Tag Archives: Risankizumab

Real-World Outcomes of Risankizumab in Children With Crohn’s Disease

Posted on by
Reply

Briefly noted:

EA Spencer et al. Journal of Crohn’s and Colitis. 2026; 20: jjag134. https://doi.org/10.1093/ecco-jcc/jjag134 Real-world effectiveness and safety of risankizumab induction and maintenance therapy in pediatric patients with Crohn’s disease: a multicenter retrospective analysis.

Methods: This was a retrospective, global multicenter cohort of patients <18 years initiating risankizumab monotherapy (2022-2025). Among the 96 study participants, 38% had prior ustekinumab exposure.

Key findings:

  • Post-induction corticosteroid-free clinical remission (CFR) was achieved in 28/68 (41%), clinical response in 37/68 (54%), and combined CFR + CRP remission in 22/68 (32%).
  • Week 30 and 54 CFR were attained in 34/68 (50%) and 34/68 (50%), respectively.
  • No serious safety events occurred.

My take: This study bolsters previous studies showing that risankizumab is an effective treatment for Crohn’s disease in the pediatric age group.

Related blog posts:

AFFIRM Study: Subcutaneous Induction-Maintenance Data for Risankizumab

Posted on by
Reply

Charlie Lees is a Professor of Gastroenterology, University of Edinburgh.

From Charlie Lees on X (10/14/26):

Related blog posts:

Comparative Safety of Advanced Therapies for Ulcerative Colitis

Posted on by

D Ahuja et al. Am J Gastroenterol 2026;121:1192–1201. Comparative Safety of Advanced Therapies in Patients With Ulcerative Colitis: An Administrative Claims-Based Study

Methods: Using an administrative claims database (OptumLabs Data Warehouse) with a ‘real-world’ cohort, the authors identified 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months.

Key findings:

Overall, the risk of serious infections was higher with infliximab than with the other therapies. The incidence of VTE in patients with UC was very low and comparable across all advanced therapies, including JAK inhibitors. Also, the incidence of MACE in patients with UC was
very low and comparable across all advanced therapies, including anti-ILs and JAK inhibitors.

From the discussion: “In a recent network meta-analysis and corresponding clinical guidelines on the management of moderate-to-severe UC, upadacitinib was ranked as having the highest efficacy for induction ofremission compared with all other agents (2,14). However, safety concerns with JAK inhibitors were raised in the pivotal ORAL Surveillance trial (15). In this noninferiority trial, tofacitinib, particularly at higher doses, was associated with a higher risk of serious and opportunistic infections, VTE, and MACE, compared with TNF antagonistsi n patients with rheumatoid arthritis. Following this, the US Food and Drug Administration changed JAK inhibitors’ labeling across all indications, restricting its use in patients with previous failure or intolerance to TNF antagonists…the ORAL Surveillance trial focused on older patients aged 50 years or older with rheumatoid arthritis and at least one cardiovascular risk factor…

[In this study, the] lack of an apparent increase in the risk of JAK inhibitors compared with other medications may be related to superior disease control achieved with JAK inhibitors or reverse causality where patients at high risk of MACE and/or VTE events are not prescribed JAK inhibitors.”

My take: This study provides additional reassurance that newer advanced therapies have similar or better safety than infliximab.

Related blog posts:

Don’t Rush to Judge Risankizumab Effectiveness for Ulcerative Colitis

Posted on by

R Panaccione et al. Clin Gastroenterol Hepatol 2026; 24: 1424-1433. Open Access! Impact of Extended Risankizumab Treatment in Patients With Ulcerative Colitis Who Did Not Respond to Induction Treatment

Methods:

  1. In the AbbVie-funded phase 3 INSPIRE induction study, 209 initial nonresponders to 12 weeks of 1200 mg intravenous (IV) risankizumab induction were rerandomized to receive 12 weeks of additional 1200 mg risankizumab (weeks 12, 16, and 20) or 180 mg or 360 mg subcutaneous [SC] risankizumab (weeks 12 and 20) in a double-blind fashion
  2. Then, the delayed responders continued to receive blinded risankizumab at their assigned dose in the phase 3 COMMAND maintenance study
  • Clinical response per adapted Mayo Score (AMS): decrease from baseline ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1
  • Clinical remission per AMS: SFS ≤1 and not greater than baseline, RBS = 0, and endoscopic subscore ≤1 without the evidence of friability

Key findings:

  • Initial nonresponders (1200 mg IV [n = 68], 180 mg SC [n = 71], or 360 mg SC [n = 70]) had week 24 clinical response rates of 50%, 56.3%, and 57.1%, respectively
  • Patients also achieved clinical remission, histologic endoscopic mucosal improvement (8.8%, 12.7%, and 15.7% for both endpoints), endoscopic improvement (17.6%, 18.3%, and 24.3%), and endoscopic remission (1.5%, 8.5%, and 5.7%)

My take: A longer trial of risankizumab is often needed to know with certainty if it will work for ulcerative colitis. More than half of initial nonresponders acquire a clinical response with extended therapy. A similar pattern was noted for risankizumab with Crohn’s disease.

