Introduction

Measurements of fecal (fe) calprotectin as a surrogate biomarker of gastrointestinal inflammation have great clinical impact in the judgement of clinical activity in inflammatory bowel disease. There is no accepted standardization procedure of ELISA-based calprotectin kits, but several commercial kits use of a combined pioneering polyclonal calprotectin antibody (CA) (1) and a monoclonal CA.

Aims & Methods

To evaluate the accuracy of a new rapid fe-calprotectin kit (RFC) including a polyclonal-based CA to predict clinical activity in comparison to a standard commercial (SCFC) kit in patients with ulcerative colitis (UC) and Crohn’s disease (CD) with special focus on clinical remission.
Included were 16 UC and 20 CD patients on ongoing treatment from May 2022 to March 2024 (5ASA, azathioprine, biological therapy). The degree of illness was evaluated at regularly visits every three months using the clinical scoring system- Ulcerative Colitits Clinical Score (UCCS), and Harvey-Bradshaw index (HBI). From the same fe-sample RFC analyses were performed at the Sami Klinikkha, Finnmark Hospital and the SCFC analyses at the University Hospital Tromsø, Norway, both with an upper normal level of 50 µg/g.
Statistical evaluation was done by correlation and limits of agreement analysis; cut-off levels were explored by Receiver Operating Characteristic (ROC) analysis against clinically defined remission

Results

The intra-assay variation of the RFC was 5.3% at a level of 133 µg/g.
Mean calprotectin values (µg/g) with 95 % confidential interval (CI) are shown at various degrees of clinical activities during the observation time (remission, slight and mild), Table 1. In general, the RFC measured lower means and CI levels compared to the SCFC. In clinical remission, the upper RFC CI interval were in proximity to the upper normal level, whereas the corresponding SCFC CI levels were almost three times higher than the upper normal level.
A ROC curve was performed for prediction of clinical remission. Both assays had significant area under the curve (AUC) in both UC and CD patients (p<0.0001). The RFC kit predicted endoscopic remission with 100% specificity at cut-off levels 139 µg/g in both UC and CD. The specificity of the SCFC kit was lower applying the same cut-off levels. Increasing the cut-off to 246 µg/g in the SCFC kit (Youden’s J index 0.68 in the UC group and 0.49 in the CD group), the specificity increased to 96.3 and 96.4% in the UC and CD group, respectively. On the other hand, the test sensitivity decreased (71.4% in UC and 52.2% in the CD patient group).
Table 1

Conclusion

The rapid fe-calprotectin test is an accurate test and predicts remission in UC and CD patients better than a conventional commercial fe-calprotectin kit

References

• Røseth A, Fagerhol MK, et al. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 1992, 27, 793-8.

Introduction

With the expanding array of therapeutic options in Crohn’s disease and ulcerative colitis, it is important to understand patient priorities regarding disease management goals in addition to those of healthcare professionals (HCPs). Views on Inflammatory Bowel Disease (IBD) Expectations and Well-being - Patients and Treatment providers (VIEW-PT): an analysis based on the IBD Disease Specific Programme (DSP)™, previously identified features of optimal disease control, with inclusion of patient and HCP perspectives¹. In order to aid with development of IBD management plans, this study aims to assess the prevalence of optimal disease control and associated factors in a real-world setting.

Aims & Methods

Features of optimal disease control identified in VIEW-PT¹ were used to evaluate prevalence and factors associated with IBD disease control. Data were drawn from the IBD DSP, a cross-sectional survey, with retrospective data collection, of HCPs and their patients with IBD in EU5 (France, Germany, Italy, Spain, the United Kingdom), and the United States of America, collected 2020-21 and 2023-24. Patients with a history of moderate-to-severe disease were included. HCPs reported patient demographics, clinical characteristics, treatment history, healthcare resource utilisation and whether treatment targets were set and subsequently achieved. Patients self-reported sex, symptoms, involvement in their current treatment decision and health-related quality of life via Visual Analogue Scale (EQ-VAS). Patients without key symptoms (bleeding, bowel urgency, fecal incontinence, abdominal pain, fatigue), and with restored bowel movement frequency, extraintestinal manifestations control, complete mucosal healing, no steroid use, no sleep disturbance, and EQ-VAS ≥80^2,3 were considered to have optimal disease control. Logistic regression was performed to determine association of factors with optimal disease control, with odds ratios (OR) and p-values reported.

