Ustekinumab combined with upadacitinib promotes endoscopic healing in moderate-to-severe Crohn's disease with anti-TNF-α failure.

BACKGROUND: Anti-tumor necrosis factor-α (TNF-α) therapy failure in moderate-to-severe Crohn's disease (CD) represents a major clinical challenge. However, the exploration of advanced combination therapy offers a promising direction. This study compared the efficacy of ustekinumab (UST) plus upadacitinib (UPA) with either agent as monotherapy in these patients. METHODS: In this multicenter, retrospective study, 110 moderate-to-severe CD patients with anti-TNF-α failure were categorized into three groups according to the treatment they received: UST + UPA 30 mg (n = 41), UST monotherapy (n = 40), or UPA 45 mg monotherapy (n = 29). The primary outcome was endoscopic remission at 12-24 weeks, with secondary outcomes including clinical remission, clinical and endoscopic response, and safety. RESULTS: Following 12-24 weeks of treatment, UST + UPA 30 mg demonstrated superior efficacy. The combination group achieved significantly higher rates of endoscopic remission (51.2% vs. 17.5% UST, 24.1% UPA; p = 0.0029). The clinical remission rate in the combination group (85.4%) was significantly higher than that in the UST group (37.5%, p < 0.0001) but not significantly different from that in the UPA group (75.9%, p = 0.3138). All groups exhibited improvements in disease activity scores and inflammatory bowel disease questionnaire from baseline. Treatment-related adverse events occurred in 19.5%, 2.5%, and 13.8% of patients in the combination, UST, and UPA groups, respectively, with no serious events reported. CONCLUSION: For moderate-to-severe CD patients with anti-TNF-α therapy failure, the UST combined with UPA 30 mg regimen showed superior endoscopic healing to either monotherapy, with a tolerable safety profile. These findings suggest that this combination strategy may represent an effective treatment option for such CD patients.