P629 Long-term effectiveness and safety of ustekinumab (UST) in patients with active Crohn’s disease (CD) in real life: Interim analysis of the SUSTAIN study
Authors: Chaparro M , Sulleiro S , Bastón-Rey I , Rodríguez C , García-Tercero I , Ramírez P , García-López S , Rojas-Feria M , Gutiérrez A , Huguet Malavés J M , García-Sepulcre M F , Sicilia B , Bermejo F , Rodríguez-Moranta F , Argüelles F , Marín I , Leo E , Arroyo M , García M J , Vázquez J M , Ginard D , Martínez Cadilla J , Rubín de Célix C , García-Herola A , Hernández-Camba A , Martín-Arranz M D , Riestra S , Varela P , Velayos B , Busquets D , Dueñas C , Fernández-Salgado E , Martínez-Montiel P , Diz-Lois M T , González-Lama Y , Muñagorri A , Navarro-Llavat M , Guisado C , Barreiro-de Acosta M , Gisbert J P 
Published: January 2020

Abstract

Background
Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice.

Methods
Retrospective, multicentre study (&gt;60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) &gt;4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring.

Results
331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2).

Conclusion
Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.