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Subcutaneous Guselkumab Proves Efficacious for IBD in Two Studies: ASTRO and GRAVITI
BERLIN — according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.
Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.
“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.
Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”
Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.
The ASTRO Study
Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.
After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).
All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).
Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).
“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.
The researchers also divided the results by prespecified subgroups based on previous treatments.
Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).
“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.
Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% 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 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).
Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).
Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).
“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”
In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.
The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.
The GRAVITI Study
In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.
The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.
In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.
The co-primary endpoints were clinical remission and endoscopic response at week 12.
Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.
At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.
Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.
Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.
In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.
Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.
“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.
As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.
Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.
It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”
Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.
A version of this article appeared on Medscape.com.
BERLIN — according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.
Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.
“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.
Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”
Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.
The ASTRO Study
Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.
After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).
All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).
Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).
“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.
The researchers also divided the results by prespecified subgroups based on previous treatments.
Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).
“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.
Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% 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 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).
Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).
Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).
“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”
In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.
The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.
The GRAVITI Study
In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.
The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.
In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.
The co-primary endpoints were clinical remission and endoscopic response at week 12.
Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.
At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.
Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.
Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.
In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.
Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.
“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.
As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.
Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.
It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”
Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.
A version of this article appeared on Medscape.com.
BERLIN — according to results from the phase 3, randomized, double-blind, placebo-controlled ASTRO study.
Importantly, the study also showed that subcutaneous induction is consistent with intravenous (IV) induction of guselkumab in UC.
“The flexibility of a fully subcutaneous treatment regimen would be a welcome option for many patients, especially those with busy and active lifestyles,” said study lead Laurent Peyrin-Biroulet, MD, head of the inflammatory bowel disease (IBD) unit at University Hospital of Nancy, France.
Peyrin-Biroulet presented the results at European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
“I think it’s an evolution and improvement in terms of IBD management,” he said. “We are happy that our patients will have the choice.”
Guselkumab is a selective dual-acting interleukin (IL)–23p19 subunit inhibitor that potently blocks IL-23 and binds to CD64, a receptor on cells that produce IL-23, and is the only full subcutaneous IL-23 available. The drug is approved in some countries, including the United States, for UC.
The ASTRO Study
Building on data from the QUASAR studies, which showed the efficacy of induction of IV guselkumab and subcutaneous maintenance in patients with UC, the ASTRO study randomly assigned 418 patients with moderately to severely active UC to receive either induction with 400 mg subcutaneous guselkumab at weeks 0, 4, and 8 or placebo.
After induction, the treatment group either received a maintenance dose of 200 mg subcutaneous guselkumab at week 12 and then every 4 weeks or 100 mg every 8 weeks (starting week 16).
All patients had an inadequate response or intolerance to conventional therapy. Around 60% were naive to biologics, Janus kinase (JAK) inhibitors, or sphingosine-1-phosphate receptor modulators (S1Ps).
Clinical remission at week 12 — the primary endpoint — was achieved by 27.6% of all patients treated with guselkumab compared with 6.5% of patients on placebo (P < .001).
“These results are in line with the QUASAR data,” in which clinical remission was 22.6% with IV guselkumab at 12 weeks, noted Peyrin-Biroulet.
The researchers also divided the results by prespecified subgroups based on previous treatments.
Clinical remission was achieved at week 12 by 36% of patients naive to biologics, JAK inhibitors, or S1Ps in the guselkumab group and by 8.9% of these patients in the placebo group (P < .001). Among patients who had previously received biologics, JAK inhibitors, or S1Ps, 16.1% of those in the guselkumab group achieved clinical remission compared with 3.6% of those in the placebo group (P = .005).
“In terms of symptomatic remission at week 12, the difference between the overall guselkumab result and placebo was 30%,” reported Peyrin-Biroulet.
Clinical response — defined as a decrease in the modified Mayo score by ≥ 30% 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 — was 65.6% in the guselkumab group compared with 34.5% in the placebo group (P < .001).
Among patients naive to biologics, JAK inhibitors, or S1Ps, clinical response was 71.3% in the guselkumab group, compared with 41.8% in the placebo group (P < .001). Among those who had previously received biologics, JAK inhibitors, or S1Ps, it was 57.1% in the guselkumab group, compared with 25.0% in the placebo group (P < .001).
Turning to endoscopic improvement (ie, an endoscopic subscore of 0 or 1 with no friability), 37.3% of those in the guselkumab group overall, compared with 12.9% of those in the placebo group who achieved this endpoint (P < .001).
“This is a treatment effect of over 20%,” said Peyrin-Biroulet. “We know that when it is over 20%, it is considered game changer.”
In patients naive to biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 45.7% with guselkumab vs 17.7% with placebo. In those who had previously received biologics, JAK inhibitors, or S1Ps, endoscopic improvement was 24.1% with guselkumab vs 7.1% with placebo. Both were statistically significant.
The safety of subcutaneous induction therapy was consistent with the well-characterized and favorable safety profile of guselkumab in approved indications.
The GRAVITI Study
In the phase 3, randomized, double-blind, placebo-controlled GRAVITI study, also presented at ECCO 2025 Congress, researchers evaluated the efficacy and safety of induction with subcutaneous guselkumab followed by subcutaneous maintenance compared with placebo in patients with moderately to severely active Crohn’s disease.
The GRAVITI study followed the same induction and maintenance dosage and treatment intervals as the ASTRO study.
In addition, the patients randomly assigned to placebo were able to receive subcutaneous guselkumab (400 mg every 4 weeks followed by 100 mg every 8 weeks) if rescue criteria were met at week 16.
The co-primary endpoints were clinical remission and endoscopic response at week 12.
Ailsa Hart, MD, director, IBD Research, and consultant gastroenterologist, St. Mark’s Hospital and Imperial College, both in London, reported the 12-week and 48-week results, which were initially presented at the American College of Gastroenterology (ACG) meeting in October 2024.
At week 12, 56.1% of patients who received guselkumab achieved clinical remission, compared with 21.4% of patients who received placebo. Endoscopic response was achieved in 41.3% of patients treated with guselkumab compared with 21.4% in the placebo group.
Regarding the 48-week results, Hart noted that the rate of clinical remission was more than three times higher with both maintenance doses of guselkumab at 66.1% (200 mg) and 60.0% (100 mg) vs 17.1% with placebo.
Endoscopic response at 48 weeks was achieved in 51.3% of patients on the 200-mg maintenance dose and in 44.3% on the 100-mg maintenance dose, compared with 6.8% of patients on placebo.
In addition, endoscopic remission was achieved in 38.3% of patients in the 200-mg guselkumab group and in 30.4% in the 100-mg guselkumab group, compared with 6.0% in the placebo group.
Safety findings were consistent with the known safety profile of guselkumab in approved indications and other studies in IBD.
“These results complement the GALAXI data and demonstrate that both IV and subcutaneous guselkumab induction are efficacious and therapeutic in Crohn’s disease,” Hart said. Furthermore, data from the ASTRO study demonstrated similar data in the UC population.
As clinicians, this gives us flexibility in how we treat our patients; although, the rationale for choosing subcutaneous or IV is likely to be pragmatic, Hart said.
Additionally, the flexibility of the maintenance therapy, that is, 200 mg subcutaneous guselkumab every 4 weeks or 100 mg every 8 weeks, “is expected to positively affect several parameters of therapy, including increased compliance, hospital avoidance, and better safety profiling,” comoderator Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, said in an interview.
It appears that multiple options will be offered to patients regarding treatment with guselkumab for patients with Crohn’s disease, Bamias said. “Interestingly, a similar multiplicity of options has also been shown for ulcerative colitis, through the QUASAR and ASTRO studies.”
Peyrin-Biroulet declared receiving grants and other/support travel from multiple companies. Hart declared receiving grants and personal fees from multiple companies. Bamias declared receiving grants and personal fees/honoraria as an advisor/lecturer from multiple companies.
A version of this article appeared on Medscape.com.
FROM ECCO 2025
New IL-7 Antagonist Lusvertikimab Shows UC Efficacy
BERLIN —
Lusvertikimab is unique in targeting the IL-7 receptor, a key player in immune-mediated inflammation.
“We have a new mode of action in ulcerative colitis,” with a strong safety profile, lead investigator, Arnaud Bourreille, MD, associate professor of gastroenterology from Nantes University Hospital, France, said in an interview.
“We achieved the primary endpoint” — improvement in the modified Mayo score (MMS) from baseline to week 10 — “for both the low dose and the high dose of lusvertikimab,” said Bourreille, who presented the findings at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress. “For us practitioners, this is very good news.”
Current treatment options for UC remain limited, especially for patients with an inadequate response to biologics or small molecules.
Overall, biologics are only effective in around half the patients, Bourreille noted. We need other treatments that have different mechanisms of action, as is the case with lusvertikimab.
The multicenter, double-blind CoTikiS study evaluated the IL-7 receptor antagonist in 136 adults with moderately to severely active UC (MMS, 4-9) and inadequate response to conventional therapies and/or failure to advanced therapies. Around 40% of the patients were exposed to one or more biologics.
