Abstract ID: A106

USTEKINUMAB IS EFFECTIVE FOR MAINTAINING CLINICAL RESPONSE IN REFRACTORY MODERATE-TO-SEVERE CROHN’S DISEASE: A MULTICENTRE COHORT STUDY

Authors: C. Ma1, R. Fedorak2, G.G. Kaplan1, L.A. Dieleman2, S. Devlin1, N. Stern2, K.I. Kroeker2, C. Seow1, Y. Leung1, K.L. Novak1, B.P. Halloran2, V. Huang2, K. Wong2, S. Ghosh1, R. Panaccione1

1. University of Calgary, Calgary, AB, Canada; 2. University of Alberta, Edmonton, AB, Canada

Background: Ustekinumab is a monoclonal antibody targeting interleukins 12 and 23. Ustekinumab has recently been approved for treatment of Crohn’s disease by the United States Food and Drug Administration but long-term maintenance of clinical response in the real-world setting is unclear.

Aims: To assess the efficacy of ustekinumab for maintaining clinical response in CD

Methods: A retrospective multicentre cohort study was performed at two institutions (University of Calgary, University of Alberta). CD patients achieving clinical response to ustekinumab induction between 2011 and 2016 were eligible for inclusion. The primary outcome was loss of clinical response, defined as ustekinumab dose escalation, ustekinumab re-induction, rescue corticosteroids, surgery, or drug discontinuation. Multivariate Cox proportional hazards regression analysis was used to assess predictors of loss of response, expressed as hazard ratios (HR) with 95% confidence intervals (CI).

Results: We identified 98 CD patients responding to ustekinumab induction. Median follow-up was 56.1 weeks (IQR 31.6-105.0). 30 patients (30.6%) lost clinical response during maintenance therapy at a median time of 48.7 weeks (IQR 34.4-84.3). 15 patients (15.3%) required dose escalation, 7 patients (7.1%) required reinduction, 9 patients (9.2%) required rescue corticosteroids, and 7 patients (7.1%) underwent surgical resection. 10 patients (10.2%) discontinued ustekinumab due to loss of response. In Cox proportional hazards regression, high dose induction at 6mg/kg (HR 0.16 [95% CI: 0.03-0.79]) and concurrent immunomodulator use were protective against loss of response (adjusted HR 0.35 [95% CI: 0.14-0.91])

Conclusions: In this large multicentre cohort of CD patients with initial response to induction therapy, ustekinumab was effective for maintaining clinical response in 70% of patients over long-term follow-up. Long-term maintenance may be improved in patients receiving higher dose induction regimens and using concomitant therapy.
Table 1 – Baseline patient demographic

 

n = 98

Male, n (%)

41 (41.8)

Median age at ustekinumab induction (years, IQR)

44.7 (40.0 – 57.7)

Median disease duration prior to ustekinumab induction (years, IQR)

13.7 (9.0 – 22.5)

Median weight (kg, IQR)

73.0 (58.0 – 85.0)

Current smoker
Former smoker
Never smoker

22 (22.4)
14 (14.3)
62 (63.3)

Ileal disease
Colonic disease
Ileocolonic disease

20 (20.4)
24 (24.5)
54 (55.1)

Inflammatory disease
Stricturing disease
Penetrating disease

44 (44.9)
24 (24.5)
30 (30.6)

Previous intestinal resections, n (%)

62 (63.3)

Previous Anti-TNF Failure, n (%)
Infliximab
Adalimumab

90 (91.8)
85 (86.7)
72 (73.5)

Disease Activity
Median CRP (mg/L, IQR)
Median HBI (IQR)
Concurrent IMM, n (%)
Concurrent steroids, n (%)

-
7.5 (2.0 – 20.8)
8 (5 – 12)
41 (41.8)
39 (39.8)

Ustekinumab Dosing
Median induction dose (mg/kg, IQR)
Maintenance q8 weeks, n (%)
Maintenance q12 weeks, n (%)

-
3.5 (2.6 – 5.0)
45 (78.9)
11 (19.3)

Median Follow-up Duration, weeks (IQR)

56.1 (31.6 – 105.0)



Figure 1 – Survival curves for the proportion of Crohn’s disease patients experiencing loss of response to ustekinumab maintenance therapy, stratified by concurrent immunomodulator (red line) and no concurrent immunomodulator (blue line) therapy at ustekinumab induction

Funding Agencies: CAG

Abstract Category: Immunology and Inflammatory Bowel Disease
Type: Poster Presentation