P717 Use of tramadol versus traditional opioids and adverse outcomes of Inflammatory Bowel Diseases: a Danish nationwide cohort study

Dalal, R.(1)*;Lund, K.(2);Zegers, F.(2);Friedman, S.(1);Allegretti, J.(1);Norgard, B.(2);

(1)Brigham and Women's Hospital- Harvard Medical School, Gastroenterology- Hepatology and Endoscopy, Boston, United States;(2)Odense University Hospital, Clinical Epidemiology, Odense, Denmark;

Background

Patients with inflammatory bowel diseases (IBD) commonly suffer from pain that requires analgesic therapies such as tramadol and opioids. However, use of traditional opioids (TOs) has been associated with severe infections and mortality in this population. Tramadol, a partial agonist of opioid receptors, has been considered to have less abuse potential compared to TOs. It is unknown if tramadol is associated with fewer IBD-related complications compared to TOs.

Methods

This was a Danish nationwide cohort study examining adverse outcomes associated with use of tramadol vs TOs in the IBD population. Patients with IBD (ICD-10 codes K50 and K51) diagnosed 1995-2021 in Denmark with subsequent prescriptions for tramadol or TOs were included. For each drug exposure, two populations were defined: initial users (“IUs”; first prescription after IBD diagnosis) and persistent users (“PUs”; first 3 consecutive prescriptions within 365 days after IBD diagnosis). Outcomes included severe (hospital-diagnosed) infection, bowel obstruction or ileus, IBD surgery, and mortality within 90 days after the IU index date (i.e. date of first prescription) and within 365 days after the PU index date (i.e. date of third prescription) (Figure 1). Multivariable logistic regression was performed to determine associations of tramadol vs TOs with outcomes while adjusting for age, sex, Charlson comorbidity index, year of IBD diagnosis, IBD type, IBD duration, and prior immunomodulator use, corticosteroid use, IBD hospitalization, severe infection, bowel obstruction or ileus, and IBD surgery within 6 months before the index date. A sensitivity analysis was performed in which patients with any diagnosis of a malignant neoplasm (ICD-10 codes C00-99) <1 year prior to the first tramadol or TO prescription were excluded.

Results

We identified 37,377 IUs and 15,237 PUs of tramadol or TOs. Baseline characteristics are presented in Table 1. IUs of tramadol had lower odds of severe infection (adjusted odds ratio [aOR] 0.80, 95% CI 0.65-0.99), bowel obstruction or ileus (aOR 0.74, 95% CI 0.53-1.03), and mortality (aOR 0.43, 95% CI 0.35-0.55), and higher odds of IBD surgery (aOR 1.27, 95% CI 1.02-1.60) vs TOs. PUs of tramadol had lower odds of severe infection (aOR 0.69, 95% CI 0.55-0.86), bowel obstruction or ileus (aOR 0.58, 95% CI 0.39-0.85), and mortality (aOR 0.35, 95% CI 0.28-0.44) but no difference in IBD surgery (aOR 1.13, 95% CI 0.86-1.47) vs TOs (Table 2). Results were unchanged after excluding patients with malignancy (Table 3).


Conclusion

Use of tramadol was associated with lower odds of severe infection, bowel obstruction or ileus, and mortality vs use of TOs among patients with IBD. Safety comparisons of tramadol to other analgesics are needed.