The 50-week study had a 10-week induction period with two doses of lusvertikimab (450 and 850 mg), followed by a 24-week open-label extension, where patients received infusions of the high dose (850 mg) every 4 weeks, and a 16-week safety follow-up period free of treatment.
For the induction period, patients were randomized 1:1:1 to receive placebo (n = 49), 450 mg lusvertikimab (n = 35), or 850 mg lusvertikimab (n = 50) intravenously at weeks 0, 2, and 6. The diagnosis in two patients was modified to Crohn’s disease; therefore, they were not included.
In meeting the trial’s primary endpoint, lusvertikimab significantly reduced disease severity, compared with placebo, at week 10 in both dose groups separately and when pooled.
The MMS in the 450-mg group showed a difference of –1.16 points vs placebo (P = .019), whereas in the 850-mg group, the MMS showed a difference of –0.9 points vs placebo (P = .036). In the pooled group, the difference was –1.00 points vs placebo (P = .010).
The secondary endpoints of clinical remission and endoscopic remission also favored lusvertikimab for the pooled doses vs placebo, at 16% vs 4% (odds ratio [OR], 4.25; P = .066) and 25% vs 13% (OR, 2.33; P = .120), respectively.
For the other secondary endpoints, 32% achieved endoscopic improvement in the pooled group vs 13% in the placebo group (OR, 3.29; P = .027), and the mean score change in the UC Endoscopic Index of Severity was –1.35 for the pooled group vs –0.32 for the placebo group (P = .007).
Fecal calprotectin was reduced by 830 μg/g in the 450-mg group (P =.009), by 635 μg/g in the 850-mg group (P = .018), and 716 μg/g in the pooled group. It was increased by 189 μg/g in the placebo group (P = .004).
No safety concerns were reported.
Bourreille noted that there was a little more lymphopenia in patients on lusvertikimab vs placebo, which is explained by the drug’s mechanism of action. However, “it was transient lymphopenia, without any infection and without any need to interrupt the treatment.”
Next, Bourreille said, we need to demonstrate the efficacy and the safety of the drug in the long term.
“There may be a place for lusvertikimab in patients with Crohn’s disease because the mechanism of action of IL-7 receptor antagonist would potentially have good efficacy in that disease too,” he added.
Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Greece, who comoderated the session, pointed out that the results supported further clinical development of lusvertikimab.
“As elevated mucosal IL-7/IL-7 [receptor] expression predicts refractoriness to currently used biologic therapies, it would be very interesting to see the potential of lusvertikimab as a treatment for patients who were exposed to advanced therapy or as part of combination therapeutics,” he said.
The study was funded by OSE Immunotherapeutics. Bourreille received funding from OSE Immunotherapeutics; grants from Takeda and Mauna Kea Technologies; and personal fees from AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. Bamias reported receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as adviser/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, Johnson & Johnson, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.
A version of this article appeared on Medscape.com.
BERLIN —
Lusvertikimab is unique in targeting the IL-7 receptor, a key player in immune-mediated inflammation.
“We have a new mode of action in ulcerative colitis,” with a strong safety profile, lead investigator, Arnaud Bourreille, MD, associate professor of gastroenterology from Nantes University Hospital, France, said in an interview.
“We achieved the primary endpoint” — improvement in the modified Mayo score (MMS) from baseline to week 10 — “for both the low dose and the high dose of lusvertikimab,” said Bourreille, who presented the findings at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress. “For us practitioners, this is very good news.”
Current treatment options for UC remain limited, especially for patients with an inadequate response to biologics or small molecules.
Overall, biologics are only effective in around half the patients, Bourreille noted. We need other treatments that have different mechanisms of action, as is the case with lusvertikimab.
The multicenter, double-blind CoTikiS study evaluated the IL-7 receptor antagonist in 136 adults with moderately to severely active UC (MMS, 4-9) and inadequate response to conventional therapies and/or failure to advanced therapies. Around 40% of the patients were exposed to one or more biologics.
The 50-week study had a 10-week induction period with two doses of lusvertikimab (450 and 850 mg), followed by a 24-week open-label extension, where patients received infusions of the high dose (850 mg) every 4 weeks, and a 16-week safety follow-up period free of treatment.
For the induction period, patients were randomized 1:1:1 to receive placebo (n = 49), 450 mg lusvertikimab (n = 35), or 850 mg lusvertikimab (n = 50) intravenously at weeks 0, 2, and 6. The diagnosis in two patients was modified to Crohn’s disease; therefore, they were not included.
In meeting the trial’s primary endpoint, lusvertikimab significantly reduced disease severity, compared with placebo, at week 10 in both dose groups separately and when pooled.
The MMS in the 450-mg group showed a difference of –1.16 points vs placebo (P = .019), whereas in the 850-mg group, the MMS showed a difference of –0.9 points vs placebo (P = .036). In the pooled group, the difference was –1.00 points vs placebo (P = .010).
The secondary endpoints of clinical remission and endoscopic remission also favored lusvertikimab for the pooled doses vs placebo, at 16% vs 4% (odds ratio [OR], 4.25; P = .066) and 25% vs 13% (OR, 2.33; P = .120), respectively.
For the other secondary endpoints, 32% achieved endoscopic improvement in the pooled group vs 13% in the placebo group (OR, 3.29; P = .027), and the mean score change in the UC Endoscopic Index of Severity was –1.35 for the pooled group vs –0.32 for the placebo group (P = .007).
Fecal calprotectin was reduced by 830 μg/g in the 450-mg group (P =.009), by 635 μg/g in the 850-mg group (P = .018), and 716 μg/g in the pooled group. It was increased by 189 μg/g in the placebo group (P = .004).
No safety concerns were reported.
Bourreille noted that there was a little more lymphopenia in patients on lusvertikimab vs placebo, which is explained by the drug’s mechanism of action. However, “it was transient lymphopenia, without any infection and without any need to interrupt the treatment.”
Next, Bourreille said, we need to demonstrate the efficacy and the safety of the drug in the long term.
“There may be a place for lusvertikimab in patients with Crohn’s disease because the mechanism of action of IL-7 receptor antagonist would potentially have good efficacy in that disease too,” he added.
Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Greece, who comoderated the session, pointed out that the results supported further clinical development of lusvertikimab.
“As elevated mucosal IL-7/IL-7 [receptor] expression predicts refractoriness to currently used biologic therapies, it would be very interesting to see the potential of lusvertikimab as a treatment for patients who were exposed to advanced therapy or as part of combination therapeutics,” he said.
The study was funded by OSE Immunotherapeutics. Bourreille received funding from OSE Immunotherapeutics; grants from Takeda and Mauna Kea Technologies; and personal fees from AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. Bamias reported receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as adviser/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, Johnson & Johnson, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.
A version of this article appeared on Medscape.com.
BERLIN —
Lusvertikimab is unique in targeting the IL-7 receptor, a key player in immune-mediated inflammation.
“We have a new mode of action in ulcerative colitis,” with a strong safety profile, lead investigator, Arnaud Bourreille, MD, associate professor of gastroenterology from Nantes University Hospital, France, said in an interview.
“We achieved the primary endpoint” — improvement in the modified Mayo score (MMS) from baseline to week 10 — “for both the low dose and the high dose of lusvertikimab,” said Bourreille, who presented the findings at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress. “For us practitioners, this is very good news.”
Current treatment options for UC remain limited, especially for patients with an inadequate response to biologics or small molecules.
Overall, biologics are only effective in around half the patients, Bourreille noted. We need other treatments that have different mechanisms of action, as is the case with lusvertikimab.
The multicenter, double-blind CoTikiS study evaluated the IL-7 receptor antagonist in 136 adults with moderately to severely active UC (MMS, 4-9) and inadequate response to conventional therapies and/or failure to advanced therapies. Around 40% of the patients were exposed to one or more biologics.
The 50-week study had a 10-week induction period with two doses of lusvertikimab (450 and 850 mg), followed by a 24-week open-label extension, where patients received infusions of the high dose (850 mg) every 4 weeks, and a 16-week safety follow-up period free of treatment.
For the induction period, patients were randomized 1:1:1 to receive placebo (n = 49), 450 mg lusvertikimab (n = 35), or 850 mg lusvertikimab (n = 50) intravenously at weeks 0, 2, and 6. The diagnosis in two patients was modified to Crohn’s disease; therefore, they were not included.
In meeting the trial’s primary endpoint, lusvertikimab significantly reduced disease severity, compared with placebo, at week 10 in both dose groups separately and when pooled.
The MMS in the 450-mg group showed a difference of –1.16 points vs placebo (P = .019), whereas in the 850-mg group, the MMS showed a difference of –0.9 points vs placebo (P = .036). In the pooled group, the difference was –1.00 points vs placebo (P = .010).
The secondary endpoints of clinical remission and endoscopic remission also favored lusvertikimab for the pooled doses vs placebo, at 16% vs 4% (odds ratio [OR], 4.25; P = .066) and 25% vs 13% (OR, 2.33; P = .120), respectively.
