P697 Efficacy and safety of ustekinumab in Crohn’s disease: A real-world study from Australia

Abstract

Background Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved in Australia for the treatment of adults with moderate to severe Crohn’s disease (CD) in 2017. The aim of this retrospective single centre study was to study the efficacy and safety of UST in CD in a real world cohort. Methods Patients with CD who began UST therapy between June 2017 and July 2019 were included. UST induction was given as an infusion (6 mg/kg) at week 0 followed by 90 mg subcutaneous injection (SC) at week 8 and 90 mg SC every 8 weeks as maintenance. Primary endpoint (PE) was steroid free clinical remission or steroid free clinical response at week 24. Secondary endpoints (SE) were: endoscopic response or remission, radiological response or remission, biochemical response (CRP < 5 mg/L or Calprotectin <150 μg/g), clinical response or remission at week 52. Results Seventy-six patients with CD were included in the study. 64.5% failed ≥1 anti-TNF and 13.1% failed anti-TNF and vedolizumab; 26(34.2%) patients were biologic-naïve. Median follow-up was 61 weeks. Ten patients (13.1%) discontinued UST, and the median time to discontinuation was 48 weeks; eight patients due to loss of response, one patient due to paradoxical worsening of arthralgia, one patient chose to stop treatment. Six patients underwent surgery whilst on UST. At week 12, 48 (63.1%) of patients achieved steroid free clinical remission or response [19/26 (73%) Anti-TNF naive and 29/49 (59%) anti-TNF exposed]; of these patients, 16/19 (84%) in the anti-TNF naive group and 19/29(65.5%) in the anti-TNF exposed group achieved PE. Forty-seven (61.8%) patients achieved PE. At 52 weeks, 68.2% (30/44), 67.5% (27/40), 56.1% (23/41), 69% (29/42) achieved endoscopic, radiological, biochemical and clinical endpoints respectively. Achieving steroid free clinical response or remission at week 12 was associated with achieving PE (79% vs. 42.8%, OR 3.6, p 0.01) and clinical SE (83.3 vs. 58.3%, p 0.001). Patients with B2/3 vs. B1(54% vs. 82%, p 0.09), ≥2 biological failure (72% vs. 33%, p 0.09), CRP < 6 baseline (55 % vs. 67.5%, p 0.3) were less likely to attain PE. Conclusion In a real-world cohort, UST appears efficacious and safe in medium and long term, with modest clinical, biochemical, radiological and endoscopic outcomes. Patients who achieve steroid-free clinical remission or response at 12 weeks are more likely to be in clinical remission or response at 24 and 52 weeks.

Real-World Evidence of the Effectiveness and Safety of Ustekinumab for the Treatment of Crohn’s Disease: Systematic Review and Meta-Analysis of Observational Studies

“…A total of 63 studies (including 8529 patients) met the inclusion criteria and were finally included in the systematic review and meta-analysis ( Figure 1 ) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , ...…”

“…Predictors of response were reported in 37 studies (59%). The most frequent predictors of poor clinical response were previous biologic exposure (anti-TNF and/or vedolizumab) [ 26 , 39 , 40 , 44 , 47 , 51 , 65 , 72 , 74 ], stricturing disease [ 19 , 20 , 39 , 44 , 65 ], penetrating disease [ 27 , 39 , 44 , 51 , 65 ], and high Harvey-Bradshaw index (HBI) at first dose [ 19 , 20 , 51 , 72 , 73 , 75 ]. Concomitant corticosteroids, extraintestinal manifestations, male sex, old age, smoking, and low body mass index were also reported in some studies.…”

An Australian Real-World Study of Treatment Persistence of Ustekinumab in Crohn’s Disease

“…In Australia, there is limited real-world evidence to guide local treatment practice 8,11 and the 10% PBS dataset provides valuable insights into the treatment patterns for patients with CD in Australia. A previous analysis of PBS data reported a median ustekinumab persistence rate of approximately 75% after a maximum follow-up of 2 In our study, we found a numerically higher persistence in those prescribed ustekinumab as the first biologic therapy compared with those who were biologic experienced.…”

“… 3 , 6 These guidelines recognize the growing real-world experience of ustekinumab, and support its clinical effectiveness. 3 , 7 , 8 …”

“…3,6 These guidelines recognize the growing real-world experience of ustekinumab, and support its clinical effectiveness. 3,7,8 Ustekinumab has been subsidized by the Australian Government through the Pharmaceutical Benefits Scheme (PBS) for CD since September 2017. 5 The PBS is an Australian Government scheme that provides subsidized prescription medicines to residents.…”