P0723 Lengthening ustekinumab treatment intervals from every 8 to every 12 weeks in IBD patients in stable remission: preliminary results of a prospective observational cohort study

Background

Ustekinumab (UST) is registered as maintenance therapy for patients with inflammatory bowel disease (IBD) in an 8- (Q8W) or 12-weekly interval (Q12W) (1,2). Although Q12W might be associated with less side effects and reduced treatment costs (3), the majority of IBD patients are on Q8W as maintenance therapy (4). This study compares the UST drug-survival between IBD patients in stable remission who lengthen the UST interval from 8 to 12 weeks versus those who continue on 8 weeks.

Methods

Adult IBD patients who lengthened the UST interval from Q8W to Q12W were included in the prospective nationwide Initiative on Crohn and Colitis (ICC) Registry between July 2022 and May 2024. Patients were screened on clinical and biochemical remission (HBI≤ 4 or SCCAI≤ 2 and CRP≤ 10 Mg/L and FC≤ 250 µg/g) and had to be on a stable Q8W interval for at least six months. The interval was lengthened at the discretion of the treating physician. The control group consisted of patients previously included in the ICC registry (March 2016 - July 2022) who were in clinical and biochemical remission on Q8W at least one year after initiating UST. Inverse Probability of Treatment Weighting was used to adjust for confounding and selection bias. A drug event was defined as escalation of UST interval, IV re-induction or UST stop. Primary outcome was 24 and 52-week cumulative drug survival (4 weeks range).

Results

In total, 105 Q12W patients and 88 Q8W controls were included (table 1). Currently, 74 Q12W patients completed the follow-up period of 52 weeks. The cumulative drug survival at 24 and 52 weeks was comparable between the Q12W and control group (87.6% vs 90.9% and 64.0% vs 77.3% (p= 0.078), respectively). In the weighted analyses, 52 week drug survival was statistically different (Q12W 63.5% vs control 79.7%; p=0.04). In CD patients, the 52 week drug survival was slightly better than in the total cohort (Q12W 67.8% vs control 77.2%; p=0.32). Out of 34 drug events in the Q12W group, 1 patient stopped UST because of a malignancy (classified as not-drug related), 1 switched to vedolizumab due to an allergic reaction, 2 switched to ozanimod due to loss of response and 30 intensified their UST interval (1 to Q10W, 25 to Q8W, 3 to Q6W and 1 to Q4W). In the Q12W group, 8 patients (7.6%) started oral steroids, all in combination with an UST intensification, compared to 10 (11.4%) in the control group (p = 0.459), where 5 patients initiated steroids without an UST intensification.

Conclusion

Lengthening the UST interval from every 8 to every 12 weeks is safe and effective in approximately two-thirds of IBD patients in stable remission. Future studies should focus on identifying patients who will benefit the most from lengthening the UST interval.

References

1.Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med 2016 Nov 17;375(20):1946-1960

2.Sands BE, Sandborn WJ, Pannaccione R, O’Brien CD, Zhang H, et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med 2019 Sept 26; 381(13):1201-1214

3.Bai Y, Sun Y, He Q, Bai X, Yang H. Comparative effectiveness and safety of ustekinumab at different intervals of maintenance phase in inflammatory bowel disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2024 Apr 1;36(4):359-370

4.Straatmijer T, Biemans VBC, Hoentjen F, de Boer NKH, Bodelier AGL, Dijkstra G, et al. Ustekinuma b for Crohn’s Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study. J Crohns Colitis 2021 Nov 8;15(11):1920-1930.