For the other secondary endpoints, 32% achieved endoscopic improvement in the pooled group vs 13% in the placebo group (OR, 3.29; P = .027), and the mean score change in the UC Endoscopic Index of Severity was –1.35 for the pooled group vs –0.32 for the placebo group (P = .007).
Fecal calprotectin was reduced by 830 μg/g in the 450-mg group (P =.009), by 635 μg/g in the 850-mg group (P = .018), and 716 μg/g in the pooled group. It was increased by 189 μg/g in the placebo group (P = .004).
No safety concerns were reported.
Bourreille noted that there was a little more lymphopenia in patients on lusvertikimab vs placebo, which is explained by the drug’s mechanism of action. However, “it was transient lymphopenia, without any infection and without any need to interrupt the treatment.”
Next, Bourreille said, we need to demonstrate the efficacy and the safety of the drug in the long term.
“There may be a place for lusvertikimab in patients with Crohn’s disease because the mechanism of action of IL-7 receptor antagonist would potentially have good efficacy in that disease too,” he added.
Giorgos Bamias, MD, professor of gastroenterology at the School of Medicine, National and Kapodistrian University of Athens, Greece, who comoderated the session, pointed out that the results supported further clinical development of lusvertikimab.
“As elevated mucosal IL-7/IL-7 [receptor] expression predicts refractoriness to currently used biologic therapies, it would be very interesting to see the potential of lusvertikimab as a treatment for patients who were exposed to advanced therapy or as part of combination therapeutics,” he said.
The study was funded by OSE Immunotherapeutics. Bourreille received funding from OSE Immunotherapeutics; grants from Takeda and Mauna Kea Technologies; and personal fees from AbbVie, Celltrion, Ferring, Galapagos, Gilead, MSD, Medtronic, OSE Immunotherapeutics, Janssen, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. Bamias reported receiving grants from Takeda, AbbVie, Mylan/Viatris/Biocon, Genesis Pharma, Ferring, Vianex, and Aenorasis and personal fees/honoraria as adviser/lecturer from AbbVie, Adacyte Therapeutics, Amgen, Bristol Myers Squibb, Ferring, Galenica, Genesis Pharma, Johnson & Johnson, Eli Lilly, MSD, Mylan/Viatris/Biocon, Pfizer, Takeda, and Vianex.
A version of this article appeared on Medscape.com.
FROM ECCO 2025
AI Improves Lesion Detection in IBD Over Standard Methods
BERLIN — in a first-of-its-kind, multicenter study.
In addition to the model’s superior diagnostic performance than standard of care, it also achieved a significant reduction in the mean reading time per exam.
Furthermore, the study clinically validated an AI model in real time for small-bowel CE.
The AI model addresses long-standing limitations of CE interpretation, including time-consuming readings and interobserver variability.
“It’s a huge improvement on the technology readiness level of the AI model,” said senior study investigator Miguel Mascarenhas, MD, PhD, head of the precision medicine unit at the Hospital São João, Faculty of Medicine, University of Porto, Portugal.
Until now, there has been no AI system using a CE platform that has proven so effective in so many real-life clinical settings, he explained. “This technology is set to transform endoscopic practice and clinical management in inflammatory bowel disease.”
The findings were presented at European Crohn’s and Colitis Organisation 2025 Congress by Francisco Mendes, MD, a resident in gastroenterology, also at the Hospital São João.
More Lesions, Less Time
Researchers conducted the prospective study involving centers in Portugal, Spain, and the United States between January 2021 and April 2024. Two CE devices (PillCamSB3 and Olympus EC-10) were analyzed for their performance across 137 CE exams in 137 patients, 49 of whom had Crohn’s disease. AI-assisted readings were compared with standard-of-care readings, with expert board consensus considered to be the gold standard. Key performance metrics included sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV).
During expert board review, ulcers and erosions were identified in 56 patients (40.9%), with a sensitivity of 60.7%, specificity of 98.8%, a PPV of 97.1%, and an NPV of 78.4%, leading to an overall accuracy for the detection of ulcers and erosions of 83.2%.
In comparison, the AI-assisted readings outperformed conventional readings with a sensitivity of 94.6%, specificity of 80.2%, a PPV of 76.8%, an NPV of 95.6%, leading to an overall accuracy of 86.1%.
The AI-assisted model diagnosis was noninferior (P < .001) and superior (P < .001) to conventional diagnosis for detection of ulcers and erosions. The AI model demonstrated consistent performance across different CE devices and centers.
In addition, the mean time taken per reading was under 4 minutes (239 seconds) per exam for AI, compared with around 1.0-1.5 hours for standard-of-care readings.
The increased diagnostic accuracy of this AI model done in far less time allows us to engage more with the patient and attend to other care-related tasks, Mascarenhas said.
CE has great potential not only in IBD but also in other gastrointestinal-related screening, including colorectal cancer screening, he added. Once the bottleneck of reading time with CE is solved, it will become the first-line tool for screening.
Reading time is “one of several barriers” to integration of CE into clinical practice, Shomron Ben-Horin, MD, director, Sheba Medical Center, Tel-Aviv University, Israel, said in an interview. But it “is the most accurate modality for detection of inflammatory activity along the entire small bowel.”
Based on these study results, AI is the way to go, said Ben-Horin, who was not involved in the study. “There was even a signal for better accuracy, which is intriguing,” he added. This study points toward AI being more accurate than the physicians in reading, and that is important.
Also commenting was Miles Parkes, MD, consultant gastroenterologist at Addenbrooke’s Hospital in Cambridge, England.
“Both the sensitivity and the specificity of the output are reassuring, but there might be some devil in the detail,” he said. “However, as a general principle the performance of this model is impressive.”
Mascarenhas and Mendes declared no financial disclosures. Ben Horin received fees from Medtronic to attend the conference. Parkes declared no financial disclosures.
A version of this article appeared on Medscape.com.
BERLIN — in a first-of-its-kind, multicenter study.
In addition to the model’s superior diagnostic performance than standard of care, it also achieved a significant reduction in the mean reading time per exam.
Furthermore, the study clinically validated an AI model in real time for small-bowel CE.
The AI model addresses long-standing limitations of CE interpretation, including time-consuming readings and interobserver variability.
“It’s a huge improvement on the technology readiness level of the AI model,” said senior study investigator Miguel Mascarenhas, MD, PhD, head of the precision medicine unit at the Hospital São João, Faculty of Medicine, University of Porto, Portugal.
Until now, there has been no AI system using a CE platform that has proven so effective in so many real-life clinical settings, he explained. “This technology is set to transform endoscopic practice and clinical management in inflammatory bowel disease.”
The findings were presented at European Crohn’s and Colitis Organisation 2025 Congress by Francisco Mendes, MD, a resident in gastroenterology, also at the Hospital São João.
More Lesions, Less Time
Researchers conducted the prospective study involving centers in Portugal, Spain, and the United States between January 2021 and April 2024. Two CE devices (PillCamSB3 and Olympus EC-10) were analyzed for their performance across 137 CE exams in 137 patients, 49 of whom had Crohn’s disease. AI-assisted readings were compared with standard-of-care readings, with expert board consensus considered to be the gold standard. Key performance metrics included sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV).
During expert board review, ulcers and erosions were identified in 56 patients (40.9%), with a sensitivity of 60.7%, specificity of 98.8%, a PPV of 97.1%, and an NPV of 78.4%, leading to an overall accuracy for the detection of ulcers and erosions of 83.2%.
In comparison, the AI-assisted readings outperformed conventional readings with a sensitivity of 94.6%, specificity of 80.2%, a PPV of 76.8%, an NPV of 95.6%, leading to an overall accuracy of 86.1%.
The AI-assisted model diagnosis was noninferior (P < .001) and superior (P < .001) to conventional diagnosis for detection of ulcers and erosions. The AI model demonstrated consistent performance across different CE devices and centers.
In addition, the mean time taken per reading was under 4 minutes (239 seconds) per exam for AI, compared with around 1.0-1.5 hours for standard-of-care readings.
The increased diagnostic accuracy of this AI model done in far less time allows us to engage more with the patient and attend to other care-related tasks, Mascarenhas said.
CE has great potential not only in IBD but also in other gastrointestinal-related screening, including colorectal cancer screening, he added. Once the bottleneck of reading time with CE is solved, it will become the first-line tool for screening.
Reading time is “one of several barriers” to integration of CE into clinical practice, Shomron Ben-Horin, MD, director, Sheba Medical Center, Tel-Aviv University, Israel, said in an interview. But it “is the most accurate modality for detection of inflammatory activity along the entire small bowel.”
Based on these study results, AI is the way to go, said Ben-Horin, who was not involved in the study. “There was even a signal for better accuracy, which is intriguing,” he added. This study points toward AI being more accurate than the physicians in reading, and that is important.
Also commenting was Miles Parkes, MD, consultant gastroenterologist at Addenbrooke’s Hospital in Cambridge, England.
“Both the sensitivity and the specificity of the output are reassuring, but there might be some devil in the detail,” he said. “However, as a general principle the performance of this model is impressive.”
