Background Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain. Objective To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease. Methods Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models. Results The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age- and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate <15 ml/min, advancing age, higher Birmingham Vasculitis Activity Score, lower haemoglobin and higher white cell count were significant negative prognostic factors for patient survival. Conclusion Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.

Introduction The previously reported randomised controlled trial of a consensus regimen of pulse cyclophosphamide suggested that it was as effective as a daily oral (DO) cyclophosphamide for remission induction of antineutrophil cytoplasm autoantibodies-associated systemic vasculitis when both were combined with the same glucocorticoid protocol (CYCLOPS study (Randomised trial of daily oral versus pulse Cyclophosphamide as therapy for ANCA-associated Systemic Vasculitis published de groot K, harper L et al Ann Int Med 2009)). The study had limited power to detect a difference in relapse. This study describes the long-term outcomes of patients in the CYCLOPS study. Methods Long-term outcomes were ascertained retrospectively from 148 patients previously recruited to the CYCLOPS Trial. Data on survival, relapse, immunosuppressive treatment, cancer incidence, bone fractures, thromboembolic disease and cardiovascular morbidity were collected from physician records retrospectively. All patients were analysed according to the group to which they were randomised. Results Median duration of follow-up was 4.3 years (IQR, 2.95–5.44 years). There was no difference in survival between the two limbs (p=0.92). Fifteen (20.8%) DO and 30 (39.5%) pulse patients had at least one relapse. The risk of relapse was significantly lower in the DO limb than the pulse limb (HR=0.50, 95% CI 0.26 to 0.93; p=0.029). Despite the increased risk of relapse in pulse-treated patients, there was no difference in renal function at study end (p=0.82). There were no differences in adverse events between the treatment limbs. Discussion Pulse cyclophosphamide is associated with a higher relapse risk than DO cyclophosphamide. However, this is not associated with increased mortality or long-term morbidity. Although the study was retrospective, data was returned in 90% of patients from the original trial.

Objective: To determine the association between characteristics at diagnosis and the time to first relapse in a large cohort of patients with antineutrophil cytoplasmic antibody–associated vasculitis (AAV).Methods: We studied long‐term followup data from 4 clinical trials that included newly diagnosed patients with a broad spectrum of AAV severity and manifestations. Patient and disease characteristics at baseline were used in competing risk regression models with relapse as the event of interest and death as the competing event.Results: We assessed 535 patients with 1,804 patient‐years at risk of relapse. At diagnosis, the median age was 60.7 years (interquartile range [IQR] 48.8–69.1 years), 284 patients (53%) had granulomatosis with polyangiitis (Wegener's), and the median creatinine level was 203 μmoles/liter (IQR 97–498). A total of 201 patients (38%) experienced a relapse and 133 patients (25%) died, 96 of whom had not had prior relapse. Anti–proteinase 3 antibodies (subhazard ratio [sHR] 1.62 [95% confidence interval 1.39–1.89]) and cardiovascular involvement (sHR 1.59 [95% confidence interval 1.07–2.37]) were independently associated with a higher risk of relapse. Compared with patients with a creatinine level ≤100 μmoles/liter, patients with higher creatinine levels had a lower risk of relapse (sHR 0.81 [95% confidence interval 0.77–0.85] for a creatinine level of 101–200 μmoles/liter; sHR 0.39 [95% confidence interval 0.22–0.69] for a creatinine level >200 μmoles/liter).Conclusion: Relapse of disease is common for patients with AAV. A creatinine level >200 μmoles/liter at the time of diagnosis is strongly associated with a reduced risk of relapse and may help guide monitoring and treatment of patients with AAV.

Objectives To describe short-term (up to 12 months) and long-term (up to 7 years) damage in patients with newly diagnosed antineutrophil-cytoplasm antibody-associated vasculitis (AAV). Methods Data were combined from six European Vasculitis Study group trials (n=735). Long-term follow-up (LTFU) data available for patients from four trials (n=535). Damage accrued was quantified by the Vasculitis Damage Index (VDI). Sixteen damage items were defined a priori as being potentially treatment-related. Results VDI data were available for 629 of 735 patients (85.6%) at baseline, at which time 217/629 (34.5%) had ≥1 item of damage and 32 (5.1%) ≥5 items, reflecting disease manifestations prior to diagnosis and trial enrolment. LTFU data were available for 467/535 (87.3%) at a mean of 7.3 years postdiagnosis. 302/535 patients (56.4%) had VDI data at LTFU, with 104/302 (34.4%) having ≥5 items and only 24 (7.9%) no items of damage. At 6 months and LTFU, the most frequent items were proteinuria, impaired glomerular filtration rate, hypertension, nasal crusting, hearing loss and peripheral neuropathy. The frequency of damage, including potentially treatment-related damage, rose over time (p<0.01). At LTFU, the most commonly reported items of treatment-related damage were hypertension (41.5%; 95% CI 35.6 to 47.4%), osteoporosis (14.1%; 9.9 to 18.2%), malignancy (12.6%; 8.6 to 16.6%), and diabetes (10.4%; 6.7 to 14.0%). Conclusions In AAV, renal, otolaryngological and treatment-related (cardiovascular, disease, diabetes, osteoporosis and malignancy) damage increases over time, with around one-third of patients having ≥5 items of damage at a mean of 7 years postdiagnosis.

The aim of the present study was to model apparent serum half-lives of polybrominated diphenyl ethers (PBDEs) with 7–10 bromine substituents. Workers with occupational exposure to PBDEs have elevated serum levels of PBDEs, but these substances are also found in the general population and are ubiquitous environmental contaminants. The calculations were based on exposure assessments of rubber workers (manufactured flame-retarded rubber compound) and electronics dismantlers who donated blood during a period with no work-related exposures to PBDEs, and referents without any known occupational exposure (clerks, cleaners, and abattoir workers). The workers had previously been found to have elevated levels of high- and medium-brominated diphenyl ethers compared with the referent populations. We performed nonlinear mixed-effects modeling of kinetics, using data from previous and present chemical analyses. The calculated apparent half-life for decabromodiphenyl ether (BDE-209) was 15 days (95% confidence interval, 11–18 days). The three nona-BDEs and four octa-BDE congeners were found to have half-lives of 18–39 and 37–91 days, respectively. BDE-209 has a short half-life in human blood. Because BDE-209 is commonly present in humans in general, the results of this study imply that humans must be more or less continuously exposed to BDE-209 to sustain the serum concentrations observed. BDE-209 is more readily transformed and/or eliminated than are lower brominated diphenyl ether congeners, and human health risk must be assessed accordingly.