Introduction

Mirikizumab (miri), an anti-IL-23p19 antibody, demonstrated efficacy and safety in patients with moderately-to-severely active ulcerative colitis (UC) in LUCENT Phase 3 trials.^1,2 Bowel urgency (BU) clinically meaningful improvement (CMI) and BU remission were associated with clinical response and remission and also contributed to the improvement in Work Productivity and Activity Impairment Questionnaire UC (WPAI:UC) scores.^3,4 This analysis evaluated if the addition of BU improvement to clinical response or remission was associated with better work productivity.

Aims & Methods

In LUCENT-1 (NCT03518086), patients were randomized 3:1 to induction miri 300mg intravenous or placebo every four weeks (Q4W). Patients who achieved clinical response to miri at week 12 (W12) were re-randomized 2:1 to maintenance subcutaneous injection of miri 200mg or placebo Q4W for 40 weeks in LUCENT-2 [52 weeks (W52) continuous treatment] (NCT03524092). Clinical response and remission were assessed along with change from baseline in WPAI:UC domain scores (activity impairment, absenteeism, presenteeism, and overall work impairment).⁵ BU was assessed using the Urgency Numeric Rating Scale (UNRS), an 11-point scale ranging from 0 (“no urgency”) to 10 (“worst possible urgency”), with both BU CMI (≥3-point change) and BU remission (UNRS score of 0 or 1), measured in patients with a baseline UNRS of ≥3.⁶ The association between BU (CMI or remission) with the change of WPAI:UC was evaluated using analysis of variance among patients with baseline UNRS ≥3 who achieved clinical response. This analysis was repeated among patients who achieved clinical remission.

Results

The addition of BU CMI was positively associated with reduction of activity impairment, presenteeism, and overall work impairment in patients who achieved clinical response or remission at both W12 and W52 (p<0.005) (Table 1). Achieving clinical response and BU remission was significantly associated with greater reduction of activity impairment, presenteeism, and overall work impairment compared to patients with clinical remission only at both W12 and W52 (p<0.01). The combined improvement of achieving both clinical remission and BU remission was significantly associated with higher reduction in activity impairment at W12 (-36.1% vs -27.3%; p=0.0147) and overall work impairment at W52 (-39.9% vs -29.8%; p=0.0394). Patients who achieved both clinical response or clinical remission and BU CMI or BU remission did not show a significant difference in absenteeism compared to those who achieved clinical response or remission alone.

TABLE 1. Association of Clinical Remission/Response with achievement of Bowel Urgency Remission/CMI on Change from Baseline of WPAI:UC Domain Scores in Patients with UC at W12 and W52 of Continuous Treatment
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Conclusion

Among patients with UC from miri phase 3 trials, the addition of BU (CMI or remission) to the achievement of clinical response or remission was associated with reduction of WPAI:UC scores: activity impairment, presenteeism, and overall work impairment.

References

1. 1. D’Haens, G., et al. "OP26 Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study." J Crohns Colitis 16. Supplement_1(2022):i028-i029.
   2. Dubinsky, M.C., et al. "867e: Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study." Gastroenterology 162.7(2022):S-1393.
   3. Dubinsky, M.C., 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.” Crohns Colitis 360, 5(1), (2023): otac044.
   4. Sands B.E., et al. “Relative association of bowel urgency clinically meaningful improvement and bowel urgency remission versus stool frequency remission and rectal bleeding remission with improvement in Work Productivity and Activity Scores in patients with moderately-to-severely active Ulcerative Colitis: An analysis from LUCENT-1 and LUCENT-2 phase 3 clinical trials.” J Crohns Colitis 17, Supplement_1(2023):i775–i777.
   5. Reilly Associates WPAI Scoring. Accessed March 28, 2022. http://www.reillyassociates.net/WPAI_Scoring.html
   6. Dubinsky, M.C., et al. "P138 Psychometric validation and interpretation of a patient-reported outcomes instrument to assess bowel urgency among adults with moderate to severe Ulcerative Colitis." J Crohns Colitis 16. Supplement_1(2022):i220-i222.

Disclosure

David T. Rubin receives grants or contracts from Takeda, and discloses consultancy fees with Abbvie, Altrubio, Allergan, Inc., American College of Gastroenterology, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Ltd., Bristol-Myers Squibb, Celgene Corp/Syneos, Cornerstones Health, Inc. (non-profit), GalenPharma/Atlantica, Genentech/Roche, Gilead Sciences, GoDuRn, LLC, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen Pharmaceuticals, Eli Lilly and Company, Materia Prima, Pfizer, Prometheus Biosciences, Reistone, Takeda and Techlab, Inc. Jianmin Wu, Bomina Park, Simin K Baygani, Nathan Morris, Theresa Hunter Gibble are employees of Eli Lilly and Company. Stefan Schreiber receives consultancy and/or personal fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, HIKMA, IMAB, Janssen, Lilly, MSD, Mylan, Pfizer, Prometheus, Takeda, and Theravance.

Introduction

The risk of colorectal advanced adenomas (CAAs) and colorectal cancer (CRC) in siblings aged ≤ 50 years of patients diagnosed with early-onset CAAs (E-CAAs), defined as having CAA at or below the age of 50 years​, is poorly understood.

