Comorbidity and response to TNF inhibitors in axial spondyloarthritis: longitudinal analysis of the BSRBR-AS

Sizheng Steven Zhao; Gareth Jones; Gary Macfarlane; David M Hughes; Robert J Moots; Nicola J Goodson

doi:10.1093/rheumatology/keaa900

Comorbidity and response to TNF inhibitors in axial spondyloarthritis: longitudinal analysis of the BSRBR-AS

Sizheng Steven Zhao
, Gareth Jones
, Gary Macfarlane
, David M Hughes
, Robert J Moots
, Nicola J Goodson^* (Corresponding Author)

^*Corresponding author for this work

University of Liverpool
Liverpool University Hospitals NHS Foundation Trust
Edge Hill University

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

16 Citations (Scopus)

7 Downloads (Pure)

Abstract

Objective. Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but theirassociation with response to TNF inhibitors (TNFi) is unclear. We examined associations betweencomorbidity history at TNFi initiation and: 1) change in disease indices over time; 2) binary responsedefinitions; 3) time-to-treatment-discontinuation.Methods. We studied participants starting their first TNFi from a national axSpA register.Comorbidity categories were created from 14 physician-diagnosed conditions and compared against:change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unitreduction) and BASDAI<4 at 6 months using logistic models; and time-to-treatment-discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education.Results. 994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 (OR 0.81; 95%CI 0.45, 1.45) and BASDAI<4 (OR0.57; 95%CI 0.32, 1.04). Treatment discontinuation was increased in those with 2 comorbidities (HR1.32; 95%CI 0.88, 2.00) and ≥3 comorbidities (HR 2.18; 95%CI 1.20, 3.93) compared to none.Conclusions. Participants with multiple comorbidities had poorer treatment outcomes, particularlyincreased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidityburden.

Original language	English
Article number	keaa900
Pages (from-to)	4158–4165
Number of pages	8
Journal	Rheumatology
Volume	60
Issue number	9
Early online date	28 Dec 2020
DOIs	https://doi.org/10.1093/rheumatology/keaa900
Publication status	Published - 30 Sept 2021

Bibliographical note

Acknowledgements:
Funding: The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it.

Disclosures: The authors declare no conflicts of interest.

Contribution: SSZ analysed the data and wrote the manuscript, with significant input from all coauthors. GJM and GTJ are Chief Investigator and Deputy Chief Investigator respectively on BSRBR-AS and designed the study and oversaw its conduct. In the current project they discussed results and provided input into drafts of the manuscript.

Data availability: Data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis are available to external investigators, on reasonable request. For information on how to access data, see: http://www.rheumatology.org.uk.

We are grateful to the staff of the BSRBR-AS register and to the recruiting staff at the clinical centres, details of which are available at: www.abdn.ac.uk/bsrbr-as

Keywords

axial spondyloarthritis
comorbidities
treatment response
TNF inhibitors
ankylosing spondylitis

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© 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 Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]
Final published version, 519 KBLicence: CC BY-NC

Cite this

@article{4bfdcfe4ac2b48889237f7f7ef644f71,

title = "Comorbidity and response to TNF inhibitors in axial spondyloarthritis: longitudinal analysis of the BSRBR-AS ",

abstract = "Objective. Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but theirassociation with response to TNF inhibitors (TNFi) is unclear. We examined associations betweencomorbidity history at TNFi initiation and: 1) change in disease indices over time; 2) binary responsedefinitions; 3) time-to-treatment-discontinuation.Methods. We studied participants starting their first TNFi from a national axSpA register.Comorbidity categories were created from 14 physician-diagnosed conditions and compared against:change in disease indices over time using linear mixed effects models; BASDAI50/2 (50\% or 2-unitreduction) and BASDAI<4 at 6 months using logistic models; and time-to-treatment-discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education.Results. 994 were eligible for analysis (68\% male, mean age 45 years); 21\% had one comorbidity and 11\% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 (OR 0.81; 95\%CI 0.45, 1.45) and BASDAI<4 (OR0.57; 95\%CI 0.32, 1.04). Treatment discontinuation was increased in those with 2 comorbidities (HR1.32; 95\%CI 0.88, 2.00) and ≥3 comorbidities (HR 2.18; 95\%CI 1.20, 3.93) compared to none.Conclusions. Participants with multiple comorbidities had poorer treatment outcomes, particularlyincreased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidityburden.",

keywords = "axial spondyloarthritis, comorbidities, treatment response, TNF inhibitors, ankylosing spondylitis",

author = "Zhao, \{Sizheng Steven\} and Gareth Jones and Gary Macfarlane and Hughes, \{David M\} and Moots, \{Robert J\} and Goodson, \{Nicola J\}",

note = "Acknowledgements: Funding: The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it. Disclosures: The authors declare no conflicts of interest. Contribution: SSZ analysed the data and wrote the manuscript, with significant input from all coauthors. GJM and GTJ are Chief Investigator and Deputy Chief Investigator respectively on BSRBR-AS and designed the study and oversaw its conduct. In the current project they discussed results and provided input into drafts of the manuscript. Data availability: Data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis are available to external investigators, on reasonable request. For information on how to access data, see: http://www.rheumatology.org.uk. We are grateful to the staff of the BSRBR-AS register and to the recruiting staff at the clinical centres, details of which are available at: www.abdn.ac.uk/bsrbr-as",

