Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor Treatment in Hidradenitis Suppurativa: A Population-Based Retrospective Cohort Study of Comorbid Risks.

Monoclonal antibodies targeting tumor necrosis factor-alpha (TNF-α) have transformed the management of moderate-to-severe hidradenitis suppurativa (HS). However, their broader safety profile remains underexplored. Using the TriNetX database, 15,416 patients with HS treated with TNF-α inhibitors (infliximab, adalimumab, certolizumab pegol, golimumab) and 201,737 untreated controls were identified. Untreated controls were defined as patients with HS who had no documented exposure to TNF-α inhibitors. This group may have included patients receiving alternative systemic therapies such as antibiotics, hormonal therapies, or non-TNF biologic agents. After propensity score matching, new-onset comorbidities, including tuberculosis, sepsis, autoimmune hepatitis, inflammatory bowel disease, and sarcoidosis, were assessed. TNF-α inhibitor use was associated with increased risk of several clinically relevant outcomes, including tuberculosis (risk ratio or RR 3.15), inflammatory bowel disease (RR 9.35), and psoriasis (RR 5.36), whereas opportunistic infections were not significantly increased. Limitations of the study included reliance on diagnostic coding and an inability to stratify by treatment duration or socioeconomic status. These findings emphasize the need for longitudinal studies examining the biologic safety and development of comorbidities in HS. Awareness of these associations can guide clinical monitoring and patient counseling regarding TNF-α inhibitor therapy.