Is there data suggesting the risankizumab is more effective than other advanced agents for more severe ulcerative colitis?

Comment by InpharmD Researcher

While there is currently a lack of direct comparative data between risankizumab and other agents for the management of severe ulcerative colitis (UC), pooled data based on indirect evidence suggest risankizumab may have the highest likelihood of achieving clinical remission as induction therapy in biologic-naive patients with moderate-to-severe UC compared to other agents, such as adalimumab. However, its effectiveness in biologic-exposed patients appears to be lessened, with agents including upadacitinib, tofacitinib, and ustekinumab having greater treatment effects.

Background

A recent evidence synthesis by the American Gastroenterological Association (AGA) describes the comparative efficacy of advanced therapies for the management of moderate-to-severe ulcerative colitis (UC). It is stated that treatments with the greatest effect size for induction of clinical remission include upadacitinib, risankizumab, and ozanimod. After excluding Janus kinase (JAK) inhibitors as potential first-line treatment, there was determined to be low-certainty evidence that risankizumab was possibly associated with a higher likelihood of achieving remission compared with adalimumab with induction therapy in biologic-naive patients. Additionally, risankizumab was determined to possibly be associated with a higher likelihood of achieving remission compared with mirikizumab with induction therapy. After excluding JAK inhibitors, among biologic-naïve patients with moderately to severely active UC, risankizumab (P score= 0.86) and ozanimod (P score= 0.83) were ranked highest for induction of clinical remission. [1]

For the outcome of endoscopic improvement in biologic-exposed patients, the highest-ranked treatments were upadacitinib (P score= 0.93), tofacitinib (P score= 0.88), and ustekinumab (P score= 0.87). It was estimated that only 14% of risankizumab-treated patients would achieve clinical remission with induction therapy in biologic-exposed patients. Similarly, for the outcome of maintenance of clinical remission, both upadacitinib and tofacitinib were superior to risankizumab, but with low-certainty of evidence. [1]

The AGA published 2020 guidelines for the management of moderate to severe UC. Risankizumab or interleukin-23 inhibitors have yet to be included within the guideline recommendations. Currently, tumor necrosis factor (TNF)-alpha inhibitors appear to be first-line treatment options with no preference for a specific agent. [2]

A 2025 systematic review and network meta-analysis of 36 phase III randomized controlled trials, involving 14,270 patients with moderate-to-severe UC, evaluated the efficacy of advanced therapies. Endoscopic improvement was the primary outcome, defined as Mayo Endoscopic Score (MES) ≤1 during the induction phase (week 6–14) and maintenance phase (week ≥30). Risankizumab demonstrated strong performance in inducing endoscopic improvement (surface under the cumulative rank area [SUCRA] score: 91.4%) and histological remission (SUCRA score: 89.4%), ranking among the top therapies. It also showed promising results in achieving clinical remission and endoscopic normalization, highlighting its potential as a robust treatment option in UC management. Overall, upadacitinib was consistently the highest-ranking treatment across most efficacy parameters. Comparative data suggests efficacy advantages of newer agents over traditional anti-TNF-α therapies, though direct head-to-head trials remain limited. Direct comparative data between risankizumab and other agents for UC was lacking. [3]

References:

[1] Ananthakrishnan AN, Murad MH, Scott FI, et al. Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Ulcerative Colitis: 2024 American Gastroenterological Association Evidence Synthesis. Gastroenterology. 2024;167(7):1460-1482. doi:10.1053/j.gastro.2024.07.046
[2] Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology. 2020;158(5):1450-1461. doi:10.1053/j.gastro.2020.01.006
[3] Shehab M, Alrashed F, Alsayegh A, et al. Comparative Efficacy of Biologics and Small Molecule in Ulcerative Colitis: A Systematic Review and Network Meta-analysis. Clin Gastroenterol Hepatol. 2025;23(2):250-262. doi:10.1016/j.cgh.2024.07.033
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there data suggesting the risankizumab is more effective than other advanced agents for more severe ulcerative colitis?

Level of evidence

A - Multiple high-quality studies with consistent results  Read more→


Please see Table 1 for your response.

