Tag Archives: guselkumab

What Caught My Eye in a Recent Anti-IL23 Commentary

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This recent commentary on the all-subcutaneous induction and maintenance treatment with guselkumab, an anti-IL23 agent, reviewed the GRAVITI study. Related post: Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study

However, what captured my attention was the last sentence: “The convenience of subcutaneous induction enhances patient friendliness, positioning guselkumab as a strong market contender. Could an oral anti–IL-23 formulation be the next game changer?14“

“Johnson & Johnson (NYSE: JNJ) today announced positive topline results from ANTHEM-UC, a Phase 2b study of icotrokinra (JNJ-2113), the first investigational targeted oral peptide that selectively blocks the IL-23 receptor, in adults with moderately to severely active ulcerative colitis (UC)…

In the ANTHEM-UC study (n=252), three doses of once daily icotrokinra were tested with all meeting the primary endpoint of clinical response at Week 12. A response rate of 63.5% for patients treated with the highest dose of icotrokinra was achieved at Week 12 versus 27% for placebo (p<0.001). Further, 30.2% of patients treated with the highest dose of icotrokinra demonstrated clinical remission at Week 12 versus 11.1% of patients who received placebo (p<0.01). Remission and response rates continued to improve through Week 28.

  • Clinical response is defined as decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
  • Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy.”

My take: It would be terrific for patients with inflammatory bowel disease (and other immune-mediated diseases) to have another excellent oral therapy. A prior study of plaque psoriasis indicated that an oral IL-23 medication is feasible (Related post: In Trials: An Oral IL-23 Antagonist Peptide).

Related joke (regarding “caught my eye” in the title of this post):

A man who lived in a block of apartments thought it was raining and put his head out the window to check.  As he did so a glass eye fell into his hand. He looked up to see where it came from in time to see a young woman looking down. “Is this yours?” he asked.

She said, “Yes, could you bring it up?” and the man agreed. On arrival she was profuse in her thanks and offered the man a drink. Shortly afterwards she said, “I’m about to have dinner.  There’s plenty; would you like to join me?” He readily accepted her offer and both enjoyed a lovely meal. As the evening was drawing to a close the lady said, “I’ve had a marvelous evening.  Would you like to stay the night?”  The man hesitated then said, “Do you act like this with every man you meet?”

“No,” she replied, “only those who catch my eye.”

The Manneporte by Claude Monet (at the Metropolitan Museum of Art)

Guselkumab for Crohn’s Disease: GALAXI-2 and GALAXI-3: 48-Week Results

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R Panaccione et al. The Lancet. Published online July 17, 2025 https://doi.org/10.1016/S0140-6736(25)00681-6. Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn’s disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials

Methods: “GALAXI-2 and GALAXI-3 were identically designed, phase 3, randomised, double-blind, triple-dummy, treat-through trials with active and placebo comparators…1048 participants were randomly assigned, treated, and followed up until week 48, of whom 1021 participants were included in the primary analysis population: 508 (49·8%) in GALAXI-2 and 513 (50·2%) in GALAXI-3.” The studies enrolled adult patients with moderately to severely active Crohn’s disease.

Key findings:

Discussion points:

  • “Guselkumab treatment in participants with moderately to severely active Crohn’s disease was also evaluated in the GRAVITI study, which had a fully subcutaneous induction and maintenance treatment regimen. Clinical and endoscopic outcomes reported with subcutaneous guselkumab induction in the GRAVITI study were similar to those in the phase 3 GALAXI studies following intravenous guselkumab induction.”
  • “The incidence of adverse events with guselkumab during induction was low and similar to placebo.”