year = "2021",

month = sep,

day = "30",

doi = "10.1093/rheumatology/keaa900",

language = "English",

volume = "60",

pages = "4158–4165",

journal = "Rheumatology",

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publisher = "Oxford University Press",

number = "9",

}

TY - JOUR

T1 - Comorbidity and response to TNF inhibitors in axial spondyloarthritis

T2 - longitudinal analysis of the BSRBR-AS

AU - Zhao, Sizheng Steven

AU - Jones, Gareth

AU - Macfarlane, Gary

AU - Hughes, David M

AU - Moots, Robert J

AU - Goodson, Nicola J

N1 - Acknowledgements: Funding: The BSRBR-AS is funded by the British Society for Rheumatology (BSR) who have received funding for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts for comments. They have no input in determining the topics for analysis or work involved in undertaking it. Disclosures: The authors declare no conflicts of interest. Contribution: SSZ analysed the data and wrote the manuscript, with significant input from all coauthors. GJM and GTJ are Chief Investigator and Deputy Chief Investigator respectively on BSRBR-AS and designed the study and oversaw its conduct. In the current project they discussed results and provided input into drafts of the manuscript. Data availability: Data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis are available to external investigators, on reasonable request. For information on how to access data, see: http://www.rheumatology.org.uk. We are grateful to the staff of the BSRBR-AS register and to the recruiting staff at the clinical centres, details of which are available at: www.abdn.ac.uk/bsrbr-as

PY - 2021/9/30

Y1 - 2021/9/30

N2 - Objective. Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but theirassociation with response to TNF inhibitors (TNFi) is unclear. We examined associations betweencomorbidity history at TNFi initiation and: 1) change in disease indices over time; 2) binary responsedefinitions; 3) time-to-treatment-discontinuation.Methods. We studied participants starting their first TNFi from a national axSpA register.Comorbidity categories were created from 14 physician-diagnosed conditions and compared against:change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unitreduction) and BASDAI<4 at 6 months using logistic models; and time-to-treatment-discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education.Results. 994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 (OR 0.81; 95%CI 0.45, 1.45) and BASDAI<4 (OR0.57; 95%CI 0.32, 1.04). Treatment discontinuation was increased in those with 2 comorbidities (HR1.32; 95%CI 0.88, 2.00) and ≥3 comorbidities (HR 2.18; 95%CI 1.20, 3.93) compared to none.Conclusions. Participants with multiple comorbidities had poorer treatment outcomes, particularlyincreased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidityburden.

AB - Objective. Comorbidities influence disease assessment in axial spondyloarthritis (axSpA), but theirassociation with response to TNF inhibitors (TNFi) is unclear. We examined associations betweencomorbidity history at TNFi initiation and: 1) change in disease indices over time; 2) binary responsedefinitions; 3) time-to-treatment-discontinuation.Methods. We studied participants starting their first TNFi from a national axSpA register.Comorbidity categories were created from 14 physician-diagnosed conditions and compared against:change in disease indices over time using linear mixed effects models; BASDAI50/2 (50% or 2-unitreduction) and BASDAI<4 at 6 months using logistic models; and time-to-treatment-discontinuation using Cox models. Models were adjusted for age, gender, BMI, deprivation and education.Results. 994 were eligible for analysis (68% male, mean age 45 years); 21% had one comorbidity and 11% had ≥2. Baseline disease severity was higher in those with comorbidities across all indices, but absolute improvement over time was comparable for BASDAI and spinal pain. Participants with ≥2comorbidities had smaller absolute improvement in BASFI and quality of life. This group also had numerically reduced odds of achieving BASDAI50/2 (OR 0.81; 95%CI 0.45, 1.45) and BASDAI<4 (OR0.57; 95%CI 0.32, 1.04). Treatment discontinuation was increased in those with 2 comorbidities (HR1.32; 95%CI 0.88, 2.00) and ≥3 comorbidities (HR 2.18; 95%CI 1.20, 3.93) compared to none.Conclusions. Participants with multiple comorbidities had poorer treatment outcomes, particularlyincreased treatment discontinuation and poorer improvements in function and quality of life. These results inform clinicians and educate patients about response to the first TNFi given comorbidityburden.

KW - axial spondyloarthritis

KW - comorbidities

KW - treatment response

KW - TNF inhibitors

KW - ankylosing spondylitis

U2 - 10.1093/rheumatology/keaa900

DO - 10.1093/rheumatology/keaa900

M3 - Article

C2 - 33369676

SN - 1462-0324

VL - 60

SP - 4158

EP - 4165

JO - Rheumatology

JF - Rheumatology

IS - 9

M1 - keaa900

ER -

Comorbidity and response to TNF inhibitors in axial spondyloarthritis: longitudinal analysis of the BSRBR-AS

Abstract

Bibliographical note

Keywords

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