Risk of infection in patients with early inflammatory arthritis: results from a large UK prospective observational cohort study

Maryam A Adas; Katie Bechman; Mark D Russell; Victoria Allen; Samir Patel; Mark Gibson; Ioasaf Karafotias; Kathryn Biddle; Benjamin Zuckerman; Kaiyang Song; Deepak Nagra; Edward Alveyn; Suma Mahendrakar; Meryem Nursoy; Fabiola Atzeni; Sarah Gallagher; Elizabeth Price; Mark Garton; Andrew Rutherford; Andrew P Cope; Sam Norton; James B Galloway

doi:10.1093/rheumatology/keaf312

Risk of infection in patients with early inflammatory arthritis: results from a large UK prospective observational cohort study

Maryam A Adas, Katie Bechman, Mark D Russell, Victoria Allen, Samir Patel, Mark Gibson, Ioasaf Karafotias, Kathryn Biddle, Benjamin Zuckerman, Kaiyang Song, Deepak Nagra, Edward Alveyn, Suma Mahendrakar, Meryem Nursoy, Fabiola Atzeni, Sarah Gallagher, Elizabeth Price, Mark Garton, Andrew Rutherford, Andrew P CopeSam Norton, James B Galloway

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Abstract

OBJECTIVE: To identify risk of serious infections-(SI) according to initial conventional synthetic disease modifying anti-rheumatic drugs-(csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit.

METHODS: An observational cohort study was used, including adults in England and Wales with new diagnoses of rheumatoid arthritis-(RA) between 2018-2023. Main outcome was SI-events, defined as infections requiring hospitalisation/or resulting in death. Secondary analyses evaluated SI-related mortality alone. Hazard ratios-(HR) were calculated using cox proportional hazards models. Primary predictor was initial treatment strategy, with confounder adjustments.

RESULTS: 17 472 patients were included, of whom 10 997 on methotrexate-based strategies; 4,540 on other csDMARDs; 13 680 received corticosteroids. There were 1307 SI-events, corresponding to incidence rates per 100 person-years of 3.02 (95% CI: 2.86-3.19) and 311 SI-related mortality (IR 0.69, 95% CI: 0.61-0.77). Methotrexate-based strategies were associated with reduced risk of SI-events compared with other csDMARDs (adjusted HR 0.72, 95% CI: 0.63-0.82). In unadjusted models, corticosteroid was associated with higher risk of SI-events, but in adjusted models this association was no longer significant (adjusted HR 0.99, 95% CI: 0.87-1.12). Increasing age, being a current/or ex-smoker (relative to non-smoker), having a comorbidity, being seropositive, and having high DAS28 all associated with increased incidence of SI. One unit increase in baseline DAS28 increases the risk of SI-event by 10%.

CONCLUSION: Methotrexate-based regimens associated with a reduced risk of SI compared with other strategies. Patient-level and disease-related factors at diagnosis are important predictors of SI in individuals with new RA.

Original language	English
Journal	Rheumatology
Early online date	5 Jun 2025
DOIs	https://doi.org/10.1093/rheumatology/keaf312
Publication status	E-pub ahead of print - 5 Jun 2025

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Risk of infection in_ADAS_Publishedonline5June2025_GOLD_AAM (CC BY)Accepted author manuscript, 738 KBLicence: CC BY

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Adas, M. A., Bechman, K., Russell, M. D., Allen, V., Patel, S., Gibson, M., Karafotias, I., Biddle, K., Zuckerman, B., Song, K., Nagra, D., Alveyn, E., Mahendrakar, S., Nursoy, M., Atzeni, F., Gallagher, S., Price, E., Garton, M., Rutherford, A., ... Galloway, J. B. (2025). Risk of infection in patients with early inflammatory arthritis: results from a large UK prospective observational cohort study. Rheumatology. Advance online publication. https://doi.org/10.1093/rheumatology/keaf312