My take (borrowed from authors): In GALAXI-2 and GALAXI-3, both guselkumab dose regimens (each including intravenous induction and subcutaneous maintenance) were superior to placebo for short-term (week 12) and long-term (week 48) endpoints and both guselkumab dose regimens were also superior to ustekinumab

Related blog posts:

Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study

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A Hart et al. Gastroenterol 2025 (ePUB Ahead of Print) Open Access! Efficacy and Safety of Guselkumab Subcutaneous Induction and Maintenance in Participants With Moderately to Severely Active Crohn’s Disease: Results From the Phase 3 GRAVITI Study

Background: “Guselkumab is a selective dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 by binding to the p19 subunit and to CD64, a receptor on cells that produce IL-23…In the double-blind Phase 2 GALAXI 1 study and the 2 identically designed double-blind Phase 3 GALAXI 2 and GALAXI 3 studies, guselkumab intravenous (IV) induction (200 mg at weeks 0, 4, and 8) followed by subcutaneous (SC) maintenance (200 mg every 4 weeks or 100 mg every 8 weeks) demonstrated efficacy compared with placebo… In addition, guselkumab demonstrated superiority to ustekinumab for multiple endoscopic-based endpoints at week 48 in pooled data from GALAXI 2 and GALAXI 3… The GRAVITI study…evaluated the efficacy and safety of guselkumab SC induction followed by SC maintenance in participants with moderately to severely active Crohn’s disease.

Methods: This was a Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study randomized 347 participants 1:1:1 to guselkumab 400 mg SC every 4 weeks→100 mg SC every 8 weeks (n = 115), guselkumab 400 mg SC every 4 weeks→200 mg SC every 4 weeks (n = 115), or placebo (n = 117).  Placebo participants meeting rescue criteria received guselkumab from week 16 onward. 

Key Findings:

  •  At week 12, significantly greater proportions of participants receiving guselkumab 400 mg achieved clinical remission vs placebo (56.1% vs 21.4%; P < .001), and endoscopic response vs placebo (41.3% vs 21.4%; P < .001)
  • At week 48, significantly greater proportions of participants in both guselkumab groups (100 mg SC every 8 weeks: 60.0%; 200 mg SC every 4 weeks: 66.1%) achieved clinical remission vs placebo (17.1%; P < .001 each) and endoscopic response (44.3%; 51.3%; vs placebo 6.8%; P < .001 each)
  • Immunogenicity: “Antibodies to guselkumab were detected in 24 (8.8%) of the 274 guselkumab-treated participants through week 48. Only 3 of 274 participants (1.1% of the total population) were positive for neutralizing antibodies. Through week 48, no impact of antibodies to guselkumab on serum guselkumab concentrations, efficacy, or injection-site reactions was observed”
At week 12: Compared to placebo, patients receiving Guselkumab had improved clinical remission and endoscopic response. Being naive to previous biologics was associated with a higher endoscopic response but with a lower clinical remission rate.
At week 48: Being naive to previous biologics was associated with a higher clinical remission
At week 48: Being naive to previous biologics was associated with a higher endoscopic remission

Discussion: “The results presented here from GRAVITI were consistent with those reported in the double-blind, treat-through GALAXI trials in which guselkumab induction was administered IV in participants with moderately to severely active Crohn’s disease. For example, 41.3% of participants in the GRAVITI study achieved endoscopic response 12 weeks … whereas 36.9% of participants in the pooled GALAXI studies achieved endoscopic response 12 weeks after guselkumab… IV induction (placebo: 12.2%).”

My take: This study shows that Guselkumab with a SC induction is safe and effective in participants with moderately to severely active Crohn’s disease. IV induction does not appear to be needed. Though IL-23 agents have been important advances, there are still a large number of patients without a good response.

Related blog posts:

Comparing Infliximab, Adalimumab, and Vedolizumab in Adults and Children with Ulcerative Colitis

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O Atia et al. Infammatory Bowel Diseases, 2025, 31, 617–624. Durability of the First Biologic in Children and Adults With Ulcerative Colitis: A Nationwide Study from the epi-IIRN

This was a nationwide Israeli study with 15,111 patients with UC, of whom 2322 (15%) received biologics, with a median follow-up of 7.0 years. The dataset includes ~98% of the Israeli population; “the accuracy of medication data is high, as the Israeli health care system provides medications almost free of charge through the HMOs, and the electronic dispensing of drugs contributes to reliable and precise data.”

