1Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Kitasato University, Tokyo, Japan
2IBD Center, Sapporo-Kosei General Hospital, Sapporo, Japan
3IBD Center, Sapporo Tokushukai Hospital, Sapporo, Japan
4Department of Gastroenterology and Proctology, Sai Gastroenterology/Proctology Clinic, Osaka, Japan
5Department of Internal Medicine, Sameshima Hospital, Kagoshima, Japan
6Department of Inflammatory Bowel Disease, Division of Internal Medicine, Hyogo College of Medicine Hospital, Nishinomiya, Japan
7IBD Center, Sapporo Higashi Tokushukai Hospital, Sapporo, Japan
8Research & Development, AstraZeneca K.K., Osaka, Japan
9Amgen, South San Francisco, CA, USA
10MedImmune LLC, Gaithersburg, MD, USA
11Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan
© Copyright 2019. Korean Association for the Study of Intestinal Diseases. All rights reserved.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
FINANCIAL SUPPORT
This work was supported by AstraZeneca K.K. and Amgen Inc. Marion Barnett of Edanz Medical Writing provided medical writing assistance, which was funded by AstraZeneca through EMC K.K. in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
CONFLICT OF INTEREST
T.H. has received consultancy fees from AbbVie Japan, JIMRO, Takeda Pharmaceuticals, Mitsubishi Tanabe Pharma, EA Pharma, Eli Lilly Japan KK, Pfizer Japan Inc., Nippon Kayaku Co. Ltd., and Nichi-Iko Pharmaceutical Co. Ltd., and grants from Zeria Pharmaceuticals, Otsuka Holdings Co. Ltd., AbbVie Japan, EA Pharma, and JIMRO. R.G. is an employee of MedImmune, LLC, a subsidiary of AstraZeneca. M.N. is an employee of AstraZeneca K.K. B.S. is a former employee and current shareholder of Amgen Inc. S.N. has received grants from Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, EA Pharma, AbbVie Japan, Asahi Kasei Medical, JIMRO, Otuka Pharmaceutical Factory, ZERIA Pharmaceuticals, Mochida Pharmaceutical, and Astellas Pharma, and lecture fees from AbbVie Japan, Janssen Pharmaceutical, EA Pharma, Mitsubishi Tanabe Pharma, ZERIA Pharmaceuticals, and Mochida Pharmaceutical. A.M., S.M., S.S., T.A., Y. Sameshima, and Y. Suzuki have no conflicts of interest to declare.
AUTHOR CONTRIBUTION
Conceptualization: Hibi T. Methodology: Hibi T, Gasser RA, Sullivan BA. Formal analysis: Hibi T, Gasser RA, Nii M, Sullivan BA. Investigation: Motoya S, Ashida T, Sai S, Sameshima Y, Nakamura S, Maemoto A, Suzuki Y, Sullivan BA. Writing, review, and editing: all authors. Approval of final manuscript: all authors.
Outcome | Placebo (n=13) |
Abrilumab |
||
---|---|---|---|---|
21 mg (n=10) | 70 mg (n=12) | 210 mg (n=9) | ||
Remission rate at week 8a | 0 | 1 (10.0) | 2 (16.7) | 1 (11.1) |
Response rate at week 8b | 7 (53.8) | 3 (30.0) | 6 (50.0) | 6 (66.7) |
Mucosal healing rate at week 8c | 4 (30.8) | 1 (10.0) | 4 (33.3) | 4 (44.4) |
Response rate at week 12d | 6 (46.2) | 3 (30.0) | 6 (50.0) | 6 (66.7) |
Sustained responsee | 4 (30.8) | 3 (30.0) | 3 (25.0) | 4 (44.4) |
Values are presented as number (%).
a Total Mayo score ≤2 points, and with no individual subscore >1 point.
b Decrease in ≥3 points and 30% in total Mayo score compared with baseline (visit 1, week 4), and with an accompanying decrease in the subscore for rectal bleeding of ≥1 point or with an absolute subscore for rectal bleeding of 0 or 1.
c An absolute Mayo subscore for rectosigmoidoscopy of 0 or 1.
d Reduction by ≥2 points and 25% in partial Mayo score compared with baseline (visit 1).
e Achieving the criteria for response assessed by partial Mayo score at both week 12 and week 24.