 

Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment

Design

Retrospective, observational chart review

N= 82

Objective

To investigate for the first time the treatment persistence, efficacy, and safety of biologics or small molecules used in 4th or 5th-line therapy

Study Groups

4th-line (n= 44)

5th-line (n= 38)

Inclusion Criteria

Age >18 years; diagnosed inflammatory bowel disease (IBD) treated with 4th- or 5th-line biologics or small molecules for at least 3 months

Exclusion Criteria

No proven diagnosis of IBD; Not treated with a 4th or 5th line of biologics or small molecules for at least 3 months

Methods

 A retrospective analysis of baseline characteristics and outcomes from medical records at Nancy University Hospital was completed. Patients with Crohn's disease (CD) and ulcerative colitis (UC) were monitored as part of routine practice. For CD, the Harvey‐Bradshaw Index (HBI) was used, and for UC, the partial Mayo Clinic score was applied to assess clinical disease activity. The evaluation took place at week 24 following the start of treatment. Clinical remission was defined as an HBI score of less than 4 for CD patients and a partial Mayo score of less than 3 for UC patients. Additionally, any adverse events during the follow-up period were documented.

Duration

Trial: July 2022 to April 2023

Median follow-up: 9 months

Outcome Measures

Primary outcomes: treatment persistence, response rates, clinical remission, restricted mean survival time (RMST) difference

Baseline Characteristics

  

4th-line (n= 44)

5th-line (n= 38)

  

Age, years

  43  42  

Female

 26 (59.1%)  25 (65.8%)  

Type of IBD

Crohn's disease

Ulcerative colitis

 

30 (68.2%)

14 (31.8%)

 

27 (71.1%)

11 (28.9%)

  

Previous treatment for IBD

Adalimumab

Certolizumab

Golimumab

Infliximab

JAK inhibitors

Risankizumab

Ustekinumab

Vedolizumab

 

77.3%

9.1%

2.3%

81.8%

11.4%

2.3%

47.7%

68.2%

 

94.7%

23.7%

5.3%

89.5%

10.5%

0%

84.2%

81.6%

  

IBD treatment at inclusion

Certolizumab

Golimumab

Infliximab

Jak inhibitors

Risankizumab

Ustekinumab

Vedolizumab

 

0%

2.3%

4.5%

6.8%

18.2%

43.2%

25%

 

5.3%

0%

5.3%

7.9%

50%

13.1%

18.4%

  

Results

Endpoint

 4th-line (n= 44)  5th-line (n= 38)

 

Treatment persistence

6 months

12 months

24 months

 

84.6%

65.4%

46.1% 

 

96.9%

76.2%

33.3%

  

Clinical response

  36.4%  57.9%  

Clinical remission

 13.6% 10.5%  

Restricted mean survival time

 Difference in RMST (95% confidence interval [CI]; N= 85) p-value

Total population

Risankizumab vs. vedolizumab

Risankizumab vs. ustekinumab

 

2.61 (−1.86 to 7.08)

1.32 (−2.33 to 4.97)

 

0.253

0.479

4th-line treatment at 36 weeks

risankizumab vs. vedolizumab

risankizumab vs. ustekinumab

 

6.64 (1.71 to 11.56)

3.23 (0.22 to 6.24)

 

0.008

0.035

5th-line treatment at 30 weeks

risankizumab vs. vedolizumab

risankizumab vs. ustekinumab

 

−1.97 (−4.48 to 0.54)

0.23 (−4.37 to 4.83)

 

0.124

0.922

Adverse Events

Common Adverse Events: 4.5% (4th-line group), 7.0% (5th-line group)

Serious Adverse Events: 0%

Percentage that Discontinued due to Adverse Events: 2.6% (5th-line group; n=1)

Study Author Conclusions

In this first real‐world setting, risankizumab could have a longer persistence rate as 4th line treatment for IBD than other agents. Persistence of biological agents was greater in Crohn's disease than in ulcerative colitis. More studies are needed to compare treatment efficacy in patients with difficult‐to‐treat IBD.

InpharmD Researcher Critique

 As both ulcerative colitis and Crohn's disease were included in the trial, results may not be generalizable in populations with only ulcerative colitis.



References:

Caron B, Habert A, Bonsack O, et al. Difficult-to-treat inflammatory bowel disease: Effectiveness and safety of 4th and 5th lines of treatment. United European Gastroenterol J. 2024;12(5):605-613. doi:10.1002/ueg2.12547