Introduction

Mirikizumab is a monoclonal antibody directed against the p19 subunit of interleukin (IL)-23 approved for the management of patients with moderate-to-severe ulcerative colitis (UC). Currently, there is no large study supporting the effectiveness of mirikizumab in UC in a real-life setting.

Aims & Methods

This study aims to evaluate the effectiveness and safety of mirikizumab in real-life setting. This was a retrospective multicenter cohort study of a prospectively collected database including adult patients with confirmed diagnosis of UC treated with mirikizumab according to clinical practice. Patients were enrolled in three third-level italian centers (San Raffaele Hospital, Humanitas Research Hospital, and Federico II Hospital) from June 2024 to February 2025. All patients with at least 3 months of follow-up after therapy initiation were eligible. The primary outcome was the clinical remission rate (defined as partial Mayo Score (pMS) < 2 with a rectal bleeding subscore of 0) at week 12. Secondary outcomes included changes in bowel urgency (measured by the Numeric Rating Scale (NRS) urgency score), changes in serum C-reactive protein (CRP) and fecal calprotectin (FC) levels from week 0 to 12, safety profile of mirikizumab during induction therapy.

Results

In total 100 patients (60% male, with median age 48.53 ± 15.36) with UC were included. Most patients had a left-sided colitis (55, 55%) or a pancolitis (41, 41%). Most patients (81, 81%) were already treated with at least one advanced therapy before starting mirikizumab (including 28 patients treated with ustekinumab, 28%). A fifth of patients (19, 19%) were exposed to ≥ 4 advanced therapies. A significant reduction in pMS was observed from baseline to week 12 (median [IQR]: 4.0 [1.75–6.0] vs. 2.0 [0.0–4.0]; Wilcoxon signed-rank test: W = 312, Z = -5.35, p < 0.00001, n = 69) with 48 (48%) patients reaching clinical remission at week 12. Moreover, a significant improvement in bowel urgency was observed from baseline to week 12 (t(98) = 6.58, p = 2.28×10⁻⁹), with a moderate-to-large effect size (g = 0.66). From baseline to week 12, both FC and CRP levels showed significant reductions following treatment (FC: V = 1153.00, p = 2.4×10⁻⁵, r = 0.67; CRP: V = 680.00, p = 0.03, r = 0.37). Effect sizes were large for FC and moderate for CRP with paired data from 53 and 47 patients being analyzed, respectively. In total, 39 patients (39%) underwent extended induction while 3 patients (3%) discontinued the drug at week 12. There were no adverse events leading to discontinuation or death. Two mild adverse events were reported (upper respiratory tract infection in 1 patient and pyrexia in 1 patients). No significant changes were observed in liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels over time (AST: χ²(2) = 0.21, p = 0.90, W = 0.005; ALT: χ²(2) = 3.73, p = 0.16, W = 0.08).

Conclusion

This is the largest study demonstrating the effectiveness and safety of mirikizumab in inducing clinical remission in patients with UC in a real-life setting. Patients treated with mirikizumab achieved a significant reduction in bowel urgency, FC and CRP levels. No statistically significant increase in liver toxicity was detected during the induction treatment.

Disclosure

F. D'Amico. OM Nardone, A. Zilli, M. Allocca, S. Danese, L. Peyrin-Biroulet and A. Armuzzi have served as speaker and advisory board member for Lilly

Introduction

Cirrhosis is characterized by structural and functional hepatic alterations. The associated metabolic imbalances and psycho-neurological factors contribute to the high prevalence of sexual disorders and erectile dysfunction among affected patients. The aim of our study was to identify factors associated with sexual dysfunction in cirrhotic patients.

Aims & Methods

We conducted a prospective cross-sectional study, collecting data from patients followed for cirrhosis at the gastroenterology department of Charles Nicolle Hospital in Tunis over a one-year period. Female sexual function was assessed using the FSFI questionnaire. Female sexual dysfunction was defined by an FSFI score below 26 (or below 20 in post menopausal women). Male sexual function was evaluated using the IIEF-15 questionnaire. Male sexual dysfunction was identified by an IIEF-15 score below 42.9. Erectile dysfunction was confirmed by an IIEF-5 score
below 26. An analytical statistical study was conducted, highlighting factors associated with sexual dysfunction in both female and male patient groups.

Results

We included 55 cirrhotic patients (24 women and 31 men), with a sex ratio (M/F) of 1.29 and a mean age at inclusion of 59.11 ± 12.16 years. Female sexual dysfunction was observed in 70.8% of female patients. Male sexual dysfunction was found in 61.3% of patients. Erectile dysfunction was reported in 74.1% of men. Our study showed that the factors associated with female sexual dysfunction were: low economic status (p = 0.007), the presence of arterial hypertension (p = 0.026), and hepatic disease severity attested by Child-Pugh class B/C and MELD score >15 (p = 0.049 and p = 0.018, respectively). In male patients, a higher prevalence of sexual dysfunction was found among smokers patients (p = 0.045; OR = 0.18; 95% CI [0.03; 1.05]) and them who consumed alcohol (p = 0.042; OR = 0.19; 95% CI [0.04; 0.94]). In multivariate analysis, only alcohol consumption was independently associated with male sexual dysfunction (p = 0.041; OR = 9.187). MELD score >15

Conclusion

In conclusion, our study highlights the high frequency of sexual disorders in cirrhotic patients and identifies several associated factors, notably the severity of liver disease, socioeconomic
status, and certain comorbidities. For these reasons, screening and appropriate management of sexual dysfunction is essential in cirrhotic patients especialy with advanced disease or comorbidities.

