Introduction
Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor approved for the treatment of moderate to severe Crohn’s disease (CD),1,2 has demonstrated efficacy and safety in clinical trials.3,4 However, real-world evidence on its effectiveness remains limited. The UPlift study evaluates speed of onset and durability of response with UPA in routine clinical practice over 3 years (study start 19 Feb 2024).
Aims & Methods
UPlift (NCT05930275) is an ongoing, multicountry, prospective, single-arm, noninterventional, phase IV study of patients (pts) with moderate to severe CD treated with UPA at the investigator’s discretion in routine clinical practice, in accordance with the terms of the local marketing authorization. Approximately 900 pts will be enrolled in 17 countries. This interim analysis included the first 500 enrolled pts. The full analysis set (FAS) included pts receiving ≥1 dose of UPA. A primary objective was time to first clinical response per PRO2 (CR-PRO2), defined as first achievement of daily CR-PRO2 based on stool frequency (SF) and abdominal pain (AP) and a prospective 7-day average of CR-PRO2 from the first CR-PRO day (full definition). Time to CR-PRO2 based on daily SF and AP score only (adapted definition), and clinical remission per Harvey–Bradshaw Index (HBI ≤4) at the end of induction therapy (week [wk] 12 or 24), were also assessed. Analyses were conducted in evaluable pts with available data for each endpoint. Kaplan–Meier methods were used to estimate time to first clinical response. Safety outcomes are reported as treatment-emergent adverse events (TEAEs).
Results
Among 497 pts in the FAS, mean (SD) age was 38.4 (13.1) years, median (min, max) disease duration was 9.7 (0.03, 51.2) years, 10.9% had baseline CD-related corticosteroid use, and 63.0% had received ≥1 prior advanced therapies (Table). Most pts (50.3%) had ileocolonic CD, followed by ileal-only (32.2%) and colonic (17.5%). Mean (SD) baseline HBI was 6.8 (4.3). Perianal fistula was present in 83 (16.7%) of pts. Extraintestinal manifestations were present in 101 (20.3%) of pts. Within 12 wks, 70.2% of evaluable pts achieved CR-PRO2 (full definition), with median time to first response of 13.0 days (95% CI, 10.0–17.0); 79.9% achieved CR-PRO2 (adapted definition), with median time to first response of 5.0 days (95% CI, 4.0–5.0). Clinical remission (HBI ≤4) was achieved by 68.1% of pts at the end of induction (wk 12 or 24). Among FAS pts who received any UPA dose and reported a TEAE with a reasonable possibility of being related to study treatment, 32% reported ≥1 TEAE, 3.8% reported serious TEAEs, and 6.6% had a TEAE leading to study drug discontinuation. There were no deaths.
| Summary of UPlift Baseline Demographics, Disease Characteristics, and Interim Effectiveness and Safety Results. |
| Any UPA dose
(N = 497)a |
Baseline Demographicsb
Sex
Female, n (%)
Male, n (%)
Age, years
Mean (SD)
<18, n (%)
18 to <40, n (%)
40 to <65, n (%)
≥65, n (%)
Age of female patients, years
18 to 29, n (%)
30 to 39, n (%)
40 to 49, n (%)
≥50, n (%)
BMI, kg/m2
Mean (SD)
<25, n (%)
25 to <30, n (%)
≥30, n (%)
Missing |
237 (47.7)
260 (52.3)
38.4 (13.1)
0
289 (58.1)
192 (38.6)
16 (3.2)
68 (28.7)
57 (24.1)
51 (21.5)
61 (25.7)
23.9 (5.5)
306 (67.0)
95 (20.8)
56 (12.3)
40 |
Disease Characteristicsb
Disease duration, years
Median (min, max)
<2, n (%)
2 to 5, n (%)
>5 to 10, n (%)
>10, n (%)
Missing
Disease location
Colonic, n (%)
Ileocolic, n (%)
Ileal only, n (%)
Missing
Baseline CD-related corticosteroid use, n (%)
