Disease and treatment-related morbidity in young and elderly patients with granulomatosis with polyangiitis and microscopic polyangiitis

https://doi.org/10.1016/j.semarthrit.2020.02.008Get rights and content

Abstract

Objective

Aging may be a risk factor for morbidity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We compared the rate and better characterized the type of disease- and treatment-related complications affecting young and elderly patients with AAV.

Methods

All new cases of granulomatosis with polyangiitis or microscopic polyangiitis diagnosed in three referral centers between 2000–2016 were included. Patients were stratified by age into young or elderly (< or ≥65 years old, respectively). Data were collected from diagnosis until end of follow-up, with scheduled annual visits or additional visits in case of relapse or complication requiring hospitalization.

Results

Of 141 patients included, 42 were elderly and 99 were young at the time of AAV diagnosis. Median follow-up was 58.0 [25–75% IQR, 31.0–60.0] months in young and 48.0 [23.25–60.0] months in elderly patients (p>0.05).

Overall, the elderly group was associated to higher damage accrual assessed by Vasculitis Damage Index during follow-up (β=0.28, p<0.05).

Sixty-three (44.7%) patients had acute kidney injury due to AAV-glomerulonephritis at diagnosis. In contrast to elderly, young patients showed significant improvement in renal function over time, particularly in the first 6 months while on induction treatment (ΔeGFR, median [25–75%IQR], 5.3 [0.4–14] versus 22.8 [5.9–52.1] ml/min/1.73m2, p=0.008), without significant changes after ANCA type stratification.

Despite similar immunosuppressive therapy approaches and relapse rates, elderly patients had a higher rate of severe infections compared to younger patients (HR 2.1, 95% CIs: 1.1–4.4, p=0.043).

Conclusions

Elderly patients with AAV had higher susceptibility to disease- and treatment-related morbidity than younger patients, particularly to renal and infective morbidity.

Introduction

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are primary systemic inflammatory disorders characterized by necrotizing vasculitis of the small-sized vessels, leading to organ- and/or life-threatening manifestations [1,2]. Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are classified as AAV because the majority of the patients with generalized disease have circulating ANCA directed towards myeloperoxidase (MPO)-ANCA or proteinase 3 (PR3)-ANCA [3].

AAV predominantly affects adults 50 years or older, and the incidence of this group of conditions increases with age, with the peak between 55–75 years [3], [4], [5], [6]. It has been shown that clinical presentation of AAV in older patients is more common in MPA rather than in GPA, and that anti-MPO-ANCA rather anti-PR3-ANCA positivity is more prevalent [7], [8], [9]. Older patients often have more prominent renal disease [9], more severe pulmonary involvement [7], are less likely to respond to treatment [7] and carry a higher risk of mortality and end-stage renal disease (ESRD) [10,11]. Furthermore, elderly patients are more prone to adverse effects of immunosuppressive therapy and serious adverse effects [7,12,13]. Although these studies contributed to identify single complications or features more often associated to older age [7,[9], [10], [11], [12]], the disease- and treatment-related complication burden in elderly versus young patients has not been systematically evaluated.

As a result of the interplay between age, vasculitis and its treatment, we may observe different mortality, morbidity and relapse rates among these patients during the disease follow-up. In this article, we focused on disease- and treatment-related morbidity in a multicentric cohort of patients presenting with GPA or MPA, comparing the rate and characterizing the type of complications affecting elderly (≥65 years old) and young (<65 years old) patients.

Section snippets

Patients, case ascertainment and data collection

Between January 1, 2000 and January 1, 2016, consecutive adult (age ≥ 18 years) patients presenting at three regional referral centers in Northern Italy (Hospital of Trento, Padova and Pavia) were included. All patients were retrospectively recruited from vasculitis databases in each center. All MPA and GPA clinical diagnoses were revised by physicians expert on vasculitis, according to the 2007 European Medical Agency (EMA) algorithm [14].