Related blog post: Over 60% of Initial Nonresponders Improve with Extended Risankizumab Therapy for Crohn’s Disease

Choosing Advanced Therapy for Crohn’s Disease Based on Disease Location

Posted on by

Methods: In the study by Lee et al, the authors identified 14 randomized controlled trials in 3139 patients with moderate-to-severe CD who were treated with different advanced therapies vs placebo, and reported efficacy in inducing clinical remission, stratified by disease location (isolated colonic vs ileal disease, excluding ileocolonic disease). The authors did not identify any RCT of TNF antagonists that reported induction of remission by disease location.

Key findings:

  • All advanced therapies had better success with colonic disease rather than ileal disease
  • Anti-interleukins (eg. IL23 o rIL12/IL23 agents) worked best for ileal disease among these advanced therapies
  • JAK inhibitors did not work well for ileal disease, but performed well for colonic disease
  • Anti-integrins, like vedolizumab, had some efficacy for ileal disease but generally a lower clinical remission rate than other agents
  • Lmitations included the use of clinical remission as the primary outcome
  • While this study did not provide data on anti-TNF therapy, in the discussion the authors note that “TNF antagonists may have advantages in small bowel CD…infliximab demonstrated the highest rate of improvement in large ileal ulcers (>0.5 cm).” [ref#45] “Additionally, infliximab has been reported to reduce fibrostenosis-associated inflammation, [Ref#46] making it currently the most suitable therapeuctic option for small bowel CD.”

In the study by Sands et al, this post-hoc analysis included week (W) 10 responders (n=329) to intravenous IFX induction therapy who were randomized to receive IFX SC 120 mg every 2 weeks or placebo (PBO) during maintenance therapy.

Key findings:

My take: These two studies indicate that anti-TNF agents (particularly infliximab) and IL-23 type agents are most effective for Crohn’s disease affecting the ileum. JAK inhibitors are best for colonic disease.

Related blog posts:

Graphic by Dr. Keith Siau

Clinical Response to Risankizumab Dose Intensification for Crohn’s Disease

Posted on by

RS Dalal et al. Clin Gastroenterol Hepatol 2025; 23: 662-664. Outcomes After Dose Intensification of Risankizumab for Crohn’s Disease

This retrospective study reviewed adults with Crohn’s disease (CD) who underwent dose intensification of maintenance from 360 mg every 8 weeks to every 6 weeks (n=11) or every 4 weeks (n=11).

Key findings:

  • Median time to first intensified dose was 228 days
  • Harvey Bradshaw Index (HBI) improved from a mean of 7.1 to 4.3 after 8 to 16 weeks
  • There was also improvement (not statistically significant) in mean CRP (1.64–>0.42 mg/dL) and mean calprotectin (774 –>650 mcg/g)
  • At 8 to 16 weeks, 64% (14 of 22) had a clinical response, 45% (10 of 22) achieved steroid free clinical remission

My take: This small study suggests that the majority of patients with a loss of response to standard dosing can be recaptured with dose intensification.

Related blog posts:

Old Town in Conyers, GA

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Over 60% of Initial Nonresponders Improve with Extended Risankizumab Therapy for Crohn’s Disease

Posted on by

R Panaccione et al. Clinical Gastroenterology and Hepatology 2025; In press. Open Access! Extended Risankizumab Treatment in Patients With Crohn’s Disease Who Did Not Achieve Clinical Response to Induction Treatment

Addendum -updated reference: R Panaccione et al. Clinical Gastroenterology and Hepatology 2025; 23: 2012-2022. Open Access! Extended Risankizumab Treatment in Patients With Crohn’s Disease Who Did Not Achieve Clinical Response to Induction Treatment

Methods: Per the study design, patients who did not achieve SF/APS clinical response following induction could receive 12 weeks of extended treatment with RZB, either via administration of the higher (1200 mg) IV RZB dose evaluated in ADVANCE and MOTIVATE or by initiation of SC RZB at doses (180 mg and 360 mg) used in FORTIFY maintenance therapy.

Key findings:

  • Over 60% of initial nonresponders achieved clinical response with extended RZB treatment. These patients also demonstrated improved clinical and endoscopic outcomes during the extended treatment period, which were sustained or continued to improve during maintenance.

My take: While there is a very good response with initial risankizumab therapy in Crohn’s disease, it looks like judgment on response needs to wait until 24 weeks as there are many who do not respond at 12 weeks who will subsequently respond to treatment.

Related blog posts:

Dr. Maria Oliva-Hemker: Positioning Therapies for Pediatric Crohn’s Disease

Posted on by

Recently, Dr. Maria Oliva-Hemker gave our group an excellent update on Crohn’s disease therapies.  My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides.