Key findings:

  • After 5 years of treatment, 43% of the patients with UC sustained their first biologic
  • The durability rate was similar between pediatric-onset and adults after 1 and 5 years from initiation of treatment (72% and 43% vs 71% and 43%, respectively)
  • Durability of adalimumab vs infliximab after 1 or 5 years was similar, whether prescribed as monotherapy (65%/46% vs 63%/33%, respectively) or combotherapy (78%/56% vs 91%/58%, respectively)
  • Durability of infliximab at 1 yr and 5 yrs was higher as combotherapy (85%/50%) vs monotherapy (69%/42%; , P = .007), while it was similar for adalimumab (80%/52% vs 74%/52%)
  • The durability rate was similar for vedolizumab monotherapy at 1 yr and 5 yrs (77%/56%) compared with adalimumab monotherapy (69%/52%), and infliximab monotherapy (73%/55% vs 62%/44%). However, combotherapy of antitumor necrosis factors (TNFs) had longer durability than vedolizumab (85%/50% vs 75%/43%), respectively;

My take: When looking at the durability plots, the three main biologics in this study, infliximab, adalimumab and vedolizumab, performed similarly. Whether therapeutic drug monitoring would influence theses results is not clear. It is interesting that a recent study in the pediatric population found that combination therapy was important for adalimumab and not infliximab (see: Why Do Children Taking Adalimumab Benefit from Methotrexate Dual Therapy?)

Related blog posts:

Also, from AGA Today (3/20/25): FDA Approves Guselkumab To Treat Patients With Crohn’s Disease

HCPlive (3/20, Campbell) reports the FDA on Thursday announced the approval of “guselkumab (Tremfya) for the treatment of adults with moderately to severely active Crohn disease.” The announcement from Johnson and Johnson claims the “approval is based on data from multiple phase 3 trials, including the GALAXI trials, which found guselkumab outperformed ustekinumab (Stelara) for multiple endoscopic endpoints. The agent now boasts indications for moderately to severely active Crohn disease and moderately to severely active ulcerative colitis (UC).” This is the fourth indication for guselkumab in the US

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.

Pivotal Study: Guselkumab Efficacy in Ulcerative Colitis (QUASAR study)

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DT Rubin et al. Lancet 2024; 405: 33-49. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies

Background: “Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64.”

Methods:  “Two phase 3, randomised, double-blind, placebo-controlled studies (QUASAR phase 3 induction and maintenance) included randomised and treated adults with moderately to severely active ulcerative colitis (induction baseline modified Mayo score from 5 to 9) with inadequate response or intolerance to conventional or advanced ulcerative colitis therapy.”

“The induction study primary population included 701 patients (guselkumab 200 mg given intravenously 60% [421 patients]; placebo 40% [280 patients]). The maintenance study primary population included 568 guselkumab induction responders randomly assigned to receive guselkumab 200 mg given subcutaneously every 4 weeks (190 [33%] patients) or 100 mg every 8 weeks (188 [33%] patients) or placebo (guselkumab withdrawal 190 [33%] patients).”

Key findings:

  • INDUCTION DATA AT 12 WEEKS:
At induction week 12
At induction week 12
Induction symptomatic endpoints -response noted in majority of guselkumab-treated patients by 4 weeks

MAINTENANCE DATA AT 44 WEEKS

Results and Discussion points:

  • “Symptomatic improvement was observed as early as induction week 1 (first assessed timepoint)”
  • “Greater reductions in C-reactive protein and faecal calprotectin concentrations with guselkumab induction compared with placebo were observed as early as induction week 4 (first assessed timepoint)”
  • “Guselkumab efficacy was shown in both biologic naive and JAK inhibitor-naive patients, and in patients with a history of inadequate response or intolerance to biologics or JAK inhibitors”
  • “Overall, 34% (129 of 378) of patients in the guselkumab groups achieved endoscopic
    remission     at maintenance week 44. Among the 180 patients in the guselkumab groups in clinical remission at maintenance week 44, 124 (69%) of 180 were in endoscopic remission”
  • “Symptomatic remission and deep symptomatic remission achieved with guselkumab induction was generally maintained to maintenance week 44 with guselkumab relative to placebo”
  • “The incidences of anti-guselkumab antibodies and NAbs were low in both the induction and maintenance studies…titres were low and did not affect serum concentration, efficacy, or safety”
  • “Head-to-head comparison data with other IL-23 antagonists are currently not available”
  • “Safety results were consistent with the known and favourable safety profile of guselkumab in its approved indications. Rates of adverse events, serious adverse events, and adverse events leading to treatment discontinuation generally did not occur more frequently in patients treated with guselkumab versus placebo-treated patients”
  • Limitation: The primary analysis population for the maintenance study included only guselkumab induction responders following 12 weeks of intravenous treatment