Mascarenhas and Mendes declared no financial disclosures. Ben Horin received fees from Medtronic to attend the conference. Parkes declared no financial disclosures.
A version of this article appeared on Medscape.com.
BERLIN — in a first-of-its-kind, multicenter study.
In addition to the model’s superior diagnostic performance than standard of care, it also achieved a significant reduction in the mean reading time per exam.
Furthermore, the study clinically validated an AI model in real time for small-bowel CE.
The AI model addresses long-standing limitations of CE interpretation, including time-consuming readings and interobserver variability.
“It’s a huge improvement on the technology readiness level of the AI model,” said senior study investigator Miguel Mascarenhas, MD, PhD, head of the precision medicine unit at the Hospital São João, Faculty of Medicine, University of Porto, Portugal.
Until now, there has been no AI system using a CE platform that has proven so effective in so many real-life clinical settings, he explained. “This technology is set to transform endoscopic practice and clinical management in inflammatory bowel disease.”
The findings were presented at European Crohn’s and Colitis Organisation 2025 Congress by Francisco Mendes, MD, a resident in gastroenterology, also at the Hospital São João.
More Lesions, Less Time
Researchers conducted the prospective study involving centers in Portugal, Spain, and the United States between January 2021 and April 2024. Two CE devices (PillCamSB3 and Olympus EC-10) were analyzed for their performance across 137 CE exams in 137 patients, 49 of whom had Crohn’s disease. AI-assisted readings were compared with standard-of-care readings, with expert board consensus considered to be the gold standard. Key performance metrics included sensitivity, specificity, positive predictive value (PPV), and negative PV (NPV).
During expert board review, ulcers and erosions were identified in 56 patients (40.9%), with a sensitivity of 60.7%, specificity of 98.8%, a PPV of 97.1%, and an NPV of 78.4%, leading to an overall accuracy for the detection of ulcers and erosions of 83.2%.
In comparison, the AI-assisted readings outperformed conventional readings with a sensitivity of 94.6%, specificity of 80.2%, a PPV of 76.8%, an NPV of 95.6%, leading to an overall accuracy of 86.1%.
The AI-assisted model diagnosis was noninferior (P < .001) and superior (P < .001) to conventional diagnosis for detection of ulcers and erosions. The AI model demonstrated consistent performance across different CE devices and centers.
In addition, the mean time taken per reading was under 4 minutes (239 seconds) per exam for AI, compared with around 1.0-1.5 hours for standard-of-care readings.
The increased diagnostic accuracy of this AI model done in far less time allows us to engage more with the patient and attend to other care-related tasks, Mascarenhas said.
CE has great potential not only in IBD but also in other gastrointestinal-related screening, including colorectal cancer screening, he added. Once the bottleneck of reading time with CE is solved, it will become the first-line tool for screening.
Reading time is “one of several barriers” to integration of CE into clinical practice, Shomron Ben-Horin, MD, director, Sheba Medical Center, Tel-Aviv University, Israel, said in an interview. But it “is the most accurate modality for detection of inflammatory activity along the entire small bowel.”
Based on these study results, AI is the way to go, said Ben-Horin, who was not involved in the study. “There was even a signal for better accuracy, which is intriguing,” he added. This study points toward AI being more accurate than the physicians in reading, and that is important.
Also commenting was Miles Parkes, MD, consultant gastroenterologist at Addenbrooke’s Hospital in Cambridge, England.
“Both the sensitivity and the specificity of the output are reassuring, but there might be some devil in the detail,” he said. “However, as a general principle the performance of this model is impressive.”
Mascarenhas and Mendes declared no financial disclosures. Ben Horin received fees from Medtronic to attend the conference. Parkes declared no financial disclosures.
A version of this article appeared on Medscape.com.
FROM ECCO 2025
New Biomarkers Identified for Treatment Response in IBD
BERLIN — presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
Differences uncovered in multiple messenger RNAs, proteins, metabolites, and gut microbiota were associated with responders and nonresponders to biologics and Janus kinase inhibitors, suggesting the potential for predictive biomarkers in IBD, including Crohn’s disease (CD) and ulcerative colitis (UC).
“With further work we hope to confirm these findings and evaluate their clinical relevance in identifying patients most likely to respond to tailored therapeutic interventions,” said Montserrat Baldan-Martin, PhD, a researcher at the University Hospital of the Princess, Madrid, Spain.
The treatment of IBD is challenging because of the heterogeneity across clinical, immunological, molecular, genetic, and microbiologic features, with one third of patients failing to respond to any one treatment.
Baldan-Martin and colleagues wanted to find predictive biomarkers of response by examining the differences across multi-omics profiles relative to different therapies.
The study analyzed 127 patients with IBD (57 with CD and 70 with UC) before and after 14 weeks of treatment with one of the following: anti–tumor necrosis factors (TNFs), ustekinumab, vedolizumab, or tofacitinib. Patient response to treatment was evaluated using endoscopic criteria that categorized them as responders or nonresponders to the different therapies.
In addition, molecular data from various biologic samples — serum, urine, extracellular vesicles, intestinal biopsies, and stool — were tested using transcriptomics, proteomics, metabolomics, and metagenomics.
Clear Differences
“The most significant differences were seen in gene expression within intestinal tissue of responder and nonresponder patients with ulcerative colitis taking vedolizumab,” Baldan-Martin reported.
Proteomic analysis revealed that a total of 1377 proteins were identified across all groups (CD, UC, and the four drug classes/therapies). Responders and nonresponders for each therapy expressed different proteins in serum extracellular vesicles and intestinal tissues.
For example, patients with CD who responded to anti-TNF therapies had 138 different proteins from those of anti-TNF nonresponders, while patients with UC who responded to anti-TNF therapies had 218 different proteins from those of anti-TNF nonresponders, reported Baldan-Martin.
Also, we observed almost no proteins “in common between ulcerative colitis responders versus nonresponders for all treatments,” she noted. And we “saw only three proteins in common with Crohn’s disease patients [on different drugs].”
Metabolomic analysis identified deregulation of 24 serum lipoproteins in CD responders to ustekinumab, compared with nonresponders.
“We observed greater differences in the lipoproteins in serum than metabolites in serum and urine,” Baldan-Martin added.
Analysis of biologic pathways also highlighted enrichment in ketone and butyrate metabolism, mitochondrial electron transport chain activity, carnitine synthesis, and fatty acid oxidation pathways, while metagenomic analysis revealed the greatest microbial differences in UC responders and nonresponders to anti-TNF therapies.
Baldan-Martin said research was ongoing with a new cohort of patients that aims to validate some of the biomarkers and help identify the patients most likely to respond to tailored therapeutic interventions.
“One of the challenges is integrating results from different omics approaches to create a more holistic understanding of the disease,” she said, adding that she hopes the research “will potentially open doors for early detection through multi-panel biomarkers.”
Session moderator Mark Samaan, MD, consultant gastroenterologist at Guy’s and St Thomas’ NHS Foundation Trust, London, England, said that “the findings related to nonresponse to specific drugs in UC and CD were interesting. With longitudinal follow-up, we’d hope this might help us pick out patients less likely to respond and who show early nonresponse to specific drugs based on serum, urine, and fecal sampling.”
“It’s very helpful to know if someone is a nonresponder within 14 weeks because we can then move the patient on to something else relatively quickly,” he added.
Baldan-Martin and Samaan declared no relevant financial disclosures.
A version of this article appeared on Medscape.com.
BERLIN — presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
Differences uncovered in multiple messenger RNAs, proteins, metabolites, and gut microbiota were associated with responders and nonresponders to biologics and Janus kinase inhibitors, suggesting the potential for predictive biomarkers in IBD, including Crohn’s disease (CD) and ulcerative colitis (UC).
“With further work we hope to confirm these findings and evaluate their clinical relevance in identifying patients most likely to respond to tailored therapeutic interventions,” said Montserrat Baldan-Martin, PhD, a researcher at the University Hospital of the Princess, Madrid, Spain.
The treatment of IBD is challenging because of the heterogeneity across clinical, immunological, molecular, genetic, and microbiologic features, with one third of patients failing to respond to any one treatment.
Baldan-Martin and colleagues wanted to find predictive biomarkers of response by examining the differences across multi-omics profiles relative to different therapies.
The study analyzed 127 patients with IBD (57 with CD and 70 with UC) before and after 14 weeks of treatment with one of the following: anti–tumor necrosis factors (TNFs), ustekinumab, vedolizumab, or tofacitinib. Patient response to treatment was evaluated using endoscopic criteria that categorized them as responders or nonresponders to the different therapies.
In addition, molecular data from various biologic samples — serum, urine, extracellular vesicles, intestinal biopsies, and stool — were tested using transcriptomics, proteomics, metabolomics, and metagenomics.
Clear Differences
“The most significant differences were seen in gene expression within intestinal tissue of responder and nonresponder patients with ulcerative colitis taking vedolizumab,” Baldan-Martin reported.
