Oral Adverse Events Associated With Anti-tumor Necrosis Factor-alpha Therapies: Using a Large Real-world Dataset
Document Type
Article
Publication Title
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Abstract
Background
Anti-tumor necrosis factor-alpha (anti-TNF-α) therapies are efficacious in managing immune-mediated inflammatory diseases, however, long-term use has been associated with notable adverse events. As patients use expands, understanding the spectrum of oral adverse events (OAEs) has become essential.
Materials and methods
We conducted a retrospective cohort study using the TriNetX research network. A five‑year observation window identified patients prescribed anti‑TNF-α therapies. Patients with prior oral conditions, concurrent cancer therapies, or antiresorptive exposure were excluded. OAEs were categorized into xerostomia, mucosal disorders, infectious disorders, gingival hyperplasia, medication-related osteonecrosis of the jaw (MRONJ), and oral squamous cell carcinoma (OSCC). Propensity score matching (1:1, age/sex) compared anti‑TNF-α users with unexposed controls.
Results
In a cohort of 1,645,751 individuals receiving anti‑TNF‑α therapy, OAEs were frequent, with oral lichenoid lesions (1.27%, 20,135), candidiasis (1.09%, 17,475), xerostomia (0.87%, 14,024), stomatitis (0.68%, 10,904), and oral herpes (0.39%, 6,343) most commonly observed. Less frequent events included MRONJ (0.01%, 173), gingival hyperplasia (0.02%, 285), and OSCC (0.07%, 1,074). Compared with the general population, anti‑TNF‑α therapy significantly increased the odds of most mucosal and infectious conditions (P < 0.001), though oral lichen planus showed no association. Interestingly, OSCC exhibited an inverse association (OR = 0.75, P < 0.0001), suggesting a potential protective effect.
Conclusion
These findings highlight the importance of routine oral health surveillance and robust pharmacovigilance amongst patients on anti‑TNF-α therapies.
DOI
10.1016/j.oooo.2026.01.001
Publication Date
1-15-2026
Keywords
MRONJ, Oral squamous cell carcinoma, Oral complications, Oral mucosal disorders
ISSN
2212-4411
Recommended Citation
Oyewole SO, Olawuyi AB, Okhuaihesuyi O, Owosho AA. Oral Adverse Events Associated With Anti-tumor Necrosis Factor-alpha Therapies: Using a Large Real-world Dataset. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology. 2026; . doi: 10.1016/j.oooo.2026.01.001.