Characteristic | Placebo (n=13) | Abrilumab |
||
---|---|---|---|---|
21 mg (n=10) | 70 mg (n=12) | 210 mg (n=9) | ||
Age (yr) | 38.0±15.1 | 45.9±15.6 | 39.8±11.5 | 33.1±11.4 |
Male sex | 8 (61.5) | 7 (70.0) | 8 (66.7) | 6 (66.7) |
Body weight (kg) | 61.6±9.6 | 59.9±8.0 | 57.0±9.2 | 61.5±8.9 |
BMI (kg/m2) | 22.23±3.22 | 20.78±1.53 | 20.00±2.65 | 21.74±2.53 |
Duration of UC (yr) | 5.41±2.16 | 6.75±6.03 | 5.43±3.68 | 3.29±2.55 |
Smoking status | ||||
Current | 0 | 1 (10.0) | 3 (25.0) | 0 |
Former | 3 (23.1) | 4 (40.0) | 4 (33.3) | 2 (22.2) |
Never | 10 (76.9) | 5 (50.0) | 5 (41.7) | 7 (77.8) |
Previous medications | ||||
Use of 5-ASA at DB baseline | 11 (84.6) | 10 (100.0) | 10 (83.3) | 8 (88.9) |
Use of oral corticosteroids at DB baseline | 3 (23.1) | 1 (10.0) | 3 (25.0) | 2 (22.2) |
Use of immunomodulators at DB baseline | 7 (53.8) | 3 (30.0) | 8 (66.7) | 5 (55.6) |
Use of 5-ASA at OL baseline | 11 (91.7) | 10 (100.0) | 10 (83.3) | 7 (100.0) |
Use of oral corticosteroids at OL baseline | 3 (25.0) | 1 (10.0) | 3 (25.0) | 1 (14.3) |
Any prior use of anti-TNF-α agents | 8 (61.5) | 5 (50.0) | 7 (58.3) | 6 (66.7) |
Outcome | Placebo (n=13) | Abrilumab |
||
---|---|---|---|---|
21 mg (n=10) | 70 mg (n=12) | 210 mg (n=9) | ||
Remission rate at week 8 |
0 | 1 (10.0) | 2 (16.7) | 1 (11.1) |
Response rate at week 8 |
7 (53.8) | 3 (30.0) | 6 (50.0) | 6 (66.7) |
Mucosal healing rate at week 8 |
4 (30.8) | 1 (10.0) | 4 (33.3) | 4 (44.4) |
Response rate at week 12 |
6 (46.2) | 3 (30.0) | 6 (50.0) | 6 (66.7) |
Sustained response |
4 (30.8) | 3 (30.0) | 3 (25.0) | 4 (44.4) |
Preferred term | Placebo (n=13) | Abrilumab |
||
---|---|---|---|---|
21 mg (n=10) | 70 mg (n=12) | 210 mg (n=9) | ||
Double-blind period | ||||
Any adverse event | 2 (15.4) | 2 (20.0) | 0 | 1 (11.1) |
Malaise | 0 | 0 | 0 | 1 (11.1) |
Injection site swelling | 1 (7.7) | 0 | 0 | 0 |
Headache | 0 | 1 (10.0) | 0 | 1 (11.1) |
Enterocolitis viral | 1 (7.7) | 0 | 0 | 0 |
White blood cell count decreased | 0 | 1 (10.0) | 0 | 0 |
Asthma | 0 | 1 (10.0) | 0 | 0 |
Open-label period | ||||
Any adverse event | 4 (33.3) | 3 (30.0) | 2 (16.7) | 1 (14.3) |
Colitis ulcerative | 0 | 0 | 2 (16.7) | 1 (14.3) |
Enteritis | 0 | 0 | 1 (8.3) | 0 |
Influenza | 1 (8.3) | 0 | 0 | 0 |
Nasopharyngitis | 0 | 1 (10.0) | 0 | 0 |
Sinusitis | 0 | 1 (10.0) | 0 | 0 |
Anemia | 1 (8.3) | 0 | 0 | 0 |
Lymphadenitis | 1 (8.3) | 0 | 0 | 0 |
Cough | 1 (8.3) | 0 | 0 | 0 |
Allergic cough | 1 (8.3) | 0 | 0 | 0 |
Edema peripheral | 0 | 1 (10.0) | 0 | 0 |
Gall bladder polyp | 1 (8.3) | 0 | 0 | 0 |
Pain in extremity | 0 | 1 (10.0) | 0 | 0 |
Genital hemorrhage | 0 | 0 | 1 (8.3) | 0 |
Values are presented as mean±SD or number (%). 5-ASA, 5-aminosalicylic acid; DB, double-blind; OL, open-label.
Values are presented as number (%). Total Mayo score ≤2 points, and with no individual subscore >1 point. Decrease in ≥3 points and 30% in total Mayo score compared with baseline (visit 1, week 4), and with an accompanying decrease in the subscore for rectal bleeding of ≥1 point or with an absolute subscore for rectal bleeding of 0 or 1. An absolute Mayo subscore for rectosigmoidoscopy of 0 or 1. Reduction by ≥2 points and 25% in partial Mayo score compared with baseline (visit 1). Achieving the criteria for response assessed by partial Mayo score at both week 12 and week 24.
Values are presented as number (%). Preferred terms in this table were coded using Medical Dictionary for Regulatory Activities (MedDRA) version 19.1.