Introduction

Ulcerative colitis (UC) is increasing in prevalence and incidence in Korea, and each patient shows a different course and treatment response. Since the 2000s, biologics have been developed and treatment options have diversified. Biologics and small-molecule therapeutics for immunological targets are currently under research and development. In the past, the goal was clinical improvement, including symptoms, but now endoscopic mucosal healing and, furthermore, the continuation of histological remission are gradually suggested. Accordingly, the purpose of this study was to identify clinical factors that could predict histological remission in patients receiving a first-line biologic agent, as well as confirm the patient's response to treatment and prognosis.

Aims & Methods

We retrospectively analyzed the medical records of 440 patients who had been diagnosed with UC and exposed to biologics for the first time in our hospital without using biologics at other hospitals between January 01, 2010 and December 31, 2022. Patients who did not undergo pre- and post-exposure endoscopy and biopsy or whose follow-up was discontinued were excluded. Clinical characteristics, blood tests, endoscopic findings, and pathological examination results of a total of 72 patients were collected. Endoscopic response was defined as a decrease in the Mayo Endoscopic Subscore (MES) compared to the score before the first exposure to the biological agent. Histological remission was defined as the result of no cryptitis, no crypt abscess, or no inflammatory cells observed on histological examination, and histological response was defined as remission in patients previously observed with active inflammation.

Results

The ratio of males to females was 53:19, and the median age at the time of diagnosis was 41 years. The average Mayo score at the time of diagnosis was 7.2, and the group with a histological response was 6.0, showing a statistically significant difference. The average albumin was 3.88 and was 4.06 in the histological response group, with a statistically significant difference. The median time to exposure to the first biologic was 1520 days. A colectomy was performed in three cases. Biologics were started with infliximab in 46.7% of patients, followed by adalimumab and vedolizumab in 22.7% and 21.3%, respectively. There was no statistical correlation between histological response and each biologic agent.
MES before exposure to biological agents was 50% in 2 and 44.4% in 3, but there was no statistical difference between each group. Multivariate logistic regression analysis was performed to identify predictors of endoscopic and histological responses after the first exposure to biological agents. As a result, it was confirmed that the Mayo score, ESR, and albumin had a causal relationship with the endoscopic response, respectively, and the odds ratio was 0.781, 1.051, and 3.319, respectively (p-value 0.044, 0.007, 0.049). In addition, it was confirmed that the Mayo score had a causal relationship with the histological response with an odds ratio of 0.796 (p-value 0.046).

Conclusion

This study confirmed that disease activity before treatment was a predictor of histological remission in UC patients using first-line biologics. It was confirmed that the histological response as well as the endoscopic response were well induced when the disease activity was low. Therefore, early escalation to biologics before the patient's condition worsens may be the basis for improving the overall prognosis.

References

Park, Sang Hyoung et al. “Clinical Characteristics and Long-term Prognosis of Elderly-Onset Ulcerative Colitis in a Population-Based Cohort in the Songpa-Kangdong District of Seoul, Korea.” Gut and liver vol. 15,5 (2021): 742-751. doi:10.5009/gnl20289
Park, Sunhee et al. “Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis.” The American journal of gastroenterology vol. 111,12 (2016): 1692-1701. doi:10.1038/ajg.2016.418

Introduction

Bowel urgency is a common and disruptive symptom in patients with ulcerative colitis (UC).¹ Fatigue is also common and has been associated with greater disease activity and lower quality of life in these patients.² However, little is known regarding the relationship between bowel urgency remission, bowel urgency clinically meaningful improvement, rectal bleeding remission, or stool frequency remission and improvement in fatigue. We examined the association between bowel urgency remission or bowel urgency clinically meaningful improvement and Fatigue Numeric Rating Scale (NRS) scores in the presence of rectal bleeding remission or stool frequency remission using pooled data from LUCENT-1 (NCT03518086) and LUCENT-2 (NCT03524092) phase 3 trials.

Aims & Methods

Bowel urgency was assessed by the Urgency NRS (UNRS), ranging from 0 (no urgency) to 10 (worst possible urgency). Bowel urgency remission was defined as a UNRS score of 0 or 1; bowel urgency clinically meaningful improvement was defined as a ≥3-point decrease in UNRS score from baseline.³ Rectal bleeding remission was defined as a modified Mayo subscore of 0; stool frequency remission was defined as a subscore of 0 or 1 with ≥1-point decrease from baseline.⁴ Fatigue was assessed by the Fatigue NRS, ranging from 0 (no fatigue) to 10 (worst possible fatigue), using change from baseline in Fatigue NRS score. Mediation analyses were performed to separately examine the relative association between the direct effects of bowel urgency remission and bowel urgency clinically meaningful improvement (predictor variables) and Fatigue NRS scores while adjusting for rectal bleeding remission and stool frequency remission (mediation variables). Analyses were treatment agnostic and combined mirikizumab and placebo treatment groups from LUCENT-1 (N=1162) and LUCENT-2 (N=544).

Results

The direct effect of bowel urgency remission at Week 12 and Week 40 (52 weeks continuous treatment) accounted for 68.3% and 62.1%, respectively, of the improvement in change from baseline in Fatigue NRS score. Substantially greater proportions of the Fatigue NRS score improvements were related to bowel urgency remission versus rectal bleeding remission (Week 12: 13.4% and Week 40: 16.4%) or stool frequency remission (Week 12: 18.3% and Week 40: 21.5%). Results were similar for bowel urgency clinically meaningful improvement at Week 12 (91.8%) and Week 40 (87.4%).

