Inflammatory bowel disease risk in patients with axial spondyloarthritis treated with biologic agents: Determined Using the BSRBR-AS and a MetaAnalysis

Gary Macfarlane; R Biallas; LE  Dean; GT Jones; Nicola J Goodson; Ovidiu Rotariu

doi:10.3899/jrheum.211034

Inflammatory bowel disease risk in patients with axial spondyloarthritis treated with biologic agents: Determined Using the BSRBR-AS and a MetaAnalysis

Gary Macfarlane^* (Corresponding Author), R Biallas, LE Dean , GT Jones, Nicola J Goodson, Ovidiu Rotariu

^*Corresponding author for this work

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

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Abstract

Objectives: To determine, amongst patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic and other therapies, and whether specifically the risk is higher in patients treated with etanercept.
Methods: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the Incidence Rate Difference (IRD) between biologic treatment and other treatment groups. We thereafter conducted a systematic review (involving observational studies and randomised controlled trials) to perform a meta-analysis to quantify the difference in incidence of IBD between treatment groups.
Results: In BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to non-exposed patients (IRD 11.9 95% CI (4.3, 19.6)). This finding was replicated across observational studies but not seen in placebo controlled RCTs IRD 2.2 95% CI (-4.1, 8.5). Data from BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to etanercept compared to other anti-TNFα therapies (IRD -6.5/1,000 pys 95% CI (-21.3, 8.5)). Trials and their extensions suggest a small (and not statistically significant) absolute increased incidence associated with etanercept of between 2.1 and 5.8 per 1,000 pys compared to other anti-TNFα therapies.
Conclusions: There was an excess risk of IBD amongst persons treated with biologics in observational studies. Only evidence from trials suggested that etanercept was associated with an increased risk compared to other anti-TNFα therapies, albeit with considerable uncertainty.

Original language	English
Pages (from-to)	175-184
Number of pages	10
Journal	Journal of Rheumatology
Volume	50
Issue number	2
Early online date	1 Feb 2023
DOIs	https://doi.org/10.3899/jrheum.211034
Publication status	Published - 1 Feb 2023

Bibliographical note

Funding: The BSRBR-AS is supported by the British Society for Rheumatology and they have received funds for the registry from Pfizer, AbbVie and UCB. These companies have no input in determining the topics for analysis or work involved in undertaking it but do receive an advance copy of the manuscript on which they may make comments.

Acknowledgements: The original idea for the study was suggested by John Mansfield and discussed with Lesley Kay (both Newcastle upon Tyne Hospitals NHS Foundation Trust). All authors discussed and contributed to designing this study and the analysis plan, which was undertaken by RLB and (updated and) overseen by OR, LED and GJM. Results were reviewed by all authors. GJM, RLB, OR and LED all contributed to drafting the manuscript which was critically reviewed by all authors. RLB undertook this work while a visiting student based at the University of Aberdeen from Ludwig-Maximilians Universität (Munich).

Data Availability Statement

Supplementary material accompanies the online version of this article.

Keywords

axial spondyloarthritis
inflammatory bowel disease
registry
metaanalysis
tumor necrosis factor
etanercept
biologics

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title = "Inflammatory bowel disease risk in patients with axial spondyloarthritis treated with biologic agents: Determined Using the BSRBR-AS and a MetaAnalysis",

abstract = "Objectives: To determine, amongst patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic and other therapies, and whether specifically the risk is higher in patients treated with etanercept. Methods: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the Incidence Rate Difference (IRD) between biologic treatment and other treatment groups. We thereafter conducted a systematic review (involving observational studies and randomised controlled trials) to perform a meta-analysis to quantify the difference in incidence of IBD between treatment groups.Results: In BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to non-exposed patients (IRD 11.9 95% CI (4.3, 19.6)). This finding was replicated across observational studies but not seen in placebo controlled RCTs IRD 2.2 95% CI (-4.1, 8.5). Data from BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to etanercept compared to other anti-TNFα therapies (IRD -6.5/1,000 pys 95% CI (-21.3, 8.5)). Trials and their extensions suggest a small (and not statistically significant) absolute increased incidence associated with etanercept of between 2.1 and 5.8 per 1,000 pys compared to other anti-TNFα therapies. Conclusions: There was an excess risk of IBD amongst persons treated with biologics in observational studies. Only evidence from trials suggested that etanercept was associated with an increased risk compared to other anti-TNFα therapies, albeit with considerable uncertainty. ",

keywords = "axial spondyloarthritis, inflammatory bowel disease, registry, metaanalysis, tumor necrosis factor, etanercept, biologics",

author = "Gary Macfarlane and R Biallas and LE Dean and GT Jones and Goodson, {Nicola J} and Ovidiu Rotariu",

note = "Funding: The BSRBR-AS is supported by the British Society for Rheumatology and they have received funds for the registry from Pfizer, AbbVie and UCB. These companies have no input in determining the topics for analysis or work involved in undertaking it but do receive an advance copy of the manuscript on which they may make comments. Acknowledgements: The original idea for the study was suggested by John Mansfield and discussed with Lesley Kay (both Newcastle upon Tyne Hospitals NHS Foundation Trust). All authors discussed and contributed to designing this study and the analysis plan, which was undertaken by RLB and (updated and) overseen by OR, LED and GJM. Results were reviewed by all authors. GJM, RLB, OR and LED all contributed to drafting the manuscript which was critically reviewed by all authors. RLB undertook this work while a visiting student based at the University of Aberdeen from Ludwig-Maximilians Universit{\"a}t (Munich). ",

