PRESENTED BY
MARIA  WEINER

Presentation Summary

Writen by Jasna Trbojevic-Stankovic
Reviewed by Maria Weiner

Clinical characteristics in elderly patients

There is an increase in incidence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in individuals over the age of 75 [1]. Renal biopsy results of the very elderly showed that pauci-immune glomerulonephritis (GN) was found in one-third of the patients with acute kidney injury [2]. Even though the elderly are increasingly diagnosed with ANCA-associated glomerulonephritis (AAGN) [3], they are frequently under-represented in randomized clinical trials.

The older population with AAV are more susceptible to lung and kidney involvement with impaired renal function [4] and are more often diagnosed with microscopic polyangiitis (MPA) and myeloperoxidase (MPO)-ANCA positivity. In line with this, they have lower incidence of ear, nose and throat symptoms [5]. Furthermore, the majority of studies found similar percentages of normal glomeruli, glomerular crescents or glomerular sclerosis in biopsy specimens as well as similar relapse and remission rates between older ( 65 years) and younger (<65 years) AAV patients [6,7, slide 9 [8]]. Proteinase 3-ANCA positivity is associated with higher relapse risk in older patients, while renal impairment and dialysis dependency are associated with lower risk [9]. Mortality in elderly patients

As advancing age is associated with a significantly increased risk of mortality [10,11] and a greater prevalence of comorbidities [12,13], both diagnosis and treatment can be complicated. As compared to the general population matched for age and calendar year, the mortality is five times higher within the first year after diagnosis in patients aged 75-84 years (slide 18 [8]), who most commonly die of infections [9]. Age and elevated serum creatinine are significant predictors of mortality and renal survival in the oldest patients, but a survival benefit has been demonstrated in patients treated with cyclophosphamide (CYC) and rituximab [12, 14]. The best renal survival in the elderly patients is found in those presenting with ANCA-GN focal histological type [15]. Immunosuppressive therapy may reduce the risk of end stage kidney disease and prolong the survival of the very elderly AAV patients [16,13]. Renal recovery thus seems like a realistic expectation even among older patients with AAV who require HD initially [16].

Adverse events of AAV treatment
Adverse events related to AAV pharmacotherapy can be measured using a combined burden of events score which, if greater than 7, is associated with mortality [17]. A study showed that each 10 years above the age of 50 was associated with a doubled risk of leucopoenia [10] despite receiving lower cumulative doses of CYC. However, other trials failed to demonstrate a difference in the development of adverse events between older and younger patients [11,14]. Moreover, another study revealed that an induction regimen limiting corticosteroid exposure with fixed low‐dose intravenous CYC pulses reduced serious adverse events in patients aged 65 years or older in comparison to conventional therapy, and did not affect the remission rate [18]. Retrospective review of rituximab treatment demonstrated high remission rates and low mortality in patients older than 60, although further studies are needed to evaluate its efficacy and safety [19].

References

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2. Moutzouris DA, Herlitz L, Appel GB, et al. Renal biopsy in the very elderly. Clin J Am Soc Nephrol.2009;4(6):1073-82. DOI: 10.2215/CJN.00990209

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8. Weiner M. ANCA-associated vasculitis in the elderly and very elderly. 56th ERA-EDTA Congress; June 14, 2019; Budapest, Hungary. View the Webcast

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12. Weiner M, Goh SM, Mohammad AJ, et al. Outcome and treatment of elderly patients with ANCA-associated vasculitis. Clin J Am Soc Nephrol. 2015;Jul 7:10(7):1128-35. DOI: 10.2215/CJN.00480115

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15. Bjørneklett R, Bostad L, Fismen AS. Prognosis and Histological Classification in Elderly Patients with ANCA-Glomerulonephritis: A Registry-Based Cohort Study. Biomed Res Int. 2018;May 31:2018:7581567. DOI: 10.1155/2018/7581567

16. Manno RL,Seo P, Geetha D. Older patients with ANCA-associated vasculitis and dialysis dependent renal failure: a retrospective study. BMC Nephrol. 2015; Jun 25:16:88. DOI: 10.1186/s12882-015-0082-9

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18. Pagnoux C, Quéméneur T, Ninet J, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis Rheumatol. 2015;Apr:67(4):1117-27. DOI: 10.1002/art.39011

19. Timlin H, Lee SM, Manno RL, Seo P, Geetha D. Rituximab for remission induction in elderly patients with ANCA-associated vasculitis. Semin Arthritis Rheum. 2015; Aug: 45(1): 67–69. DOI: 10.1016/j.semarthrit.2015.02.005

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