ANCA-associated vasculitis (AAV) diagnoses increased and overall and renal survival improved over a period of 23 years, a real-world study in the U.K regions of Lancashire and South Cumbria reports.
These improved outcomes may be due to earlier diagnosis and better management of AAV and chronic kidney disease in recent decades, the findings suggest.
The study, “Comparing outcomes of biopsy-proven anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis patients treated with cyclophosphamide in the 20th and 21st centuries: a 23-year study,” appeared in the Clinical Kidney Journal.
Treatment of AAV with immunosuppressants has contributed to significantly longer patient survival. Reduced use of cyclophosphamide and prednisolone could help explain improved outcomes in infection-related vasculitis. Changes in the management of chronic kidney disease, as well as tight blood pressure targets, could lead to further benefits, the investigators said.
The team from the Royal Preston Hospital and the University of Central Lancashire conducted a retrospective analysis of AAV’s incidence and outcomes from Jan. 1, 1988 to Dec. 31, 2010 (followed until Jan. 1, 2014), at their tertiary care center serving the populations of Lancashire and South Cumbria.
A total of 314 patients with AAV were identified, 41 of whom were excluded from subsequent analyses due to insufficient data. From the remaining 273 patients (median age of 62 years, average age at diagnosis of 59 years), 101 were diagnosed between 1988 and 1999 (group 1, 62 men) and 172 between 2000 and 2010 (group 2, 96 men).
All patients were treated with intravenous (into-the-vein) pulse cyclophosphamide and tapering doses of glucocorticoids. Those with severe AAV, defined as a creatinine concentration — a kidney function marker — of 500 micromoles (μmol) per liter or higher and/or pulmonary hemorrhage, were treated with plasma exchange.
Results revealed an increased incidence of biopsy-proven AAV with renal involvement, from 2.2 per 1 million in 1988 to 10.3 per 1 million in 2010. This incidence was particularly high in patients ages 75–79. According to the team, this may be due to underdiagnosis of AAV until the widespread use of assays to detect ANCA-related antibodies in the late 1990s.
Median follow-up of all patients was 57 months, and 81 months among patients still alive by the end of the study.
Comparing the two groups, group 1 showed a higher proportion of patients with a creatinine concentration higher than 500 μmol/L at diagnosis (56.4% vs. 30.2%). This higher value of creatinine in group 1 persisted when only analyzing people with known AAV-associated antibody status (614 μmol/L vs. 330 μmol/L).
“We postulate that this observation suggests earlier diagnosis in the later cohort of patients,” the scientists wrote.
Group 1 also showed a lower proportion of patients 75 years and older than group 2. However, this difference was not sustained when only looking at patients with known antibody status. Only 59 patients in group 1 had available AAV antibody results, which the investigators attributed to the rare use of antibody screening in the early 1990s.
The analysis then showed that one-year patient survival was 78.8%, five-year survival was 49.5%, and 10-year survival was 19.1%. Median survival was 60 months. Median survival was lower in group 1 (59 months) than in group 2 (125 months), which the scientists attributed to potential differences in treatment.
Patients diagnosed at 75 years or older and with creatinine not lower than 500 μmol/L had worse survival rates. In a subsequent analysis, patients in group 1 and those older than 75 years had a worse prognosis.
Renal survival at 12 months was 54.2%, which decreased to 33.7% at five years and to 12.5% at 10 years. Group 1 had a median renal survival of nine months, compared with 43 months in group 2. Of all patients who required initial renal replacement therapy, 17% experienced renal recovery, a rate that the researchers considered poor.
Males and those with a concentration of creatinine of 500 μmol/L or higher were associated with worse renal survival. This creatinine threshold was the only factor that remained significantly associated with poorer renal survival in a subsequent, or adjusted, analysis.
“This study shows that AAV is being diagnosed at an earlier stage, resulting in improved outcomes,” the scientists wrote. “We hope that this study will provide further insight to clinicians treating these complex vasculitis patients in their day-to-day practice.”