Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis

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

doi:10.1093/rheumatology/keab242

Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis

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

^*Corresponding author for this work

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Abstract

OBJECTIVES: Depression and anxiety are associated with more severe disease in cross-sectional studies of axial spondyloarthritis (axSpA). We examined the association between baseline symptoms of depression or anxiety and response to TNF inhibitors (TNFi) in axSpA.

METHODS: Biologic naïve participants from a national axSpA register completed the Hospital Anxiety and Depression Scale (HADS) before initiating TNFi. Symptoms of anxiety and depression were each categorised as moderate-severe (≥11), mild (8-10), and 'none' (≤7), and compared against: change in disease indices (BASDAI and ASDAS) over time and time to treatment discontinuation using marginal structural models. Inverse-probability weights balanced baseline age, gender, BMI, deprivation, education, and baseline values of respective indices.

RESULTS: Of the 742 participants (67% male, mean age 45 years), 156 (23%) had moderate-severe and 26% mild depression; 256 (39%) had moderate-severe and 23% mild anxiety. Baseline disease activity was higher in higher HADS symptom categories for both depression and anxiety. Participants with moderate-severe depression had significantly poorer response compared with those with 'none' throughout follow-up. At 6 months, the difference was ∼2.2 BASDAI and 0.8 ASDAS units after balancing their baseline values. Equivalent comparisons for anxiety were 1.7 BASDAI and 0.7 ASDAS units. Treatment discontinuation was HR1.59 higher (95%CI 1.12, 2.26) in participants with moderate-severe anxiety compared with 'none'.

CONCLUSIONS: Symptoms of depression and anxiety at TNFi initiation are associated with significantly poorer treatment outcomes. Targeted interventions to optimise mental health have potential to substantially improve treatment response and persistence.

Original language	English
Pages (from-to)	5734–5742
Number of pages	9
Journal	Rheumatology
Volume	60
Issue number	12
Early online date	13 Mar 2021
DOIs	https://doi.org/10.1093/rheumatology/keab242
Publication status	Published - Dec 2021

Keywords

axial spondyloarthritis
depression
mental health
anxiety
treatment response

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© The Author(s) 2021. 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 journals.permissions@oup.com
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Cite this

@article{4eed212bcfff4d85a42d243e8ebc6170,

title = "Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis",

abstract = "OBJECTIVES: Depression and anxiety are associated with more severe disease in cross-sectional studies of axial spondyloarthritis (axSpA). We examined the association between baseline symptoms of depression or anxiety and response to TNF inhibitors (TNFi) in axSpA.METHODS: Biologic na{\"i}ve participants from a national axSpA register completed the Hospital Anxiety and Depression Scale (HADS) before initiating TNFi. Symptoms of anxiety and depression were each categorised as moderate-severe (≥11), mild (8-10), and 'none' (≤7), and compared against: change in disease indices (BASDAI and ASDAS) over time and time to treatment discontinuation using marginal structural models. Inverse-probability weights balanced baseline age, gender, BMI, deprivation, education, and baseline values of respective indices.RESULTS: Of the 742 participants (67% male, mean age 45 years), 156 (23%) had moderate-severe and 26% mild depression; 256 (39%) had moderate-severe and 23% mild anxiety. Baseline disease activity was higher in higher HADS symptom categories for both depression and anxiety. Participants with moderate-severe depression had significantly poorer response compared with those with 'none' throughout follow-up. At 6 months, the difference was ∼2.2 BASDAI and 0.8 ASDAS units after balancing their baseline values. Equivalent comparisons for anxiety were 1.7 BASDAI and 0.7 ASDAS units. Treatment discontinuation was HR1.59 higher (95%CI 1.12, 2.26) in participants with moderate-severe anxiety compared with 'none'.CONCLUSIONS: Symptoms of depression and anxiety at TNFi initiation are associated with significantly poorer treatment outcomes. Targeted interventions to optimise mental health have potential to substantially improve treatment response and persistence.",

keywords = "axial spondyloarthritis, depression, mental health, anxiety, treatment response",