Proteomic analysis revealed that a total of 1377 proteins were identified across all groups (CD, UC, and the four drug classes/therapies). Responders and nonresponders for each therapy expressed different proteins in serum extracellular vesicles and intestinal tissues.
For example, patients with CD who responded to anti-TNF therapies had 138 different proteins from those of anti-TNF nonresponders, while patients with UC who responded to anti-TNF therapies had 218 different proteins from those of anti-TNF nonresponders, reported Baldan-Martin.
Also, we observed almost no proteins “in common between ulcerative colitis responders versus nonresponders for all treatments,” she noted. And we “saw only three proteins in common with Crohn’s disease patients [on different drugs].”
Metabolomic analysis identified deregulation of 24 serum lipoproteins in CD responders to ustekinumab, compared with nonresponders.
“We observed greater differences in the lipoproteins in serum than metabolites in serum and urine,” Baldan-Martin added.
Analysis of biologic pathways also highlighted enrichment in ketone and butyrate metabolism, mitochondrial electron transport chain activity, carnitine synthesis, and fatty acid oxidation pathways, while metagenomic analysis revealed the greatest microbial differences in UC responders and nonresponders to anti-TNF therapies.
Baldan-Martin said research was ongoing with a new cohort of patients that aims to validate some of the biomarkers and help identify the patients most likely to respond to tailored therapeutic interventions.
“One of the challenges is integrating results from different omics approaches to create a more holistic understanding of the disease,” she said, adding that she hopes the research “will potentially open doors for early detection through multi-panel biomarkers.”
Session moderator Mark Samaan, MD, consultant gastroenterologist at Guy’s and St Thomas’ NHS Foundation Trust, London, England, said that “the findings related to nonresponse to specific drugs in UC and CD were interesting. With longitudinal follow-up, we’d hope this might help us pick out patients less likely to respond and who show early nonresponse to specific drugs based on serum, urine, and fecal sampling.”
“It’s very helpful to know if someone is a nonresponder within 14 weeks because we can then move the patient on to something else relatively quickly,” he added.
Baldan-Martin and Samaan declared no relevant financial disclosures.
A version of this article appeared on Medscape.com.
BERLIN — presented at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
Differences uncovered in multiple messenger RNAs, proteins, metabolites, and gut microbiota were associated with responders and nonresponders to biologics and Janus kinase inhibitors, suggesting the potential for predictive biomarkers in IBD, including Crohn’s disease (CD) and ulcerative colitis (UC).
“With further work we hope to confirm these findings and evaluate their clinical relevance in identifying patients most likely to respond to tailored therapeutic interventions,” said Montserrat Baldan-Martin, PhD, a researcher at the University Hospital of the Princess, Madrid, Spain.
The treatment of IBD is challenging because of the heterogeneity across clinical, immunological, molecular, genetic, and microbiologic features, with one third of patients failing to respond to any one treatment.
Baldan-Martin and colleagues wanted to find predictive biomarkers of response by examining the differences across multi-omics profiles relative to different therapies.
The study analyzed 127 patients with IBD (57 with CD and 70 with UC) before and after 14 weeks of treatment with one of the following: anti–tumor necrosis factors (TNFs), ustekinumab, vedolizumab, or tofacitinib. Patient response to treatment was evaluated using endoscopic criteria that categorized them as responders or nonresponders to the different therapies.
In addition, molecular data from various biologic samples — serum, urine, extracellular vesicles, intestinal biopsies, and stool — were tested using transcriptomics, proteomics, metabolomics, and metagenomics.
Clear Differences
“The most significant differences were seen in gene expression within intestinal tissue of responder and nonresponder patients with ulcerative colitis taking vedolizumab,” Baldan-Martin reported.
Proteomic analysis revealed that a total of 1377 proteins were identified across all groups (CD, UC, and the four drug classes/therapies). Responders and nonresponders for each therapy expressed different proteins in serum extracellular vesicles and intestinal tissues.
For example, patients with CD who responded to anti-TNF therapies had 138 different proteins from those of anti-TNF nonresponders, while patients with UC who responded to anti-TNF therapies had 218 different proteins from those of anti-TNF nonresponders, reported Baldan-Martin.
Also, we observed almost no proteins “in common between ulcerative colitis responders versus nonresponders for all treatments,” she noted. And we “saw only three proteins in common with Crohn’s disease patients [on different drugs].”
Metabolomic analysis identified deregulation of 24 serum lipoproteins in CD responders to ustekinumab, compared with nonresponders.
“We observed greater differences in the lipoproteins in serum than metabolites in serum and urine,” Baldan-Martin added.
Analysis of biologic pathways also highlighted enrichment in ketone and butyrate metabolism, mitochondrial electron transport chain activity, carnitine synthesis, and fatty acid oxidation pathways, while metagenomic analysis revealed the greatest microbial differences in UC responders and nonresponders to anti-TNF therapies.
Baldan-Martin said research was ongoing with a new cohort of patients that aims to validate some of the biomarkers and help identify the patients most likely to respond to tailored therapeutic interventions.
“One of the challenges is integrating results from different omics approaches to create a more holistic understanding of the disease,” she said, adding that she hopes the research “will potentially open doors for early detection through multi-panel biomarkers.”
Session moderator Mark Samaan, MD, consultant gastroenterologist at Guy’s and St Thomas’ NHS Foundation Trust, London, England, said that “the findings related to nonresponse to specific drugs in UC and CD were interesting. With longitudinal follow-up, we’d hope this might help us pick out patients less likely to respond and who show early nonresponse to specific drugs based on serum, urine, and fecal sampling.”
“It’s very helpful to know if someone is a nonresponder within 14 weeks because we can then move the patient on to something else relatively quickly,” he added.
Baldan-Martin and Samaan declared no relevant financial disclosures.
A version of this article appeared on Medscape.com.
FROM ECCO 2025
Not All Plant-based Diets Are Equal in IBD Risk Mitigation
BERLIN — according to the results of a large cohort study.
The study, which included both Crohn’s disease (CD) and ulcerative colitis (UC), also showed that diet quality may affect disease progression and surgery risk for individuals already diagnosed with IBD.
“Not all plant-based foods are equal — they don’t all have the same effect on health outcomes,” said study researcher, Judith Wellens, MD, PhD, gastroenterology resident at Leuven University Hospital in Belgium.
“We need to look at what people are eating more carefully because it isn’t black and white, with all plant-based food being good and animal-based food being bad,” said Wellens, who presented the data at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
Although she advocates for plant-based diets, Wellens stressed that “they need to be individualized to ensure the overall dietary quality is good. Just cutting out meat products is not very helpful. We think it is the unhealthy additions to some plant-based diets that drive the IBD risk.”
Is It the Plants or the Processed Ingredients?
“Preclinical studies have already taught us that plant-based diets alter the gut microbiota in a beneficial way. However, many diets promoted for IBD — for example the Crohn’s disease exclusion diet — contain ingredients that are animal based. This is confusing for patients and for clinicians,” said Wellens.
To look more closely at the question, she and her colleagues analyzed data for 187,888 participants from the UK Biobank and 341,539 participants from across eight European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. None of the participants had IBD at baseline.
Based on participant 24-hour dietary recalls, the researchers constructed plant-based diet indices (PDIs) with diets categorized as healthy (eg, whole grains, fruits, vegetables, legumes, and vegetarian protein alternatives) or unhealthy (eg, emulsifiers, refined grains, fries, fruit juices, sweets, desserts, sugar-sweetened beverages, and processed foods).
The primary outcome was the incidence of IBD (either CD or UC), whereas the secondary outcome was IBD-related surgery, thereby marking disease progression. Cox regression analysis estimated IBD risk and progression. Incidences of IBD were similar between the two cohorts.
In the UK Biobank cohort, 925 participants developed IBD over a median follow-up of 11.6 years. Participants who followed a healthy PDI had a 25% reduced IBD risk, whereas those who followed an unhealthy PDI had a 48% increased risk for disease development. Both CD and UC showed similar outcomes.
The EPIC cohort had a longer median follow-up time of 14.5 years, during which 548 people developed IBD. Healthy PDIs were linked to a 29% reduced risk for IBD, whereas unhealthy PDIs were associated with a 54% increased risk.
A healthy PDI halved the risk for surgery in participants from the UK Biobank, whereas an unhealthy PDI was associated with a twofold higher risk for surgery.
There were no significant associations between PDIs and other outcomes, such as cardiovascular disease, diabetes, or all-cause mortality.
The researchers also looked at the interactions between genetics and plant-based diets, but those results were not presented at the meeting.
However, Wellens said in an interview that people with a moderate to high risk for IBD based on their polygenetic risk score showed increased odds for IBD risk.
“We don’t test people for their genetic risk of IBD, but if people have close relatives with IBD, then there is probably an increased genetic risk of its development,” she added.
Commenting on the findings, James Lindsay, PhD, professor of inflammatory bowel disease, Queen Mary University of London in England, said that several recent epidemiological studies have highlighted “the negative impact of ultra-processed foods on increasing the risk of developing Crohn’s disease.”