Results

Of 2614 patients with IBD, just 10.0% had optimal disease control aligned with features identified in VIEW-PT¹. Patient demographics are in Table 1a. Logistic regression analysis included 1833 patients with complete data (Table 1b). Patients involved in treatment decisions (OR=4.82, p<0.001) and patients who achieved their set treatment targets (OR=2.17, p=0.002) had higher odds of achieving optimal disease control, while patients who had not achieved their set treatment targets (OR=0.31, p=0.002) had lower odds of achieving optimal disease control. Other factors associated with optimal disease control included a previous history of smoking (OR=2.13, p=0.004) or having never smoked (OR=1.91, p=0.013), having a psychological comorbidity (OR=0.27, p=0.002), not receiving advanced therapy (OR=0.54, p=0.005), and having >4 HCP visits in the past 12 months (OR=0.42, p<0.001).

Conclusion

Patient involvement in treatment decisions and achievement of treatment targets were most strongly associated with optimal disease control in patients with IBD. Other significantly associated factors included no psychological comorbidities, none or ex-smoking status, and advanced therapy prescription. This real-world evidence suggests that involving patients in treatment decisions and setting and reaching targets may support achievement of optimal disease control in patients with IBD.

References

1. Rubin et al. J Crohn’s Colitis. 2025 Jan 1;19(1): i1376-i1377.
2. Jiang et al. Qual Life Res. 2021; 30(3):803-816.
3. Janssen et al. Eur J Health Econ. 2021;22(9):1467-1475.

Disclosure

MD has received consultant and advisory fees from Abbvie, Abivax, Astra Zeneca, Boehringer Ingelheim International GmbH, Bristol-Meyer Squibb, Celltrion, Eli Lilly and Company, Genentech , Janssen Pharmaceuticals, Johnson and Johnson, Merck, Pfizer Inc, Prometheus Labs, Sanofi, Spyre, Takeda Pharmaceuticals.

ST has received grants/research support from AbbVie, Celgene, Celsius, ECCO, Galapagos, GSK, Helmsley Trust, IOIBD, Janssen, Eli Lilly and company, Pfizer, Takeda, UKIERI, Vifor, and Norman Collisson Foundation;
consulting fees from Alimentiv, Apexian, Apollo, Arcturis, AstraZeneca, BMS, Clario, Cosmo, Endpoint Health, EQrX, Equillium, Ferring, Galapagos, Genentech/Roche, Gilead, GSK, Janssen, Iterative Health, Eli Lilly and company, Mestag, Microbiotica, ONO, Pfizer, Phesi, Protagonist, Sanofi, Satisfai, Sensyne Health, Spyre, Takeda, Teva, Theravance, Tr1X Bio; has received speaker fees from BMS, Ferring, GSK, Janssen, Eli Lilly and company, Pfizer, Sun Pharma, Takeda; and has share options from Satisfai Health Inc.

APB, EK and SF are employees of Eli Lilly and Company and may hold stock or stock options.

GM is part of the speaker bureau for Lilly- 2023-present, Omvoh (mirikizumab); and Pfizer, 2018-present, Xeljanz (tofacitinib), Velsipity (etrasimod)

NA has no conflict of interest to disclose.

LW has no conflict of interest to disclose.

CO is a former employee and shareholder of Eli Lilly and Company.

XZ has no conflict of interest to disclose.

VP and GC are employees of Adelphi Real World.

RP is a consultant for Abbott, AbbVie, Abbivax, Alimentiv,Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly and company, Ferring, Galapagos, Inviva, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mirador, Novartis, Oppilan Pharma, Odyssey, Organon, Pandion.

Introduction

Mirikizumab is a humanized IgG4 monoclonal, anti-interleukin-23p19 antibody. VIVID-2 (NCT04232553), an ongoing open-label study, has demonstrated sustained clinical and endoscopic efficacy at 2 years of treatment of mirikizumab for Crohn’s disease (CD).¹ Here we present the long-term quality of life (QoL) up to 2 years from VIVID-2.

