Insights from a veteran cohort: Does tumor necrosis factor-alpha (TNF-α) inhibitor use impact COVID-19 breakthrough infection risk in vaccinated dermatology patients?

Summary: Abstract Body: This study evaluated whether TNF-α inhibitor use influenced the frequency, timing (relative to last COVID-19 vaccination), or severity of COVID-19 breakthrough infections(BTIs) among dermatology patients in the Veterans Health Administration. Using a nationwide retrospective cohort design, we analyzed data from 20,304 patients receiving TNF-α inhibitors and 115,667 controls not on biologics, systemic steroids, or immunosuppressants. All participants were vaccinated against COVID-19 and received dermatologic care between January 1, 2017, and December 1, 2024. BTI incidence, timing, and severity were assessed using Kaplan-Meier survival analysis and Cox proportional hazards regression. Among TNF-α inhibitor users, 10.8% experienced BTIs compared to 12.7% of controls, with similar times from COVID-19 vaccination to BTI(median: 228 vs. 242 days; mean: 298 vs. 305 days; p = 0.205). BTI severity was milder in TNF-α inhibitor users, with lower 30-day mortality (0.8% vs. 1.6%; p < 0.001). Patients on TNF-α inhibitors were younger (mean age: 61.0 vs. 67.8 years; p < 0.001), more likely female (14.5% vs. 11.4%; p < 0.001), and had fewer comorbidities (Charlson Comorbidity Index 2.14 vs. 2.72; p < 0.001). Psoriasis was the predominant dermatologic condition in the TNF-α inhibitor group (67.4% vs. 12.9%; p < 0.001). After adjusting for race, age, sex, overall health, dermatologic condition, and COVID-19 boosters, the hazard ratio for developing a COVID-19 BTI among TNF-α inhibitor users compared to controls was 0.99 (95% CI: 0.94–1.04; p = 0.6). Kaplan-Meier analysis showed a 50% infection-free survival rate approximately 8 months post-vaccination in both groups (p = 0.18). These findings suggest TNF-α inhibitor use does not increase BTI incidence, timing, or severity in dermatology patients. Both groups experienced waning immunity 8 months post-vaccination, supporting the need for ongoing boosters to sustain protection. Jacqueline Breunig^{1, 3}, Joyce Cheng³, Laura Romero^{2, 3} 1. Harvard T H Chan School of Public Health, Boston, MA, United States. 2. Veterans Health Administration, San Diego, CA, United States. 3. University of California San Diego, La Jolla, CA, United States. Clinical Research: Epidemiology and Observational Research