Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study

Shifa H Sarica; Neeraj Dhaun; Jan Sznajd; John Harvie; John McLaren; Lucy McGeoch; Vinod Kumar; Nicole Amft; Lars Erwig; Angharad Marks; Corri Black; Neil Basu

doi:10.1093/rheumatology/keaa070

Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study

Shifa H Sarica, Neeraj Dhaun, Jan Sznajd, John Harvie, John McLaren, Lucy McGeoch, Vinod Kumar, Nicole Amft, Lars Erwig, Angharad Marks, Corri Black, Neil Basu^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

OBJECTIVES: Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally quantify, characterize and contextualize infection risk in AAV.

METHODS: We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries.

RESULTS: A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9-5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio [IRR] 7.3 [95% confidence interval (CI) 5.6, 9.6]; severe infections: IRR 4.4 [95% CI 3.3, 5.7]; antibiotic prescriptions: IRR 2.2 [95% CI 1.9, 2.6]}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes [IRR 12.5 (95% CI 3.7, 42.6)] and Candida [IRR 11.4 (95% CI 2.4, 55.4)].

CONCLUSION: AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.

Original language	English
Pages (from-to)	3014-3022
Number of pages	9
Journal	Rheumatology
Volume	59
Issue number	10
Early online date	11 Mar 2020
DOIs	https://doi.org/10.1093/rheumatology/keaa070
Publication status	Published - Oct 2020

Bibliographical note

We wish to thank Information Division Services Scotland for assisting with data linkage and data access in the National Safe Haven. Information presented in this article was previously presented as a poster at the American College of Rheumatology Annual Conference 2018, Chicago, IL, USA. The study was conceived by S.H.S., A.M., C.B. and N.B. All authors contributed to the study design and data collection. Data analysis and interpretation and drafting of the manuscript were conducted by all authors. C.B. and N.B. were joint senior authors. All authors critically reviewed the manuscript and approved the final version.

Funding: S.H.S. and the study were funded by the Aberdeen Development Trust and the Farr Institute of Health Informatics Research. The Farr Institute is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates) and the Wellcome Trust (Scotland MR/K007017/1).

Disclosure statement: L.E. is a GlaxoSmithKline employee. The other authors have declared no conflicts of interest.

Keywords

eosinophilic granulomatosis with polyangiitis
microscopic polyangitis
Infections
Longitudal study
granulomatosis with polyangiitis
eosinophilic granulomatosis with polyangiitis
microscopic polyangiitis
infections
longitudinal study

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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(c) The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, andreproduction in any medium, provided the original work is properly cited
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Sarica, S. H., Dhaun, N., Sznajd, J., Harvie, J., McLaren, J., McGeoch, L., Kumar, V., Amft, N., Erwig, L., Marks, A., Black, C., & Basu, N. (2020). Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study. Rheumatology, 59(10), 3014-3022. https://doi.org/10.1093/rheumatology/keaa070

Sarica, SH, Dhaun, N, Sznajd, J, Harvie, J, McLaren, J, McGeoch, L, Kumar, V, Amft, N, Erwig, L, Marks, A, Black, C & Basu, N 2020, 'Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study', Rheumatology, vol. 59, no. 10, pp. 3014-3022. https://doi.org/10.1093/rheumatology/keaa070

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title = "Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study",

abstract = "OBJECTIVES: Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally quantify, characterize and contextualize infection risk in AAV.METHODS: We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries.RESULTS: A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9-5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio [IRR] 7.3 [95% confidence interval (CI) 5.6, 9.6]; severe infections: IRR 4.4 [95% CI 3.3, 5.7]; antibiotic prescriptions: IRR 2.2 [95% CI 1.9, 2.6]}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes [IRR 12.5 (95% CI 3.7, 42.6)] and Candida [IRR 11.4 (95% CI 2.4, 55.4)].CONCLUSION: AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.",

keywords = "eosinophilic granulomatosis with polyangiitis, microscopic polyangitis, Infections, Longitudal study, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis, infections, longitudinal study",