Yes
No
Prior lines of advanced therapy, n (%)
0
1
2
≥3
HBI
n
Mean (SD)
SES-CD
n
Median (min, max)
Number of EIMs c, n (%)
0
1
2
>2
Perianal fistula - draining, n (%)
Yes
No
Perianal fistula - nondraining, n (%)
Yes
No |
9.7 (0.03, 51.2)
65 (13.2)
68 (13.8)
120 (24.3)
241 (48.8)
3
86 (17.5)
247 (50.3)
158 (32.2)
6
54 (10.9)
443 (89.1)
184 (37.0)
94 (18.9)
82 (16.5)
137 (27.6)
435
6.8 (4.3)
150
8.0 (0, 37.0)
396 (79.7)
85 (17.1)
12 (2.4)
4 (0.8)
42 (8.5)
455 (91.5)
41 (8.2)
456 (91.8) |
Effectiveness
Time to first achievement of daily CR-PRO2 (full definition) d
Events analysed – n/N (%)
Median, days [95% CI]
Time to first achieving of daily CR-PRO2 (modified definition) e
Events analysed – n/N (%)
Median, days [95% CI]
Clinical remission per HBIf at the end of the induction period
(week 12/week 24)g, n/Nh (%) [95% CIi]
|
243/346 (70.2)
13.0 [10.0, 17.0]
286/358 (79.9)
5.0 [4.0, 5.0]
207/304 (68.1) [62.9, 73.3]
|
Overall TEAEs through Week 26,j n (%)k
TEAE with a reasonable possibility of being related to study treatmentl
Severe TEAE
Serious TEAE
TEAE leading to discontinuation of the study drug
TEAE resulting in death |
159 (32.0)
19 (3.8)
19 (3.8)
33 (6.6)
0 |
AP, abdominal pain; BMI, body mass index; CI, confidence interval; CD, Crohn’s disease; CR-PRO2, clinical remission based on a 2-item patient-reported outcome score; EIM, extraintestinal manifestation; FAS, full analysis set; HBI, Harvey–Bradshaw Index; SES-CD, simple endoscopic score for Crohn’s disease; SF, stool frequency; TEAE, treatment-emergent adverse event; UPA, upadacitinib.
a The FAS included patients who initiated UPA among the first 502 patients who signed the informed consent and satisfied eligibility criteria. Six patients signed the informed consent on the same date as the 497th patient and satisfied eligibility criteria for inclusion in interim analysis 1.
b Percentages were calculated based on nonmissing values.
c Including rheumatologic, ophthalmologic, dermatologic, and other EIMs.
d Defined as the first day with ≥30% decrease in daily very soft or liquid SF and/or ≥30% decrease in daily AP score and both not worse than baseline AND a prospective 7-day average daily CR-PRO starting on the first day of daily CR-PRO; prospective 7-day average daily CR-PRO was defined as ≥30% decrease in average daily very soft or liquid SF and/or ≥30% decrease in average daily AP score and both not worse than baseline. Only patients with either baseline SF or AP >0 and both nonmissing with at least one postbaseline assessment of CR-PRO2 are included.
e Defined as time to first achievement of daily CR-PRO2 based on the individual daily SF and AP score only. Only patients with either baseline daily SF or AP >0 and both nonmissing with at least one postbaseline assessment of daily CR-PRO2 (determined based on individual daily SF and AP scores) are included.
f Defined as HBI ≤4.
g If a patient discontinued UPA due to lack of effectiveness or intolerability before the time point of interest, then that patient’s outcome was set to nonresponder. If a patient discontinued UPA due to other reasons before this specific time point, then that patient’s outcome was set to missing.
h Number of patients with scores at the visit after handling intercurrent events.
i Construction of CIs for response rate is based on the normal approximation.
j Included events through week 26.
k Patients are counted once in each row within a column, regardless of the number of events they had.
l As assessed by the investigator.
