Comparative Safety of Advanced Therapies in Patients with Ulcerative Colitis: An Administrative Claims-based Study

We conducted a retrospective cohort study comparing the safety of advanced therapies in patients with ulcerative colitis (UC).

Using an administrative claims database (OptumLabs® Data Warehouse), we identified patients with UC who initiated treatment with tumor necrosis factor-α (TNF) antagonists, anti-integrin agents, anti-interleukin, Janus kinase inhibitors (JAK) or sphingosine-1 phosphate receptor (S1PR) modulators between 2016 and 2022 and had follow-up for at least 1y before and after treatment initiation. We compared risk of serious infections, venous thromboembolism (VTE), and major adverse cardiovascular events (MACE) through multinomial propensity score-based inverse probability weighting (IPW), with propensity scores estimated through generalized boosted models, accounting for disease characteristics, healthcare utilization, comorbidities, and prior and concomitant medications, and competing risk of mortality. We calculated cause-specific hazard ratios (HR) and 95% confidence intervals (CI) for multiple treatment comparisons.

We included 9,430 patients with UC treated with TNF antagonists (n=4,111), anti-integrins (n=3,165), anti-interleukins (n=1,342), JAK inhibitors (n=701) or S1PR modulators (n=111), followed over median 27 months. After adjusting for confounding variables, anti-interleukins were associated with lower risk of serious infections compared with TNF antagonists [HR,0.66 (95%CI, 0.51-0.87)] and anti-integrins [HR,0.75 (0.57-0.98)]. JAK inhibitors were associated with a lower risk of serious infections compared with TNF antagonists [HR,0.66 (0.46-0.94)]. The incidence of VTE (incidence rate, 1.4-2.0 per 100py) and MACE (0.5-1.0 per 100py) was very low, without any significant differences across agents.

In a real-world cohort of patients with UC, anti-interleukins and JAK inhibitors were associated with lower risk of serious infections and may offer net benefit, especially in patients with prior TNF antagonist exposure.