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doi = "10.3899/jrheum.211034",

language = "English",

volume = "50",

pages = "175--184",

journal = "Journal of Rheumatology",

issn = "0315-162X",

publisher = "Journal of Rheumatology",

number = "2",

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T1 - Inflammatory bowel disease risk in patients with axial spondyloarthritis treated with biologic agents

T2 - Determined Using the BSRBR-AS and a MetaAnalysis

AU - Macfarlane, Gary

AU - Biallas, R

AU - Dean , LE

AU - Jones, GT

AU - Goodson, Nicola J

AU - Rotariu, Ovidiu

N1 - Funding: The BSRBR-AS is supported by the British Society for Rheumatology and they have received funds for the registry from Pfizer, AbbVie and UCB. These companies have no input in determining the topics for analysis or work involved in undertaking it but do receive an advance copy of the manuscript on which they may make comments. Acknowledgements: The original idea for the study was suggested by John Mansfield and discussed with Lesley Kay (both Newcastle upon Tyne Hospitals NHS Foundation Trust). All authors discussed and contributed to designing this study and the analysis plan, which was undertaken by RLB and (updated and) overseen by OR, LED and GJM. Results were reviewed by all authors. GJM, RLB, OR and LED all contributed to drafting the manuscript which was critically reviewed by all authors. RLB undertook this work while a visiting student based at the University of Aberdeen from Ludwig-Maximilians Universität (Munich).

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N2 - Objectives: To determine, amongst patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic and other therapies, and whether specifically the risk is higher in patients treated with etanercept. Methods: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the Incidence Rate Difference (IRD) between biologic treatment and other treatment groups. We thereafter conducted a systematic review (involving observational studies and randomised controlled trials) to perform a meta-analysis to quantify the difference in incidence of IBD between treatment groups.Results: In BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to non-exposed patients (IRD 11.9 95% CI (4.3, 19.6)). This finding was replicated across observational studies but not seen in placebo controlled RCTs IRD 2.2 95% CI (-4.1, 8.5). Data from BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to etanercept compared to other anti-TNFα therapies (IRD -6.5/1,000 pys 95% CI (-21.3, 8.5)). Trials and their extensions suggest a small (and not statistically significant) absolute increased incidence associated with etanercept of between 2.1 and 5.8 per 1,000 pys compared to other anti-TNFα therapies. Conclusions: There was an excess risk of IBD amongst persons treated with biologics in observational studies. Only evidence from trials suggested that etanercept was associated with an increased risk compared to other anti-TNFα therapies, albeit with considerable uncertainty.

AB - Objectives: To determine, amongst patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic and other therapies, and whether specifically the risk is higher in patients treated with etanercept. Methods: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the Incidence Rate Difference (IRD) between biologic treatment and other treatment groups. We thereafter conducted a systematic review (involving observational studies and randomised controlled trials) to perform a meta-analysis to quantify the difference in incidence of IBD between treatment groups.Results: In BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to non-exposed patients (IRD 11.9 95% CI (4.3, 19.6)). This finding was replicated across observational studies but not seen in placebo controlled RCTs IRD 2.2 95% CI (-4.1, 8.5). Data from BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to etanercept compared to other anti-TNFα therapies (IRD -6.5/1,000 pys 95% CI (-21.3, 8.5)). Trials and their extensions suggest a small (and not statistically significant) absolute increased incidence associated with etanercept of between 2.1 and 5.8 per 1,000 pys compared to other anti-TNFα therapies. Conclusions: There was an excess risk of IBD amongst persons treated with biologics in observational studies. Only evidence from trials suggested that etanercept was associated with an increased risk compared to other anti-TNFα therapies, albeit with considerable uncertainty.

KW - axial spondyloarthritis

KW - inflammatory bowel disease

KW - registry

KW - metaanalysis

KW - tumor necrosis factor

KW - etanercept

KW - biologics

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DO - 10.3899/jrheum.211034

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C2 - 35777821

SN - 0315-162X

VL - 50

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EP - 184

JO - Journal of Rheumatology

JF - Journal of Rheumatology

IS - 2

ER -

Inflammatory bowel disease risk in patients with axial spondyloarthritis treated with biologic agents: Determined Using the BSRBR-AS and a MetaAnalysis

Abstract

Bibliographical note

Data Availability Statement

Keywords

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