Aims & Methods

Patients enrolled in the phase 3 VIVID-1 study who achieved an endoscopic response to mirikizumab continued maintenance treatment in VIVID-2, while endoscopic non-responders received mirikizumab induction therapy followed by maintenance treatment. Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). The proportion of patients who achieved IBDQ response/remission, as well as mean changes from VIVID-1 baseline in IBDQ total scores at W64 and104 were reported. EQ-5D-5L Visual Analog Scale (VAS) scores (range 0-100, with 100 being best imaginable health state) were assessed at W64. Work productivity was assessed at W64 using Work Productivity and Activity Impairment Questionnaire in Crohn's Disease (WPAI:CD) (4 scores including absenteeism, presenteeism, work productivity loss and activity impairment are derived as percentages with higher values indicating greater impairment). Modified non-responder imputation (mNRI) was used for binary missing data imputation, and modified baseline observation carried forward (mBOCF) was used for continuous missing data imputation. Estimates of mean changes from baseline were calculated with analysis of covariance (ANCOVA).

Results

Analysis of endoscopic responders showed IBDQ response and IBDQ remission were maintained through W104 (85.0% and 71.3%, respectively) while endoscopic non-responders also maintained IBDQ response and remission through the same time (72.6% and 60.8%, respectively). (Table 1) Mean change from baseline in IBDQ total score was maintained through W104 for endoscopic responders and non-responders (least squares mean (standard error); 57.2 (2.1) and 46.8 (2.4), respectively). Similarly, EQ-5D-5L VAS improvement was observed for both groups at W64 (27.0 (1.0) and 22.3 (1.2), respectively). WPAI:CD improvements in both groups ranged from −13.9 (1.8) to −34.3 (1.5) for the different scores collected at W64.

Conclusion

Patients continuing mirikizumab maintenance and those receiving reinduction achieved meaningful long-term QoL improvement that was maintained at 2 years of treatment.

References

1. Barnes E, Sands B, D'Haens G, et al. Long-term efficacy and safety of mirikizumab following 104 weeks of continuous treatment for Crohn's disease: results from the VIVID-2 open-label extension study. Gastroenterology. 2025;168(3 Suppl):S14-S15. doi:10.1053/j.gastro.2025.01.073.

Introduction

In complex perianal fistulizing Crohn’s disease (PFCD), rectal involvement is associated with worse outcomes, likely due to persistent inflammation at fistula internal openings. It is linked to lower remission rates and higher failure rates after anti-TNF-alpha induction, and current guidelines consider it a contraindication to surgical repair. However, its predictive value for secondary loss of response (LOR) to anti-TNF-alpha therapy remains unclear. While endoscopy and MRI can assess rectal disease, the former is limited to mucosal findings, whereas MRI provides comprehensive evaluation of transmural and pelvic inflammation.

Aims & Methods

This study aimed to assess the predictive value of rectal involvement for secondary LOR using both modalities. We conducted a longitudinal study (2000–2023) at a tertiary inflammatory bowel disease center. Included were PFCD patients naïve to anti-TNF-alpha therapy who achieved response or remission after induction. Patients with inadequate follow-up or poor adherence were excluded. Rectal involvement was defined as wall thickening >3 mm on MRI, and mucosal inflammation, a single ulcer >5 mm, or ≥3 ulcers <5 mm on endoscopy. Patients were stratified by MRI findings. Logistic regression identified predictors of secondary LOR, and Kaplan–Meier analysis assessed recurrence-free survival (RFS).

Results

A total of 80 patients were included (male-to-female ratio: 1.33). MRI-detected rectal wall thickening was present in 49 patients (61.3%). The two groups were comparable in baseline demographics and disease phenotype. Mean age at Crohn’s disease diagnosis was 28.9 years in the thickening group and 27.4 years in the non-thickening group; mean age at PFCD onset was 32.5 and 31.5 years, respectively. Most patients were treated with infliximab (88%), and the remainder received adalimumab (12%). Endoscopic rectal involvement was documented in 37 patients (46.3%). Secondary LOR occurred in 64.3% of patients overall, with a mean time to LOR of 17.8 months. Notably, MRI-defined rectal thickening was independently associated with increased odds of LOR (OR = 6.35, p = 0.002), whereas endoscopic assessment did not show a significant association. Patients without MRI-defined thickening had significantly higher RFS at 12, 36, and 60 months (86%, 72%, 57%) compared to those with rectal thickening (57%, 35%, 28%; p < 0.001).

