P751 Off-label dose escalation of Ustekinumab in Inflammatory Bowel Disease patients. Safety profil of different patterns

Abstract

Abstract Background Approved maintenance regimens for UST in patients with inflammatory bowel disease (IBD) are 90 mg subcutaneously every 8 (Q8) or 12 weeks (Q12). In the real world, off-label dose escalation is frequently performed after inadequate response or loss of response, and has been shown to be effective. However, different dosing regimens are used and the best strategy is still unknown. Our aim is to evaluate the safety profile of UST dose escalation in IBD patients. Methods We performed an observational cohort study in 2 hospitals in Vigo-Spain. All patients who started UST between 1 June 2017 and 31 December 2022 to control their active IBD were enrolled. The primary endpoints were the rate of serious adverse events (AE) and the need to discontinue UST treatment in off-label dose escalation patients. Results 173 IBD patients received UST: females 53,8% (93), mean age 49.7(15.5) years, Crohn´s disease 82% (142), previous anti-TNF 93,6% (162) and vedolizumab 22,5% (39) (Table 1). At 16 weeks, subcutaneous UST was maintained Q8 in 110 (63.6%) and Q12 in 60 (34.7%). Dose escalation was performed in 56 patients (32,4%) with different patterns: 30 Q4 (54,5%), 12 intravenous reinduction plus Q4 (21,8%), 7 Q6 (12.7%) and 6 only intravenous reinduction (10,9). In 11 patients (6,4%) a second dose escalation was performed. 196 adverse events were reported in 95 patients (54,9%), mostly infections 63 (32,1%) and musculoskeletal disorders 46 (23,5%) (Figure 1). More than one AE was reported in 67 patients (38.7%), showing 2 AE in 41 (23.7%), 3 AE in 12 (6.9%) and 4 AE in 14 (8.1%). Twelve adverse events were considered serious (12,5%) as they lead to hospitalization and in 4 cases to discontinuation of treatment (0.02%). Infections were the most frequent cause of serious AE (50%). With a fmedian ollow-up time of 13,5 (11) months, IBD patients scheduled to off-label UST dose escalation regimens showed no higher incidence of AE or severe AE than standard regimens. Conclusion In IBD patients, off-label UST dose escalation showed a good safety profile. Most of the reported adverse events were mild infections that did not change the UST treatment regimen. The schemes of dose-escalation were very heterogeneous between the participants.