Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries

Benedicte Delcoigne; Lotta Ljung; Sella A Provan; Bente Glintborg; Merete Lund Hetland; Kathrine Lederballe Grøn; Ritva Peltomaa; Heikki Relas; Carl Turesson; Björn Guðbjörnsson; Brigitte Michelsen; Johan Askling

doi:10.1136/annrheumdis-2021-221996

Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries

Benedicte Delcoigne, Lotta Ljung, Sella A Provan, Bente Glintborg, Merete Lund Hetland, Kathrine Lederballe Grøn, Ritva Peltomaa, Heikki Relas, Carl Turesson, Björn Guðbjörnsson, Brigitte Michelsen, Johan Askling

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Abstract

OBJECTIVES: To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.

METHODS: Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.

RESULTS: 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.

CONCLUSION: The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.

Original language	English
Pages (from-to)	789-797
Number of pages	9
Journal	Annals of the Rheumatic Diseases
Volume	81
Issue number	6
DOIs	https://doi.org/10.1136/annrheumdis-2021-221996
Publication status	Published - 22 Mar 2022

Bibliographical note

Funding Information:
Competing interests LL: chairs the steering committee of the Swedish Rheumatology Quality Register, SRQ. Karolinska University Hospital and its principal investigator SRQ has had agreements for register data analyses with AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, Sanofi, Sobi and UCB. BG: research grants: Pfizer, BMS, Sandoz and AbbVie. MLH: grants: AbbVie, Biogen, BMS, Celltrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeckfonden, MSD, Pfizer, Roche, Samsung Bioepis and Sandoz; chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies, and cochairs Eurospa, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis. KLG: grants: BMS. RP: lecturer: Actelion, Boehringer Ingelheim, Pfizer, Sanofi and Janssen; grants: Mylen and data safety monitoring: Boehringer Ingelheim, Lilly, Janssen and AbbVie. HR: Congress fees and speaker fees from AbbVie and consulting fees: Celgene and Pfizer. CT: speaker fees: AbbVie, Bristol-Myers Squibb, Nordic Drugs, Pfizer and Roche. BG: consultant and lecturer fees: Novartis. BM: research grant (paid to employer) and consultancy fees: Novartis. JA: grants: AbbVie, Astra-Zeneca, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB. AbbVie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system.

Funding Information:
Funding This work was supported by NordForsk and the Foundation for Research in Rheumatology (Foreum), Vinnova. The research infrastructure was supported by funds from the Swedish Research Council, the Swedish Heart Lung Foundation, the Swedish Cancer Society and Region Stockholm–Karolinska Institutet (ALF).

Publisher Copyright:
© 2022 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Other keywords

biological therapy
cardiovascular diseases
rheumatoid arthritis
tumor necrosis factor inhibitors
Tumor necrosis factor inhibitors
Rheumatoid arthritis
Biological therapy
Cardiovascular diseases

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10.1136/annrheumdis-2021-221996

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Delcoigne, B., Ljung, L., Provan, S. A., Glintborg, B., Hetland, M. L., Grøn, K. L., Peltomaa, R., Relas, H., Turesson, C., Guðbjörnsson, B., Michelsen, B., & Askling, J. (2022). Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries. Annals of the Rheumatic Diseases, 81(6), 789-797. https://doi.org/10.1136/annrheumdis-2021-221996

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title = "Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries",

abstract = "OBJECTIVES: To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.METHODS: Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.RESULTS: 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.CONCLUSION: The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.",

keywords = "biological therapy, cardiovascular diseases, rheumatoid arthritis, tumor necrosis factor inhibitors, Tumor necrosis factor inhibitors, Rheumatoid arthritis, Biological therapy, Cardiovascular diseases",

author = "Benedicte Delcoigne and Lotta Ljung and Provan, {Sella A} and Bente Glintborg and Hetland, {Merete Lund} and Gr{\o}n, {Kathrine Lederballe} and Ritva Peltomaa and Heikki Relas and Carl Turesson and Bj{\"o}rn Gu{\dh}bj{\"o}rnsson and Brigitte Michelsen and Johan Askling",

note = "Funding Information: Competing interests LL: chairs the steering committee of the Swedish Rheumatology Quality Register, SRQ. Karolinska University Hospital and its principal investigator SRQ has had agreements for register data analyses with AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, Sanofi, Sobi and UCB. BG: research grants: Pfizer, BMS, Sandoz and AbbVie. MLH: grants: AbbVie, Biogen, BMS, Celltrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeckfonden, MSD, Pfizer, Roche, Samsung Bioepis and Sandoz; chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies, and cochairs Eurospa, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis. KLG: grants: BMS. RP: lecturer: Actelion, Boehringer Ingelheim, Pfizer, Sanofi and Janssen; grants: Mylen and data safety monitoring: Boehringer Ingelheim, Lilly, Janssen and AbbVie. HR: Congress fees and speaker fees from AbbVie and consulting fees: Celgene and Pfizer. CT: speaker fees: AbbVie, Bristol-Myers Squibb, Nordic Drugs, Pfizer and Roche. BG: consultant and lecturer fees: Novartis. BM: research grant (paid to employer) and consultancy fees: Novartis. JA: grants: AbbVie, Astra-Zeneca, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB. AbbVie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system. Funding Information: Funding This work was supported by NordForsk and the Foundation for Research in Rheumatology (Foreum), Vinnova. The research infrastructure was supported by funds from the Swedish Research Council, the Swedish Heart Lung Foundation, the Swedish Cancer Society and Region Stockholm–Karolinska Institutet (ALF). Publisher Copyright: {\textcopyright} 2022 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2022",

month = mar,

day = "22",

doi = "10.1136/annrheumdis-2021-221996",

language = "English",

volume = "81",

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Delcoigne, B, Ljung, L, Provan, SA, Glintborg, B, Hetland, ML, Grøn, KL, Peltomaa, R, Relas, H, Turesson, C, Guðbjörnsson, B, Michelsen, B & Askling, J 2022, 'Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries', Annals of the Rheumatic Diseases, vol. 81, no. 6, pp. 789-797. https://doi.org/10.1136/annrheumdis-2021-221996

Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries. / Delcoigne, Benedicte; Ljung, Lotta; Provan, Sella A et al.
In: Annals of the Rheumatic Diseases, Vol. 81, No. 6, 22.03.2022, p. 789-797.

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

TY - JOUR

T1 - Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs

T2 - results from four Nordic countries

AU - Delcoigne, Benedicte

AU - Ljung, Lotta

AU - Provan, Sella A

AU - Glintborg, Bente

AU - Hetland, Merete Lund

AU - Grøn, Kathrine Lederballe

AU - Peltomaa, Ritva

AU - Relas, Heikki

AU - Turesson, Carl

AU - Guðbjörnsson, Björn

AU - Michelsen, Brigitte

AU - Askling, Johan

N1 - Funding Information: Competing interests LL: chairs the steering committee of the Swedish Rheumatology Quality Register, SRQ. Karolinska University Hospital and its principal investigator SRQ has had agreements for register data analyses with AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, Sanofi, Sobi and UCB. BG: research grants: Pfizer, BMS, Sandoz and AbbVie. MLH: grants: AbbVie, Biogen, BMS, Celltrion, Eli Lilly Denmark A/S, Janssen Biologics B.V, Lundbeckfonden, MSD, Pfizer, Roche, Samsung Bioepis and Sandoz; chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies, and cochairs Eurospa, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis. KLG: grants: BMS. RP: lecturer: Actelion, Boehringer Ingelheim, Pfizer, Sanofi and Janssen; grants: Mylen and data safety monitoring: Boehringer Ingelheim, Lilly, Janssen and AbbVie. HR: Congress fees and speaker fees from AbbVie and consulting fees: Celgene and Pfizer. CT: speaker fees: AbbVie, Bristol-Myers Squibb, Nordic Drugs, Pfizer and Roche. BG: consultant and lecturer fees: Novartis. BM: research grant (paid to employer) and consultancy fees: Novartis. JA: grants: AbbVie, Astra-Zeneca, BMS, Eli Lilly, Galapagos, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB. AbbVie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system. Funding Information: Funding This work was supported by NordForsk and the Foundation for Research in Rheumatology (Foreum), Vinnova. The research infrastructure was supported by funds from the Swedish Research Council, the Swedish Heart Lung Foundation, the Swedish Cancer Society and Region Stockholm–Karolinska Institutet (ALF). Publisher Copyright: © 2022 Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2022/3/22

Y1 - 2022/3/22

N2 - OBJECTIVES: To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.METHODS: Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.RESULTS: 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.CONCLUSION: The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.

AB - OBJECTIVES: To compare the 1-year, 2-year and 5-year incidences of acute coronary syndrome (ACS) in patients with rheumatoid arthritis (RA) starting any of the biologic disease-modifying antirheumatic drugs (bDMARDs) currently available in clinical practice and to anchor these results with a general population comparator.METHODS: Observational cohort study, with patients from Denmark, Finland, Norway and Sweden starting a bDMARD during 2008-2017. Time to first ACS was identified through register linkages. We calculated the 1-year, 2-year and 5-year incidence rates (IR) (on drug and ever since treatment start) and used Cox regression (HRs) to compare ACS incidences across treatments taking ACS risk factors into account. Analyses were further performed separately in subgroups defined by age, number of previous bDMARDs and history of cardiovascular disease. We also compared ACS incidences to an individually matched general population cohort.RESULTS: 24 083 patients (75% women, mean age 56 years) contributing 40 850 treatment courses were included. During the maximum (5 years) follow-up (141 257 person-years (pyrs)), 780 ACS events occurred (crude IR 5.5 per 1000 pyrs). Overall, the incidence of ACS in RA was 80% higher than that in the general population. For all bDMARDs and follow-up definitions, HRs were close to 1 (etanercept as reference) with the exception of the 5-year risk window, where signals for abatacept, infliximab and rituximab were noted.CONCLUSION: The rate of ACS among patients with RA initiating bDMARDs remains elevated compared with the general population. As used in routine care, the short-term, intermediate-term and longer-term risks of ACS vary little across individual bDMARDs.

KW - biological therapy

KW - cardiovascular diseases

KW - rheumatoid arthritis

KW - tumor necrosis factor inhibitors

KW - Tumor necrosis factor inhibitors

KW - Rheumatoid arthritis

KW - Biological therapy

KW - Cardiovascular diseases

UR - http://www.scopus.com/inward/record.url?scp=85127536600&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2021-221996

DO - 10.1136/annrheumdis-2021-221996

M3 - Article

C2 - 35318218

SN - 0003-4967

VL - 81

SP - 789

EP - 797

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 6

ER -

Short-term, intermediate-term and long-term risks of acute coronary syndrome in cohorts of patients with RA starting biologic DMARDs: results from four Nordic countries

Abstract

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