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

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 (>60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) >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.

Systematic review with meta‐analysis: loss of response and requirement of ustekinumab dose escalation in inflammatory bowel diseases

“…On the other hand, three factors were associated with a lower risk of LOR, including colonic disease (Montreal classification L2 vs L1), 30 ileocolonic diseases (Montreal classification L3 vs L1) 30 and concurrent immunomodulation therapy (yes vs no) 30 . Of note, neither Chaparro et al 23 nor Hanauer et al (data not shown) 24 identified concurrent immunomodulation therapy as a significant predictor of LOR. Details are shown in Figure 5.…”

“…The characteristics of the included studies are shown in Tables 1 and S4. Eight studies were full‐text articles, 5,22,25,26,29,30,32,33 and six were conference abstracts 21,23,24,27,28,31 . Three studies were multicentre randomised controlled trials, 5,24,31 and the remaining 11 were retrospective cohort studies (six multicentres and five single centres) 21‐23,25‐30,32,33 .…”

“…Eight studies reported a regained response after dose escalation among CD patients who lost response to ustekinumab (Table 2). 5,23,25,27‐30,33 The random effects pooled clinical response rate was 58% (95% CI 49–67%, I 2 = 47%, P = .07, 279 patients; Figure 4A). The subgroup analyses demonstrated similar estimates of clinical response rates after dose escalation by publication type, study design, induction regimen, maintenance regimen, and dose escalation modality (Figure 4B).…”

“…Eight studies were full-text articles, 5,22,25,26,29,30,32,33 and six were conference abstracts. 21,23,24,27,28,31 Three studies were multicentre randomised controlled trials, 5,24,31 and the remaining 11 were retrospective cohort studies (six multicentres and five single centres). [21][22][23][25][26][27][28][29][30]32,33 Thirteen studies included CD patients, 5,[21][22][23][24][25][26][27][28][29][30]32,33 and one included UC patients.…”

“…Eight studies reported a regained response after dose escalation among CD patients who lost response to ustekinumab (Table 2). 5,23,25,[27][28][29][30]33 The random effects pooled clinical response rate was 58% (95% CI 49-67%, I 2 = 47%, P = .07, 279 patients;…”