Key points:

  • Early advanced therapy results in better outcomes (see The PROFILE study results below as one example)
  • Anti-TNFs are the only therapy with a specific FDA pediatric indication. Medications can take 8-10 years after use in adults for pediatric labeling
  • IL-23 specific agents (like risankizumab) are more effective than ustekinumab that target both IL-23/IL-12
  • Recent studies show that ustekinumab is effective in children. Also, in patients who respond to ustekinumab, there is good durability
  • Infliximab is a top-line therapy in Crohn’s disease
  • Risankizumab is a top-line therapy in both biologic-naive and biologic-exposed patients with Crohn’s disease. Higher maintenance doses may capture more patients.
  • Upadacitinib is a very good therapy in patients with prior advanced therapies with either Crohn’s or ulcerative colitis. It also has a rapid onset of action (within 2 weeks)
  • Vedolizumab is less effective in those who are biologic-exposed. However, patients with predominantly colonic (UC-like) involvement may be better-suited for this therapy
  • Close monitoring and treat-to-target approaches are recommended. Usually followup scope is undertaken after one year (&/or one year after switching therapy)
  • Combination advanced therapies have shown effectiveness but it is unclear which combinations are optimal
This slide shows the Montreal Classification, an organ-based phenotype, to describe the anatomic extent and behaviors of Crohn’s disease;. The figure on the right illustrates extraintestinal manifestations of IBD. It is expected that disease classification will rely more on a molecular based approach.
The STRIDE project which defined goals of treatment was the result of consensus achieved by the International Organization of IBD. The first recommendations came out in 2015 and then these were updated in 2021 to incorporate a pediatric component.
The PROFILE study with 386 adults showed how important early effective advanced therapies. Patients receiving infliximab/azathioprine within a median of 15 days from diagnosis had remarkably better outcomes compared to step up treatment with prednisone + azathioprine.
The cytokine IL12 and IL23 shown as circles with 2 subunits attaching to their receptors share a p40 subunit (shown in red). Ustekinumab binds to that p40 subunit thereby inhibiting both the IL12 and IL23 pathways. IL23 inhibitor. Risankizumab, Mirkizumab, Guselkumab inhibit only the p19 subunit (shown in blue) and so  they only downregulate the IL-23 pathway.
Jak inhibitors targets are intracellular in location.
Pediatric data: Multicenter 2015-2020; primary outcome was CS-free remission after 1 yr. Prior to use, 50% failed 1 anti TNF and 30% 2 anti TNF. At one year, 59/101 were in steroid free remission
Upadactinib studies: Oral induction dose for UC and CD is 45 mg daily for induction
and with reduction in maintenance to 30 mg or 15 mg
Due to limited head-to-head studies, network meta analyses provides indirect evidence of comparative effectiveness. It relies on how effective a medication was compared to placebo. One of the problems with these comparisons is that there are different populations in each of these studies.
In patients who need speed to reduce symptoms, upadacitinib is favored over IL-23 agents

Though Dr. Oliva-Hemker’s lecture did not focus on ulcerative colitis, she did note that their center has recommended frequent colonoscopies (often yearly) in many of their patients with the combination of ulcerative colitis and PSC. This is due cases of colon cancer in their pediatric cohort.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Key Advances in 2024: An Overview from GutsandGrowth (Part 1)

Posted on by

This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Risankizumab for Ulcerative Colitis

Posted on by

E Louis et al. JAMA 2024; doi:10.1001/jama.2024.12414. Risankizumab for Ulcerative ColitisTwo Randomized Clinical Trials

In June, risankizumab (Skyrizi) received FDA approval as a treatment for moderate to severe ulcerative colitis in adults. FDA approval relied on the data from these two randomized trials.

Methods:  For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks.

Key findings:

  • In the 12-week induction INSPIRE study with 975 patients, the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (P < .001)
  • In the induction trial, a greater proportion of treated patients achieved endoscopic improvement (36.5% vs. 12.1%; P < 0.00001) and endoscopic histologic mucosal improvement (24.5% vs. 7.7%; P < 0.00001) after 12 weeks
  • In the induction trial, a clinical response at 12 weeks was noted in 418/650 (64.3%) of risankizumab-treated patients and 116/325 (35.7%) of the placebo-treated patients
  • In the COMMAND maintenance trial with 548 patients, the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo. Both doses were statistically-significant compared to placebo, P < .001 and P = .002, respectively
  • After 1 year of treatment with either maintenance dose of risankizumab, more than 40% of patients had histologic and endoscopic improvement
  • More than 75% of patients in the maintenance trial had a history of inadequate response to advanced therapies

My take: The published results of risankizumab for Crohn’s disease are much more impressive than the results in this study.

Related blog posts:

Matterhorn (shared by MH) in September 2024