Based on these studies, “one might assume that plant-based diets would be protective,” he said, however, the current study shows us “that plant-based diets are not all equal and there are unhealthy aspects to some.”
“Of course, showing that a diet is associated with an outcome is not the same as knowing that changing a diet will reduce the risk,” Lindsay added. “That requires a well-designed, carefully controlled trial.”
Wellens and Lindsay reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
BERLIN — according to the results of a large cohort study.
The study, which included both Crohn’s disease (CD) and ulcerative colitis (UC), also showed that diet quality may affect disease progression and surgery risk for individuals already diagnosed with IBD.
“Not all plant-based foods are equal — they don’t all have the same effect on health outcomes,” said study researcher, Judith Wellens, MD, PhD, gastroenterology resident at Leuven University Hospital in Belgium.
“We need to look at what people are eating more carefully because it isn’t black and white, with all plant-based food being good and animal-based food being bad,” said Wellens, who presented the data at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
Although she advocates for plant-based diets, Wellens stressed that “they need to be individualized to ensure the overall dietary quality is good. Just cutting out meat products is not very helpful. We think it is the unhealthy additions to some plant-based diets that drive the IBD risk.”
Is It the Plants or the Processed Ingredients?
“Preclinical studies have already taught us that plant-based diets alter the gut microbiota in a beneficial way. However, many diets promoted for IBD — for example the Crohn’s disease exclusion diet — contain ingredients that are animal based. This is confusing for patients and for clinicians,” said Wellens.
To look more closely at the question, she and her colleagues analyzed data for 187,888 participants from the UK Biobank and 341,539 participants from across eight European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. None of the participants had IBD at baseline.
Based on participant 24-hour dietary recalls, the researchers constructed plant-based diet indices (PDIs) with diets categorized as healthy (eg, whole grains, fruits, vegetables, legumes, and vegetarian protein alternatives) or unhealthy (eg, emulsifiers, refined grains, fries, fruit juices, sweets, desserts, sugar-sweetened beverages, and processed foods).
The primary outcome was the incidence of IBD (either CD or UC), whereas the secondary outcome was IBD-related surgery, thereby marking disease progression. Cox regression analysis estimated IBD risk and progression. Incidences of IBD were similar between the two cohorts.
In the UK Biobank cohort, 925 participants developed IBD over a median follow-up of 11.6 years. Participants who followed a healthy PDI had a 25% reduced IBD risk, whereas those who followed an unhealthy PDI had a 48% increased risk for disease development. Both CD and UC showed similar outcomes.
The EPIC cohort had a longer median follow-up time of 14.5 years, during which 548 people developed IBD. Healthy PDIs were linked to a 29% reduced risk for IBD, whereas unhealthy PDIs were associated with a 54% increased risk.
A healthy PDI halved the risk for surgery in participants from the UK Biobank, whereas an unhealthy PDI was associated with a twofold higher risk for surgery.
There were no significant associations between PDIs and other outcomes, such as cardiovascular disease, diabetes, or all-cause mortality.
The researchers also looked at the interactions between genetics and plant-based diets, but those results were not presented at the meeting.
However, Wellens said in an interview that people with a moderate to high risk for IBD based on their polygenetic risk score showed increased odds for IBD risk.
“We don’t test people for their genetic risk of IBD, but if people have close relatives with IBD, then there is probably an increased genetic risk of its development,” she added.
Commenting on the findings, James Lindsay, PhD, professor of inflammatory bowel disease, Queen Mary University of London in England, said that several recent epidemiological studies have highlighted “the negative impact of ultra-processed foods on increasing the risk of developing Crohn’s disease.”
Based on these studies, “one might assume that plant-based diets would be protective,” he said, however, the current study shows us “that plant-based diets are not all equal and there are unhealthy aspects to some.”
“Of course, showing that a diet is associated with an outcome is not the same as knowing that changing a diet will reduce the risk,” Lindsay added. “That requires a well-designed, carefully controlled trial.”
Wellens and Lindsay reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
BERLIN — according to the results of a large cohort study.
The study, which included both Crohn’s disease (CD) and ulcerative colitis (UC), also showed that diet quality may affect disease progression and surgery risk for individuals already diagnosed with IBD.
“Not all plant-based foods are equal — they don’t all have the same effect on health outcomes,” said study researcher, Judith Wellens, MD, PhD, gastroenterology resident at Leuven University Hospital in Belgium.
“We need to look at what people are eating more carefully because it isn’t black and white, with all plant-based food being good and animal-based food being bad,” said Wellens, who presented the data at the European Crohn’s and Colitis Organisation (ECCO) 2025 Congress.
Although she advocates for plant-based diets, Wellens stressed that “they need to be individualized to ensure the overall dietary quality is good. Just cutting out meat products is not very helpful. We think it is the unhealthy additions to some plant-based diets that drive the IBD risk.”
Is It the Plants or the Processed Ingredients?
“Preclinical studies have already taught us that plant-based diets alter the gut microbiota in a beneficial way. However, many diets promoted for IBD — for example the Crohn’s disease exclusion diet — contain ingredients that are animal based. This is confusing for patients and for clinicians,” said Wellens.
To look more closely at the question, she and her colleagues analyzed data for 187,888 participants from the UK Biobank and 341,539 participants from across eight European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. None of the participants had IBD at baseline.
Based on participant 24-hour dietary recalls, the researchers constructed plant-based diet indices (PDIs) with diets categorized as healthy (eg, whole grains, fruits, vegetables, legumes, and vegetarian protein alternatives) or unhealthy (eg, emulsifiers, refined grains, fries, fruit juices, sweets, desserts, sugar-sweetened beverages, and processed foods).
The primary outcome was the incidence of IBD (either CD or UC), whereas the secondary outcome was IBD-related surgery, thereby marking disease progression. Cox regression analysis estimated IBD risk and progression. Incidences of IBD were similar between the two cohorts.
In the UK Biobank cohort, 925 participants developed IBD over a median follow-up of 11.6 years. Participants who followed a healthy PDI had a 25% reduced IBD risk, whereas those who followed an unhealthy PDI had a 48% increased risk for disease development. Both CD and UC showed similar outcomes.
The EPIC cohort had a longer median follow-up time of 14.5 years, during which 548 people developed IBD. Healthy PDIs were linked to a 29% reduced risk for IBD, whereas unhealthy PDIs were associated with a 54% increased risk.
A healthy PDI halved the risk for surgery in participants from the UK Biobank, whereas an unhealthy PDI was associated with a twofold higher risk for surgery.
There were no significant associations between PDIs and other outcomes, such as cardiovascular disease, diabetes, or all-cause mortality.
The researchers also looked at the interactions between genetics and plant-based diets, but those results were not presented at the meeting.
However, Wellens said in an interview that people with a moderate to high risk for IBD based on their polygenetic risk score showed increased odds for IBD risk.
“We don’t test people for their genetic risk of IBD, but if people have close relatives with IBD, then there is probably an increased genetic risk of its development,” she added.
Commenting on the findings, James Lindsay, PhD, professor of inflammatory bowel disease, Queen Mary University of London in England, said that several recent epidemiological studies have highlighted “the negative impact of ultra-processed foods on increasing the risk of developing Crohn’s disease.”
Based on these studies, “one might assume that plant-based diets would be protective,” he said, however, the current study shows us “that plant-based diets are not all equal and there are unhealthy aspects to some.”
“Of course, showing that a diet is associated with an outcome is not the same as knowing that changing a diet will reduce the risk,” Lindsay added. “That requires a well-designed, carefully controlled trial.”
Wellens and Lindsay reported no relevant financial disclosures.
A version of this article appeared on Medscape.com.
FROM ECCO 2025
Guselkumab Efficacy in Crohn’s Disease Unaffected by Prior Biologic Use
VIENNA — according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.
“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.
These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.
Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.
Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
GALAXI 2 and 3 Pooled Dataset
In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.
Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.
Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.
The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.
Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.
The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.
The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
Short- and Long-Term Endpoints in Both Subgroups
In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).
In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).
“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.
Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).
Sands noted that the drug has an excellent safety profile.
“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.
Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.
A version of this article appeared on Medscape.com.
VIENNA — according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.
“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.
These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.
Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.
Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
GALAXI 2 and 3 Pooled Dataset
In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.
Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.
Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.
The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.
Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.
The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.
The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
Short- and Long-Term Endpoints in Both Subgroups
In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).
In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).
“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.
Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).
Sands noted that the drug has an excellent safety profile.
“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.
Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.
A version of this article appeared on Medscape.com.
VIENNA — according to a pooled analysis of the two phase 3 double-blind GALAXI 2 and 3 studies.
“We found that guselkumab was effective in both biologic-naive and biologic-inadequate subpopulations,” said coinvestigator Bruce E. Sands, MD, AGAF, gastroenterologist from Icahn School of Medicine at Mount Sinai, New York City.
These latest results add to the primary results of these studies reported earlier in 2024 that guselkumab was shown to be superior to both placebo and ustekinumab in the same patient population with moderately to severely active CD.
Sands reported the new data in a presentation at the United European Gastroenterology (UEG) Week 2024.
