Risk of Infections With Ustekinumab and Tofacitinib Compared to Tumor Necrosis Factor α Antagonists in Inflammatory Bowel Diseases.

BACKGROUND & AIMS: The comparative safety of therapies is important to inform relative positioning within the therapeutic algorithm. Tumor necrosis factor α antagonists (anti-TNF) are associated with an increased risk of infections. Whether there is a similar increase with ustekinumab (UST) or tofacitinib has not been established.

METHODS

We identified patients with Crohn's disease or ulcerative colitis from a national commercial health insurance plan in the United States between 2008 and 2019. Infectious outcomes were ascertained for patients newly initiating anti-TNF, UST, or tofacitinib therapy. Cox proportional hazards models were fit in propensity score-weighted cohorts to compare rates between patients treated with UST or tofacitinib and anti-TNF therapy.

RESULTS

Our study included 19,096, 2420, and 305 patients with inflammatory bowel disease initiating anti-TNF, UST, and tofacitinib therapy, respectively. Over follow-up on-treatment, 7% and 44% of anti-TNF patients had infection-related hospitalizations and developed infections, respectively, compared with 4% and 32% of UST patients and 6% and 41% of tofacitinib patients. In the weighted Cox analysis, UST was associated with a significantly lower risk of infection (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.86-0.99) compared with anti-TNF therapy. There was a trend towards a reduction in infection-related hospitalizations (HR, 0.84; 95% CI, 0.66-1.03). The risk of infections (HR, 0.97; 95% CI, 0.75-1.24) or infection-related hospitalizations (HR, 0.59; 95% CI, 0.27-1.05) were similar between patients on tofacitinib and anti-TNF.

CONCLUSIONS

UST is associated with reduced risk of infections compared to anti-TNF biologics in inflammatory bowel disease, whereas no difference was observed between tofacitinib and anti-TNF therapy.