All the patients were included in the cohort at the

Demographic, clinical and laboratory findings at diagnosis

Of 176 patients collected, 141 were followed for at least one year after diagnosis and had sufficient baseline and follow-up data to allow the morbidity analyses. Patients excluded (n = 35) had similar clinical and laboratory features than patients included (Supplementary Table 1). We excluded all those patients followed for less than one year after diagnosis (n = 7; 4 of them died, Supplementary Table 2) and those that did not have sufficient baseline and/or follow-up data to allow the

Discussion

The current study shows that elderly patients (≥65 years old at the time of AAV diagnosis) have a higher burden of morbidity related to vasculitis or its treatment compared to younger patients during a prolonged follow-up, up to 5 years. Older age is associated with a higher damage accrual assessed by VDI during follow-up, while the most common complications’ rates of the elderly population (i.e. malignancy, arterial hypertension, heart failure, ischemic cardiovascular complications, and

Declaration of Competing Interest

None.

References (43)

  • M. Chen et al.

    Antineutrophil cytoplasmic autoantibody-associated vasculitis in older patients

    Medicine (Baltimore)

    (2008)
  • L. Harper et al.

    ANCA-associated renal vasculitis at the end of the twentieth century–a disease of older patients

    Rheumatology (Oxford)

    (2005)
  • M. Weiner et al.

    Outcome and treatment of elderly patients with ANCA-associated vasculitis

    Clin J Am Soc Nephrol: CJASN

    (2015)
  • D.D. Hoganson et al.

    ANCA vasculitis in the elderly

    J Clin Rheumatol: Pract Rep Rheumat Musculoskelet Dis

    (2008)
  • C. Pagnoux 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 (Hoboken, NJ)

    (2015)
  • Z.S. Wallace et al.

    Nationwide trends in hospitalizations and in-hospital mortality of granulomatosis with polyangiitis

    Arthritis Care Res (Hoboken)

    (2016)
  • R. Watts et al.

    Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies

    Ann Rheum Dis

    (2007)
  • A.S. Levey et al.

    A new equation to estimate glomerular filtration rate

    Ann Intern Med

    (2009)
  • C. Mukhtyar et al.

    Modification and validation of the Birmingham Vasculitis activity score (version 3)

    Ann Rheum Dis

    (2009)
  • A.R. Exley et al.

    Development and initial validation of the vasculitis damage index for the standardized clinical assessment of damage in the systemic vasculitides

    Arthritis Rheum

    (1997)
  • B. Hellmich et al.

    EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis

    Ann Rheum Dis

    (2007)

    • Cited by (14)

    • Current clinical and therapeutic approach to tumour-like mass lesions in granulomatosis with polyangiitis

      2022, Autoimmunity Reviews
      Citation Excerpt :

      In the last decade, new treatment regimens have modified the clinical course of AVV, from an acute form, characterized by high mortality rate, to a chronic condition [109,110]. Many patients experience persistent disease activity, long-term exposure to toxic therapies, and irreversible damage leading to a poor quality of life [111–113]. Unfortunately, mass lesions remain almost unchanged in a high proportion of patients despite induction therapy with high dose glucocorticoids and immunosuppressive drugs.

    • Granulomatosis with polyangiitis and cardio vascular co-morbidity in Denmark. A registry-based study of 21 years of follow-up

      2021, Journal of Translational Autoimmunity
      Citation Excerpt :

      Pearce et al. reported IR at 14/1,000,000 in United Kingdom [28]. The peak age of incident cases was above the age of 50 in accordance with recent studies demonstrating the importance of paying special attention to elderly with GPA as this subgroup apparently has increased susceptibility to disease and treatment related morbidity [29]. Our prevalence figures were, although higher than many of the previous reports, still in accordance with the GPA PP at 218/1,000,000 in Minnesota reported by Berti et al. [30].

    • Treatment response and complications of older patients with ANCA(antineutrophil cytoplasmatic antibody)-associated vasculitis

      2023, Zeitschrift fur Gerontologie und Geriatrie

    • Outcomes of remission induction therapy for ANCA-associated vasculitis in the elderly

      2023, Clinical Rheumatology

    • Pulmonary hypertension in ANCA-associated vasculitis: A retrospective analysis

      2023, Sarcoidosis Vasculitis and Diffuse Lung Diseases

    • Diagnosing and treating ANCA-Associated vasculitis: An updated review for clinical practice

      2023, Rheumatology (United Kingdom)
    View all citing articles on Scopus

    Financial disclosures: The authors declare no financial support or potential conflict of interest in this study.

    View full text
    © 2020 Elsevier Inc. All rights reserved.