author = "Sarica, {Shifa H} and Neeraj Dhaun and Jan Sznajd and John Harvie and John McLaren and Lucy McGeoch and Vinod Kumar and Nicole Amft and Lars Erwig and Angharad Marks and Corri Black and Neil Basu",

note = "We wish to thank Information Division Services Scotland for assisting with data linkage and data access in the National Safe Haven. Information presented in this article was previously presented as a poster at the American College of Rheumatology Annual Conference 2018, Chicago, IL, USA. The study was conceived by S.H.S., A.M., C.B. and N.B. All authors contributed to the study design and data collection. Data analysis and interpretation and drafting of the manuscript were conducted by all authors. C.B. and N.B. were joint senior authors. All authors critically reviewed the manuscript and approved the final version. Funding: S.H.S. and the study were funded by the Aberdeen Development Trust and the Farr Institute of Health Informatics Research. The Farr Institute is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates) and the Wellcome Trust (Scotland MR/K007017/1). Disclosure statement: L.E. is a GlaxoSmithKline employee. The other authors have declared no conflicts of interest. ",

year = "2020",

month = oct,

doi = "10.1093/rheumatology/keaa070",

language = "English",

volume = "59",

pages = "3014--3022",

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T1 - Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis

T2 - results from a longitudinal, matched-cohort data linkage study

AU - Sarica, Shifa H

AU - Dhaun, Neeraj

AU - Sznajd, Jan

AU - Harvie, John

AU - McLaren, John

AU - McGeoch, Lucy

AU - Kumar, Vinod

AU - Amft, Nicole

AU - Erwig, Lars

AU - Marks, Angharad

AU - Black, Corri

AU - Basu, Neil

N1 - We wish to thank Information Division Services Scotland for assisting with data linkage and data access in the National Safe Haven. Information presented in this article was previously presented as a poster at the American College of Rheumatology Annual Conference 2018, Chicago, IL, USA. The study was conceived by S.H.S., A.M., C.B. and N.B. All authors contributed to the study design and data collection. Data analysis and interpretation and drafting of the manuscript were conducted by all authors. C.B. and N.B. were joint senior authors. All authors critically reviewed the manuscript and approved the final version. Funding: S.H.S. and the study were funded by the Aberdeen Development Trust and the Farr Institute of Health Informatics Research. The Farr Institute is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates) and the Wellcome Trust (Scotland MR/K007017/1). Disclosure statement: L.E. is a GlaxoSmithKline employee. The other authors have declared no conflicts of interest.

PY - 2020/10

Y1 - 2020/10

N2 - OBJECTIVES: Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally quantify, characterize and contextualize infection risk in AAV.METHODS: We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries.RESULTS: A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9-5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio [IRR] 7.3 [95% confidence interval (CI) 5.6, 9.6]; severe infections: IRR 4.4 [95% CI 3.3, 5.7]; antibiotic prescriptions: IRR 2.2 [95% CI 1.9, 2.6]}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes [IRR 12.5 (95% CI 3.7, 42.6)] and Candida [IRR 11.4 (95% CI 2.4, 55.4)].CONCLUSION: AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.

AB - OBJECTIVES: Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally quantify, characterize and contextualize infection risk in AAV.METHODS: We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries.RESULTS: A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9-5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio [IRR] 7.3 [95% confidence interval (CI) 5.6, 9.6]; severe infections: IRR 4.4 [95% CI 3.3, 5.7]; antibiotic prescriptions: IRR 2.2 [95% CI 1.9, 2.6]}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes [IRR 12.5 (95% CI 3.7, 42.6)] and Candida [IRR 11.4 (95% CI 2.4, 55.4)].CONCLUSION: AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.

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KW - Longitudal study

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KW - eosinophilic granulomatosis with polyangiitis

KW - microscopic polyangiitis

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KW - longitudinal study

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Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study

Abstract

Bibliographical note

Keywords

UN SDGs

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