Introduction

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

Aims & Methods

IBD patients (aged ≥ 18 years) who lengthened their UST interval from Q8W to Q12W (Q12W group) 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 (Harvey Bradshaw Index ≤ 5 or Simple Clinical Colitix Activity Index ≤ 2 and C-reactive protein ≤ 10 Mg/L and fecal calprotectin ≤ 250 µg/g) and had to be on a stable Q8W interval for at least six months. The interval was lengthened at discretion of the treating physician.
The control group consisted of patients previously included in the registry (March 2016 - July 2022) and 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 any change in dosage interval or re-induction during the follow-up period. The primary outcome was 24-week and 52-week cumulative drug survival computed by the Kaplan-Meier method and compared using the log-rank test.

Results

In total, 105 Q12W patients and 88 control patients were included (table 1). Currently, 93 Q12W patients have completed 24 weeks of follow-up and 61 patients 52 weeks. 92.4% of the Q12W group versus 96.6% of the control group were previously treated with anti-TNF therapy and 29.5% versus 34.1% with vedolizumab (p=0.351 and p=0.497, respectively). Cumulative drug survival at 24- and 52 weeks was comparable between the Q12W group and control group (83.8% vs 88.6% (p=0.370) and 70.2% vs 76.1% (p= 0.451), respectively). The weighted analysis showed no difference in drug survival between the two groups. The median time to drug event was 5.2 months (0.3 – 11.4). Of the 26 drug events in the Q12W group, one patient stopped UST because of a malignancy, one switched to vedolizumab due to an allergic reaction, two switched to ozanimod due to loss of response and 24 intensified their UST interval (one to Q10W, 18 to Q8W, one to Q6W and two to Q4W).

Table 1. Baseline characteristics and outcomes of patients who lengthened their UST interval to every 12 weeks versus those who continued on an 8-weekly interval

Conclusion

Lengthening the UST interval from every 8 weeks to every 12 weeks appears to be safe and effective in the majority of IBD patients who are in stable remission on an 8 weekly interval. Further research should focus on identifying patients at lowest relapse risk after lengthening UST dosing intervals and the role of UST trough levels.

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.