Introduction

Risankizumab (RZB) is a high-affinity humanised immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to the p19 subunit of the interleukin-23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor.^1,2 Long-term RZB therapy for 3 years of maintenance showed durable efficacy and a well-tolerated safety profile in patients with ulcerative colitis (UC) in the COMMAND open-label extension (OLE) study.^1,3 This post hoc analysis evaluated the long-term efficacy of RZB in improving patient-reported outcomes through week (wk) 96 of the ongoing COMMAND OLE study.

Aims & Methods

COMMAND OLE is a 220-wk study enrolling patients who completed 52-wks maintenance dosing or enrolled directly as responders to induction.^1,3 This analysis included patients who completed 52 wks maintenance and an additional 96 wks of RZB treatment in the OLE. All patients received subcutaneous (SC) RZB180 Q8w starting at OLE wk 0, except patients who had prior rescue therapy (single RZB 1200 mg intravenous dose, then SC RZB360 Q8w) who continued RZB360 in the OLE. The OLE study was not designed to compare RZB180 and RZB360 groups. The data cut-off date for this interim analysis was 30 June 2024. Efficacy outcomes included the percentage of patients who achieved the absence of abdominal pain, bowel urgency, faecal incontinence, nocturnal bowel movements, tenesmus, sleep disruption due to UC symptoms; Inflammatory Bowel Disease Questionnaire (IBDQ) response; a meaningful within-person change (MWPC) in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, Short-Form Health Survey-36 version 2 Mental Component Score (SF-36v2 MCS), and SF-36v2 Physical Component Score (PCS). Results were reported using as-observed (AO; Table) and nonresponder imputation (NRI) methods (Table). Safety was reported previously.³

Results

Of the 1003 patients (RZB180 = 701; RZB360 = 302) who entered the OLE, 398 (39.7%) patients (RZB180 = 262; RZB360 = 136) completed wk 96 at data cut-off date. In the AO analysis, RZB180- or RZB360-treated patients showed sustained improvements from OLE wks 0 to 96 in the absence of abdominal pain, bowel urgency, nocturnal bowel movements, tenesmus, faecal incontinence, sleep disruption due to UC symptoms, IBDQ response, MWPC in FACIT-Fatigue, SF-36 PCSv2, and SF-36v2 MCS (Table). Using the more conservative NRI analysis, similar results were observed for most endpoints through OLE wk 96 (Table). Despite RZB360-treated patients were more likely to have numerically higher clinical and endoscopic activity at OLE wk 0 compared with RZB180-treated patients (Adapted Mayo Score [AMS], mean [standard deviation], RZB180, 2.0 [1.4]; RZB360, 3.5 [2.0]; endoscopic subscore: RZB180, 1.1 [1.0]; RZB360, 1.9 [1.0]; clinical remission per AMS, RZB180, 54.8%; RZB360, 24.8%), at OLE wk 96, both RZB dosing regimens exhibited consistent and similar sustained improvements throughout all investigated patient-reported outcomes.

Conclusion

RZB-treated patients who completed OLE wk 96 (3 years of total maintenance therapy) experienced sustained improvement in quality of life and patient-reported outcomes.

References

1. Louis E, et al. JAMA. 2024; 332:881-97.
2. Singh S, et al. mAbs. 2015;7:778-91.
3. Atreya R, et al. J Crohn’s Colitis. 2025;19(S1):i108-i110 [Abstract].

Disclosure

Funding: AbbVie funded this study (COMMAND; NCT03398135) 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; S. Michael Austin, of AbbVie, provided editorial support.
Disclosures: Luc Biedermann has received lecture and consulting fees from Takeda, Sanofi, AbbVie, Falk, Bristol Myer Squibb, and Pfizer and is on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, Falk, Janssen, Pfizer, Takeda, and Sanofi.
Julian Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.
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.
Satoshi Tanida received speaker fees from JIMRO, Mitsubishi Tanabe Pharma, AbbVie, Janssen, Kissei, writing fees from Pfizer, and research funding from AbbVie.
Parambir S. Dulai received research support and/or consulting for AbbVie, Abivax, Adiso, Alimentiv, Bristol Meyer Squibb, Celltrion, Genentech/Roche, Geneoscopy, Janssen, Pfizer, Takeda.
Nidhi Shukla, Jasmina Kalabic, Pierre Morisset, Cecile Holweg, and Dolly Sharma, are employees of AbbVie and may own stock options.
Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Galapagos, Janssen, and Pfizer.

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

Upadacitinib, a selective JAK inhibitor, is approved for moderate-to-severe Crohn’s disease (CD). However, real-world data on its effectiveness and safety, particularly in highly refractory populations, remain scarce. The UPITA-Crohn registry was established to evaluate the outcomes of upadacitinib in clinical practice across multiple centers in Andalusia, Spain.

Aims & Methods

This ambispective, multicenter registry included 142 patients with refractory CD treated with upadacitinib in 12 Andalusian hospitals. Clinical and biochemical data were collected at baseline, weeks 12 and 16, and at 6 months. Clinical remission (CR) was defined as a Harvey-Bradshaw Index (HBI) <5; clinical-biochemical remission (CBR) as HBI <5, CRP <5 mg/L, and fecal calprotectin <250 μg/g; and steroid-free remission (SFR) as HBI <5 without corticosteroids from week 12. Outcomes were also analyzed overall and according to prior exposure to advanced therapies.

Results

The UPITA-Crohn registry cohort included 142 patients with refractory Crohn’s disease. The mean age was 40.8 years (range 18–76), with 40% male. The mean disease duration at the time of upadacitinib initiation was 13.3 years (range 1–42), with a mean of 2.7 failed advanced therapies, highlighting a population with longstanding and complex disease. Most patients had ileocolonic involvement (50%), 22% had perianal disease, and 32% had previously undergone resective surgery.
The majority (74.4%) received induction with upadacitinib 45 mg for 12 weeks. At week 12, clinical remission was achieved by 54% of patients, with 15% reaching clinical-biochemical remission. At 6 months, among those still on treatment, 48.3% maintained clinical remission, 16.1% achieved clinical-biochemical remission, and 18.4% achieved steroid-free remission (Table 1).
When stratified by prior therapy, 6-month clinical remission was similar between patients with ≥2 prior advanced therapies (48.5%) and those with only 1 prior therapy (47.4%), with no significant difference. Steroid-free and clinical-biochemical remission rates were also slightly higher among less refractory patients, but differences were modest.
A total of 31 patients (21.8%) discontinued upadacitinib before 6 months, mainly due to primary non-response (70.9%). Adverse events were reported in 21.1% of patients, most commonly infections (9 cases), acne (7), transient transaminase elevation (5), and herpes zoster (2). Seven discontinuations were due to serious adverse events, including thrombosis, stroke, myocardial infarction, fever, and severe infections.

Table 1: Effectiveness Outcomes

Conclusion

Upadacitinib demonstrated meaningful effectiveness and a manageable safety profile in a real-world cohort of refractory Crohn’s disease patients. Notably, clinical remission rates remained stable even in those with multiple prior advanced therapies, suggesting upadacitinib may be a valuable option for patients with limited alternatives.