Guselkumab potently blocks interleukin (IL)–23 and binds to CD64, a receptor on cells that produce IL-23. The dual-acting IL-23p19 subunit inhibitor agent is currently under review by the Food and Drug Administration (FDA) for moderately to severely active CD. In September, guselkumab (Tremfya, Johnson & Johnson) was approved for use in moderately to severely active ulcerative colitis.
GALAXI 2 and 3 Pooled Dataset
In the two independent, identically designed GALAXI 2 and 3 studies, patients were randomized to guselkumab treatment at either 200 mg intravenous (IV) induction at weeks 0, 4, and 8, followed by 200 mg subcutaneous maintenance every 4 weeks, starting at week 12, or 200 mg IV induction at weeks 0, 4, and 8, followed by 100 mg subcutaneous maintenance every 8 weeks, starting at week 16; or to ustekinumab; or to placebo.
Participants were required to remain on their treatment of initial randomization for a long-term extension study (up to 5 years) looking at clinical, endoscopic, and safety outcomes, except for participants on placebo who were allowed to switch to ustekinumab if clinical response was not met at week 12.
Inclusion criteria for the studies comprised a Crohn’s Disease Activity Index score between 220 and 450, a mean daily stool frequency count > 3 or an abdominal pain score > 1, and a simple endoscopic score for CD score ≥ 6. Participants were also required to have shown an inadequate response or intolerance to oral corticosteroids, 6-mercaptopurine/azathioprine/methotrexate, or biologic therapies.
The pooled dataset included patients on either dose of guselkumab and patients on placebo (total n = 730). Of these, 52% of participants had shown a prior inadequate response to a biologic, 42% were biologic naive, and 6% had prior exposure to biologics but no documented failure. Patients on ustekinumab were not included in this analysis.
Almost all patients (97%) in the biologic-inadequate response group had previously received at least one anti–tumor necrosis factor agent, and around 15% had received vedolizumab. As expected, the biologic-inadequate responders were a lot sicker than the biologic-naive patients, Sands reported.
The composite co–primary endpoints for each guselkumab regimen vs placebo were clinical response at week 12 plus clinical remission at week 48, and clinical response at week 12 plus endoscopic response at week 48.
The major secondary endpoints comprised clinical remission at week 12 and endoscopic response also at week 12.
Short- and Long-Term Endpoints in Both Subgroups
In the biologic-naive subgroup, 54.7% of patients receiving the 200-mg dose regimen of guselkumab and 51.7% of those receiving the 100-mg dose regimen showed a clinical response at week 12 plus clinical remission at week 48, compared with 11.5% in the placebo group (P < .001 for both compared with placebo).
In the biologic-inadequate response group, 49.7% of those receiving the 200-mg dose regimen of guselkumab and 45.8% on the 100-mg dose regimen reached the composite endpoint, compared with the placebo response of 12.8% (P < .001 for both compared with placebo).
“You can see a slight decrease in response in the biologic-inadequate responders, but on the whole, the confidence intervals are highly overlapping,” said Sands.
Turning to major secondary endpoints at week 12, clinical remission was reached by 49.6% of the biologic-naive group on the 200-mg guselkumab regimen vs 16.4% on placebo, and by 46.0% of the biologic-inadequate group on the 200-mg regimen vs 19.2% on placebo (P < .001 for both subgroups). Endoscopic response was achieved by 46.3% of patients in the biologic-naive group and 29.0% in the biologic-inadequate group on the 200-mg regimen vs 18.0% and 6.4%, respectively, on placebo (P < .001 for both subgroups).
Sands noted that the drug has an excellent safety profile.
“These data show the drug works for naive patients who have failed conventional therapies, as well as for those who have failed biologic therapies,” so it could be used as a first- or second-line biologic, he added.
Sands reported potential conflicts of interest with AbbVie, Abivax, Adiso Therapeutics, Agomab, Alimentiv, Amgen, AnaptysBio, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Biora Therapeutics, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol-Myers Squibb, Calibr, Celgene, Celltrion, ClostraBio, Equillium, Enthera, Evommune, Ferring, Fresenius Kabi, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, Index Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Janssen, Kaleido, Kallyope, Lilly, Merck, Microbiotica, Mobius Care, Morphic Therapeutic, MRM Health, Pfizer, Nexus Therapeutics, Nimbus Discovery, Odyssey Therapeutics, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Q32 Bio, Rasayana Therapeutics, Recludix Pharma, Reistone Biopharma, Sun Pharma, Surrozen, Target RWE, Takeda, Teva, Theravance Biopharma, TLL Pharmaceutical, Tr1X, UNION Therapeutics, and Ventyx Biosciences.
A version of this article appeared on Medscape.com.
FROM UEG 2024
Patients With IBD More Likely to Develop, or Have Prior, T1D
VIENNA —
Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.
Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.
“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.
Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.
Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
Exploring the Bidirectional Relationship
Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.
These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.
In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors.
The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).
The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.
The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.
Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.
In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.
In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.
Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.
That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.
“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”
Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”
“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.
Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.
Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.
A version of this article appeared on Medscape.com.
VIENNA —
Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.
Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.
“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.
Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.
Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
Exploring the Bidirectional Relationship
Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.
These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.
In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors.
The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).
The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.
The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.
Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.
In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.
In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.
Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.
That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.
“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”
Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”
“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.
Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.
Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.
A version of this article appeared on Medscape.com.
VIENNA —
Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.
Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told this news organization.
“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.
Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.
Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.
Exploring the Bidirectional Relationship
Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.
These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.
In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors.
The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).
The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.
The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.
Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.
In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly because of the sample size of these latter categories, noted Sun.
In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.
Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.
That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.
“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”
Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Denmark, said: “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”
“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.
Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.
Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.
A version of this article appeared on Medscape.com.
FROM UEG 2024
Ultraprocessed Foods Associated With Relapse Risk in Crohn’s Disease
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM UEG 2024
Cendakimab That Targets IL-13 Shows Promise in Eosinophilic Esophagitis
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM UEG 2024
When It Comes to Polyp Diagnosis With CADx, Location Matters
VIENNA —
In particular, the diagnostic performance of CADx for polyps showed significantly lower specificity in the proximal colon than in the distal colon.
“While current CADx systems are suitable for use in the distal colon, they should not be employed for diagnosing polyps in the proximal colon until new, higher performing systems are developed specifically for these lesions,” said study lead Tommy Rizkala, MD, Endoscopy Unit, IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.
The “main strength” of the review is that the researchers contacted each study author for more specific information and were therefore able to divide the data into the proximal colon and the rectosigmoid colon, he explained.
“This is the first paper that has really collected these data. Most papers provide data for the entire colon or just for the rectosigmoid colon,” said Rizkala, who presented the findings at the United European Gastroenterology (UEG) Week 2024.
The study was also recently published in Clinical Gastroenterology and Hepatology.
Optical diagnosis enables real-time histologic predictions of polyps 5 mm or smaller during colonoscopy, offering potential clinical and cost-saving benefits. Two optical diagnostic strategies are used for polyps in this size range based on location: A leave-in-situ strategy (applied only in the rectosigmoid colon when there is high confidence of non-neoplastic polyps) and a resect-and-discard strategy (applied only in the whole colon when there is high confidence of neoplastic polyps upon optical diagnosis).
Rizkala carried out a review of studies that evaluated the performance of real-time CADx alone — independent of endoscopist judgment — for predicting the histology of colorectal polyps 5 mm or smaller. The primary endpoints were CADx sensitivity and specificity in the proximal colon (the portion extending from the descending colon to the cecum) and the distal colon (limited to the rectosigmoid region). Secondary outcomes were the negative predictive value (NPV), positive predictive value (PPV), and accuracy of the CADx alone in the proximal colon and the distal colon.
Lower Specificity in the Proximal Colon
An analysis of data based on 7782 polyps ≤ 5 mm from 11 studies found specificity values of 0.62 (95% CI, 0.52-0.71) and 0.85 (95% CI, 0.75-0.92) for the proximal and distal regions of the colon, respectively, with a risk ratio (RR) of 0.74 (95% CI, 0.72-0.84), meaning that CADx accuracy was significantly lower in the proximal colon than in the distal colon.
“According to the optical diagnosis strategy, we can use the leave-in-situ approach for the distal colon because the performance is adequate, but for the rest of the colon, CADx requires further enhancement,” Rizkala said.
Sensitivity values were 0.89 (95% CI, 0.83-0.93) and 0.87 (95% CI, 0.80-0.92) for the proximal and distal regions, respectively, with an RR of 1.00 (95% CI, 0.97-1.03).
Regarding the secondary outcomes, the NPV was 0.64 vs 0.93 for the proximal vs distal colon, with an RR of 0.71 (95% CI, 0.64-0.79), and accuracy was 0.81 vs 0.86, with an RR of 0.95 (95% CI, 0.91-0.99).
With the higher prevalence of neoplastic lesions in the proximal colon than in the distal colon, a lower NPV was observed in the proximal colon, Rizkala noted.
