Introduction
Upadacitinib (UPA) is an oral, reversible Janus kinase inhibitor (JAKi) approved for the treatment of patients with moderate-to-severe ulcerative colitis (UC).1-2 Despite substantial evidence from clinical trials supporting the use of UPA for treating UC, real-world (RW) data on its effectiveness and safety remain limited.3 The Prospective Real-World Study of UPA in UC (PROFUNDUS) is an ongoing multi-country, open-label, noninterventional, observational study aimed to evaluate the effectiveness and safety of UPA in patients with moderate-to-severe UC in RW practice (initiated 15 Aug 2022).
Aims & Methods
PROFUNDUS recruited 785 adult patients (18 to 75 years [yrs] of age) with moderate-to-severe UC initiating UPA in 16 countries worldwide. UPA was administered in accordance with the terms of the local marketing authorization, with patient treatment determined by the investigator, and patients followed for up to 3 yrs (156 weeks [wk]). This analysis represents data available after the first 500 patients completed 6 months of treatment or discontinued before 6 months, with a data cut-off of 28 Feb 2025. Of the first 500 patients who provided informed consent and met the inclusion criteria, the full analysis set (FAS) included 490 patients who initiated a once-daily UPA dosing regimen. This analysis reported baseline demographics and disease characteristics among FAS; the time to achievement of first clinical response per daily Partial Adapted Mayo Score (pAMS) and the percentage of patients achieving clinical response per pAMS at the end of UPA induction (wk 8) or extended induction (wk 16) were reported among evaluable patients who took at least 1 dose of UPA and had available scores to define the outcomes, a subset of FAS. Safety outcomes were analysed through week 26 (6 months), with treatment-emergent adverse events (TEAEs) presented as patient numbers and percentages.
Results
Among FAS, the patient age range was 18 to 79 yrs; 43.3% were female. At baseline (defined as the last available assessment on or before the first dose date of UPA), pAMS were as follows: < 2: 26.5%; 2-4: 48.1%; > 4-5: 18.8%; > 5-6: 6.6%; with score 0 indicative of inactive disease, while a score of 6 indicates active disease and spontaneous bleeding.4 At baseline, 51.3% of patients had a history of intolerance or inadequate response (IR) to advanced therapies (AT-IR), with 13.1% of patients who failed ≥ 1 JAKi. Among evaluable patients, the median (IQR) time to achieve the first clinical response per daily pAMS was 4 (3.0-8.0) days (N = 373; Table). By the end of induction treatment (wk 8 or 16), 79.6% (258/324) of the evaluable UPA-treated patients achieved clinical response per pAMS (Table). Among UPA-treated patients, the occurrence rates of any treatment-emergent adverse events (TEAEs) and TEAEs possibly related to the study treatment were as follows: any adverse event (AE) (51.2%; 34.9%), serious AEs (5.5%; 2.2%), and severe AEs (5.1%; 2.2%) (Table).
Effectivenessa
| Any UPA dose
|
Time to first achievementb of clinical response per Daily pAMSb
Events analysed – n/N (%)
Median (IQR), days
Clinical response per pAMSc at week 8 or 16 of induction, n/N (%) [95% CI]
|
364/373 (97.6)
4.0 (3.0-8.0)
258/324 (79.6) [75.2, 84.0] |
Overall TEAEs, Week 26 of Therapy,d n (%)
Any AE
AE with a reasonable possibility of being related to study treatmente
Severe TEAE
Serious TEAE
AE leading to discontinuation of the study drug
AE resulting in deathf | Any UPA dose
(N = 490)
251 (51.2)
171 (34.9)
25 (5.1)
27 (5.5)
34 (6.9)
1 (0.2) |
Overview of TEAEs With Reasonable Possibility of Being Related to Study Treatment Through Week 26,d n (%)
Any AEe
Severe TEAE
Serious TEAE
AE leading to discontinuation of the study drug
AE resulting in death | Any UPA dose
(N = 490)
171 (34.9)
11 (2.2)
11 (2.2)
24 (4.9)
0 |
Table. Summary of PROFUNDUS Interim Effectiveness and Safety Results.
