Introduction

Risankizumab, a selective interleukin-23 (IL-23) inhibitor, has emerged as a promising therapeutic option for Crohn’s disease (CD). This study aimed to evaluate the real-life efficacy and safety of risankizumab in patients with CD, based on data from the Apulian Network for Inflammatory Bowel Disease (AN-IBD).

Aims & Methods

This multicenter, observational study included all consecutive CD patients initiating risankizumab therapy from its availability within the AN-IBD network. Clinical, biochemical, and ultrasound data were collected retrospectively at baseline (T0) and at the end of induction (week 12, T1).

Results

A total of 81 patients were enrolled. The mean age was 43 years, and 58% were male. Most patients (over 85%) were bio-exposed, with prior failure of at least one biologic. Ileocolonic involvement (L3 by Montreal classification) was the most common disease location, 60% of patients exhibited stricturing behavior (B2), 20% non-stricturing non penetrating pattern (B1) and 20% penetrating phenotype (B3).
At week 12 (T1), 21.6% of patients achieved the clinical response (≥3-point HBI reduction), and 19.6% the clinical remission (HBI <5). 71 out of 81 patients achieved steroid free remission (87,65%).
Inflammatory biomarkers improved significantly: mean CRP value decreased from 3.55 mg/L (T0) to 1.12 mg/L (T1); mean ESR value from 6.55 mm/h to 2.09 mm/h, respectively; mean fecal calprotectin from 57.2 µg/g to 0.81 µg/g.
Ultrasound (BUSS score) identified lower scores at T1 in responders vs. non-responders. Median BUSS scores were T0 (0.6 vs 3.4), T1 (0.5 vs 3.5), with statistically significant differences at T0 (p=0.032), T1 (p=0.031), suggesting a predictive role for early ultrasound response.
Regarding safety, one patient discontinued due to gait impairment, one for a cutaneous desquamative reaction, and another following a severe cutaneous reaction post-induction. Four additional patients discontinued due to lack of response, including one who developed a perianal fistula. No infections were reported.

Conclusion

These preliminary real-world data support the efficacy of risankizumab in inducing clinical response in CD, with a low rate of primary failure. Ultrasound response may have predictive value. No new safety signals were identified.

Disclosure

None

Clinical Case Summary

Inflammatory Bowel Disease (IBD) can be a chronic, disabling condition. Long-term symptoms, failed therapies, repeated hospital admissions and impairment of social functioning can result in significant emotional trauma (Taft et al., 2022). Such patients are at an increased risk of mood disorders and abnormal eating behaviours. Severely affected patients can be managed using a trauma informed approach (Bugwadia et al., 2024).
A 50-year-old woman with a BMI of 14.9 kg/m2, history of ileocolic resection for Crohn’s Disease (CD), anxiety, depression, anorexia nervosa and irritable bowel syndrome presented with symptoms of abdominal pain, diarrhoea and weight loss despite advanced medical therapy. A stricture at the site of her ileocolic anastomosis was identified, with chronic distention of the upstream ileum. Surgical resection with stoma formation was recommended by the multidisciplinary team.
Due to the number and complexity of her co-morbidities, a tailored, trauma-informed approach was used to facilitate her care. Pre-operatively, counselling was performed in a compassionate, staged manner in multidisciplinary consultations. Input from clinical psychology, nutrition and stoma care helped to de-escalate catastrophic thoughts, building trust. Encouragement to engage with peer-support groups improved her confidence. Post-operative care was responsive to her needs with further support from clinical psychology and nutrition. Early closure of the ileostomy allowed return to normal function as soon as was possible.
A trauma-informed care approach combining a team of IBD clinicians, dieticians, stoma nurses and clinical psychologists was crucial in managing a complex case of co-morbid anxiety, depression, anorexia and CD.

References

Bugwadia, A. K., Reed, S., Shapiro, M., Dave, S., Jayswal, N., Kohler, D. & Keefer, L. (2024) Medical trauma in young adults with inflammatory bowel disease: The role of trauma-informed care. Health Care Transitions. 2 100044. 10.1016/j.hctj.2024.100044.
Taft, T. H., Quinton, S., Jedel, S., Simons, M., Mutlu, E. A. & Hanauer, S. B. (2022) Posttraumatic Stress in Patients With Inflammatory Bowel Disease: Prevalence and Relationships to Patient-Reported Outcomes. Inflammatory Bowel Diseases. 28 (5), 710–719. 10.1093/ibd/izab152.