Data cutoff date was 31 Aug 2025. |
Conclusion
In this interim analysis of the UPlift study, UPA showed rapid onset of clinical response in a refractory pt population and high rates of clinical remission through wk 12/24 in pts with moderate to severe CD. These findings support the effectiveness of UPA in clinical practice. The safety profile for UPA in pts with CD was consistent with previous analyses.3,4
References
- AbbVie Inc. RINVOQ (Upadacitinib) [package insert] U.S. Food and Drug Administration website. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf. Revised Oct 2025.
- AbbVie DG& CoK. RINVOQ. (Upadacitinib) [package insert] Summary of Product Characteristics. European Medicine Agency website. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Revised Nov 2025.
- Loftus EV, Jr. and Panés J et al. N Engl J Med. 2023;88:1966–80.
- Burmester GR, et al. Adv Ther. 2025;42:5215–37.
Disclosure
Financial arrangements of the authors with companies whose products may be related to the present publication are listed, as declared by the authors.
Raja Atreya has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, CED Service GmbH, Celltrion Healthcare, Falk Foundation, Galapagos, Gilead, InDex Pharmaceuticals, Johnson & Johnson, Lilly, MSD Sharp & Dohme, Pfizer, Pandion Therapeutics, Roche Pharma, Takeda Pharma, and Viatris.
Vipul Jairath has received consulting/advisory board fees from AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Enthera, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Innomar, JAMP, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Roivant, Sandoz, SCOPE, Second Genome, Sorriso, Takeda, TD Securities, Teva, Topivert, Ventyx, Vividion; received speaker’s fees from AbbVie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Shire, Takeda, and Fresenius Kabi.
Remo Panaccione has received consulting fees from AbbVie, Abbott, Alimentiv, Amgen, Arena, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Schering-Plough, Shire, Sublimity Therapeutics, Theravance, UCB, and Takeda; speaker fees from AbbVie, Arena, Celgene, Ferring, Gilead Sciences, Janssen, Lilly, Merck, Pfizer, Roche, Sandoz, Shire, and Takeda; and research/educational support from AbbVie, Ferring, Janssen, Pfizer, and Takeda. He has served on an advisory board for AbbVie, Amgen, Arena, Bristol Myers Squibb, Celgene, Celltrion, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Lilly, Merck, Mylan, Oppilan Pharma, Pandion Pharma, Pfizer, Sandoz, Shire, Sublimity Therapeutics, Takeda, and Theravance.
Hiroshi Nakase reports receiving personal fees from Abbvie Inc., KYORIN Pharmaceutical Co., Ltd, Janssen Pharmaceutical K.K, Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., EA Pharma Co., Ltd., Mochida Pharmaceutical Co., Ltd., Gilead Sciences Inc., JIMRO Co., Ltd., Bristol Myers Squibb company and grants for commissioned/joint research from Hoya Group Pentax Medical; and being endowed chair by Miyarisan Pharmaceutical Co., Mochida Pharmaceutical Co., Ltd. JIMRO Co., Ltd., and KYORIN Pharmaceutical Co., Ltd.
Xiang Gao has received research grants, served as an advisor, and/or has supported educational activities for AbbVie, Abbott, Janssen, and Takeda.
Tafadzwa Kasambira, Jae Rok Kim, Madhuja Mallick, Naiara Michelena, and Yafei Zhang are full-time employees of AbbVie and may own AbbVie stock or stock options.
Silvio Danese has received consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Enthera, Ferring, Gilead, Hospira, Janssen, Johnson & Johnson, Lilly, Merck Sharp and Dohme, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB and Vifor.
Funding: AbbVie funded this study (UPlift; NCT05930275) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.
Acknowledgements: AbbVie and the authors thank the participants, study sites, and investigators who participated in this clinical trial. Kathleen Richter, MS, of AbbVie, provided medical writing support, and Catherine Barone, PhD, of AbbVie, provided editorial support.