OP0135 RISK OF CARDIOVASCULAR EVENTS UNDER JANUS KINASE INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS: OBSERVATIONAL DATA FROM THE GERMAN RABBIT REGISTER

Autor: Y. Meissner, K. Albrecht, J. Kekow, S. Zinke, H. P. Tony, M. Schaefer, A. Strangfeld
Rok vydání: 2022
Předmět:
Zdroj: Annals of the Rheumatic Diseases. 81:86.2-87
ISSN: 1468-2060
0003-4967
Popis: BackgroundIn 2021, the European and US-American regulatory agencies EMA and FDA issued warnings about the cardiovascular (CV) safety of the Janus kinase inhibitor (JAKi) tofacitinib and required changes in labelling. These actions were based on results of the post-authorisation safety trial Oral Surveillance(1).ObjectivesTo analyse major cardiovascular events (MACE) under treatment with JAKi, tumor necrosis factor inhibitors (TNFi) or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs - bionaive) in patients with rheumatoid arthritis (RA) observed in daily rheumatological care.MethodsData from patients enrolled in the biologics register RABBIT with treatment episodes from 01/2017 - 04/2021 were included. Incidence rates (IR) of MACE per 100 patient-years (PY) with 95% confidence intervals (CI) and adjusted risk ratios (RR) were calculated for all and for high-risk patients (age ≥ 50 years and ≥ 1 CV risk factor). Poisson regression analysis was adjusted for age, sex, smoking, disease activity, prior therapies, glucocorticoids and comorbidities.ResultsStarting from 2017, 2030 JAKi, 2338 TNFi and 871 csDMARD initiations were documented. Patients with a JAKi start were slightly older, more often women and had a longer RA disease duration (Table 1). The proportion with positive autoantibodies was higher than in the TNFi and csDMARD group, the physical function was lower, and they had received more previous biologic treatments. Characteristics of high-risk patients are also given in the Table 1.Table 1.Patient characteristics at the start of a JAKi, TNFi or csDMARD.ALL PATIENTSHIGH RISK PATIENTS*JAKiTNFicsDMARDJAKiTNFicsDMARD# treatment starts2030233887112151254508Age59.9 ± 11.657.6 ± 13.059.5 ± 12.764.3 ± 8.963.5 ± 8.964.4 ± 9.2Women1573 (77.5)1707 (73.0)627 (72.0)907 (74.7)864 (68.9)355 (69.9)Disease duration12.6 ± 9.68.9 ± 8.55.7 ± 6.613.3 ± 9.99.7 ± 9.16.0 ± 7.0Rheumatoid factor/ ACPA positive1531 (79.2)1672 (74.2)548 (66.3)917 (79.7)890 (73.7)321 (66.5)# previous bDMARDs2.0 ± 1.80.7 ± 1.202.0 ± 1.80.7 ± 1.20DAS28-ESR4.2 ± 1.44.5 ± 1.44.2 ± 1.34.4 ± 1.54.7 ± 1.34.3 ± 1.3Percentage of full physical function63.3 ± 24.168.6 ± 22.472.3 ± 21.960.3 ± 24.264.4 ± 23.369.6 ± 22.7Glucocorticoids ≥10 mg/d170 (17.5)239 (21.5)49 (12.4)112 (18.6)142 (22.3)23 (10.0)BMI >30 kg/m2565 (28.2)631 (27.4)271 (31.7)383 (31.8)413 (33.3)180 (36.0)Sum of comorbidities2.9 ± 2.52.6 ± 2.42.2 ± 2.23.7 ± 2.63.5 ± 2.53.1 ± 2.3Current smokers461 (26.3)617 (28.5)274 (33.5)355 (33.5)466 (39.5)202 (42.3)Previous smokers551 (31.4)692 (31.9)230 (28.1)300 (28.3)338 (28.6)114 (23.9)Values are given as mean ± standard deviation or number (percentage). *Age ≥50 years and ≥ 1 CV risk factor (hypertension, coronary heart disease, diabetes, hyperlipoproteinaemia, current smoking)In total, 28 incident MACE were reported. Patients under treatment with JAKi, TNFi and csDMARD showed comparable IR for MACE between 0.26 and 0.41 events per 100 PY (Figure 1). High-risk patients showed higher IRs. The median time under treatment was 10 months on JAKi and TNFi, and 12 months on csDMARDs. The majority of events were reported in the first year after treatment start. In the adjusted analyses, JAKi (RR 0.94 [95% CI 0.39; 2.28]) and csDMARDs (RR 0.85 [0.25; 2.88]) did not show a significantly increased risk for MACE compared with TNFi in unselected patients, and also not in high-risk patients (JAKi: RR 0.90 [0.37; 2.17]; csDMARDs: RR 0.61 [0.16; 2.28]).Figure 1.Incidence rates of MACE per 100 patient years by treatment group.ConclusionIR of MACE in patients receiving JAKi in a real-world setting was lower than the IR reported for tofacitinib in the Oral Surveillance study. We found no evidence of an increased risk of MACE with JAKi compared to TNFi, although patients in the JAKi group were older and had longer disease duration.References[1]Pfizer Press Release (27 Jan 2021):https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-co-primary-endpoint-results-post-marketingAcknowledgementsRABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Fresenius-Kabi, Galapagos, Hexal, Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis, VIATRIS and UCB.Disclosure of InterestsYvette Meissner Speakers bureau: Pfizer, Katinka Albrecht: None declared, Jörn Kekow: None declared, Silke Zinke Speakers bureau: Biogen, Galapagos, UCB, Lilly, Consultant of: Abbvie, Biogen, Galapagos, Novartis, Hans-Peter Tony Consultant of: AbbVie, Astra-Zeneca, BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Martin Schaefer: None declared, Anja Strangfeld Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, Pfizer, Roche, Sanofi, UCB.
Databáze: OpenAIRE
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