Conclusion

Baseline MRI-detected rectal thickening is a strong, independent predictor of secondary LOR and reduced RFS in PFCD. MRI should be integrated into early disease assessment to identify high-risk patients who may benefit from intensified therapy and close monitoring. Resolution of rectal inflammation may restore eligibility for surgical repair. Further prospective studies comparing MRI and endoscopic markers are warranted to guide tailored treatment strategies.

Introduction

While three JAK inhibitors are now available in Ulcerative Colitis (UC), no direct comparison exists between these drugs making difficult the hierarchization of these therapeutic options.

Aims & Methods

We performed a systematic review and network meta-analysis to compare the short and long-term efficacy of the three available JAK inhibitors (JAKi) (Tofacitinib/TOFA, filgotinib/FILGO, upadacitinib/UPA) in patients with moderat-to-severe UC.
We performed a systematic review and network meta-analysis (PRISMAguidelines) of randomized controlled trials (including post-hoc analyses) conducted in adults, evaluating the efficacy of JAKi in moderate-to-severe UC.
The outcome mesures were 1) steroid-free clinical remission (CFREM) after induction therapy (partial Mayo score ≤ 2), 2) CFREM with endoscopic improvement (endoscopic Mayo score ≤ 1) after induction therapy, 3) CFREM at one year among induction-responders, 4) CFREM at one year among patients in clinical remission after induction.
The network meta-analysis was carried out according to a random effects model. The results are presented as relative risk (RR) with 95% confidence interval. The risk of bias of the studies was assessed according to the Cochrane risk-of-bias tool for randomized trials and overall statistical heterogeneity between studies was assessed using τ .
The SUCRA ranking method (surface under the cumulative ranking) was used to rank the treatments.

Results

Nine studies were included in this network meta-analysis, including a total of 2015 patients.
TOFA 10mg bid, FILGO 200 mg qd and UPA 45mg qd were more effective than placebo to induce CFREM and CFREM with endoscopic improvement. Side-by-side comparisons between JAKi found a higher efficacy of UPA 45 mg qd versus FILGO 200 mg qd (RR=0.22[0.10; 0.45]) for induction but no other significant difference between JAKi. SUCRA ranking hierarchizes induction therapies as following : UPA 45 mg qd (0.99), TOFA 10mg bid (0.75), FILGO 200 mg qd (0.27) and placebo (0.01).
Among induction-responders, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with the following SUCRA ranking : UPA 30mg qd (0.85), TOFA 10mg bid (0.80), FILGO 200 mg qd (0.64), TOFA 5mg bid (0.56), UPA 15 mg (0.44), and placebo (0.01).
Among patients in CFREM after induction phase, all JAKi maintenance regimen (TOFA 10mg bid, TOFA 5mg, bid, FILGO 200mg qd, FILGO 100 mg qd, UPA 30 mg qd, UPA 15 mg qd) were more effective than placebo to achieve CFREM at one year with a different ranking (SUCRA) : TOFA 10 mg bid (0.84), FILGO 200 mg bid (0.74), TOFA (5mg bid) (0 .66), UPA 30mg qd (0.63), UPA 15 mg (0.44) and placebo (0.09).

Conclusion

While this network meta-analysis confirms the efficacy of JAKi to induce and maintain CFREM in moderate-to-severe UC, UPA seems to be the most effective JAKi to induce and maintain CFREM. However, once CFREM achieved after induction, continuing the same dose than during induction such as TOFA (10mg bid) or FILGO 200 mg seems to be more effective than reducing the dose (UPA 30 mg or UPA 15 mg) to maintain remission highlighting the dose-efficacy relationship of JAKi.

