P740 Results at 52 weeks of Intravenous Ustekinumab as Maintenance Treatment in Patients with Loss of Response to Subcutaneous Doses: A Multicenter Retrospective Observational Study
Authors: Valdés Delgado T , González Antuña J , Javier Rodriguez González F , Gutierrez Martinez F , Maldonado Pérez B , Castro Laria L , Belvis Jiménez M , Caunedo Álvarez Á , Alcain Martinez G , Camargo Camero R , Martos Van Dussen J V , Fernández Castañer A , Argüelles-Arias F 
Published: January 2024

Background

Ustekinumab (UST) is indicated for the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). Despite having shown clinical effectiveness in the real world,some patients may lose response over time or need a higher dose to achieve it. In this context, UST intravenous (IV) maintenance has been proposed. The primary endpoint of our study was to evaluate the efficacy and safety of maintenance IV UST treatment in Inflammatory Bowel Disease (IBD) patients who present with partial response or loss of response to subcutaneous UST.

Methods

We performed a multicenter observational retrospective study including patients with active IBD on maintenance treatment with IV UST. The study conducted at 2 hospitals in Andalusia.The clinical response and remission was analyzed at week 12 and 52, defined as either Harvey-Bradshaw Index (HBI) ≤4 for CD or partial Mayo Score (pMS) ≤2 for UC. The reduction of objective markers of disease activity, fecal calprotectin (FCal) and C-reactive protein (CRP) was evaluated. Moreover, UST trough levels were measured pre-and post UST IV maintenance, drug persistence at the end of the follow-up and any adverse events were assessed.

Results

A total of 59 patients were included in the study, with a median age of 41 years [IQR32-52]. 84.7% (50/59) had Crohn's disease (CD). 91.5% (53/59) had previously received at least one biologic or JAK inhibitor treatment. 58.6% (34/59) werepreviously on subcutaneous UST every 4 weeks (Table 1).

In patients with CD, the median baseline HBI value was 9 (IQR 6-12), which decreased to 5 (IQR 4-7) at week 12 and 4 (IQR 3-6) at week 52 (p&lt;0.001) (Figure 2A). In patients with ulcerative colitis (UC), the median baseline pMayo value was 8.5 (IQR 6.5-9.0), which decreased to 5.5 (IQR 4.3-6.0) at week 12 and 3 (IQR 2.0-4.8) at week 52 (p=0.017) (Figure 2B). The median baseline FCal was 800.2 μg/g, which decreased to 520 μg/g at week 12 and 220 μg/g at week 52 (p&lt;0.001). Regarding CRP, the median baseline was 7.1 mg/L, which decreased to 4 mg/L at week 12 and 3 mg/L at week 52 (p&lt;0.001).

The median UST levels with subcutaneous maintenance treatment were 3.1 mcg/mL (IQR 1.1-7.4) compared to 12 mcg/mL (IQR 9-20) with intravenous treatment (p&lt;0.001) (Figure 2C).

Clinical remission at week 12 and 52, was achieved by 47,5% and 64,3% of the patients respectively. At the end of the follow-up, 96.6% of the patients continued with intravenous UST (Figure 2D). No adverse events were recorded in any patient for the duration of the study.

Conclusion

Intravenous UST for maintenance is able to rescue up to 64% of patients who have failed on subcutaneous doses. 97% of patients continue intravenous UST treatment after one year with an excellent safety profile. UST levels increase fourfold.