The prevalence, burden of disease, and healthcare utilization of patients with eosinophilic granulomatosis with polyangiitis in Japan: a retrospective, descriptive cohort claims database study.

OBJECTIVES: To estimate eosinophilic granulomatosis with polyangiitis (EGPA) prevalence and disease burden in patients with newly diagnosed EGPA in Japan. METHODS: This retrospective descriptive cohort study (GSK ID: 209751, HO-18-19652) used administrative claim data from patients (aged ≤74 years) with EGPA (study period: January 1, 2005-December 31, 2017), identified from their first ICD-10 code for EGPA (index). Data were examined during the 12 months before (baseline) and 12 months following the index date (follow-up). EGPA prevalence, respiratory comorbidities, all-cause healthcare utilization, and oral corticosteroid (OCS) use were assessed. RESULTS: EGPA prevalence (95%CI) increased from 4.2 (0,23.7)/million people (2005) to 38.0 (31.8,45.1)/million people (2017), was generally more common in females versus males, and increased with age. Of the 45 patients with newly diagnosed EGPA, 57.8% had acute bronchitis and 42.2% had upper respiratory tract infections during baseline. During follow-up, 60.0% of patients were hospitalized at least once and 77.8% used OCS (OCS dependent [≥80% of days]: 73.1%). CONCLUSIONS: In Japan, EGPA prevalence increased over time, was generally more common in females, and increased with patient age. EGPA burden was high; respiratory comorbidities were common, and most patients required hospitalization and OCS use. Our data suggest additional EGPA treatment options are needed.

Intra- and inter-rater reliability of the modified ENT assessment score (ENTAS 2) in granulomatosis with polyangiitis: a prospective randomised trial.

OBJECTIVES: Ears nose and throat (ENT) involvement is found on a substantial proportion of patients with granulomatosis with polyangiitis (GPA). Structured, reliable ENT assessment is essential in the management of GPA patients. It is the aim of this study to determine the repeatability (intra-rater reliability) and reproducibility (inter-rater reliability) of the ENT Assessment Score (ENTAS 2). METHODS: The ENTAS 2 built the fundament of the prospective randomized trial. Anamnestic, video endoscopic and diagnostic data of 47 patients were used. A single assessor reference was created. GPA/ENT activity and damage were evaluated by three physicians at two time points (T1/T2). GPA/ENT activity was evaluated in dichotomy (yes/no) and grading (none/mild/moderate/high) and GPA/ ENT damage in dichotomy. RESULTS: ENTAS 2 activity evaluations intra-rater reliability was 80.7% (κ=0.56) in dichotomy and 72.8% (κ=0.41) in grading. ENTAS 2 damage evaluations showed 87.8% (κ=0.74) intra-rater reliability. ENTAS 2 activity inter-rater reliability at T1 was 62.2% (κ=0.43) in dichotomy and 51.1% (κ=0.29) in grading, at T2 it was 68.2% (κ=0.48) in dichotomy and 55.32% (κ=0.33) in grading. Inter-rater reliability of ENTAS 2 damage evaluation was 84.4% (κ=0.79) at T1 and 72.5% (κ=0.64) at T2. CONCLUSIONS: ENTAS 2 intra-rater reliability was high in dichotomous and graded GPA/ENT activity and damage evaluations. Inter-rater reliability was high in dichotomous activity and damage evaluations, but low in graded activity evaluations. The data demonstrate that the ENTAS 2 is a reliable score-system considering GPA/ENT activity and damage evaluations.

Presentation and initial assessment of ENT problems in patients with granulomatosis with polyangiitis (Wegener's).

BACKGROUND: Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis) is a primary systemic vasculitis that affects medium to small sized vessels throughout the body. It often presents with symptoms and signs involving the ear, nose, and head and neck area. OBJECTIVE: To highlight salient features of ENT-related issues in granulomatosis with polyangiitis, and raise awareness of the condition. METHODS: A case report of a patient with limited disease and an insidious onset is presented, along with a review of the current literature. In addition, basic initial management is described. RESULTS: Eighty-six publications were used to describe salient features of ENT-related issues in granulomatosis with polyangiitis. CONCLUSION: The time to diagnosis has not reduced significantly in the last 10 years in the UK. A high index of suspicion is required for an earlier diagnosis of granulomatosis with polyangiitis.

Brief report: The value of a patient global assessment of disease activity in granulomatosis with polyangiitis (Wegener's).

