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Research ArticleAccepted Article

The Longitudinal Course of Fatigue in Anca Associated Vasculitis

Lucy O’Malley, Katie Druce, Dimitrios Chanouzas, Matthew Morgan, Rachel Jones, David Jayne, Neil Basu and Lorraine Harper
The Journal of Rheumatology July 2019, jrheum.190113; DOI: https://doi.org/10.3899/jrheum.190113
Lucy O’Malley
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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Katie Druce
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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Dimitrios Chanouzas
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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Matthew Morgan
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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Rachel Jones
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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David Jayne
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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Neil Basu
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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Lorraine Harper
From the Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT; Arthritis Research UK Centre for Epidemiology, University of Manchester, Manchester, United Kingdom; Department of Medicine, University of Cambridge; Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow. This work was supported by Vifor Pharma (previously Aspreva Pharmaceuticals) who provided a research grant to cover the trial and MMF costs for MYCYC and F. Hoffmann–La Roche who provided the rituximab and a research grant that contributed to trial costs for RITUXIVAS. The funding sources had no role in the design and conduct of the study, collection, management, analysis and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The study was conducted within the Birmingham National Institute for Health Research (NIHR) / Wellcome Trust (WT) Clinical Research Facility (CRF) (Birmingham, United Kingdom). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Disclosures – LH, DJ, RB. have received research grants and speakers fees from J Hofman La Roche. LH, RB, DJ, MM have been involved in studies in which rituximab was given free of charge by Roche and Mycophenolate was given free of charge by Vifor (previously Aspreva). Address for correspondence: Prof Lorraine Harper Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT Email: L.Harper@bham.ac.uk
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Abstract

Objective Fatigue is common and burdensome in ANCA-associated vasculitis (AAV). This study aimed to understand how fatigue changes over time following treatment initiation and determine whether individuals with the poorest prognosis can be robustly identified.

Methods 149 patients with AAV and new onset disease recruited to two clinical trials (RITUXIVAS and MYCYC) were followed for 18 months. Fatigue was measured at baseline and 6 monthly intervals using the vitality domain of the SF-36 quality of life questionnaire and compared to a cohort of 470 controls. Group-based trajectory modelling (GBTM) determined trajectories of the symptom between which baseline characteristics and on-going fatigue scores were compared.

Results Fatigue levels at diagnosis were worse in patients than controls (median 30 IQR 10, 48 vs 70 IQR 55, 80; p<0.001), with 46% of patients reporting severe fatigue. Fatigue improved after 6 months treatment but remained worse than controls (p<0.001). GBTM revealed varied trajectories of fatigue: low fatigue stable (n=23), moderate baseline fatigue improver (n=29), high baseline fatigue improver (n=61) and stable baseline high fatigue (n=37). Participants who followed stable high fatigue trajectories had lower vasculitis activity compared to improvers but no other demographic or clinical variables differed.

Conclusion This study longitudinally measured fatigue levels in patients with AAV. Although, most patients improve following treatment, an important subgroup of patients report persistent high levels of fatigue that does not change. Few clinical or laboratory markers distinguished these patients, suggesting alternative interventions specific for fatigue are required.

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Vol. 49, Issue 7
1 Jul 2022
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Accepted manuscript
The Longitudinal Course of Fatigue in Anca Associated Vasculitis
Lucy O’Malley, Katie Druce, Dimitrios Chanouzas, Matthew Morgan, Rachel Jones, David Jayne, Neil Basu, Lorraine Harper
The Journal of Rheumatology Jul 2019, jrheum.190113; DOI: 10.3899/jrheum.190113

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Accepted manuscript
The Longitudinal Course of Fatigue in Anca Associated Vasculitis
Lucy O’Malley, Katie Druce, Dimitrios Chanouzas, Matthew Morgan, Rachel Jones, David Jayne, Neil Basu, Lorraine Harper
The Journal of Rheumatology Jul 2019, jrheum.190113; DOI: 10.3899/jrheum.190113
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