Tumor Necrosis Factor-Alpha Inhibitor Use and Malignancy Risk: A Systematic Review and Patient Level Meta-Analysis
by
, , , ,
Conor B. Driscoll
1,*
,
Jordan M. Rich
1,
Dylan Isaacson
1,
Joseph Nicolas
1,
Yu Jiang
2,
Xinlei Mi
3,
Christopher Yang
1,
Victoria Kocsuta
1,
Regine Goh
1,
Niti Patel
4,
Eric Li
1,
Mohammad Rashid Siddiqui
1,
Travis Meyers
5,
John S. Witte
2,6,
Linda Kachuri
2,6,
Hui Zhang
3
,
Molly Beestrum
7,
Philip Silberman
8,
Edward M. Schaeffer
1 and
Shilajit D. Kundu
1 1
Department of Urology, Northwestern University Feinberg School of Medicine, 676 North St Clair Street, Suite 2300, Chicago, IL 60611, USA
2
Department of Epidemiology and Population Health, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA
3
Division of Biostatistics, Department of Preventative Medicine, Northwestern University Feinberg School of Medicine, 680 N. Lake Shore Dr, Suite 1400, Chicago, IL 60611, USA
4
Department of Medicine, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Arkes Suite 2330, Chicago, IL 60611, USA
5
Department of Epidemiology and Biostatistics, University of California at San Francisco, 550 16th St., Floor 2, San Francisco, CA 94143, USA
6
Department of Biomedical Data Science, Stanford University, 1265 Welch Road MC5464MSOB West Wing, Third Floor, Stanford, CA 94305, USA
7
Galter Health Sciences Library and Learning Center, Northwestern University, 303 E Chicago Ave #2-212, Chicago, IL 60611, USA
8
Department of Information Technology, Northwestern University Feinberg School of Medicine, 710 N. Lake Shore Dr, Abbott Hall, 4th Floor, Chicago, IL 60611, USA
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(3), 390; https://doi.org/10.3390/cancers17030390
Submission received: 26 November 2024
/
Revised: 16 January 2025
/
Accepted: 22 January 2025
/
Published: 24 January 2025
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
Simple Summary
TNF-α inhibitors are widely prescribed immunosuppressive medications for multiple chronic inflammatory disorders. Chronic immunosuppression can lead to malignancy due to decreased immune surveillance, but TNF-α inhibitors have been found to be largely safe aside from the development of non-melanoma skin cancer. However, these studies all have short-term follow-up, rely on spontaneous reporting systems, and investigate a disease or drug subset. Previous meta-analyses similarly have investigated either interventional or observational studies only. Here, we reviewed over 17,000 abstracts with the most stringent inclusion criteria in the published literature to analyze 46 interventional studies and 10 observational studies for malignancy risk in patients exposed to TNF-α inhibitors. Using patient-level data, our findings for both interventional and observational studies found no statistically significant increased risk of malignancy but with poor quality of adverse event reporting. This is the most comprehensive and up-to-date meta-analysis and underscores the need for high-quality studies with a longer follow-up of these patients.
Excerpt
Note: In lieu of an abstract, this is an excerpt from the first page.
Over the last two decades, tumor necrosis factor-alpha inhibitors (TNF-Is) have become standard therapies for chronic inflammatory disorders, with an ongoing expansion of indications and off-label applications [...]
Keywords:
meta-analysis; cancer; TNF-alpha; adalimumab; infliximab; etanercept; certolizumab; golimumab
