Introduction
Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor that demonstrated efficacy compared with placebo (PBO) in 2 double-blind, multicenter induction studies, U-EXCEED (NCT03345836) and U-EXCEL (NCT03345849), and 1 maintenance study, U-ENDURE.1-3UPA is approved for patients with moderately to severely active Crohn’s disease (CD).4,5 This post hoc analysis evaluated the efficacy and safety of UPA in the induction treatment of East Asian patients in U-EXCEED and U-EXCEL.
Aims & Methods
In U-EXCEL and U-EXCEED, patients with CD were randomized 2:1 to receive UPA 45 mg or PBO once daily (QD) for 12 weeks. Clinical remission per average daily very soft or liquid stool frequency (SF) ≤ 2.8 and average daily abdominal pain score (APS) ≤ 1.0 and neither greater than baseline; clinical remission per CD Activity Index (CDAI) < 150; clinical response (CR-100, decrease of ≥ 100 in CDAI from baseline); endoscopic response (decrease in Simple Endoscopic Score for CD [SES-CD] > 50% from baseline); endoscopic remission (SES-CD ≤ 4 and at least 2-point reduction from baseline, and no subscore > 1 in any individual variable); and absence of draining fistulas through 12 weeks were evaluated. Nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.
Results
Of the 1021 patients enrolled in U-EXCEL and U-EXCEED, 204 were included in this analysis of East Asian patients; patient demographics and baseline disease characteristics were similar for the UPA 45 mg and PBO treatment groups (Table). A greater proportion of patients treated with UPA achieved clinical remission vs PBO (SF/APS: 62.5% vs 20.6%; nominal P < .0001; CDAI: 50.7% vs 20.6%; nominal P < .0001) at week 12. At week 2, CR-100 was achieved by 33.8% vs 7.6% of patients receiving UPA and PBO, respectively. Similarly, a greater proportion of patients treated with UPA achieved endoscopic outcomes vs PBO at week 12 (endoscopic response: 61.8% vs 10.3%; nominal P < .0001; endoscopic remission: 27.9% vs 5.9%; nominal P < .0001). In patients taking corticosteroids for CD at baseline, 57.1% receiving UPA discontinued corticosteroid use and achieved clinical remission per CDAI vs 20.0% of patients receiving PBO (nominal P < .0001). Among patients with draining fistulas at baseline, 28.6% of patients receiving UPA vs 0% of patients receiving PBO had no draining of their fistulas at week 12. The rate of adverse events (AEs) in the UPA group was comparable to that of patients receiving PBO (69.9% vs 70.6%). AEs leading to study discontinuation occurred in 5.9% and 4.4% of patients, and severe AEs in 10.3% and 13.2% of patients in the UPA and PBO groups, respectively. There were no treatment-emergent deaths in either group. AEs of special interest (including serious infections, opportunistic infections, and herpes zoster) occurred at similar rates regardless of treatment group; no malignancies, adjudicated major cardiovascular events, or venous thromboembolic events were reported.
| Table. Baseline Disease Characteristics |
| Baseline Characteristicsa | PBO
(n = 68) | UPA 45 mg
(n = 136) |
Demographics
Age (years), mean (SD)
Female, n (%) |
33.1 (9.7)
24 (35.3) |
32.7 (10.6)
50 (36.8) |
Disease Characteristics
Disease duration (years), mean (SD)
Corticosteroid use, n (%)
Prior biologic failures, n (%)
0
1
2
≥3
CDAI, mean (SD)
SES-CD, mean (SD)
Average daily SF, mean (SD)
Average daily APS, mean (SD)
hs-CRP, median (range)
FCP, median (range)
Draining fistulas, n (%) |
5.9 (3.8)
20 (29.4)
16 (23.5)
35 (51.5)
14 (20.6)
3 (4.4)
280.8 (82.7)
15.6 (6.5)
4.3 (2.4)
1.7 (0.7)
11.3 (0.2–94.1)
1908 (30–18,191)
5 (7.4) |
6.4 (6.1)
49 (36.0)
30 (22.1)
71 (52.2)
28 (20.6)
7 (5.1)
284.8 (79.0)
16.8 (7.8)
4.2 (2.0)
1.7 (0.8)
15.0 (0.2–144.0)
2361 (31–28,800)
14 (10.3) |
APS, abdominal pain score; CDAI, Crohn’s Disease Activity Index; hs-CRP, high-sensitivity C-reactive protein; PBO, placebo; SES-CD, Simple Endoscopic Score for Crohn’s Disease; SF, stool frequency, UPA, upadacitinib.
