Abstract Background AntiTNF agents (infliximab, adalimumab) remain the cornerstone for preventing and treating post-operative recurrence (POR) in Crohn’s disease (CD), even in individuals who failed them preoperatively (1-3). However, evidence is limited about the use of a second anti-TNF versus newer biologic agents in the case of primary or secondary failure to a first-line anti-TNF (4). Our retrospective study aimed to evaluate the efficacy of alternative biologic therapies in patients with postoperative Crohn’s disease who have failed anti-TNF-alpha therapy. Methods We retrospectively collected data in CD patients with POR. The primary aim was to assess the efficacy of a second-line therapy in terms of clinical response and endoscopic remission at the end of induction (T1), after one year (T2), and long-term follow-up (T3). Clinical response was defined as Harvey-Bradshaw Index (HBI) 5 or ≥ 3-point reduction. Endoscopic remission was defined as Simple Endoscopic Score for CD (SES-CD) 4 or Rutgeerts’ i2b. Secondary aims included comparing a second anti-TNF versus other biologics. Adverse events were recorded. Results We included 40 CD patients (57.7% male; mean age 52.7 ± 12.4 years; disease duration 20.1 ± 11.6 years). Demographic characteristics are shown in Table 1. Mean HBI was 5.8 ± 4.0 at baseline, 4.2 ± 3.3 at T1, and 4.4 ± 4.1 at T2. Clinical response was observed in 29 (72.5%) patients at T1 and T2. None of them were in endoscopic remission according to SES-CD at T1, and only one patient (2.5%) was in endoscopic remission at T2. 3 (7.5%) patients were in endoscopic remission according to Rutgeerts’ score. Second-line therapies included infliximab (n = 2), adalimumab (n = 3), vedolizumab (n = 9), ustekinumab (n = 24), and one case each of upadacitinib and risankizumab. Clinical response for each therapy is shown in Figure 1. During the long-term period (40.1±23.7 months), 19 (47.5%) patients discontinued therapy, 14 (73.7%) for failure, 1 (5.3%) for adverse events, 3 (15.8%) for new surgery, and 1 (5.3%) for deep remission. Only two (5%) adverse events have been recorded; one under Upadacitinb (increase of CPK) and one under Ustekinumab (perianal abscess); however, only the perianal abscess led to a discontinuation of the drug. Conclusion In postoperative CD with prior anti-TNF failure, switching to another anti-TNF or to ustekinumab resulted in comparable clinical response rates in this single-centre retrospective cohort. Multicentre studies are needed to clarify the optimal second-line strategy. References: 1. Lichtenstein GR, Loftus EV Jr, Isaacs KL, et al. ACG clinical guideline: management of Crohn’s disease in adults. Am J Gastroenterol. 2018;113(4):481-517 2. Gordon H, Minozzi S, Kopylov U, et al. ECCO guidelines on therapeutics in Crohn’s disease: medical treatment. J Crohns Colitis. 2024;18(10):1531-1555. doi:10.1093/ecco-jcc/jjae091 3. Le Cosquer G, Altwegg R, Rivière P, et al. Prevention of postoperative recurrence of Crohn’s disease among patients with prior anti–TNFα failure: a retrospective multicenter study. Dig Liver Dis. 2023;55(6):727-734. doi:10.1016/j.dld.2022.09.004 4. Gisbert JP, Chaparro M. Anti-TNF agents and new biological agents (vedolizumab and ustekinumab) in the prevention and treatment of postoperative recurrence after surgery in Crohn’s disease. Drugs. 2023;83(13):1179-1205. doi:10.1007/s40265-023-01916-2 Conflict of interest: Cannatelli, Rosanna: No conflict Dr. Ferretti, Francesca: No conflict of interest Carvalhas Gabrielli, Anna Maria: No conflict of interest Massari, Alessandro: No conflict of interest Del Zanna, Elena: No conflict of interest Maconi, Giovanni: No conflict of interest
Cannatelli et al. (Thu,) studied this question.