My take: Overall, this is a pivotal study showing that guselkumab is an effective agent for moderately to severely active ulcerative colitis in those with and without prior treatments. More head-to-head studies are needed to determine the optimal positioning of therapies for UC. Currently, AGA guidelines (AGA Living Guideline for Moderate-to-Severe Ulcerative Colitis –The Good and The Bad) suggest that guselkumab should be considered in the top tier of medications used in patients naive to biologics/advanced therapies and in the second tier for those with prior biologic treatments.

Related blog posts:

IBD Updates: Insurance Barriers Hindering Care, Guselkumab vs Ustekinumab, IBD Pain Management Guidelines

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B Constant et al. AJG 2024;  DOI: 10.14309/ajg.0000000000002851. Insurer-Mandated Medication Utilization Barriers are Associated With Decreased Insurance Satisfaction and Adverse Clinical Outcomes: An Inflammatory Bowel Disease Partners Survey

Key findings: In this longitudinal survey with 2017 patients, 72% experienced an insurer-mandated barrier, most commonly prior authorizations (51%). Fifteen percent were denied an IBD medication by their insurer, 22% experienced an insurance-related gap in therapy, and 8% were forced by their insurer to switch from an effective medication.  Several insurance barriers were linked to negative downstream clinical outcomes, including prior authorizations associated with corticosteroid rescue (odds ratio [OR] 2.24]), forced medication switches associated with continued disease activity (OR 3.28), and medication denials associated with IBD-related surgery (OR 8.92).

Related blog posts:

S Danese et al. Lancet Gastroenterol Hepatol 2024; 9: 133-146. Efficacy and safety of 48 weeks of guselkumab for patients with Crohn’s disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial

In this phase 2 randomised, multicentre, double-blind trial with 309 adults, the authors report on the safety and efficacy of subcutaneous guselkumab maintenance regimens to week 48 in the GALAXI-1 study. Key findings:

  • “At week 48, the numbers of patients with CDAI clinical remission were 39 (64%) in the guselkumab 200→100 mg group, 46 (73%) in the guselkumab 600→200 mg group, 35 (57%) in the guselkumab 1200→200 mg group, and 37 (59%) in the ustekinumab group.”
  • “Eendoscopic remission was seen in 11 (18%), 11 (17%), 20 (33%), and four (6%) patients, respectively.”

Related blog posts:

L Keefer et al. Gastroenterology 2024; 166: 1182-1189. AGA Clinical Practice Update on Pain Management in Inflammatory Bowel Disease: Commentary

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.

New IBD Medication: Guselkumab for UC (QUASAR study)

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Previous work has established Guselkumab, a IL-23p19 subunit antagonist for Crohn’s disease (Guselkumab: Expanding the GALAXI of Treatments for Crohn’s Disease).

Peyrin-Biroulet et al now provide data showing its efficacy for ulcerative colitis (UC): Gastroenterol 2023; 165: 1443-1457. Open access! Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study

Background/Methods: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. In this double-blind, placebo-controlled, dose-ranging, induction study, adult patients (n=313), with median disease duration of 7.5 years, were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8.

Key findings:

  • Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P < .001). (Patients received IV induction at 0,4, and 8 weeks)
  • Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12
  • Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24 (after another dose of guselkumab (2nd dose SC). Thus, by week 24, 80.2% (81/101) of patients in the 200 mg IV induction and 78.5% *84/107) in the 400 mg IV induction had a clinical response.
  • Clinical response was noted as early as 2 weeks (first timepoint assessed)
  • Safety was similar among guselkumab and placebo groups.