Disclosure

Consulting fees from: Abbvie, Amgen, Arena, Biocon, Biogen, Celltrion Healthcare, CTMA, Ferring, Galapagos/AlfaSigma, GutyCare/Resilience Janssen, Lilly, MSD, Nexbiome, Pfizer, Roche, Sandoz, Takeda et Tillotts
Lecture fees from: Abbvie, Amgen, Biogen, Celltrion Healthcare Galapagos/AlfaSigma, Ferring, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Norgine, Pfizer, Roche, Takeda, Tillotts and Vifor Pharma
Research grants/fundings from: Abbvie, Celltrion Healthcare, Janssen, Lessaffre, Lilly, Pfizer, Sandoz and Takeda

Introduction

Mirikizumab, a monoclonal antibody targeting the p19 subunit of IL-23, was approved in Germany in May 2024 for the treatment of moderately to severely active ulcerative colitis (UC), following favorable results in clinical trials (1,2). We aimed to evaluate the effectiveness and safety of mirikizumab (MIRI) in a real-world setting, focusing on a population of patients with prior exposure to three or more advanced therapies.

Aims & Methods

​​​​​In October 2023, we initiated a prospective observational study, collecting clinical, biochemical, and endoscopic data from adult patients (n > 100) with moderate to severe UC who began MIRI treatment in our tertiary referral center in Munich, Germany. The primary endpoints were clinical remission, defined as a Clinical Activity Index (CAI, Lichtiger score) <4 and endoscopic remission, defined as an endoscopic Mayo score ≤1 at 12 months. Secondary outcomes included monthly (1-4 mo) and bimonthly (6-12 mo) trends in fecal calprotectin levels, CAI scores, urgency numeric rating scale (NRS), frequency of re-induction therapy (300 mg every 4 weeks for 3 doses), and steroid discontinuation during the observation period. Adverse events were systematically recorded. All statistical analysis was performed by SolidPulse Software in Phyton using pandas, scipy and statsmodels. This report presents the first key results from patients who have completed at least 6 months of treatment.

Results

To date, 73 patients have initiated MIRI therapy as approved; none have discontinued treatment. Of these, 55 patients have reached the 6-month follow-up. These 55 had a median disease duration of 11 years (range 3–43), and 55% were female. All 55 patients had been exposed to three or more advanced therapies before starting MIRI, and 23 patients (42%) received MIRI concomitantly in combination with another targeted therapy. Among the 55 patients, 29 (53%) had previously lost response to ustekinumab (90 mg every 8 weeks), and 19 (35%) were on concomitant corticosteroids at the start of MIRI therapy. At baseline, 36 patients had a Mayo endoscopic score of II or III, and 19 had a score of 0 or I.
Main results:

• The rates of clinical remission (CAI <4) increased from 36% (30/55) at baseline to 42% (23/55) at 1 month (p=0,6), 40% (22/55) at 2 months (p=0,8), 49% (27/55) at 3 months (p=0,09), 58% (32/55) at 4 months (p=0,008), and 58% (32/55) at 6 months (p=0.008, McNemar test).
• Median urgency NRS scores improved from 5 (range 0–10) at baseline to 1 (range 0–9) at 6 months (p<0.0001, two-sided Wilcoxon test).
• Median calprotectin decreased from 460 (range 20–2100) at baseline to 75 (range 20–2100) at 6 months (p<0.0001, two-sided Wilcoxon test).
• Among the 29 patients with prior ustekinumab use, clinical remission increased from 41% (12/29) at baseline to 55% (16/29) at 6 months, though this change did not reach statistical significance (p = 0.3, McNemar test), possibly due to the low number of patients.

Conclusion

Mirikizumab demonstrated clinical effectiveness and was well tolerated in a real-world UC cohort, including patients with longstanding disease and multiple prior treatments with advanced therapies.

References

1) D’Haens G, Dubinsky M, Kobayashi T et al. Mirikizumab as induction and maintenance therapy for ulcerative colitis. NEJM. 2023; 388: 2444–2455.
2) Dubinsky MC, Clemow DB, Hunter Gibble T et al. Clinical effect of mirikizumab treatment on bowel urgency in patients with moderately to severely active ulcerative colitis and the clinical relevance of bowel urgency improvement for disease remission. Crohn's Colitis 360. 2023; 360: 1–13.

Disclosure

This work has been funded by a grant from Eli Lilly