Risk of hematologic malignancies in psoriasis and rheumatoid arthritis patients using long term TNF-α inhibitors - Retrospective nationwide study

Q: Which TNF-α inhibitors were evaluated in the nationwide cohort study?

The study included etanercept, infliximab, adalimumab, and golimumab among Korean patients with psoriasis and rheumatoid arthritis.

Q: Did long-term TNF-α inhibitor use increase the risk of solid cancers overall?

Adjusted hazard ratios for colorectal, liver, lung, kidney, breast, and thyroid cancers were not significantly increased or decreased.

Q: Which TNF-α inhibitors showed statistically significant increased risks of hematologic malignancies?

Lymphoma risk increased significantly in infliximab users, while leukemia risk increased significantly in etanercept and adalimumab users.

Sep 23, 2026

Uploaded by Asher

Retrospective cohort evidence was generated from Korean users of tumor necrosis factor-α inhibitors (etanercept, infliximab, adalimumab, golimumab) for psoriasis and rheumatoid arthritis, compared with matched non-users diagnosed with the same diseases and never exposed to TNFi (N=7,645 users). Cumulative TNFi use was assessed between diagnosis and an index date 2 years later, with adjusted hazard ratios for major solid cancers showing no significant change. Statistically significant increases were observed for lymphoma in infliximab users and for leukemia in etanercept and adalimumab users, suggesting careful long-term prescribing.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Background

Rationale for long-term TNF-α inhibitor safety

Methods

Study design and population

Exposure window and statistical measures

Results

Study population characteristics

Site-specific cancer risk

Conclusions

Clinical implications for TNF-α prescribing

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Risk of hematologic malignancies in psoriasis and rheumatoid arthritis patients using long term TNF-α inhibitors: a retrospective nationwide study Jihun Song1, Seong Rae Kim2, Yu-Jin Kim3, Sun Jae Park1, Seogsong Jeong4 & Sang Min Park1,5􀀍 This retrospective cohort study included all user of tumor necrosis factor-α inhibitors (TNFi), including etanercept, infliximab, adalimumab, and golimumab, among Korean patients with psoriasis and rheumatoid arthritis (N of user = 7,645) and the non-user who was diagnosed with same diseases, never used TNFi, and was served as the reference. Cumulative usage of TNFi was calculated between the newly diagnosed date and index date (2-year from the diagnosed date). Adjusted hazard ratio (aHR [95% confidence intervals (CIs)]) for colorectal, liver, lung, kidney, breast, and thyroid cancer were not significantly increased or decreased: 0.92 [0.61–1.38], 0.90 [0.53–1.53], 1.00 [0.73–1.37], 1.20 [0.62–2.34], 0.91 [0.62–1.34], and 0.91 [0.66–1.26], respectively. The increased risk of lymphoma in the infliximab user (2.49 [1.33–4.66]; p < 0.01) was statistically significant. Similarly, the risk of leukemia increased significantly in the etanercept (3.87 [1.71–8.76]; p < 0.01) and adalimumab (3.36 [1.65, 6.84]; p < 0.001) user. Accumulated prescriptions ofTNFi for two years did not increase the incidence of cancer, except lymphoma and leukemia. Since the use of TNFi increases the risk of leukemia and lymphoma, a decision for frequent prescription ofTNF-α inhibitors should be more careful. Keywords Cohort study, TNF-alpha, Cancer, Leukemia, Lymphoma The long-term use of immunosuppressive drugs (immunosuppressant) raises many concerns, as they might be potentially harmful and then cause unforeseen diseases such as the initiation and development of cancer1,2. Biologics, which consist of mono-clonal antibody immunosuppressants such as tumor necrosis factor-alpha (TNF-α) inhibitors, are not exempt from these concerns as they usually disrupt the immune system3. In fact, since several biologics, including the most commonly used TNF-α inhibitors, were approved and introduced to the market in the mid-2000s and early 2010s, reports of their adverse and side effects have been continuously emerging4,5. Acute complications such as thrombosis and cardiovascular disease6,7 and long-term harmful events such as dementia and liver injury8,9 are reported. TNF-α, as a major mediator of inflammation, can easily disrupt the balance of immunity when its production and secretion are disrupted. Since TNF-α contributes to the destruction and recovery of tissue in chronic inflammatory conditions, inhibition and hypo-activation of TNF-α can cause serious diseases such as leukemia10, 11. Recently, anti-TNF-α (etanercept, infliximab, adalimumab, and golimumab) has been progressively used due to their high efficacy for autoimmune diseases. However, there is a lack of information and evidence although it is necessary to secure safety. From this perspective, one of the unexpected adverse outcomes is the potential association between long-term exposure to TNF-α inhibitors and cancer risk, which remains questionable. Previous studies suggested that TNF-α inhibitors could act as the risk factor for the increased risk 1Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea. 2Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea. 3Center for Biomaterials, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea. 4Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea. 5Department of Family Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, Republic of Korea. 􀀍 email: [smpark.snuh@gmail.com](smpark.snuh@gmail.com) [www. nature.com/s

FAQs

Which TNF-α inhibitors were evaluated in the nationwide cohort study?

The study included etanercept, infliximab, adalimumab, and golimumab among Korean patients with psoriasis and rheumatoid arthritis.

Did long-term TNF-α inhibitor use increase the risk of solid cancers overall?

Adjusted hazard ratios for colorectal, liver, lung, kidney, breast, and thyroid cancers were not significantly increased or decreased.

Which TNF-α inhibitors showed statistically significant increased risks of hematologic malignancies?

Lymphoma risk increased significantly in infliximab users, while leukemia risk increased significantly in etanercept and adalimumab users.

Sep 23, 2026

Uploaded by Asher