My take: This is an era with rapidly expanding medical treatments for inflammatory bowel disease; it should help reduce the problem of individuals who are refractory to available treatments.

Guselkumab: Expanding the GALAXI of Treatments for Crohn’s Disease

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WJ Sandborn et al. Gastroenterol 2022; 162: 1650-1664. Open Access: Guselkumab for the Treatment of Crohn’s Disease: Induction Results From the Phase 2 GALAXI-1 Study

Background: Guselkumab, a selective p19 interleukin-23 antagonist, is approved for the treatment of plaque psoriasis and psoriatic arthritis.

Methods: GALAXI-1, a phase 2, double-blind, placebo-controlled study, randomized patients with moderate to severe Crohn’s disease 1:1:1:1:1 to intravenous guselkumab 200 mg, 600 mg, or 1200 mg at weeks 0, 4, and 8; intravenous ustekinumab approximately 6 mg/kg at week 0 and 90 mg subcutaneously at week 8; or placebo. n=309 with ~50% having disease refractory to prior biologics

Key findings:

  • At week 12, significantly greater reductions in Crohn’s Disease Activity Index from baseline (least squares means: 200 mg: –160.4, 600 mg: –138.9, and 1200 mg: –144.9 vs placebo: –36.2; all, P < .05) and significantly greater proportions of patients achieved clinical remission in each guselkumab group vs placebo
  • Improvement compared to placebo was evident as early as week 4
  • Safety event rates were generally similar across treatment groups

My take: This is an exciting time for practitioners taking care of patients as there are an increasing number of pharmacologic and dietary treatments for inflammatory bowel disease. With guselkumab, there may be an overlapping mechanism with ustekinumab which targets IL-12/23.

Related blog post: Emerging Data on Risankizumab for Crohn’s Disease

Economic Burden of Inflammatory Bowel Disease, Fewer Operations and Emerging Treatments

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Pouillon, L., Travis, S., Bossuyt, P. et al. Head-to-head trials in inflammatory bowel disease: past, present and future. Nat Rev Gastroenterol Hepatol (2020). https://doi.org/10.1038/s41575-020-0293-9 (Thanks to KT Park for this reference)

An excerpt:

This Perspective provides an overview of the past, current and future concepts in IBD trial design, with a detailed focus on the role of comparative research and the challenges and pitfalls in undertaking and interpreting the results from such studies.

Related blog posts:

GR Lichenstein et al. Clin Gastroenterol Hepatol 2020; 18: 889-97.  Using Truven MarketScan Insurance Claims data (2008-2015) from more than 160,000 patients with inflammatory bowel disease (IBD), the authors estimated economic burdens from Crohn’s disease (CD) and ulcerative colitis (UC).

  • For CD, lifetime incremental cost was $416,352 on average, but was $707,711 if diagnosis was established between 0-11 years of age. The lifetime costs, $622,056, consisted of $273,056 for outpatient care, $164,298 for inpatient care, $163,722 for pharmacy costs, and $20,979 for emergency room care.
  • For UC, lifetime incremental cost averaged $230,102, but was $369,955 if diagnosis was established between 0-11 years of age. The lifetime costs, $405,496, consisted of $153,670 for outpatient care, $123,190 for inpatient care, $105,142 for pharmacy costs, and $13,493 for emergency room care.
  • The lifetime costs for UC and CD were both greater than that for rheumatoid arthritis ($100,273) and for type 2 diabetes ($89,064).
  • Related blog post: IBD Shorts 2020  Cost of IBD Care is Increasing. From Healio Gastro: Chronic inflammatory disease expenditures nearly double over last 2 decades

T Shinagawa et al. Clin Gastroenterol Hepatol 2020; 18: 898-907.  In this study from Japan with 1871 patients with CD, the 5- and 10-year reoperation rates were 23.4% and 48.0% respectively.  However, reoperation rates were significantly lower after 2002 than prior with HR 0.72.  Postoperative use of immunomodulators (OR 0.60) and anti-TNF therapy (HR 0.71) were associated with a reduced the risk of reoperation.