Z Gastroenterol 2019; 57(05): e136
DOI: 10.1055/s-0039-1691867
POSTER
CED
Georg Thieme Verlag KG Stuttgart · New York

Effects of Ustekinumab Induction Therapy on Endoscopic and Histologic Healing in the UNIFI Phase 3 Study in Ulcerative Colitis

K Li
1   Janssen Research & Development, LLC., Spring House, United States
,
FR Joshua
1   Janssen Research & Development, LLC., Spring House, United States
,
C Marano
1   Janssen Research & Development, LLC., Spring House, United States
,
H Zhang
1   Janssen Research & Development, LLC., Spring House, United States
,
F Yang
1   Janssen Research & Development, LLC., Spring House, United States
,
BG Feagan
2   Robarts Clinical Trials, Robarts Research Institute, Western University, London, Canada
,
L Peyrin-Biroulet
3   Nancy University Hospital, Université de Lorraine, Nancy, France
,
G De Hertogh
4   University Hospitals KU Leuven, Leuven, Belgium
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
16. Mai 2019 (online)

 

Background:

Ustekinumab (UST) is an effective therapy for moderate-to-severe ulcerative colitis (UC), however data regarding histologic healing and the combination of histologic and endoscopic healing are unknown.

Methods:

We evaluated the effects of UST on histologic and endoscopic activity in the UNIFI Phase 3 induction study of UST in moderate-to-severe UC (n = 961). Two colonic biopsies were collected from the distal colon at Week 8. Subjects not in response to PBO at Week 8 received UST6 mg/kg IV, and those not in response to UST IV received UST90 mg SC; biopsies were obtained from these groups at Week 16. Endoscopic healing (EH) was defined as a Mayo endoscopy score ≤1; histologic healing (HH) comprised the Geboes score-based criteria. Histo-endoscopic mucosal healing (HEMH) was defined as achieving both EH and HH.

Results:

At Week 8, EH was achieved in 26.6% and 13.8% of subjects treated with UST (combined 130 mg and 6 mg/kg IV doses) and PBO, respectively. HH was achieved in 36.8% and 21.9% of UST and PBO-treated subjects, respectively. HEMH was achieved in 19.3% and 8.9% of UST and PBO-treated subjects, respectively. Similar rates of EH, HH, and HEMH were achieved following induction treatment with UST130 mg or 6 mg/kg IV. Subjects not in response at Week 8 were treated with UST re-evaluated at Week 16; of these, 12.1% and 16.5% of subjects who initially received UST or PBO IV, respectively, achieved HEMH. HH at Week 8 or Week 16 was significantly associated with EH and HEMH (Tab. 1).

Table 1:

Clinical Outcomes for Subjects with or without Histologic Healing at Week 8 and Week 16 in the UNIFI Phase 3 Induction Study

Clinical Outcomes

Histologic Healinga

Without Histologic Healinga

p-valueb

Week 8

N = 283

N = 533

Mayo Score

3.95 ± 2.57

6.89 ± 2.53

< 0.0001

Partial Mayo Score

2.45 ± 1.84

4.39 ± 2.21

< 0.0001

Stool Frequency

1.09 ± 0.95

1.81 ± 1.03

< 0.0001

Rectal Bleeding

0.30 ± 0.56

0.86 ± 0.89

< 0.0001

Change in Mayo Score

-4.53 ± 2.65

-2.15 ± 2.39

< 0.0001

Change in Partial Mayo Score

-3.46 ± 2.14

-1.89 ± 2.12

< 0.0001

Change in Stool Frequency

-1.08 ± 1.01

-0.63 ± 0.90

< 0.0001

Change in Rectal Bleeding

-1.18 ± 0.91

-0.69 ± 0.96

< 0.0001

Week 16

N = 140

N = 209

Mayo Score

3.71 ± 1.94

6.01 ± 2.43

< 0.0001

Partial Mayo Score

1.98 ± 1.27

3.44 ± 2.08

< 0.0001

Stool Frequency

0.96 ± 0.83

1.56 ± 1.02

< 0.0001

Rectal Bleeding

0.13 ± 0.38

0.51 ± 0.69

< 0.0001

Change in Mayo Score

-4.95 ± 2.02

-3.08 ± 2.32

< 0.0001

Change in Partial Mayo Score

-4.04 ± 1.63

-2.83 ± 2.07

< 0.0001

Change in Stool Frequency

-1.31 ± 0.90

-0.92 ± 0.99

0.0003

Change in Rectal Bleeding

-1.30 ± 0.89

-0.99 ± 0.85

0.0012

a: Values are reported as mean ± SD.

b: P-values based on t-test.

Conclusions:

Among subjects with moderately-to-severely active UC, those receiving IV UST induction had higher rates of EH, HH, and HEMH than those receiving PBO. Approximately 10% of subjects who did not achieve clinical response 8 weeks after IV UST achieved HEMH following a second dose.