Clinical Case Summary

Immunotherapy with checkpoint inhibitors (CPI) has transformed oncology management, achieving durable remissions. However, its widespread has also led to significant immune-mediated side effects, whose treatment is a challenge in today's medicine.
We present the case of a 59-year-old man diagnosed with non-small-cell lung cancer who started treatment with Nivolumab(anti-PD1). After 6 months, the patient was admitted for 3 weeks diarrhoea(4 liquid stools/day).
A colonoscopy was done, identifying severe pancolitis with oedema, erythema, nodularity and superficial ulcers. PA revealed diffuse non-specific colitis with CMV IHC -. Given the suspicion of immune-mediated colitis vs de novo IBD, treatment was started with iv GCC, with no improvement.
Given the contraindication of long-term use of anti-TNF in IBD patients with active malignancies, induction with IV Ustekinumab (anti-IL12/23) was decided. Ustekinumab 390 mg iv was given, after which the patient showed clinical improvement until complete resolution. He continued with Ustekinumab 90 mg/8 weeks. A follow-up colonoscopy showed pancolic scarring with pseudopolyps and no inflammatory activity. Given these findings Ustekinumab was discontinued after 1 year, with the patient remaining asymptomatic and without oncologic progression.
Immune-mediated colitis is a common side effect, being mild in most cases. When severe cases occur, CPI should be discontinued indefinitely, and high-dose iv GCC (up to 2 mg/kg) should be initiated. Up to one-third of GCC-treated patients don't respond and are candidates for immunosuppressive therapy with biologic drugs.
Although clinical guidelines recommend Infliximab/Vedolizumab for induction as 2º line treatment, the therapeutic decision should be individualized, as they are contraindicated in IBD patients with active malignancies. Therefore, in this context of complex differential diagnosis, Ustekinumab (with lower rate of oncological side effects) appears to be an effective option.

References

Photo 1: Initial colonoscopy: severe pancolitis with erythema, oedema, superficial ulcers and mucosal nodularity.
Photo 2: Abdominal CT: Diffuse thickening of the colon with increased uptake of the wall.
Photo 3: Follow-up colonoscopy: Chronic scar changes without signs of acute activity.

Introduction

A significant proportion of patients with inflammatory bowel disease (IBD) have concomitant rheumatological manifestations. On the other hand, patients with spondyloarthritis (SpA) often report gastrointestinal symptoms, some of them being associated to IBD. However, the exact prevalence of this disorder is still controversial, and the optimal approach to its diagnosis remains unknown.

Aims & Methods

Our main was to determine the prevalence of undiagnosed IBD in patients with axial SpA (radiographic and non-radiographic) and psoriatic arthritis (PA). EISER is a multicenter, nationwide, observational, and cross-sectional study where 13 Spanish hospitals participated. Patients ≥18 years-old diagnosed with PA or SpA according to the CASPAR or ASAS criteria, respectively, were selected. Patients receiving biologics or systemic steroids at baseline or within the previous 30 days were not included. Regarding patients older than 50 years, only those without valid colonoscopy in the previous 3 years were included. Rheumatologist performed a baseline visit and collected demographic, clinical, and treatment data. Fecal calprotectin (FC) was determined by the Quantum Blue rapid test and this was followed by a gastroenterologist consultation. A complete colonoscopy was indicated on all patients with symptoms, FC≥80 µg/g without NSAIDs, or 160 µg/g if they were on NSAIDs. Capsule endoscopy or magnetic resonance enterography were performed in those with no findings on colonoscopy.

Results

A total of 559 patients were included (51% men; mean 52.2 years; mean disease duration of SpA/PA was 12.3 years). The most frequent rheumatological disease was radiographic SpA (37%), followed by peripheral APs (36%). Abnormal FC was observed in 47% and 53% of patients with PA and EspAx (80% radiographic-SpA vs 20% non-radiographic-SpA), respectively. Mean FC levels were higher among radiographic-SpA (395 µg/g) compared to the rest of the groups (306 µg/g for non-radiographic-SpA and 306 µg/g in PA). Overall, 11,5% had gastrointestinal symptoms, with the most common being abdominal pain (16%) and chronic diarrhea (11%). In total, 189 colonoscopies were performed, 40% demonstrating at least one abnormal finding, mostly aphthous ulcers (66%), superficial ulcers (21%) and erythema (14%), and they were mainly located in the terminal ileum (41%). Finally, 23 patients were diagnosed with IBD (4.4%), mostly with radiographic-SpA (83%), followed by peripheral PA (8.7%) and non-radiographic-SpA and axial PA (4.3% each). All patients but two were diagnosed with CD (91.3%), with 1 case of unclassified IBD (4.3%) and 1 with nonspecific ileitis (4.3%).

Conclusion

FC levels in patients with SpA and PA, followed by an appropriate endoscopic and/or radiological diagnostic algorithm, allows the identification of a relevant subgroup of patients with previously undiagnosed IBD