OBJECTIVE: To 1) describe the distribution of patient global assessment (PtGA) scores of disease activity in patients with granulomatosis with polyangiitis (GPA; Wegener's), 2) explore the discordance between PtGA scores and physician global assessment (PhGA) scores of disease activity, and 3) explore whether PtGA scores during disease remission are associated with future disease relapse. METHODS: Data from the Wegener's Granulomatosis Etanercept Trial (WGET) were used. PtGA and PhGA scores were assessed on 100-mm visual analog scales (VAS). Presence of active disease was determined using the Birmingham Vasculitis Activity Score for WG (BVAS/WG), and remission was defined as a BVAS/WG score of 0. Disease relapse was defined as a BVAS/WG score of >0 after remission had been achieved. Discordance between PtGA and PhGA scores was defined as a difference of ≥20 points between the two measures. Mixed linear models were used in longitudinal analysis of PtGA scores. RESULTS: Data were obtained from 180 patients in the WGET cohort, seen at a total of 1,719 study visits. The mean ± SD PtGA and PhGA disease activity scores (on 100-mm VAS) at baseline were 64.2 ± 27.4 and 55.5 ± 23.4, respectively. PtGA-PhGA discordance occurred in 53% of patients at baseline, and this was inversely associated with newly diagnosed disease (as opposed to relapsing disease) at baseline (odds ratio 0.37, 95% confidence interval [95% CI] 0.20-0.68) but not with age, sex, or presence of renal or pulmonary disease. Patients were in disease remission during 62% of the study visits. The mean PtGA score during visits immediately prior to relapse was 4.52 points higher (95% CI 0.66-8.4) than that at other remission visits (P = 0.03). CONCLUSION: PtGA-PhGA discordance is common in GPA. A rise in the PtGA disease activity score during times defined by physicians as periods of remission is associated with subsequent occurrence of disease relapse. These findings support the addition of PtGA as an outcome measure for GPA.

Performance of Birmingham Vasculitis Activity Score and disease extent index in childhood vasculitides.

OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS: The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS: This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.

Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's).

OBJECTIVE: To assess a generic measure of health-related quality of life (HRQOL) as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: Subjects were participants in the Wegener's Granulomatosis Etanercept Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study (VCRC-LS). HRQOL was assessed with the Short Form 36 (SF-36) health survey that includes physical and mental component summary scores (PCS and MCS, respectively). Disease activity was assessed with the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). RESULTS: The data from 180 subjects in the WGET (median followup 2.3 years, mean number of visits 10) and 237 subjects in the VCRC-LS (median followup 2.0 years, mean number of visits 8) were analyzed. A 1 unit increase in the BVAS/WG corresponded to a 1.15 unit (95% confidence interval [95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI 0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39) in the VCRC-LS. In both arms of the WGET study, SF-36 measures improved rapidly during the first 6 weeks of treatment followed by gradual improvement among patients achieving sustained remission (0.5 improvement in PCS per 3 months), but worsened slightly (0.03 decrease in PCS every 3 months) among patients not achieving sustained remission (P = 0.005). CONCLUSION: HRQOL, as measured by the SF-36, is reduced among patients with GPA. SF-36 measures are modestly associated with other disease outcomes and discriminate between disease states of importance in GPA.

Measurement of damage in systemic vasculitis: a comparison of the Vasculitis Damage Index with the Combined Damage Assessment Index.

OBJECTIVES: To compare the Vasculitis Damage Index (VDI) with the Combined Damage Assessment Index (CDA) as measures of damage from vasculitis. METHODS: A total of 283 patients with vasculitis from 11 European centres were evaluated in a cross-sectional study using the VDI and CDA. RESULTS: Wegener's granulomatosis (58.4%) and microscopic polyangiitis (11.0%) were the most common diagnoses. Agreement between VDI and CDA scores (Spearman's correlation) was 0.90 (95% CI 0.87 to 0.92). There was good correlation between individual comparably evaluated organ systems (Spearman's correlation 0.70-0.94). Interobserver reliability (assessed by intraclass correlation coefficient (ICC)) was 0.94 (95% CI 0.89 to 0.98) for VDI and 0.78 (95% CI 0.63 to 0.93) for CDA. Intraobserver reliability was 0.92 (95% CI 0.83 to 1.00) for VDI and 0.87 (95% CI 0.75 to 1.00) for CDA. A total of 13 items were not used in the VDI compared to 23 in the CDA. Observers agreed that the CDA covered the full spectrum of damage attributable to vasculitis but was more time consuming and thus possibly less feasible for clinical and research purposes. CONCLUSIONS: The VDI and CDA capture reliable data on damage among patients with vasculitis. The CDA captures more detail but is more complex and less practical than the VDI. Further evolution of damage assessment in vasculitis is likely to include key elements from both instruments.