@article{2faaf31e886c4fa98bcbf9e99afbb29d,

title = "Risk of infection in patients with early inflammatory arthritis: results from a large UK prospective observational cohort study",

abstract = "OBJECTIVE: To identify risk of serious infections-(SI) according to initial conventional synthetic disease modifying anti-rheumatic drugs-(csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit.METHODS: An observational cohort study was used, including adults in England and Wales with new diagnoses of rheumatoid arthritis-(RA) between 2018-2023. Main outcome was SI-events, defined as infections requiring hospitalisation/or resulting in death. Secondary analyses evaluated SI-related mortality alone. Hazard ratios-(HR) were calculated using cox proportional hazards models. Primary predictor was initial treatment strategy, with confounder adjustments.RESULTS: 17 472 patients were included, of whom 10 997 on methotrexate-based strategies; 4,540 on other csDMARDs; 13 680 received corticosteroids. There were 1307 SI-events, corresponding to incidence rates per 100 person-years of 3.02 (95% CI: 2.86-3.19) and 311 SI-related mortality (IR 0.69, 95% CI: 0.61-0.77). Methotrexate-based strategies were associated with reduced risk of SI-events compared with other csDMARDs (adjusted HR 0.72, 95% CI: 0.63-0.82). In unadjusted models, corticosteroid was associated with higher risk of SI-events, but in adjusted models this association was no longer significant (adjusted HR 0.99, 95% CI: 0.87-1.12). Increasing age, being a current/or ex-smoker (relative to non-smoker), having a comorbidity, being seropositive, and having high DAS28 all associated with increased incidence of SI. One unit increase in baseline DAS28 increases the risk of SI-event by 10%.CONCLUSION: Methotrexate-based regimens associated with a reduced risk of SI compared with other strategies. Patient-level and disease-related factors at diagnosis are important predictors of SI in individuals with new RA.",

author = "Adas, {Maryam A} and Katie Bechman and Russell, {Mark D} and Victoria Allen and Samir Patel and Mark Gibson and Ioasaf Karafotias and Kathryn Biddle and Benjamin Zuckerman and Kaiyang Song and Deepak Nagra and Edward Alveyn and Suma Mahendrakar and Meryem Nursoy and Fabiola Atzeni and Sarah Gallagher and Elizabeth Price and Mark Garton and Andrew Rutherford and Cope, {Andrew P} and Sam Norton and Galloway, {James B}",

note = "{\textcopyright} The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology.",

year = "2025",

month = jun,

day = "5",

doi = "10.1093/rheumatology/keaf312",

language = "English",

journal = "Rheumatology",

issn = "1462-0324",

publisher = "OXFORD UNIV PRESS",

}

Adas, MA , Bechman, K , Russell, MD , Allen, V , Patel, S , Gibson, M , Karafotias, I, Biddle, K, Zuckerman, B, Song, K, Nagra, D , Alveyn, E, Mahendrakar, S, Nursoy, M, Atzeni, F, Gallagher, S, Price, E, Garton, M, Rutherford, A, Cope, AP , Norton, S & Galloway, JB 2025, 'Risk of infection in patients with early inflammatory arthritis: results from a large UK prospective observational cohort study', Rheumatology. https://doi.org/10.1093/rheumatology/keaf312

