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.

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

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by esophageal dysfunction and a peak eosinophil count of >15 cells per high power field (HPF). Recent studies suggest that mast cells play a key role in its pathophysiology. This study investigates the presence of mast cells in different groups of patients with EoE.

Aims & Methods

Biopsy samples from patients newly diagnosed with EoE were analyzed, and the Eosinophilic Esophagitis Histology Scoring System (EOEHSS) grade and stage scores were calculated. Biopsy samples were divided in two groups: t0 (before the starting of EoE therapy) and t1 (after EoE therapy). Mast cells were detected using tryptase immunohistochemistry, and the maximum number of mast cells counted in a high-power field (PMC), was recorded. Univariate correlation analysis were performed between PMC and peak eosinophil count (PEC), PMC and EOEHSS grade, PMC and EOEHSS stage, PMC and EREFS.

Results

12 patients affected by EoE were divided in group 1, treated with PPIs [Esomeprazole 40 mg, bis in die (bid)] and group 2, treated with BOT (budesonide oral tablets 1 mg, bid). Univariate correlation analysis were performed at t0 and t1. Results from Pearson’s R for analysis at t0 are showed a positive linear correlation in PEC-PMC (0,567, p=0,043) and EOEHSS grade-PMC (0,559, p=0,047). At t1, EREFS-PMC had a positive correlation (0,726, p 0,005), like also EOEHSS grade-PMC (0,74, p=0,002) and EOEHSS stage-PMC (0,818, p<0,001).

Conclusion

PCM positively correlates with PEC, EOEHSS grade, EOEHSS stage and EREFS in untreated samples, supporting their role in EoE and type-2 inflammation. In treated cases, PMC correlate with PEC, EOEHSS grade, EREFS. A highly statistically significant strong positive linear correlation was found between PMC and EOEHSS stage, as the latter is more likely to reflect the whole esophageal histologic changes.
Our study suggests that mast cell count, alongside eosinophil counts, could be an important factor in evaluating anti-inflammatory therapeutic interventions and it may be a useful adjunct to existing endoscopic and histologic markers in assessing EoE severity, supporting their role in EoE and type-2 inflammation. To confirm these findings, further longitudinal prospective studies are required.

References

N. de Bortoli, P. Visaggi, R. Penagini et al., The 1st EoETALY consensus on the diagnosis and management of eosinophilic esophagitis – Definition, clinical presentation and diagnosis, Digestive and Liver Disease
Collins MH, et al. Eosinophilic esophagitis histology remission score: significant relations to measures of disease activity and symptoms. J. Pediatr. Gastroenterol. Nutr. 2020;70(5):598–603
Kanamori A, et al. Esophageal mast cells may be associated with the perception of symptoms in patients with eosinophilic esophagitis. Esophagus. 2023 Apr;20(2):333-341
Bolton SM, et al. Mast Cell Infiltration Is Associated With Persistent Symptoms and Endoscopic Abnormalities Despite Resolution of Eosinophilia in Pediatric Eosinophilic Esophagitis. Am J Gastroenterol. 2020 Feb;115(2):224-233.