Introduction

We conducted a retrospective cohort study to evaluate the risk of serious infections in patients with Ulcerative Colitis (UC) initiating advanced biological or small molecule therapies

Aims & Methods

Using a large U.S. administrative, Optum Labs® database, we identified adult UC patients who initiated treatment with either tumor necrosis factor-α (TNF) antagonists (infliximab, adalimumab, and certolizumab pegol), IL-12/23 antagonists (ustekinumab), IL-23 antagonists (risankizumab), anti-integrin agents (vedolizumab), S1PR modulators (ozanimod), or Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) between 2016-2023. Eligible patients had at least one year of continuous insurance enrollment before and after treatment initiation. The primary outcome was the incidence and risk of serious infections requiring hospitalization. We used stabilized inverse probability of treatment weighting (IPW) based on multinomial propensity scores to balance baseline patient and disease characteristics. Comparative risk of serious infections was assessed through Cox proportional hazards models incorporating stabilized weights.

Results

A total of 9,430 UC patients were included (mean age: 47.5 ± 17.7 years; 49.2% female; 50% on concomitant corticosteroids), followed for a mean duration of 2.3 ± 0.8 years. The incidence rates (IR) per 100 person-years of serious infections were: TNF antagonists (n = 4,111; IR: 6.08 [5.47; 6.70]), vedolizumab (n = 3,165; IR: 5.03 [0.44; 5.65]), IL-12/23 or IL-23 antagonists (n = 1,342; IR: 4.25 [3.34; 5.21]), S1PR modulators (n = 111; IR: 5.17 [1.03; 10.34]) and JAK inhibitors (n = 701; IR: 4.09 [2.79; 5.49]). Risk of serious infections was lower with JAK inhibitors and IL-12/23, or IL-23 antagonists compared to TNF antagonists, and lower with IL-12/23 or IL-23 antagonists compared to vedolizumab. Hazard ratios are represented in the table 1.

Table 1: Risk of serious infections in patients with ulcerative colitis taking advanced biological therapies

Conclusion

In this large real-world cohort of UC patients, initiation with newly developed efficaeous agents like JAK inhibitors and drugs inhibiting the IL-23 pathway was associated with a lower risk of serious infection compared to TNF antagonists.

Disclosure

CM: Consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Mirador Therapeutics, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Eli Lilly, Ferring, Pfizer.
VJ: Consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
SS: Research grants from Pfizer