Aims & Methods

This study aimed to compare the risks of adenomas, CAA, and CRC in siblings aged ≤ 50 years of patients diagnosed with E-CAA to those in individuals aged ≤ 50 without such a family history.
This case-control study was conducted at a tertiary hospital in Vietnam. The participants included 96 cases who were siblings aged ≤ 50 years of patients diagnosed with E-CAA. Controls were randomly selected from consecutive patients aged ≤ 50 years who did not have siblings diagnosed with E-CAA. The absence of a family history of CAA in the control group was confirmed through comprehensive history taking. ​The controls were matched to cases in a 2:1 ratio for age (±3 years), sex, and smoking status. Individuals with alarming features of CRC or a family history of CRC were excluded. All the participants underwent standard bowel preparation and colonoscopy.

Results

The mean age was similar between cases (40.9 ± 6.0 years) and controls (41.1 ± 6.0 years). Except for the indications for colonoscopy, there were no significant differences in the baseline demographics between the two groups. A higher risk of CAA was documented in cases compared with controls (odds ratio [OR] = 6.33; 95% confidence interval [CI], 1.43–43.8; P = 0.018). This increased risk of CAA was more pronounced among male participants (OR = 13.7; 95% CI, 1.23–262; P = 0.006). Higher risks of colorectal adenomas (OR = 2.43; 95% CI, 1.27–4.67; P = 0.009) and colorectal neoplasia (OR = 2.23; 95% CI, 1.24–4.40; P = 0.011) were also found in cases compared with controls. CRC was found in one case and two controls.

Conclusion

Siblings aged ≤ 50 years of patients diagnosed with E-CAA have an increased risk of adenomas, CAA, and colorectal neoplasia. CRC screening should be initiated early in high-risk individuals.

Table 1. Risk of Colorectal Neoplasia among Siblings of Patients Diagnosed with Advanced Adenomas (n = 288)

References

Ng SC, Lau JY, Chan FK, et al. Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study. Gastroenterology. 2016;150(3):608-e17.
Cottet V, Pariente A, Nalet B, et al. Colonoscopic screening of first-degree relatives of patients with large adenomas: increased risk of colorectal tumors. Gastroenterology. 2007;133(4):1086-1092.

Introduction

Pancreatic exocrine insufficiency (PEI) is characterized by a significant reduction in pancreatic exocrine activity within the intestine, impairing normal digestive processes ⁽¹⁾. This condition results in malnutrition-related complications and a diminished quality of life. Faecal pancreatic elastase serves as an optimal biomarker for evaluating pancreatic function in individuals with PEI. Its high stability ensures that faecal pancreatic elastase is concentrated during intestinal transit, thereby accurately reflecting total pancreatic secretion. The BÜHLMANN fPELA^® turbo is a particle-enhanced turbidimetric immunoassay (PETIA) that is commercially available for the automated quantification of pancreatic elastase in faecal extracts using clinical chemistry analyzers. Additionally, BÜHLMANN has developed the Quantum Blue^® fPELA, a lateral flow immunoassay (LFIA) designed for environments requiring lower sample volumes. This study aimed to evaluate the clinical performance of both assays and compare them to a commercially available ELISA reference method.

Aims & Methods

A total of 189 symptomatic patients, comprising 82 non-PEI controls and 107 PEI-diagnosed patients, were utilized to compare the clinical performance of PETIA and LFIA against the ELISA reference assay. Sensitivity and specificity for both assays were determined using cutoffs of 100 μg/g and 200 μg/g.

Results

The area under the curve (AUC) was 0.809 for the BÜHLMANN fPELA^® turbo (optimal cut-off: 166 μg/g), 0.792 for the Quantum Blue^® fPELA (optimal cut-off: 109 μg/g), and 0.814 for the reference ELISA (optimal cut-off: 154 μg/g). At clinically relevant cut-offs of 100 μg/g and 200 μg/g, the BÜHLMANN fPELA^® turbo demonstrated sensitivity of 0.57 and 0.74, and specificity of 0.9 and 0.76, respectively. The Quantum Blue^® fPELA showed sensitivity of 0.62 and 0.71, and specificity of 0.93 and 0.74, respectively. The reference ELISA exhibited sensitivity of 0.64 and 0.73, and specificity of 0.87 and 0.70, respectively. A direct method comparison using at least 60 samples within the linear measuring range of all assays revealed a relative median difference in Bland-Altman analysis of 9.3% between the BÜHLMANN fPELA^® turbo and the reference ELISA, 10.8% between the ELISA and the Quantum Blue^® fPELA, and 11.0% between the PETIA and the LFIA.

Conclusion

The study demonstrated that both the BÜHLMANN fPELA^® turbo and the Quantum Blue^® fPELA exhibit strong diagnostic performance to detect PEI in symptomatic patient population and high concordance with the reference ELISA assay. The BÜHLMANN fPELA^® turbo, a particle-enhanced turbidimetric immunoassay, is an accurate, non-invasive, automated test ideal for large-scale determination of pancreatic elastase levels in faecal extracts. Meanwhile, the Quantum Blue^® fPELA rapid test is well-suited for smaller laboratories, offering a faster time to result compared to traditional ELISA methods, while offering a coequal clinical performance.

References

(1) Philips ME, et al. BMJ Open Gastro 2021; 8: e000643

Disclosure

Conflict of interest: CR, DT, HI, AT, MU, RT, MS, TS, SN and CG are employees of BÜHLMANN Laboratories AG