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

note = "Acknowledgment We are grateful to Professor Gary Macfarlane for commenting on the manuscript. 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. We also thank Dr Lewis Carpenter for suggesting splines for modelling time. Contribution: SSZ analysed the data and wrote the manuscript with significant input from all co- authors. GTJ is the Deputy Chief Investigator 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. 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. ",

year = "2021",

month = dec,

doi = "10.1093/rheumatology/keab242",

language = "English",

volume = "60",

pages = "5734–5742",

journal = "Rheumatology",

issn = "1462-0324",

publisher = "OXFORD UNIV PRESS INC",

number = "12",

}

TY - JOUR

T1 - Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis

AU - Zhao, Sizheng Steven

AU - Jones, Gareth T

AU - Hughes, David M

AU - Moots, Robert J

AU - Goodson, Nicola J

N1 - Acknowledgment We are grateful to Professor Gary Macfarlane for commenting on the manuscript. 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. We also thank Dr Lewis Carpenter for suggesting splines for modelling time. Contribution: SSZ analysed the data and wrote the manuscript with significant input from all co- authors. GTJ is the Deputy Chief Investigator 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. 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.

PY - 2021/12

Y1 - 2021/12

N2 - OBJECTIVES: Depression and anxiety are associated with more severe disease in cross-sectional studies of axial spondyloarthritis (axSpA). We examined the association between baseline symptoms of depression or anxiety and response to TNF inhibitors (TNFi) in axSpA.METHODS: Biologic naïve participants from a national axSpA register completed the Hospital Anxiety and Depression Scale (HADS) before initiating TNFi. Symptoms of anxiety and depression were each categorised as moderate-severe (≥11), mild (8-10), and 'none' (≤7), and compared against: change in disease indices (BASDAI and ASDAS) over time and time to treatment discontinuation using marginal structural models. Inverse-probability weights balanced baseline age, gender, BMI, deprivation, education, and baseline values of respective indices.RESULTS: Of the 742 participants (67% male, mean age 45 years), 156 (23%) had moderate-severe and 26% mild depression; 256 (39%) had moderate-severe and 23% mild anxiety. Baseline disease activity was higher in higher HADS symptom categories for both depression and anxiety. Participants with moderate-severe depression had significantly poorer response compared with those with 'none' throughout follow-up. At 6 months, the difference was ∼2.2 BASDAI and 0.8 ASDAS units after balancing their baseline values. Equivalent comparisons for anxiety were 1.7 BASDAI and 0.7 ASDAS units. Treatment discontinuation was HR1.59 higher (95%CI 1.12, 2.26) in participants with moderate-severe anxiety compared with 'none'.CONCLUSIONS: Symptoms of depression and anxiety at TNFi initiation are associated with significantly poorer treatment outcomes. Targeted interventions to optimise mental health have potential to substantially improve treatment response and persistence.

AB - OBJECTIVES: Depression and anxiety are associated with more severe disease in cross-sectional studies of axial spondyloarthritis (axSpA). We examined the association between baseline symptoms of depression or anxiety and response to TNF inhibitors (TNFi) in axSpA.METHODS: Biologic naïve participants from a national axSpA register completed the Hospital Anxiety and Depression Scale (HADS) before initiating TNFi. Symptoms of anxiety and depression were each categorised as moderate-severe (≥11), mild (8-10), and 'none' (≤7), and compared against: change in disease indices (BASDAI and ASDAS) over time and time to treatment discontinuation using marginal structural models. Inverse-probability weights balanced baseline age, gender, BMI, deprivation, education, and baseline values of respective indices.RESULTS: Of the 742 participants (67% male, mean age 45 years), 156 (23%) had moderate-severe and 26% mild depression; 256 (39%) had moderate-severe and 23% mild anxiety. Baseline disease activity was higher in higher HADS symptom categories for both depression and anxiety. Participants with moderate-severe depression had significantly poorer response compared with those with 'none' throughout follow-up. At 6 months, the difference was ∼2.2 BASDAI and 0.8 ASDAS units after balancing their baseline values. Equivalent comparisons for anxiety were 1.7 BASDAI and 0.7 ASDAS units. Treatment discontinuation was HR1.59 higher (95%CI 1.12, 2.26) in participants with moderate-severe anxiety compared with 'none'.CONCLUSIONS: Symptoms of depression and anxiety at TNFi initiation are associated with significantly poorer treatment outcomes. Targeted interventions to optimise mental health have potential to substantially improve treatment response and persistence.

KW - axial spondyloarthritis

KW - depression

KW - mental health

KW - anxiety

KW - treatment response

U2 - 10.1093/rheumatology/keab242

DO - 10.1093/rheumatology/keab242

M3 - Article

C2 - 33713118

VL - 60

SP - 5734

EP - 5742

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 12

ER -

Depression and anxiety symptoms at TNF inhibitor initiation are associated with impaired treatment response in axial spondyloarthritis

Abstract

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