FAS, full analysis set; IQR, interquartile range; pAMS, partial Adapted Mayo Score; RBS, rectal bleeding score; SF, stool frequency; TEAE, treatment-emergent adverse event; UPA, upadacitinib.
aEffectiveness population included evaluable patients who took at least 1 dose of UPA and had available diary scores to define the corresponding outcome among the first 500 patients who provided informed consent and satisfied eligibility criteria. Patients who discontinued due to lack of effectiveness or intolerability were categorised as nonresponders, while those who discontinued due to other reasons were treated as missing data for the responder outcome and censored for the time-to-event outcome.
bDefined as a decrease in daily pAMS ≥ 1 point and ≥ 30% from baseline, in addition to a decrease in daily RBS ≥ 1 or a daily RBS ≤ 1. Time to first achievement was based on the difference in time between the date of first achievement and first dose of UPA. Only patients with baseline daily pAMS > 0 with at least one post-baseline score are included. If a patient never achieved this outcome within 183 days (week 26), then that patient's time to first achievement was censored at day 183 (week 26), UPA discontinuation, study discontinuation, or cut-off date, whichever comes earlier. Kaplan-Meier nonparametric estimates were reported.
cDefined as a decrease from baseline in pAMS ≥ 1 point and ≥ 30%, in addition to a decrease from baseline in the RBS ≥ 1 or absolute RBS ≤ 1. Patients with baseline score ≥1 and available score at end of induction are included.
dIncluded patients with at least 1 dose of UPA among the first 500 patients who provided informed consent and satisfied eligibility criteria. Included events within 26 weeks (183 days) of starting study treatment.
eAs assessed by study investigator.
fThere was 1 death due to drowning that was determined to have no reasonable possibility of being related to the study drug.
Data cut-off date was 28 Feb 2025. |
Conclusion
In this interim analysis of the PROFUNDUS study, UPA demonstrated rapid effectiveness in achieving clinical response in patients with moderate-to-severe UC in RW practice, in a wide variety of age ranges, consistent with the efficacy observed in the UPA UC clinical trials.1 Overall, UPA was well-tolerated, with few serious AEs reported, and most of these were assessed as unrelated to UPA by the investigator.
References
- AbbVie Inc. RINVOQ (Upadacitinib) [package insert] U.S. Food and Drug Administration website. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf. Revised May 2023. Accessed 25 Feb 2025.
- AbbVie DG& CoK. RINVOQ. Summary of Product Characteristics. European Medicine Agency website. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Revised Feb 2025. Accessed 25 Feb 2025.
- Seidelin J, et al. J Crohn’s Colitis. 2025;19(1):i1260-i1262. [Abstract].
- Louis E, et al. JAMA. 2024;332(11):881-897.
Disclosure
Funding: AbbVie funded this study (PROFUNDUS; NCT05494606) 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.
Acknowledgments: AbbVie and the authors thank the participants, study sites, and investigators who participated in this clinical trial. Paulette A. Krishack, PhD, of AbbVie, provided medical writing support.
Disclosures: Remo Panaccione has received consulting fees, speaker fees, and research support from Abbott, AbbVie, Abbivax, Alimentiv Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen Pharmaceuticals, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Satisfai Health, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.
Gareth Parkesreports personal payments, honoraria, speaker fees, travel grants and/or fellowships from AbbVie, Allergan, Bristol Myers Squibb, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts, and directorship and shareholding with Ampersand Health. TR reports personal grants from AbbVie; personal consulting fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, MonteRosa, Mylan, MSD, Novartis, Numab, Pfizer, Roche, Sandoz, Takeda, UCB and XAP; membership of the ECCO Scientific Committee, and membership in the UEG Scientific Committee; director of Endoread.
Mathurin Fumery has received lecture and consulting fees from AbbVie, Amgen, Biogen, BI, BMS, Celgene, Celltrion, CTMA, Ferring, Fresenius, Galapagos, Gilead, Janssen, Pfizer, Lilly, MSD, Sandoz, Takeda, Tillots, and Viatris.
Dominik Bettenworth is on the advisory board or consultant for Amgen, AbbVie, Dr. Falk Foundation, Ferring, MSD, Pfizer, Pharmacosmos, Roche, Takeda, Tillotts Pharma, and Vifor. Silvio Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grünenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor.
Pierre A Morisset, Madhuja Mallick, Shirley H. Chen, and Smitha Suravaram are employees of AbbVie and may own stock options.