Introduction

Tulisokibart, a TL1A monoclonal antibody, has demonstrated significantly higher rates of clinical remission and endoscopic and histologic improvements vs. placebo in participants with moderately to severely active ulcerative colitis (UC) in the ARTEMIS-UC clinical trial ¹. Although histologic remission has been associated with improved long-term outcomes in UC, histology is inconsistently performed and heterogeneously evaluated in routine clinical care as an assessment of remission depth.

Aims & Methods

This analysis of ARTEMIS-UC explores the correlation between changes in clinical, biomarker, endoscopic, and histologic endpoints following tulisokibart treatment over 50 weeks, potentially providing additional accessible indicators of treatment efficacy. ARTEMIS-UC enrolled two cohorts based on a genetic diagnostic test (Dx) for anti-TL1A treatment response: Cohort 1 (participants regardless of Dx results) and Cohort 2 (only Dx positive participants). We examined 15 relationships between five clinical, endoscopic, and biomarker endpoints and three histologic endpoints at Week 12 after induction (Cohort 1) and Week 50 (Cohorts 1 and 2) among induction responders continuing maintenance tulisokibart. Histologic endpoints included histologic improvement, histologic-endoscopic mucosal improvement (HEMI), and mucosal healing (Table) assessed in the Histology Analysis Set (HAS), i.e., participants who received ≥1 dose of study medication and had Geboes scores at both Baseline and Week 12. Clinical/endoscopic/biomarker endpoints included Modified Mayo Score for clinical remission, clinical response, endoscopic improvement, normalization of fecal calprotectin, and hsCRP normalization. The Phi correlation coefficient assessed pairwise correlations between clinical/endoscopic/biomarker and histologic endpoints.

Results

There were 65 and 34 tulisokibart participants included in the HAS population for the Week 12 and Week 50 analyses, respectively. The strongest correlations were the following: endoscopic improvement:HEMI, endoscopic improvement:mucosal healing, clinical remission:HEMI, and clinical remission:mucosal healing, all >0.8 at Week 12 (post-induction in Cohort 1) and >0.9 at Week 50 (post-maintenance dosing in Cohorts 1 and 2). Normalization of fecal calprotectin also demonstrated a strong correlation with histologic endpoints (>0.7) at Week 50 (Table).

Table: Correlation between Clinical and Histologic Endpoints

Conclusion

Strong correlations exist between clinical, endoscopic, and histologic endpoints after 12 weeks of induction therapy with tulisokibart, followed by 38 weeks of maintenance therapy in induction responders. These findings underscore the potential for clinical remission to reflect both endoscopic and histologic healing in UC patients, which may enhance patient management strategies and enable a more comprehensive understanding of treatment efficacy. Moreover, these findings indicate the potential of tulisokibart in achieving deep remission² in patients with ulcerative colitis.

References

1) Sands BE et al. N Engl J Med. 2024 ;391:1119-1129; 2) Lobatón T et al. United European Gastroenterol J. 2018;6:765-772.

Disclosure

The submitting author of an abstract is requested to declare any potential conflict of interest for all authors during the abstract submission. Moreover, the authors’ names (full first names, family names), gender and affiliation (places of work/institution, city, country) must be provided.
CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Roche, Sanofi, Takeda, Tillotts Pharma; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Ferring, Pfizer
RWL discloses advisory board membership: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Takeda; research grant recipient: Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer, Joanna Tiddy grant, McKusker Charitable Foundation.
JL reports no financial competing interests
XH reports support from AbbVie, Abivax, Alphasigma, Arena, Cellgen, Gilead, Eli Lilly, Enterome, Janssen, InDex Pharmaceuticals, Pfizer, MSD, Roche, Salix, Sangamo, Takeda, and Theravance for clinical research; consulting fees from AbbVie, Abivax, Arena, Galapagos, Gilead, Janssen, Pfizer, Roche, Sangamo, Takeda, and Viatris; and lecture fees from AbbVie, Abivax, Amgen, Arena, Galapagos, Gilead, Fresenius-Kabi, Janssen, Pfizer, Roche, Sangamo, Takeda, and Mylan.
Brigid S. Boland: BSB has research grants from MSD, Mirador, Gilead as well as serves as a consultant for Abbvie, MSD, Celltrion.
JX, WZ, and MY are employees of MSD.