A80 ENDOSCOPIC HEALING WITH USTEKINUMAB IN CROHN’S DISEASE: THE UNITI ENDOSCOPY SUB-STUDY

Abstract

Aims

To evaluate endoscopic healing in the ustekinumab (UST) induction (UNITI-1&2) & maintenance (IM-UNITI) phase 3 studies.

Methods

Substudy patients (pts) had colonoscopies at baseline (UNITI Wk0), then 8 & 52 weeks later (IM-UNITI Wk44). Video-endoscopies were centrally read by a single blinded reader for ulcerations & SES-CD. In UNITI, pts received one IV dose (UST 130mg, UST ~6mg/kg, or PBO). Pts with clinical response [CR] (CDAI drop≥100) in UNITI were re-randomized to subcutaneous (SC) PBO or UST 90mg (q12w or q8w) [primary randomized IM-UNITI population]. Non-randomized pts were added to the pooled IM-UNITI population: UST IV non-responders - SC UST 90mg, then SC UST 90mg q8w if in CR 8wks later; PBO IV non-responders - UST IV 130mg, then SC UST 90mg q12w if in CR 8wks later; PBO induction responders - PBO throughout. Pts required SES-CD ≥3 at UNITI Wk0 to be included. Primary outcome: Change in SES-CD at UNITI Wk8 (combined UST vs PBO). IM-UNITI Wk44 efficacy was evaluated for both the IM-UNITI populations.

Results

At wk8, UST reduced SES-CD significantly more vs PBO. Results were similar across UST doses, studies, & other endpoints (Table 1a). At IM-UNITI Wk44, in the primary randomized IM-UNITI population trends favoured UST vs PBO maintenance (especially UST 90mg q8w) but small sample sizes (UST n=46; PBO n=24) limited conclusions. In the post-hoc pooled IM-UNITI population (Table 1b), trends supporting UST maintenance were favourable, especially 90mg q8w.

Conclusions

The endoscopy substudy primary endpoint was met: One IV UST dose significantly reduced SES-CD vs PBO, as early as Wk8. More pts receiving UST maintenance achieved wk44 endpoints vs PBO. These data support efficacy of UST in inducing & maintaining endoscopic healing in CD.

(Table 1a) Week 8 Results from UNITI-1/2

	PBO (N=97)	UST (N=155)
SES-CD Change from BL, mean (SD)§	-0.7 (4.97)	-2.8 (8.10)*
Clinically meaningful endoscopic improvement1	29.9%	47.7%*
Endoscopic Response2	13.4%	20.6%
Endoscopic Remission3	4.1%	7.7%
Mucosal Healing4	4.1%	9.0%

(Table 1b) IM-UNITI Week 44 Results

	PBO (N=51)	90mg q12w (N=47)	90mg q8w (N=74)
SES-CD Change from BL, mean (SD)	-2.0 (5.35)	-1.5 (4.22)	-3.8 (6.02)
Clinically meaningful endoscopic improvement1	27.5%	29.8%	48.6%*
Endoscopic Response2	4.2%	5.9%	24.1%*
Endoscopic Remission3	9.8%	12.8%	20.3%
Mucosal Healing4	9.8%	12.8%	21.6%

*P ˂0.05 §Primary endpoint

1SES-CD reduction ≥3 from UNITI BL

2SES-CD reduction ≥50% from UNITI BL

3SES-CD ≤2

4No ulcerations

Funding Agencies

Janssen Research & Development, LLC