aThe East Asian subpopulation consisted of patients in China, Japan, Korea, Malaysia, and Taiwan; patients from Hong Kong and Singapore would also be included in this analysis, but none enrolled. |
Conclusion
East Asian patients with moderately to severely active CD treated with UPA 45 mg achieved clinical and endoscopic outcomes at higher rates than did patients receiving PBO, with a tolerable safety profile.
References
1. Loftus E, et al. United European Gastroenterol J. 2022;10:OP129.
2. Colombel JF, et al. Gastroenterology. 2022;162:867f.
3. Panés J, et al. Am J Gastroenterol. 2022;117:S10.
4. AbbVie. RINVOQ. Summary of Product Characteristics. AbbVie Deutschland GmbH & Co. KG; 2023. Accessed 24 April 2023. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf.
5. Electronic Medicines Compendium. Rinvoq (upadacitinib) 30 mg prolonged-release tablets: summary of product characteristics. Updated March 16, 2023. Accessed March 27, 2023. https://www.medicines.org.uk/emc/product/12830/smpc/.
Disclosure
MC has received research grants from Janssen and Takeda; served as an advisory board member for Boehringer Ingelheim and Janssen; and provided educational activities for AbbVie, China Medical System, IPSEN, Janssen, and Takeda.
XG reports no conflicts of interest.
KW has received consulting fees from AbbVie, EA Pharma, GlaxoSmithKline, Janssen, JIMRO, Kissei, Kyorin, Mitsubishi Tanabe, Mochida, Nippon Kayaku, Olympus, Pfizer, Sandoz, Takeda, and Zeria; and research grants from AbbVie, EA Pharma, EP CRSU, Helmsley Charitable Trust, JIMRO, Mitsubishi Tanabe, Mochida, Nippon Kayaku, and Takeda.
TF has received speaker’s fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, EA Pharma, Eisai, Janssen, Kissei Pharma, Kyorin Pharma, Kyowa Hakko Kirin, Mitsubishi-Tanabe, Mochida, Nichiiko, Nippon Kayaku, Pfizer, Taiho, Takeda, and Zeria Pharma; and research grants from AbbVie, Alfresa, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, EA Pharma, Eisai, Gilead Sciences, Janssen, Kissei, Lilly, Mebix, Sanofi, and Takeda.
JHC has received lecture fees from AbbVie, Celltrion, Eisai, Ferring, Janssen, Pfizer, and Takeda.
SCW has been a consultant or served as an advisory board member for AbbVie, Bristol-Myers Squibb, Celltrion, Ferring Pharmaceuticals, Janssen, Pfizer, Takeda, and Tanabe. She has received lecture fees from AbbVie, Bristol-Myers Squibb, Celltrion, Ferring Pharmaceuticals, Janssen, Pfizer, Takeda, and Tanabe.
DT, APL, and VPR are full-time employees of AbbVie and may hold AbbVie stock or stock options.
HN has received honoraria from AbbVie, Janssen, Mylan EPD, Pfizer, Takeda, and Tanabe Mitsubishi; grants for commissioned/joint research from AbbVie, AYUMI, HOYA Pentax Medical, Mochida, and Tanabe Mitsubishi; and scholarship grants from AbbVie, EA Pharma, Nippon Kayaku, Otsuka, Taiho, Tanabe Mitsubishi, and Takeda.
Funding: AbbVie Inc. funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of this abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. AbbVie and the authors thank the patients who participated in the study and all study investigators for their contributions. AbbVie funded the research for this study and provided writing support for this abstract. Medical writing assistance was provided by Spencer Hughes, PhD, of JB Ashtin, and funded by AbbVie.
