Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study
BackgroundThe ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis...
| Main Authors: | , , , , , , , , , , , , |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267749/full |
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| author | Shuhei Yoshida Masayuki Miyata Eiji Suzuki Takashi Kanno Yuya Sumichika Kenji Saito Haruki Matsumoto Jumpei Temmoku Yuya Fujita Naoki Matsuoka Tomoyuki Asano Shuzo Sato Kiyoshi Migita |
| author_facet | Shuhei Yoshida Masayuki Miyata Eiji Suzuki Takashi Kanno Yuya Sumichika Kenji Saito Haruki Matsumoto Jumpei Temmoku Yuya Fujita Naoki Matsuoka Tomoyuki Asano Shuzo Sato Kiyoshi Migita |
| author_sort | Shuhei Yoshida |
| collection | DOAJ |
| description | BackgroundThe ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis.MethodsWe retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups.ResultsAfter PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67–7.42) for malignancy and 3.03 (95% CI: 0.77–15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23–2.97).ConclusionThe IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed. |
| first_indexed | 2024-03-11T19:48:22Z |
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| id | doaj.art-500f3f8aa0e34e498ccf9b9d180ceb89 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T19:48:22Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-500f3f8aa0e34e498ccf9b9d180ceb892023-10-05T15:25:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12677491267749Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort studyShuhei Yoshida0Masayuki Miyata1Eiji Suzuki2Takashi Kanno3Yuya Sumichika4Kenji Saito5Haruki Matsumoto6Jumpei Temmoku7Yuya Fujita8Naoki Matsuoka9Tomoyuki Asano10Shuzo Sato11Kiyoshi Migita12Department of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Japanese Red Cross Fukushima Hospital, Fukushima, JapanDepartment of Rheumatology, Ohta Nishinouchi General Hospital Foundation, Koriyama, JapanDepartment of Rheumatology, Ohta Nishinouchi General Hospital Foundation, Koriyama, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanDepartment of Rheumatology, Fukushima Medical University School of Medicine, Fukushima, JapanBackgroundThe ORAL Surveillance trial showed a potentially higher incidence of malignancy and major adverse cardiovascular events (MACEs) associated with tofacitinib than those associated with tumor necrosis factor (TNF) inhibitors (TNFis). However, few studies have compared the safety of non-TNFis or other Janus kinase (JAK) inhibitors (JAKis). This study was aimed at comparing the incidence rates (IRs) of malignancies and MACEs in patients with rheumatoid arthritis (RA) treated using interleukin-6 (IL-6) inhibitors (IL-6is) or JAKis.MethodsWe retrospectively analyzed 427 patients with RA who were treated using an IL-6i (n = 273) or a JAKi (n = 154). We determined the IRs of malignancy and MACEs, and the standardized incidence ratio (SIR) of malignancies and investigated factors related to malignancy and MACEs. After adjusting the clinical characteristic imbalance by propensity score matching (PSM), we compared the IRs of adverse events between the JAKi and IL-6i groups.ResultsAfter PSM, the observational period was determined to be 605.27 patient-years (PY), and the median observational period was determined to be 2.28 years. We identified seven cases of malignancy (IR: 2.94 per 100 PY) in the JAKi-treated group and five cases (IR: 1.36 per 100 PY) in the IL-6i-treated group after PSM. The IR of MACEs was 2.56 and 0.83 (per 100 PY) in the JAKi- and IL-6i-treated groups. The IRRs of JAKi-treated patients versus IL-6i-treated patients were 2.13 (95% confidence interval (CI): 0.67–7.42) for malignancy and 3.03 (95% CI: 0.77–15.21) for MACE. There were no significant differences in IRR for malignancy and MACE between both groups after PSM. Univariate and multivariable Cox regression analyses revealed that older age and JAKi use were independent risk factors for malignancy, while older age, hypertension, and JAKi use were independent risk factors for MACEs. The overall malignancy SIR was significantly higher in the JAKi-treated group compared to the general population (2.10/100 PY, 95% CI: 1.23–2.97).ConclusionThe IRs of malignancy and MACE in patients with RA after PSM were comparable between IL-6i-treated and JAKi-treated patients. However, the SIR of malignancy in JAKi treatment was significantly higher than in the general population; therefore, further safety studies comparing JAKi to non-TNFi biologic disease-modifying antirheumatic drugs (bDMARDs) are needed.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267749/fullrheumatoid arthritistofacitinibbaricitinibJAK inhibitorIL-6 inhibitormalignancy |
| spellingShingle | Shuhei Yoshida Masayuki Miyata Eiji Suzuki Takashi Kanno Yuya Sumichika Kenji Saito Haruki Matsumoto Jumpei Temmoku Yuya Fujita Naoki Matsuoka Tomoyuki Asano Shuzo Sato Kiyoshi Migita Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study Frontiers in Immunology rheumatoid arthritis tofacitinib baricitinib JAK inhibitor IL-6 inhibitor malignancy |
| title | Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study |
| title_full | Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study |
| title_fullStr | Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study |
| title_full_unstemmed | Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study |
| title_short | Safety of JAK and IL-6 inhibitors in patients with rheumatoid arthritis: a multicenter cohort study |
| title_sort | safety of jak and il 6 inhibitors in patients with rheumatoid arthritis a multicenter cohort study |
| topic | rheumatoid arthritis tofacitinib baricitinib JAK inhibitor IL-6 inhibitor malignancy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1267749/full |
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