TY - JOUR

T1 - Risk of infection in patients with early inflammatory arthritis

T2 - results from a large UK prospective observational cohort study

AU - Adas, Maryam A

AU - Bechman, Katie

AU - Russell, Mark D

AU - Allen, Victoria

AU - Patel, Samir

AU - Gibson, Mark

AU - Karafotias, Ioasaf

AU - Biddle, Kathryn

AU - Zuckerman, Benjamin

AU - Song, Kaiyang

AU - Nagra, Deepak

AU - Alveyn, Edward

AU - Mahendrakar, Suma

AU - Nursoy, Meryem

AU - Atzeni, Fabiola

AU - Gallagher, Sarah

AU - Price, Elizabeth

AU - Garton, Mark

AU - Rutherford, Andrew

AU - Cope, Andrew P

AU - Norton, Sam

AU - Galloway, James B

PY - 2025/6/5

Y1 - 2025/6/5

N2 - OBJECTIVE: To identify risk of serious infections-(SI) according to initial conventional synthetic disease modifying anti-rheumatic drugs-(csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit.METHODS: An observational cohort study was used, including adults in England and Wales with new diagnoses of rheumatoid arthritis-(RA) between 2018-2023. Main outcome was SI-events, defined as infections requiring hospitalisation/or resulting in death. Secondary analyses evaluated SI-related mortality alone. Hazard ratios-(HR) were calculated using cox proportional hazards models. Primary predictor was initial treatment strategy, with confounder adjustments.RESULTS: 17 472 patients were included, of whom 10 997 on methotrexate-based strategies; 4,540 on other csDMARDs; 13 680 received corticosteroids. There were 1307 SI-events, corresponding to incidence rates per 100 person-years of 3.02 (95% CI: 2.86-3.19) and 311 SI-related mortality (IR 0.69, 95% CI: 0.61-0.77). Methotrexate-based strategies were associated with reduced risk of SI-events compared with other csDMARDs (adjusted HR 0.72, 95% CI: 0.63-0.82). In unadjusted models, corticosteroid was associated with higher risk of SI-events, but in adjusted models this association was no longer significant (adjusted HR 0.99, 95% CI: 0.87-1.12). Increasing age, being a current/or ex-smoker (relative to non-smoker), having a comorbidity, being seropositive, and having high DAS28 all associated with increased incidence of SI. One unit increase in baseline DAS28 increases the risk of SI-event by 10%.CONCLUSION: Methotrexate-based regimens associated with a reduced risk of SI compared with other strategies. Patient-level and disease-related factors at diagnosis are important predictors of SI in individuals with new RA.

AB - OBJECTIVE: To identify risk of serious infections-(SI) according to initial conventional synthetic disease modifying anti-rheumatic drugs-(csDMARD) and corticosteroids, in patients recruited to the National Early Inflammatory Arthritis Audit.METHODS: An observational cohort study was used, including adults in England and Wales with new diagnoses of rheumatoid arthritis-(RA) between 2018-2023. Main outcome was SI-events, defined as infections requiring hospitalisation/or resulting in death. Secondary analyses evaluated SI-related mortality alone. Hazard ratios-(HR) were calculated using cox proportional hazards models. Primary predictor was initial treatment strategy, with confounder adjustments.RESULTS: 17 472 patients were included, of whom 10 997 on methotrexate-based strategies; 4,540 on other csDMARDs; 13 680 received corticosteroids. There were 1307 SI-events, corresponding to incidence rates per 100 person-years of 3.02 (95% CI: 2.86-3.19) and 311 SI-related mortality (IR 0.69, 95% CI: 0.61-0.77). Methotrexate-based strategies were associated with reduced risk of SI-events compared with other csDMARDs (adjusted HR 0.72, 95% CI: 0.63-0.82). In unadjusted models, corticosteroid was associated with higher risk of SI-events, but in adjusted models this association was no longer significant (adjusted HR 0.99, 95% CI: 0.87-1.12). Increasing age, being a current/or ex-smoker (relative to non-smoker), having a comorbidity, being seropositive, and having high DAS28 all associated with increased incidence of SI. One unit increase in baseline DAS28 increases the risk of SI-event by 10%.CONCLUSION: Methotrexate-based regimens associated with a reduced risk of SI compared with other strategies. Patient-level and disease-related factors at diagnosis are important predictors of SI in individuals with new RA.

U2 - 10.1093/rheumatology/keaf312

DO - 10.1093/rheumatology/keaf312

M3 - Article

C2 - 40471746

SN - 1462-0324

JO - Rheumatology

JF - Rheumatology

ER -

Risk of infection in patients with early inflammatory arthritis: results from a large UK prospective observational cohort study

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