P1043 Efficacy of intravenous ustekinumab maintenance treatment in patients with Inflammatory Bowel Disease with partial response or loss of response to subcutaneous ustekinumab: A single centre, observational, retrospective study
Authors: Jarrín Pesantes V C , Moralejo Lozano Ó , Abanades Tercero M , Ruano Pérez L , Salmoral Luque R , Muñoz Rosas C , Gómez Rodríguez R Á 
Published: January 2025

Background

Ustekinumab (UST) is approved for patients with moderate to severe Crohn’s Disease (CD) and Ulcerative Colitis (UC) who do not respond to standard treatment and/or anti-TNF. Clinical remission at week 52 is reported up to 53,1-43,8%; however, up to 35% of patients experience loss of response over time. In this context, intravenous (IV) UST maintenance has been proposed as an alternative. Our aim is to evaluate the efficacy of UST IV maintenance in patients with Inflammatory Bowel Disease (IBD) with partial response or loss of response to subcutaneous (SQ) UST.

Methods

We conducted an observational, retrospective, unicentric study including patients with active IBD despite SQ UST. Primary endpoint is clinical remission defined as Harvey-Bradshaw Index (HBI) ≤4 for CD, and partial Mayo Score (pMS) ≤2 for UC. Biochemical remission is a secondary endpoint, defined as Fecal Calprotectin &lt;250μg/g, or C Reactive Protein (CRP) &lt;5mg/L. Other secondary endpoints are UST trough levels and any adverse effects. Variables are analyzed at week 12 and at the end of follow up.

Results

25 patients were included. Full demographic description can be found in Table 1. End of follow up for IHB was on day 127.5 (101.5, 215), and for pMS on day 112 (83, 173). In CD, clinical remission is significantly improved both at week 12 (baseline 37.5%, week 12 81.25%, p=0.0156) and at the end of follow up (75.0%, p=0.0312). Conversely, in UC, clinical remission shows no significant reduction (baseline: 22.22%, week 12: 22.22%, end: 55.56% [p=0.25]); however, pMS is significantly reduced at week 12 (baseline: 5.11 [SD 2.71]; week 12: 3.67 [SD 2.18], p=0.026) and at the end of follow up (2.78, SD 2.44, p=0.0407). Fecal calprotectin did not significantly decrease (baseline: 1900.4 [539, 2690]; week 12: 1580.95 [1006.8, 2111.2]; end 1689.3 [1006.8, 2192.7]; p&gt;0.05) nor showed significant biochemical remission (baseline: 4.35%; week 12: 18.18%; end: 17.39%; p&gt;0.05). Nevertheless, CRP had a significant decrease (baseline: 5.8 [2, 11.5]; week 12: 3.8 [2.1, 10.9] p=0.1382; end 3.6 [1.65, 7.85] p=0.0075), but not significant biochemical remission (baseline: 40%; week 12 56.52% p=0.1250; end 62.50% p=0.0703). No differences in Calprotectin or CRP results are noted if subgroups of CD or UC patients are analyzed. UST through levels increased throughout the study (baseline: 4.47 [SD 4.50]; week 12 8.45 [SD 3.69] p=0.1960; end: 11.02 [SD 4.22] p=0.0345). Adverse effects were recorded in 3/25 patients: arthralgias and asthenia, only one discontinuing due to them.

Conclusion

Intravenous UST maintenance treatment may be an alternative in IBD patients with partial response or loss of response to SQ UST, particularly in CD.

References

-Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease. N Engl J Med. 2016;375(20):1946-1960. doi:10.1056/NEJMoa1602773.

-Sands BE, Sandborn WJ, Panaccione R, et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2019;381(13):1201-1214. doi:10.1056/NEJMoa1900750.

-Suárez Ferrer C, Arroyo Argüelles J, Rueda García JL, et al. Intensification with Intravenous Ustekinumab in Refractory Crohn’s Disease. J Clin Med. 2024;13(3):669. Published 2024 Jan 24. doi:10.3390/jcm13030669.

-López-Sáez B, Brunet-Mas E, Melcarne L, et al. P895 Analysis of the efficacy of intravenous ustekinumab maintenance treatment in patients with refractory Inflammatory Bowel Disease. J Crohns Colitis. 2024;18(Suppl 1):i1643. doi:10.1093/ecco-jcc/jjad212.1025.