The association between long-term opioid therapy and composite infection-related dental outcomes

BACKGROUND: The Food and Drug Administration's warning that transmucosal buprenorphine, a partial opioid agonist used to treat opioid use disorder and chronic pain, may cause dental disease opens questions about potential class-wide adverse effects involving more widely prescribed opioid analgesics. METHODS: This was a retrospective matched national cohort study of patients in care at the Department of Veterans Affairs (VA) between October 2010-September 2019. Patients prescribed LTOT were matched 1:2 to patients not prescribed LTOT on age, sex, service region, and VA dental coverage. Cox regression models estimated the association between LTOT and a composite infection-related dental outcome (CIDO). Sensitivity analyses excluded patients with cancer, restricted to patients with comprehensive dental coverage, and to patients with ≥180 days of follow-up time, respectively. RESULTS: The cohort comprised 2,173,435 patients including 787,825 (36%) receiving LTOT; 612,101 (28%) experienced CIDO. In both simple and multivariable regression models, LTOT exposure was associated with greater CIDO risk; HR (95% CI) =1.24 (1.23, 1.25); aHR (95% CI) =1.08 (1.07, 1.08), respectively; p < 0.001. Sensitivity analyses showed similar results except among patients with full dental coverage for whom CIDO rates were substantially higher and LTOT was not statistically significantly associated with risk. CONCLUSIONS: he observed positive association between LTOT and CIDO in this large VA sample may inform patient-provider discussions and decision-making around use of LTOT. High CIDO rates among patients with full VA dental coverage may reflect their unique vulnerability to dental infection associated with service-related dental or disabling conditions. Limitations include risk for ascertainment bias, unclear generalizability to a broader clinical population, and the potential for residual confounding.