Conclusion

These findings provide strong evidence for a direct association between improvement or remission in bowel urgency and improvement in fatigue in patients with moderately-to-severely active UC.

References

1. Hibi T, et al. Inflamm Intest Dis. 2020;5(1):27.
2. Regueiro MD, et al. Adv Ther. Online Nov 12, 2022. doi: 10.1007/s12325-022-02364-2.
3. Dubinsky MC, et al., J Patient Rep Outcomes. 2022;6(1):114.
4. ClinicalTrials.gov. Updated October 27, 2022. Access December 1, 2022. clinicaltrials.gov/ct2/show/NCT03518086.

Disclosure

D. T. Rubin has been a consultant for and/or received research grants from: AbbVie, AbGenomics, Allergan, Biomica, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos Health, Check-Cap, Dizal Pharma, Eli Lilly and Company, Galen/Atlantica, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Ichnos Sciences, InDex Pharmaceuticals, Janssen, Narrow River Management, Pfizer, Prometheus Therapeutics and Diagnostics, Reistone Biopharma, Shire, Takeda, and TechLab; is a shareholder at: AbGenomics and Biomica; is on the Board of Trustees at: American College of Gastroenterology; is cofounder and CFO of: Cornerstones Health (non-profit); and is cofounder of: GoDuRn; P. Hindryckx has received consulting fees from: AbbVie, Boston Scientific, Eli Lilly and Company, Janssen, Taewoong Medical, and Takeda; has received speaker fees from: AbbVie, Chiesi, Dr. Falk Pharma, Ferring Pharmaceuticals, Takeda, Tillotts Pharma AG, and Vifor Pharma; and has received research support from: Eli Lilly and Company; T. Hibi has received lecture fees from: AbbVie, EA Pharma, Janssen, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, Sand K.K., Takeda, and Zeria Pharmaceutical; has received advisory and/or consultancy fees from: AbbVie, Celltrion, EA Pharma, Eli Lilly and Company, Gilead Sciences, Janssen, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Nippon Kayaku, Takeda, and Zeria Pharmaceutical; has received research grants from: AbbVie, Activaid, Alfresa Pharma, Bristol Myers Squibb, Eli Lilly Japan K.K., Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceutical K.K., JMDC, Mochida Pharmaceutical, Nippon Kayaku, Pfizer Japan Inc., and Takeda; has received scholarship•contributions from: Mitsubishi Tanabe Pharma, Nippon Kayaku, Pfizer Japan Inc., and Zeria Pharmaceutical; has belonged to study group sponsorship by: Alfresa Pharma, JIMRO, Kyorin, and Mochida Pharmaceutical; and has received grants and/or funds from: MIYARISAN Pharmaceutical Co., Ltd. and Zeria Pharmaceutical; K. McGinnis, T. Hunter Gibble, and A. Keohane are employees and shareholders of:
Eli Lilly and Company; M. Regueiro has received consulting fees from: AbbVie, Allergan, Amgen, Celgene, Eli Lilly and Company, Genentech, Gilead Sciences, Janssen, Miraca Life Sciences, Pfizer, Prometheus Therapeutics and Diagnostics, Salix Pharmaceuticals, Seres Therapeutics, Takeda, Target RWE, and UCB Pharma; and has received research support from: AbbVie, Janssen, Pfizer, and Takeda

Clinical Case Summary

Pancreatic tuberculosis is rare, even in regions where the disease is highly prevalent. Its incidence is less than 4.7% (14/297 cases) in a large tuberculosis autopsy series by Auerbach et al. (1944). Symptoms are vague and non-specific, while radiologic features can mimic pancreatic carcinoma. Due to its nature of presenting as a pancreatic mass, unwarranted surgical interventions may diminish the patient’s quality of life. We presented a case of a 53-year-old male with a ten-week history of abdominal pain, febrile episodes, and weight loss. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed a pancreatic head and body mass causing moderate extrahepatic, intrahepatic, and mild pancreatic ductal dilatation. There was also infiltration of the medial wall of the second part of the duodenum and the posteroinferior wall of the first portion of the duodenum. Endoscopy showed duodenal narrowing due to the mass encroaching on the duodenum; hence malignancy was highly considered. However, a biopsy of left cervical lymphadenopathies seen revealed chronic granulomatous inflammation morphologically compatible with a tuberculous etiology. The patient underwent exploratory laparotomy with pancreatic head mass biopsy, where the frozen section revealed chronic granulomatous inflammation, possibly tuberculous in etiology, hence proceeded with gastrojejunostomy and cholecystojejunostomy. Postoperatively, the patient was stable and sent home with six months of anti-Koch medication, with a final diagnosis of pancreatic tuberculosis. Repeat MRCP revealed a resolution of the previously seen pancreatic head and body mass and biliary dilatation. Conservative management usually successfully alleviates symptoms and even the complete regression of mass lesions. The excellent response to anti-Koch’s medication makes it imperative that these patients are diagnosed early and managed appropriately to avoid unwarranted surgery and associated morbidity.

References

Auerbach O. Acute Generalized Miliary Tuberculosis. The American Journal of Pathology. 1944Jan;1(20):121–136.
Chaudhary P, Bhadana U, Arora MP. Pancreatic tuberculosis. Indian Journal of Surgery. 2015;77(6):517–24.

Disclosure

No conflict of interest was foreseen by the authors.