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Review
. 2025 Jan 24;17(3):390.
doi: 10.3390/cancers17030390.

Tumor Necrosis Factor-Alpha Inhibitor Use and Malignancy Risk: A Systematic Review and Patient Level Meta-Analysis

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 , Shilajit D Kundu  1
Affiliations
Review

Tumor Necrosis Factor-Alpha Inhibitor Use and Malignancy Risk: A Systematic Review and Patient Level Meta-Analysis

Conor B Driscoll et al. Cancers (Basel). .

Abstract

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: TNF-alpha; adalimumab; cancer; certolizumab; etanercept; golimumab; infliximab; meta-analysis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram (2020).
Figure 2
Figure 2
Malignancy rate ratio in patients exposed to any TNF-I excluding NMSC in interventional studies [47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91].
Figure 3
Figure 3
Calculated malignancy rate ratio in patients exposed to any TNF-alpha inhibitor (TNF-I) using cancers excluding non-melanoma skin cancer (NMSC) in 45 interventional studies for (A) adalimumab (ADA); (B) infliximab (INX); (C) etanercept (ETN); (D) certolizumab (CTZ); (E) golimumab (GOL) [47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91].
Figure 3
Figure 3
Calculated malignancy rate ratio in patients exposed to any TNF-alpha inhibitor (TNF-I) using cancers excluding non-melanoma skin cancer (NMSC) in 45 interventional studies for (A) adalimumab (ADA); (B) infliximab (INX); (C) etanercept (ETN); (D) certolizumab (CTZ); (E) golimumab (GOL) [47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91].
Figure 3
Figure 3
Calculated malignancy rate ratio in patients exposed to any TNF-alpha inhibitor (TNF-I) using cancers excluding non-melanoma skin cancer (NMSC) in 45 interventional studies for (A) adalimumab (ADA); (B) infliximab (INX); (C) etanercept (ETN); (D) certolizumab (CTZ); (E) golimumab (GOL) [47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91].
Figure 4
Figure 4
Malignancy rate ratio in patients exposed to any TNF-I excluding NMSC in observational studies [25,92,93,94,95,96,97,98,99,100].
Figure 5
Figure 5
Calculated malignancy rate ratio in patients exposed to any TNF-alpha inhibitor (TNF-I) using cancers excluding non-melanoma skin cancer (NMSC) in 10 observational studies for (A) adalimumab (ADA); (B) infliximab (INX); (C) etanercept (ETN) [25,92,93,94,95,96,97,98,99,100].
Figure 5
Figure 5
Calculated malignancy rate ratio in patients exposed to any TNF-alpha inhibitor (TNF-I) using cancers excluding non-melanoma skin cancer (NMSC) in 10 observational studies for (A) adalimumab (ADA); (B) infliximab (INX); (C) etanercept (ETN) [25,92,93,94,95,96,97,98,99,100].
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