Assessment of the item selection and weighting in the Birmingham vasculitis activity score for Wegener's granulomatosis.

OBJECTIVE: To assess the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) with respect to its selection and weighting of items. METHODS: This study used the BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial. The scoring frequencies of the 34 predefined items and any "other" items added by clinicians were calculated. Using linear regression with generalized estimating equations in which the physician global assessment (PGA) of disease activity was the dependent variable, we computed weights for all predefined items. We also created variables for clinical manifestations frequently added as other items, and computed weights for these as well. We searched for the model that included the items and their generated weights yielding an activity score with the highest R(2) to predict the PGA. RESULTS: We analyzed 2,044 BVAS/WG assessments from 180 patients; 734 assessments were scored during active disease. The highest R(2) with the PGA was obtained by scoring WG activity based on the following items: the 25 predefined items rated on >or=5 visits, the 2 newly created fatigue and weight loss variables, the remaining minor other and major other items, and a variable that signified whether new or worse items were present at a specific visit. The weights assigned to the items ranged from 1 to 21. Compared with the original BVAS/WG, this modified score correlated significantly more strongly with the PGA. CONCLUSION: This study suggests possibilities to enhance the item selection and weighting of the BVAS/WG. These changes may increase this instrument's ability to capture the continuum of disease activity in WG.

[Survival and relapses assessment in patients with Wegener's granulomatosis and predominant renal involvement]. / Ocena czasu prezycia i ryzyka nawrotów u pacjentów z ziarniniakowatoscia Wegenera z dominujqcym zajqciem nerek.

INTRODUCTION: Wegener's granulomatosis (WG) is a potentially fatal condition with remissions and high relapses rates. OBJECTIVES: Assessment of survival and relapses in a population based cohort of patients with WG with predominant renal involvement. PATIENTS AND METHODS: A prospective cohort study including 60 patients--median age of 42 years with different dynamics and clinical presentation. Patients were divided into 3 groups (group 1, group 2 and group 3 respectively, and subgroups: 3.1, 3.2, 3.3): group 1--WG patients without renal involvement, group 2--WG patients with abnormalities in urinary sediment, group 3.1--WG patients with chronic renal failure, group 3.2--WG patients with diffuse alveloar hemorrhage (DAH) and rapid progressive glomerulonephritis (RPGN), and group 3.3--WG patients with RPGN. The clinical analysis has been conducted using the disease extent index (DEl) only and Birmingham Vasculitis Activity Score-Wegener's granulomatosis (BVAS-WG) disease activity questionnaire. Logistic regression analysis and the Wilcoxon test were used. Survival time and death risk were assessed using the Kaplan-Meier estimator and Cox proportional hazard model. RESULTS: Eighty-eight percent of patients survived the first year follow-up since the diagnosis, while 84% of patients remained alive after the second year of observation. Life expectancy was 67.1 +/- 4.4 months. During the first year of observation 9.8% of patients died, after 2 years death hazard amounted to 3.7% per year, and after 4 years 2.6% per year (p < 0.05). Death risk was 1.3-fold higher in group 2 and 3.3-fold higher in group 3 compared to group 1 (p > 0.05). Mortality in patients from group 3.1 was 6-fold lower than in patients from group 3.2 (p < 0.03) and in group 3.3 was more than 4-fold lower than in patients from group 3.2 (p < 0.04). Relapse risk after first the year of follow-up was 20% per year and minimally changed after 3 years of observation, then decreased to 6% after 5 years. Relapse hazard ratio in group 2 was significantly lower in comparison with group 1 (HR1/3.6, p < 0.04). CONCLUSIONS: We found significant differences in survival and relapses in various subpopulationsof WG patients.

A 2-phase screening process for patients with Wegener's granulomatosis: a pilot study.

A 2-phase screening process for patients with persistent upper respiratory tract manifestations for the detection of Wegener's granulomatosis (WG) was tested in 28 patients in this pilot study. One patient with WG was identified. A larger study is warranted.

Renal biopsy and antineutrophil antibodies in the diagnosis and assessment of Wegener's granuloma.

Seventeen patients with Wegener's granuloma (WG), all of whom had renal biopsies taken at presentation, are reviewed. In conjunction with nasal or transbronchial biopsies renal biopsies aided diagnosis and also yielded prognostic information. The detection of antineutrophil cytoplasm antibodies in the serum of patients with WG is a useful supplementary diagnostic tool.