Comparative Effectiveness of Upadacitinib vs Ustekinumab for Ulcerative Colitis at 8-16 Weeks: A Multicenter Retrospective Cohort Study

Several advanced therapies for UC are now available that include ustekinumab, an inhibitor of IL-12/23 p40, and JAK inhibitors such as upadacitinib.^1,2 However, no clinical randomized trials have directly compared these agents. Real-world data have suggested similar effectiveness of tofacitinib and ustekinumab in the treatment of UC, but the comparative effectiveness of upadacitinib to ustekinumab has not been established.³ At the ACG 2023 Annual Scientific Meeting, Dalal and colleagues presented data from a multicenter retrospective cohort study of adults with UC who initiated treatment with either upadacitinib or ustekinumab for UC between January 2021 and February 2023.⁴ This study compared both clinical and endoscopic outcomes at weeks 8 to 16 among these patients.

This cohort included 70 patients treated with upadacitinib and 148 patients treated with ustekinumab. Baseline demographics were overall similar between groups. However, an important difference was the proportion of patients with experience with advanced therapies, which was higher in the upadacitinib group (100%) than in the ustekinumab group (79.1%). A similar proportion of patients in each group were receiving prednisone or oral budesonide at baseline (54.3% and 55.4%, respectively).

The analysis utilized inverse probability of treatment-weighted logistic regression to adjust for baseline differences in the treatment groups. Covariate balance was confirmed by requiring a standardized mean difference of less than 10%. The primary endpoint was clinical response at 8 to 16 weeks; secondary endpoints included corticosteroid-free clinical remission at 8 to 16 weeks and endoscopic response and remission within 52 weeks.

The unadjusted outcomes showed that a relatively higher proportion of patients in the upadacitinib group than in the ustekinumab group achieved the outcomes of clinical response (82.9% vs 63.5%, respectively), corticosteroidfree clinical remission (62.1% vs 34.7%, respectively), and endoscopic remission (37.5% vs 15.9%, respectively), as well as improved arthralgia (64.3% vs 23.4%, respectively) (Figure 2). Similar proportions of patients achieved the outcomes of endoscopic response (66.7% vs 63.6%, respectively), biochemical remission (60.9% vs 58.6%, respectively), and treatment discontinuation (10.0% vs 10.8%, respectively). Treatment discontinuation in both groups was primarily owing to nonresponse.

Figure 2.

Outcomes from a multicenter retrospective cohort study comparing patients with ulcerative colitis treated with upadacitinib vs ustekinumab.

Adapted from Dalal et al. Abstract 72. Presented at: ACG 2023; October 20-25, 2023; Vancouver, Canada.⁴

The results of the weighted logistic regression demonstrated a higher weighted odds ratio (OR) for clinical response (OR, 2.39; 95% CI, 1.04-5.49), corticosteroid-free clinical remission (OR, 3.17; 95% CI, 1.55-6.46), and endoscopic remission (OR, 5.10; 95% CI, 1.34-19.3), all of which favored upadacitinib over ustekinumab. There were similar odds of endoscopic response in both groups (OR, 1.49; 95% CI, 0.45-4.95).

The study investigators found higher odds of clinical response and corticosteroid-free remission at 8 to 16 weeks and endoscopic remission within 52 weeks for upadacitinib compared with ustekinumab. The main strength of the study was the successful balancing of covariates using inverse probability of treatment-weighted logistic regression, although limitations included the retrospective design. Additionally, the investigators noted there were incomplete data for certain markers of disease severity, such as C-reactive protein. Overall, these results suggest that among a largely bio-exposed population of patients with UC, upadacitinib may be more effective than ustekinumab for the induction of remission.