Journal Article

AB0405 NO DIFFERENCE IN RISK OF MYOCARDIAL INFARCTION AMONG PATIENTS RECEIVING EITHER IL6 OR TNF INHIBITORS FOR RHEUMATOID ARTHRITIS

Mclaughlin, J., Tian, Z., Haughton, S., Hyrich, K., Lauper, K., Kearsley-Fleet, L., Lunt, M., Watson, K., Verma, A.

2023

Overview

BackgroundInterleukin 6 inhibitors (IL-6i) can increase LDL cholesterol levels, which raises concerns about the risk of myocardial infarction (MI) in patients with rheumatoid arthritis (RA) receiving this therapy.ObjectivesThis study aims to compare the risk of MI between people with RA in the UK clinical setting receiving IL-6i or tumour necrosis factor inhibitors (TNFi) overall or by line of therapy (LoT).MethodsPatients with RA registered between 01/10/2001 and 30/05/2022 with BSRBR-RA starting IL-6i or TNFi treatments were included. Occurrence of MI was identified from clinical follow-up forms and through cause of death reported by the national UK death register. Only those MIs occurring whilst patient was actively receiving drug were included. The risk of MI in patients receiving IL6i compared to TNFi was compared using Cox regression, adjusted for baseline co-variates using propensity scores (PS, see Table 1). Follow-up commenced at the start of the drug of interest and patients were censored at occurrence of MI, death, discontinuation of therapy or last follow-up visit, whichever came first. Multiple imputation was used for missing data. To account for known differences in LoT use of TNFi and IL6i (with IL6i more likely as a later line bDMARD), overall analyses adjusted for LoT in PS and secondary analyses by LoT were conducted. Direct switches between originator to biosimilars were considered the same treatment.ResultsA total of 30,022 IL6i or TNFi LoTs in 20,898 patients were included (3,278 IL-6i; 26,744 TNFi), representing 119,797 person-years of exposure. Compared to patients receiving TNFi, patients starting IL-6i treatment were older, had longer disease duration, less likely to use methotrexate and steroids, and had more comorbidities. During follow-up, 409 MIs occurred, 30 on IL-6i and 379 on TNFi. After PS adjustment, the risk of MI was not significantly different between the two treatment overall (HR 0.87, 95% CI 0.56-1.37) or when stratified by LoT (Table 1).ConclusionThis study could not identify any difference in risk of MI between IL-6i and TNFi treatment after patient characteristics and LoT were considered.TableMI in RA patients treated with IL-6i or TNFinPerson-yearsEventsIR per 1000 person year (95% CI)Crude HRPS Adjusted HR (95% CI)(95% CI)All lines of therapy TNFi26,744110,9813793.41 (3.09, 3.78)RefRef IL-6i3,2788,816303.40 (2.38, 4.87)0.93 (0.64, 1.35)0.87 (0.56, 1.37)First line TNFi16,38371,6542443.41 (3.00, 3.86)RefRef IL-6i3521,05743.78 (1.42, 10.08)1.04 (0.39, 2.80)1.26 (0.46, 3.41)Second line TNFi766631,4731023.24 (2.67, 3.94)RefRef IL-6i7491,89942.11 (0.79, 5.61)0.59 (0.22, 1.61)0.64 (0.23, 1.76)Third line TNFi1,7185,652264.60 (3.13, 6.76)RefRef IL-6i1,0592,838113.88 (2.15, 7.00)0.79 (0.38, 1.60)0.80 (0.37, 1.70)Fourth line and above TNFi9772,20373.18 (1.51, 6.67)RefRef IL-6i1,1183,023113.64 (2.92, 6.57)1.16 (0.45, 3.01)0.90 (0.33, 2.47)*Baseline variables used for propensity score adjustment: age, gender, time between BSRBR-RA registration and drug start, DAS28, disease duration, RF status, smoking history, BMI, current methotrexate, total number of prior csDMARDs, line of therapy (only in analyses of all LoTs), prior use of TNFi (not in analyses of first LoT only), prior use of IL6i (not in analyses of first or second LoT only), current use of steroids, ever use of antiplatelet or anticoagulant drugs; history of: hypertension, dyslipidaemia, diabetes, lung disease, renal disease, depression, cancer, venous thromboembolism, ischemic heart disease (myocardial infarction and angina), strokeReference[1]Atzeni, F., Rodríguez-Carrio, J., Popa, C. D., Nurmohamed, M. T., Szűcs, G. & Szekanecz, Z. (2021). ‘Cardiovascular effects of approved drugs for rheumatoid arthritis’, Nat Rev Rheumatol.Acknowledgements:NIL.Disclosure of InterestsZixing Tian: None declared, Lianne Kearsley-Fleet: None declared, Kim Lauper: None declared, Sally Haughton: None declared, Kath Watson: None declared, Mark Lunt: None declared, John Mclaughlin: None declared, Arpana Verma: None declared, Kimme Hyrich Consultant of: Honoraria from Abbvie, Grant/research support from: Grant income from Pfizer and BMS.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier B.V,Elsevier Limited
• Subject: Angina / bDMARD / Cardiovascular disease / Cerebral infarction / Cholesterol / Comorbidity / Death / Diabetes mellitus / Dyslipidemia / Heart attacks / Heart diseases / Interleukin 6 / Ischemia / Low density lipoprotein / Lung diseases / Methotrexate / Myocardial infarction / Patients / Rheumatoid arthritis / Scientific Abstracts / Steroid hormones / Thromboembolism / TNF inhibitors / Tumor necrosis factor-TNF