Comparison of Upadacitinib Induction in Tofacitinib Exposed and Naive Patients With Inflammatory Bowel Disease: A Real World Multi-Center Study

Introduction: Upadacitinib (UPA) is a selective janus kinase (JAK) 1 inhibitor recently approved for the treatment of ulcerative colitis (UC) and Crohn’s disease (CD). It is unclear if previous exposure to non-selective JAK inhibitors such as tofacitinib impacts response rates to upadacitinib. The aim of this study is to compare clinical outcomes of UPA induction in inflammatory bowel disease (IBD) patients with and without previous exposure to tofacitinib. Methods: This was a multicenter study of consecutive patients with a diagnosis of inflammatory bowel disease who received UPA from 1/1/2022-6/1/2023. Data was abstracted for baseline demographics, disease location/phenotype, previous medication exposures, UPA dosing and duration. Outcomes were assessed at week 4, week 8 and week 16 post initiation of UPA. The primary outcomes were clinical response and steroid free clinical remission as evaluated by physician global assessment. Secondary outcomes included normalization of C-reactive protein (CRP < 5) and fecal calprotectin response (FCP < 250). Results: A total of 36 patients [median age 30 years (interquartile range (IQR) 24-41.8); 52.8% were male]. UPA was utilized for UC in 75% (n=27), CD in 19.4% (n=7) and IBD-unclassified in 5.6% (n=2) (Table 1). All patients received the 45 mg induction dose except 1 patient received 30 mg. Extended induction to 16 weeks was necessary in 33.3% (n=12). In the entire cohort, week 8 outcomes of clinical response were achieved in 84.9% (28/33), steroid free clinical remission in 56.3% (18/32), normal CRP in 58.3% (7/12) and FCP response in 22.2% (2/9). A total of 9 patients were previously exposed to tofacitinib (66.7% UC, 22.2% CD, 11.1% IBD-U; 44.4% were male). Extended induction beyond 8 weeks was necessary in 33.3% (3/9). Week 8 outcomes of clinical response were achieved in 75% (6/8), steroid free clinical remission in 50% (4/8). At week 16, 83.3% (5/6) of these patients achieved steroid free clinical remission. Conclusion: Upadacitinib resulted in steroid-free clinical remission in half (at week 8) and more than three-quarters (at week 16) of patients with IBD and previous exposure to tofacitinib. Clinical response and remission rates during induction with UPA were similar in tofacitinib exposed and naïve patients. Larger studies are needed to corroborate our findings. Table 1. - Baseline Characteristics Variable Value Age (years), median (IQR) 30 (24-41.8) Male, n (%) 19 (52.8) BMI, median (IQR) 25.4 (21.3-31.6) Disease duration (years), median (IQR) 5 (2-9.8) IBD subtype Crohn’s disease, n (%) 7 (19.4) L1 0 L2 2 L3 5 L4 0 B1 2 B2 0 B3 5 Perianal disease, n (%) 5 Ulcerative colitis, n (%)* 27 (75) Proctitis 1 Left-sided colitis 7 Pancolitis 20 Indeterminate colitis, n (%) 2 (5.6) Prior bowel resection, n (%) 5 (13.9) Current smoker, n (%) 1 (2.8) Previous advanced therapies, n (%) 35 (87.2) Mean number of biologics tried, median (IQR) 2 (1-3) Previous exposure to tofacitinib, n (%) 9 (25) Week 4 Week 8 Week 16 Clinical response Steroid-free clinical remission Clinical response Steroid-free clinical remission Clinical response Steroid-free clinical remission Tofacitinib -naïve, % (n) 95% (19/20) 45% (9/20) 88% (22/25) 58.3% (14/24) 89.5% (17/19) 63.2% (12/19) Tofacitinib exposed, % (n) 88.9% (8/9) 33.3% (3/9) 75% (6/8) 50% (4/8) 83.3% (5/6) 83.3% (5/6) IQR: interquartile range; BMI: body mass index; IBD: inflammatory bowel disease.