for progression to ESRD or the doubling of serum creatinine. CONCLUSIONS: Age, serum creatinine level at diagnosis and ILD were independent predictors of mortality in MPA patients with renal involvement. Serum creatinine level at diagnosis, ILD and immunosuppressive treatment were independently related to renal survival.

Fibrosis-4 index at diagnosis is associated with all-cause mortality in patients with microscopic polyangiitis and granulomatosis with polyangiitis.

BACKGROUND: The fibrosis-4 index (FIB-4) has been reported to be associated with all-cause mortality in several chronic diseases. In this study, we investigated whether at diagnosis could be associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We retrospectively reviewed the medical records of 132 MPA and GPA patients without chronic liver diseases. Conventional risk factors included old age (≥ 65 years), male gender, diabetes mellitus (DM) and hypertension (HTN) at diagnosis, and disease-related risk factor included GPA, antineutrophil cytoplasmic antibody, Birmingham vasculitis activity score (BVAS) and five factor score (FFS (2009)). The cut-off of FIB-4 for significant liver fibrosis (S2-4) was set at 1.45. RESULTS: The mean age was 57.2 years and 27 patients (20.5%) had significant liver fibrosis (FIB-4 ≥ 1.45). Fifteen patients (11.4%) died during follow-up. In the univariable Cox Hazards model, age ≥ 65 years (Hazard ratio (HR) 5.055), DM (HR 3.446), HTN (HR 4.611), FFS (2009) ≥ 2 (HR 4.849) and FIB-4 ≥ 1.45 (HR 9.958) at diagnosis were significantly associated with all-cause mortality. In the multivariable Cox Hazards model, only FIB-4 at diagnosis ≥1.45 (HR 6.253, 95% confidence interval 1.398, 27.963) was associated with all-cause mortality during the follow-up in patients with MPA and GPA. CONCLUSIONS: FIB-4 at diagnosis ≥1.45 is an independent predictor of all-cause mortality during follow-up in patients with MPA and GPA, and furthermore its predictive potential is higher than those of conventional and AAV-related risk factors for all-cause mortality.

Clinical Effect of Alpha-1 Antitrypsin Deficiency in Antineutrophil Cytoplasmic Antibody-associated Vasculitis: Results from a French Retrospective Monocentric Cohort.

OBJECTIVE: Deficiency in alpha-1 antitrypsin (AAT) is a possible pathogenic cofactor in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the clinical effect of AAT deficiency remains poorly established in this setting. This study aimed to describe the clinical phenotypes and outcomes of AAV according to AAT phenotypes. METHODS: This study was conducted retrospectively at Caen University Hospital and included all consecutive granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) patients with positive proteinase 3-ANCA or myeloperoxidase-ANCA, from January 2000 or September 2011, respectively, to June 2016. AAT dosage (nephelometry) and phenotyping (isoelectric focusing in agarose gel) were performed. RESULTS: Among the 142 patients with AAV, including 88 GPA and 54 MPA, 102 (72%) had the MM phenotype, 5 (4%) had a nonpolymerogenic M-variant phenotype, 18 (13%) had the deficient allele MZ, 12 (8%) had MS, 2 (1%) had ZZ, 2 (1%) had SZ, and 1 (1%) had SS. M, Z, and S allele frequencies were 84%, 8%, and 6%, respectively. No association was observed between AAT deficiency and ANCA subtype or AAV phenotype, except for intraalveolar hemorrhage (IAH), which was more frequent in patients harboring at least 1 of the deficient Z or S alleles than in those without any deficient alleles (p < 0.01). Global, renal, or relapse-free survival rates were similar for all subgroups. CONCLUSION: This study shows that AAT deficiency confers, independently of ANCA subtype, a higher risk of IAH. Prospective studies are required to refine these data and to assess the need for replacement therapy in AAT-deficient patients with AAV.

Clinical impact of subgrouping ANCA-associated vasculitis according to antibody specificity beyond the clinicopathological classification.

OBJECTIVES: In ANCA-associated vasculitis (AAV), classifications have emerged to individualize homogeneous clinical and outcomes patterns, including the recently defined anti-MPO granulomatosis with polyangiitis (GPA) subgroup. This study aimed to retrospectively evaluate the impacts of re-classification based on clinicopathological criteria and/or ANCA specificity. METHODS: A retrospective monocentric study conducted at Caen University Hospital led to the identification of PR3 or MPO-ANCA AAV patients from January 2000 or September 2011, respectively, to June 2016. Eosinophilic GPA patients were excluded. AAVs were thereby also classified either as GPA or microscopic polyangiitis (MPA) according to the European Medicines Agency vasculitis algorithm. RESULTS: A total of 150 AAV patients were included (94 GPA, 56 MPA; 87 anti-PR3 and 63 anti-MPO patients). GPA patients exhibited a worse relapse-free survival but a better renal survival (P < 0.001 and P = 0.021, respectively) than MPA patients. Overall, relapse-free and renal survival rates were similar between anti-PR3 and anti-MPO patients (P = 0.35, 0.17 and 0.15, respectively). Similarly, the prognosis was identical between anti-MPO MPA patients and anti-PR3 MPA patients (P = 0.33, 0.19 and 0.65, respectively), and between anti-MPO GPA patients and anti-PR3 GPA patients (P = 0.06, 0.99 and 0.64, respectively). Moreover, anti-PR3 GPA and anti-MPO GPA patients exhibited no differences in clinical manifestations or BVAS score. CONCLUSION: Clinicopathological classification appeared to be the strongest criterion for distinguishing among homogeneous prognoses of AAV. Individualizing the anti-MPO GPA subgroup does not appear to bring additional value to clinical practice, but multicentre studies are required to confirm this trend.

Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates. RESULTS: 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ±â€¯78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83). CONCLUSION: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.

Clinical role of albumin to globulin ratio in microscopic polyangiitis: a retrospective monocentric study.

We investigated whether albumin to globulin ratio (AGR) at diagnosis may be associated with all-cause mortality in immunosuppressive drug-naïve patients with microscopic polyangiitis (MPA). We retrospectively reviewed the medical records of 88 MPA patients, who were first classified and in whom medications was first initiated in our tertiary Hospital. We collected clinical and laboratory data as well as the rate of all-cause mortality. AGR at diagnosis was calculated as a ratio of serum albumin over globulin fraction (protein-albumin). We compared variables between survived and deceased patients. The multivariable Cox hazard model was conducted to appropriately obtain the hazard ratios (HRs). The mean age at diagnosis was 56.3 years and 24 patients (27.3%) were men. Seven patients died for the mean follow-up period of 49.7 months. Deceased patients were elder than survived patients (P = 0.048). Five factor score (FFS) (2009) (P = 0.001), creatinine (P = 0.026) and AGR (P = 0.007) at diagnosis in deceased patients were higher than those in the survived. In the multivariable Cox hazard model analysis, only AGR at diagnosis (HR 0.004) was inversely associated with all-cause mortality during the follow-up. Furthermore, when the cutoff of AGR for death was set as 0.88, patients with AGR ≤ 0.88 exhibited the lower cumulative patients survival rate than those with AGR > 0.88 (P = 0.006). Among the conventional and MPA-related risk factors for mortality, AGR at diagnosis is inversely associated with all-cause mortality during follow-up in MPA patients.

C-Reactive Protein to Serum Albumin Ratio Is an Independent Predictor of All-Cause Mortality in Patients with ANCA-Associated Vasculitis.

PURPOSE: We investigated whether C-reactive protein (CRP) to serum albumin ratio (CAR) could be an independent predictor of all-cause mortality in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 170 patients with AAV. We collected clinical and laboratory data. We also examined AAV-related and traditional risk factors of all-cause mortality. To assess the hazard ratios of variables, we performed univariable and multivariable Cox hazard model analyses. RESULTS: The mean age was 55.0 years and 53 patients (31.2%) were male among 170 patients with AAV (88 microscopic polyangiitis, 43 granulomatosis with polyangiitis, and 39 eosinophilic granulomatosis with polyangiitis). ANCA was detected in 129 patients (75.9%). The initial mean CRP and serum albumin were 41.1 (mg/L) and 3.6 (g/dL), and the mean CAR at diagnosis was 14.8. The most common risk factor of mortality was hypertension (42.4%), followed by chronic kidney disease ≥stage 3 (25.9%). Fourteen patients (8.2%) died during the mean follow-up of 56.7 months. In both multivariable Cox hazard model analyses, CAR at diagnosis was identified as an independent predictor of all-cause of mortality comparable to diabetes mellitus (DM). Moreover, patients with CAR ≥10.35 and having DM exhibited a higher frequency of all-cause mortality than those without. CONCLUSION: CAR at diagnosis can be an independent predictor of all-cause mortality, comparable to DM, the conventional risk factor of mortality.

The initial predictors of death in 153 patients with ANCA-associated vasculitis in a single Korean centre.

OBJECTIVES: We estimated the cumulative patient survival rates, the causes of death and the initial predictors of death in Korean patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). METHODS: We reviewed the medical records of 153 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We collected clinical and laboratory data including ANCA, Birmingham vasculitis activity score (BVAS), five factor score (FFS) (2009), comorbidities, medications and prognosis (death and relapse). The hazard ratio (HR) of variables at diagnosis for death in the disease course was assessed by the Cox hazard model analysis. RESULTS: The mean age of 153 AAV patients (47 men and 106 women) was 55.2 years and the mean follow-up duration was 51.5 months. Fourteen of 153 patients (9.2%) died (7 MPA and 7 GPA patients) during the mean follow-up of 56.9 months. In all patients with AAV, 1 year-, 5 year- and 10 year-cumulative patient survival rates were 96.1%, 94.8% and 92.8%, respectively. The most common cause of death was infection of various causes. FFS (2009) ≥2 (HR 16.520, p=0.012) and diffuse alveolar haemorrhage (DAH) (HR 3.705, p=0.042) at diagnosis could predict death during the follow-up in AAV patients in multivariate COX regression analysis. CONCLUSIONS: The overall mortality rate was 9.2% and 10-year cumulative patient survival rate was 92.8%. At diagnosis, FFS (2009) ≥ 2 and DAH were independent predictors of death during the follow-up in Korean patients with MPA, GPA and EGPA.

Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial.

OBJECTIVES: The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV. METHODS: In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity. RESULTS: Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed. CONCLUSIONS: MTX may be effective and safe for remission-maintenance in AAV. TRIAL REGISTRATION: clinicaltrials.gov NCT00751517.