Abstract Background Optimal sequencing of therapy in Crohn’s disease after anti-TNF failure remains uncertain. We compared the real-world effectiveness and safety of vedolizumab and ustekinumab in this setting. Methods This retrospective multicenter cohort included 482 patients with moderate-to-severe Crohn’s disease from 14 tertiary centers in Türkiye who received vedolizumab (n = 247) or ustekinumab (n = 235) after ≥1 anti-TNF. Clinical remission (Harvey–Bradshaw Index 5) and steroid-free clinical remission at weeks 14 and 52 were primary outcomes. Long-term response, treatment persistence, and safety were also assessed using inverse probability of treatment weighting. Results At week 14, ustekinumab showed higher clinical remission (aOR = 1.49, 95% CI: 1.15–1.94) and steroid-free clinical remission (aOR = 1.42, 95% CI:1.10–1.83) than vedolizumab (Table 1). Superiority persisted in patients with prior biologic exposure, though outcomes were similar among those with ≥2 biologics (Figure 1). At weeks 52 and 104, clinical remission and steroid-free clinical remission rates were comparable between groups (Table 1). Treatment persistence was significantly greater with ustekinumab (78.5% vs 53.1% after inverse probability of treatment weighting; aOR = 3.22, 95% CI: 2.43–4.27), and secondary loss of response was lower (14.5% vs 38.5%, p 0.001). Adverse events were infrequent and similar across groups, with few serious events Conclusion In anti-TNF–experienced Crohn’s disease, ustekinumab provided superior early remission and higher treatment persistence compared with vedolizumab, while long-term efficacy and safety were similar. ustekinumab may be favored where rapid disease control and treatment durability are required, though both agents remain important therapeutic options. Conflict of interest: Sezgin, Orhan: Barutcu, Sezgin: No conflict of interest Dr. Araz, Filiz: No conflict of interest Bengi, Goksel: no conflicts Unal, Nalan Gulsen: No conflict of interest Akpinar, Hale: No conflict of interest Özer, Birol: No conflict of interest Hakim, Gozde: No conflict of interest Oruç, Nevin: No conflict of interest Karaogullarindan, Umit: No conflict of interest Altintas, Engin: No conflict of interest Ozseker, Burak: No conflict of interest Kasap, Elmas: No conflict of interest Ates, Fehmi: No conflict of interest Atay, Kadri: No conflict of interest Ucbilek, Enver: No conflict of interest Gişi, Kadir: No conflict of interest Kara, Banu: No conflict of interest Cekin, Ayhan Hilmi: No conflict of interest Akbay Harmandar, Ferda: No conflict of interest Yilmaz, Nimet: No conflict of interest Tasdogan, Burcak Evren: No conflict of interest Seydaoğlu, Gülşah: No conflict of interest Harput, Zekiye Nur: none Şahan, Mehmet Ali: No conflict of interest Aykut, Burak Mert: No conflict of interest Dolu, Süleyman: No conflict of interest Odabaş, Emre: No conflict of interest Kara, Taner: No conflict of interest Mamadov, Etibar: No conflict of interest Tuncel, Elif Tuğba: No conflict of interest Kuş, Mesut: No conflict of interest Çapar, Halil: No conflict of interest Çetin, Duran Deha: No conflict of interest Atar, Galip Egemen: No conflict of interest Yücel, Sevinç Püren: No conflict of interest
Sezgin et al. (Thu,) studied this question.