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).

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

1. 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.
2. 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.
3. Seidelin J, et al. J Crohn’s Colitis. 2025;19(1):i1260-i1262. [Abstract].
4. 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.

Introduction

The options for treating chronic inflammatory bowel disease (IBD) with biologics and small molecules (advanced therapies (AT)) have expanded considerably in recent years with the approval of new targeted drugs, some of which have novel mechanisms of action. Direct comparison of effectiveness in the real world is not easy. Therapy persistence measures the willingness of physicians and patients to continue treatment and is therefore a long-term indicator of the effectiveness and safety of a therapy.

Aims & Methods

The aim is to indirectly compare the treatment persistence of different ATs (adalimumab (ADA), infliximab (IFX), vedolizumab (VDZ), IL-12/23 and IL-23 inhibitors (IL-12/23) and JAK inhibitors (JAKi)) stratified by Crohn's disease (CD) and ulcerative colitis (UC).
The TARGET register collects data on the effectiveness and safety of ATs in IBD patients throughout Germany and is designed as a prospective, indication-stratified (CD and UC), multicentre, non-interventional cohort. Data are currently being collected after weekly follow-up during the induction phase and then every 6 months during maintenance therapy. In this analysis, data from 807 patients who were enrolled between November 2019 and December 2023 and followed in the TARGET registry for at least 12 months were analysed up to the cut-off date of 31 December 2024. Treatment persistence was calculated up to 5 years and compared using Kaplan-Meier (KM) curves (log-rank test).

Results

In patients with CD, there were 610 treatment courses with a newly started AT: 198 ADA, 161 IFX, 89 VDZ, 147 IL12/23 (140 UST, 7 RISA), 15 JAKi (1 TOFA, 14 UPA) with a mean observation period of 38, 38, 31, 31 and 9 months. The treatment groups differed in terms of disease duration and the proportion of biologic-experienced patients: both were lowest in the anti-TNF group (Table 1). The persistence rates at 5 years were 79.8% for ADA, 82.0% for IFX, 74.2% for VDZ, 85.7% for IL-12/23 and 100% for JAKi and were not statistically different (p=0.167).
In patients with UC, there were 339 treatment courses with newly initiated AT: 45 ADA, 102 IFX, 111 VDZ, 47 IL12/23 (46 UST, 1 MIRI), 34 JAKi (8 TOFA, 10 FIL, 16 UPA) with a mean observation period of 33, 35, 34, 23 and 16 months. The treatment groups differed in the proportion of patients with prior biologic exposure, which was lowest in the anti-TNF group (Table 1). The persistence rates at 5 years were 66.7% for ADA, 78.4% for IFX, 70.3% for VDZ, 59.6% for IL-12/23 and 91.2% for JAKi. IFX was statistically superior to IL-12/23 (p=0.014).

Conclusion

All patients showed high AT persistence rates of approximately 60-80% up to 5 years, with only minor differences between the different lines of therapy in this current analysis.

Disclosure

PE has received personal fees from: AbbVie, BMS, Galapagos, Janssen, and Amgen, outside the submitted work.
WM has received consulting fees from: AbbVie, Advanz, Amgen, Biogen, Bristol-Myers Squibb, Ferring, Fresenius Kabi, Galapagos, Hexal, Janssen, and Takeda, outside the submitted work. Fees for lectures and further education from: AbbVie, alanta health service, Bristol-Myers Squibb, Galapagos, Janssen, Pfizer, Takeda, and Tillotts, outside the submitted work. He is an active member of the following public law bodies: Advisory Commission of the Examination Office for the Saarland, the State Committee of Physicians and Health Insurance Companies and the Extended State Committee, and an employee in a company belonging to Alanta health group GmbH, Hamburg, Germany, outside the submitted work. Shares, other fees from: AbbVie outside the submitted work.
UT has served as a consultant for Ferring, Abbvie, Janssen-Cilag, Falk-Foundation outside the submitted work.
BB has served as a consultant or advisory board member for Abbvie, MSD, Shire, Ferring, Takeda, Movetis, Shield Therapeutics, Pfizer, Biogen, Janssen, Hexal, Cellgene, Allergan, Galapagos, Arena, BMS, Merckle, Falk and Celltrion outside the submitted work.
SS has served as a consultant or advisory board member for AbbVie, Amgen, Arena, Bristol Myers Squibb, Biogen, Celltrion, Celgene, Ferring, Fresenius, Galapagos, Gilead, HIKMA, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, Theravance and UCB outside the submitted work.
SPD, EG, FHE, MvdO, SFS and TW have no relevant financial or non-financial interests to disclose.

Introduction

Prevalence of inflammatory bowel disease (IBD) is increasing worldwide, while incidence is tending to stabilize. Moreover, the use of biological treatments is increasing, some studies suggest that surgeries and hospitalizations are decreasing instead.

Aims & Methods

A population-based, retrospective cohort study was conducted using data from the Catalan Health Surveillance System (CHSS). All patients diagnosed with IBD were included between 2017-2023. Crude incidence and prevalence rates were calculated for all the Catalan population. Data on pharmacological therapy, surgical procedures, hospitalizations, and mortality were analyzed. Trends in age-sex-adjusted rates were also estimated, and logistic regression was used to calculate the adjusted mortality odds ratio (OR). Data for Crohn’s disease (CD) and ulcerative colitis (UC) were analyzed separately.

Results

The number of prevalent IBD cases rose from 28,752 in 2017 to 41,423 in 2023. Despite incidence rates remained stable (30.8 in 2017 and 29.9 per 100,000 inhabitants in 2023) prevalence rates increased (386.9 and 510.9 per 100,000 inhabitants respectively). The use of biologics significantly increased (from 13.5% in 2017 to 21.0% in 2023), particularly ustekinumab and vedolizumab. In parallel, a decline in the use of immunosuppressants were observed. IBD-related surgeries and hospitalizations decreased during study period, particularly among CD patients. Mortality remained low but was higher among IBD patients compared to the general population.

Conclusion

Incidence of IBD in Catalonia has stabilized, while its prevalence continues rising, suggesting a transition to Stage 3 (compounding prevalence). The use of biological treatments is increasing steadily, whereas rates of surgeries and hospitalizations are consistently decreasing.

Disclosure

None