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Comparative Study
. 2024 Jun 17;10(2):e003885.
doi: 10.1136/rmdopen-2023-003885.

Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database

Ryoko Sakai  1   2 , Eiichi Tanaka  2   3 , Eisuke Inoue  4 , Masayoshi Harigai  5   3
Affiliations
Comparative Study

Increased risk of cardiovascular events under the treatments with Janus kinase inhibitors versus biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a retrospective longitudinal population-based study using the Japanese health insurance database

Ryoko Sakai et al. RMD Open. .

Abstract

Objectives: To compare the risk of cardiovascular events among Janus kinase inhibitors (JAKIs), biological disease-modifying antirheumatic drugs (bDMARDs) (tumour necrosis factor inhibitors (TNFIs) and non-TNFIs) and methotrexate (MTX) in Japanese patients with rheumatoid arthritis (RA).

Methods: Using Japanese claims data, patients with RA were enrolled in this study if they had at least one ICD-10 code (M05 or M06), were new users of JAKIs, bDMARDs or MTX between July 2013 and July 2020 and being 18 years old or older. The incidence rate (IR), IR ratio and adjusted hazard ratio (aHR (95% CI)) of cardiovascular events including venous thromboembolism, arterial thrombosis, acute myocardial infarction and stroke were calculated. A time-dependent Cox regression model adjusted for patient characteristics at baseline was used to calculate aHR.

Results: In 53 448 cases, IRs/1000 patient-years of the overall cardiovascular events were 10.1, 6.8, 5.4, 9.1 and 11.3 under the treatments with JAKIs, bDMARDs, TNFIs, non-TNFIs and MTX, respectively. The adjusted HRs of JAKIs for overall cardiovascular events were 1.7 (1.1 to 2.5) versus TNFIs without MTX and 1.7 (1.1 to 2.7) versus TNFIs with MTX.

Conclusions: Among patients with RA, individuals using JAKIs had a significantly higher risk of overall cardiovascular events than TNFIs users, which was attributed to the difference in the risk between JAKIs and TNFIs versus MTX. These data should be interpreted with caution because of the limitations associated with the claims database.

Keywords: arthritis, rheumatoid; biological therapy; cardiovascular diseases; epidemiology.

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Conflict of interest statement

Competing interests: Ryoko Sakai has nothing to declare. Eiichi Tanaka has received research funding from Pfizer Inc., UCB Japan Co. Ltd, and has received lecture fees or consulting fees from AbbVie, Asahi Kasei Pharma Co., Astellas Pharmaceutical, Ayumi Pharmaceutical, Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical, Daiichi-Sankyo, Inc., Eisai Pharmaceutical, Eli Lilly Japan K.K., Gilead Sciences, Inc., GlaxoSmithKline K.K., Kyowa Pharma Chemical Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical, and Teijin Pharma Ltd., and Viatris Japan. Eisuke Inoue has received lecture fees or consulting fees from Nippn tect systems Co., Ltd., Cyberdine Inc., Bristol-Myers Squibb, Eisai Co., Ltd., and Chugai Pharmaceutical Co., Ltd. Masayoshi Harigai has received grants or contacts from AbbVie Japan GK, Asahi Kasei Corp., Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Kaken Pharmaceutical Co., Mitsubishi 16 Tanabe Pharma Co., Mochida Pharmaceutical Co., Nippon Shinyaku Co., Ltd., Taisho Pharmaceutical Co., Ltd., Teijin Pharma Ltd., UCB Japan Co., Ltd., and Viatris Japan, and has received lecture fees or consulting fees from Bristol Myers Squibb Co., Ltd., Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AbbVie Japan GK, AbbVie Japan GK, Asahi Kasei Corp., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Gilead Sciences Inc., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Taisho Pharmaceutical Co., Ltd., Teijin Pharma Ltd and UCB Japan.

Figures

Figure 1
Figure 1
Patients selection flowchart. Figure shows the selection process of the study population. *Prescription of either JAKIs, bDMARDs nor MTX 6 months prior to the index month for MTX new users; no prescription of bDMARDs irrespective of MTX or JAKIs 6 months prior to the index month for bDMARDs new users; no prescription of JAKIs irrespective of MTX or bDMARDs for new users of JAKIs. bDMARDs, biological disease-modifying antirheumatic drugs; JAKIs, Janus kinase inhibitors; MTX, methotrexate; RA, rheumatoid arthritis.
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References

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