The PPV was 0.87 vs 0.76 for the proximal vs distal colon, with an RR of 1.11 (95% CI, 1.06-1.17), so the two parts of the colon were comparable, he reported.
In the future, CADx systems should focus on using lesions from the proximal colon to train more accurately because currently CADx systems are trained on the available endoscopic data in which most of those polyps are from the rectosigmoid colon, Rizkala said.
We would also “like manufacturers of CADx systems to provide public access to data balanced between the proximal and distal regions of the colon,” he added.
Diagnosis More Challenging Than Detection With CADx
Commenting on the study, comoderator David G. Graham, MD, consultant gastroenterologist at University College London Hospital in England, remarked: “The key questions here relate to why are these systems underperforming in the proximal colon, and how can we improve this?”
Are these results “due to the very different appearance of adenomas in the distal colon vs the proximal colon on CADx (which is not what we see as endoscopists but seems to be what the systems are seeing), or is it due to a different characterization of polyps,” that is, more sessile serrated lesions in the proximal colon than in the distal colon, he asked.
Also commenting on the study was Raf Bisschops, MD, head of endoscopy at KU Leuven in Belgium. He remarked that the review underscores the fact that optical diagnosis by artificial intelligence is a more challenging task than detection.
It is “not entirely clear” what would explain the difference in performance of CADx between the distal colon and proximal colon, he said. It can’t be excluded that the inclusion of different CADx systems, some of which clearly underperformed, may account for the difference.
He went on to suggest that the differences might be down to location beyond proximal and distal.
“The difference in performance between the right and left colon is also interesting, since recent insights in the molecular and morphological features of hyperplastic polyps indicates that there are different classes with more goblet cell–rich hyperplastic polyps in the right colon, and more microvesicular hyperplastic polyps in the left.”
These have “distinct microscopic and endoscopic appearances” that could account for a difference in performance of a CADx system if not included in the training and validation sets, he explained.
Rizkala and Graham reported no relevant disclosures. Bisschops reported receiving research grants and speaker fees from Medtronic, Fujifilm, and Pentax.
A version of this article first appeared on Medscape.com.
VIENNA —
In particular, the diagnostic performance of CADx for polyps showed significantly lower specificity in the proximal colon than in the distal colon.
“While current CADx systems are suitable for use in the distal colon, they should not be employed for diagnosing polyps in the proximal colon until new, higher performing systems are developed specifically for these lesions,” said study lead Tommy Rizkala, MD, Endoscopy Unit, IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.
The “main strength” of the review is that the researchers contacted each study author for more specific information and were therefore able to divide the data into the proximal colon and the rectosigmoid colon, he explained.
“This is the first paper that has really collected these data. Most papers provide data for the entire colon or just for the rectosigmoid colon,” said Rizkala, who presented the findings at the United European Gastroenterology (UEG) Week 2024.
The study was also recently published in Clinical Gastroenterology and Hepatology.
Optical diagnosis enables real-time histologic predictions of polyps 5 mm or smaller during colonoscopy, offering potential clinical and cost-saving benefits. Two optical diagnostic strategies are used for polyps in this size range based on location: A leave-in-situ strategy (applied only in the rectosigmoid colon when there is high confidence of non-neoplastic polyps) and a resect-and-discard strategy (applied only in the whole colon when there is high confidence of neoplastic polyps upon optical diagnosis).
Rizkala carried out a review of studies that evaluated the performance of real-time CADx alone — independent of endoscopist judgment — for predicting the histology of colorectal polyps 5 mm or smaller. The primary endpoints were CADx sensitivity and specificity in the proximal colon (the portion extending from the descending colon to the cecum) and the distal colon (limited to the rectosigmoid region). Secondary outcomes were the negative predictive value (NPV), positive predictive value (PPV), and accuracy of the CADx alone in the proximal colon and the distal colon.
Lower Specificity in the Proximal Colon
An analysis of data based on 7782 polyps ≤ 5 mm from 11 studies found specificity values of 0.62 (95% CI, 0.52-0.71) and 0.85 (95% CI, 0.75-0.92) for the proximal and distal regions of the colon, respectively, with a risk ratio (RR) of 0.74 (95% CI, 0.72-0.84), meaning that CADx accuracy was significantly lower in the proximal colon than in the distal colon.
“According to the optical diagnosis strategy, we can use the leave-in-situ approach for the distal colon because the performance is adequate, but for the rest of the colon, CADx requires further enhancement,” Rizkala said.
Sensitivity values were 0.89 (95% CI, 0.83-0.93) and 0.87 (95% CI, 0.80-0.92) for the proximal and distal regions, respectively, with an RR of 1.00 (95% CI, 0.97-1.03).
Regarding the secondary outcomes, the NPV was 0.64 vs 0.93 for the proximal vs distal colon, with an RR of 0.71 (95% CI, 0.64-0.79), and accuracy was 0.81 vs 0.86, with an RR of 0.95 (95% CI, 0.91-0.99).
With the higher prevalence of neoplastic lesions in the proximal colon than in the distal colon, a lower NPV was observed in the proximal colon, Rizkala noted.
The PPV was 0.87 vs 0.76 for the proximal vs distal colon, with an RR of 1.11 (95% CI, 1.06-1.17), so the two parts of the colon were comparable, he reported.
In the future, CADx systems should focus on using lesions from the proximal colon to train more accurately because currently CADx systems are trained on the available endoscopic data in which most of those polyps are from the rectosigmoid colon, Rizkala said.
We would also “like manufacturers of CADx systems to provide public access to data balanced between the proximal and distal regions of the colon,” he added.
Diagnosis More Challenging Than Detection With CADx
Commenting on the study, comoderator David G. Graham, MD, consultant gastroenterologist at University College London Hospital in England, remarked: “The key questions here relate to why are these systems underperforming in the proximal colon, and how can we improve this?”
Are these results “due to the very different appearance of adenomas in the distal colon vs the proximal colon on CADx (which is not what we see as endoscopists but seems to be what the systems are seeing), or is it due to a different characterization of polyps,” that is, more sessile serrated lesions in the proximal colon than in the distal colon, he asked.
Also commenting on the study was Raf Bisschops, MD, head of endoscopy at KU Leuven in Belgium. He remarked that the review underscores the fact that optical diagnosis by artificial intelligence is a more challenging task than detection.
It is “not entirely clear” what would explain the difference in performance of CADx between the distal colon and proximal colon, he said. It can’t be excluded that the inclusion of different CADx systems, some of which clearly underperformed, may account for the difference.
He went on to suggest that the differences might be down to location beyond proximal and distal.
“The difference in performance between the right and left colon is also interesting, since recent insights in the molecular and morphological features of hyperplastic polyps indicates that there are different classes with more goblet cell–rich hyperplastic polyps in the right colon, and more microvesicular hyperplastic polyps in the left.”
These have “distinct microscopic and endoscopic appearances” that could account for a difference in performance of a CADx system if not included in the training and validation sets, he explained.
Rizkala and Graham reported no relevant disclosures. Bisschops reported receiving research grants and speaker fees from Medtronic, Fujifilm, and Pentax.
A version of this article first appeared on Medscape.com.
VIENNA —
In particular, the diagnostic performance of CADx for polyps showed significantly lower specificity in the proximal colon than in the distal colon.
“While current CADx systems are suitable for use in the distal colon, they should not be employed for diagnosing polyps in the proximal colon until new, higher performing systems are developed specifically for these lesions,” said study lead Tommy Rizkala, MD, Endoscopy Unit, IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.
The “main strength” of the review is that the researchers contacted each study author for more specific information and were therefore able to divide the data into the proximal colon and the rectosigmoid colon, he explained.
“This is the first paper that has really collected these data. Most papers provide data for the entire colon or just for the rectosigmoid colon,” said Rizkala, who presented the findings at the United European Gastroenterology (UEG) Week 2024.
The study was also recently published in Clinical Gastroenterology and Hepatology.
Optical diagnosis enables real-time histologic predictions of polyps 5 mm or smaller during colonoscopy, offering potential clinical and cost-saving benefits. Two optical diagnostic strategies are used for polyps in this size range based on location: A leave-in-situ strategy (applied only in the rectosigmoid colon when there is high confidence of non-neoplastic polyps) and a resect-and-discard strategy (applied only in the whole colon when there is high confidence of neoplastic polyps upon optical diagnosis).
Rizkala carried out a review of studies that evaluated the performance of real-time CADx alone — independent of endoscopist judgment — for predicting the histology of colorectal polyps 5 mm or smaller. The primary endpoints were CADx sensitivity and specificity in the proximal colon (the portion extending from the descending colon to the cecum) and the distal colon (limited to the rectosigmoid region). Secondary outcomes were the negative predictive value (NPV), positive predictive value (PPV), and accuracy of the CADx alone in the proximal colon and the distal colon.
Lower Specificity in the Proximal Colon
An analysis of data based on 7782 polyps ≤ 5 mm from 11 studies found specificity values of 0.62 (95% CI, 0.52-0.71) and 0.85 (95% CI, 0.75-0.92) for the proximal and distal regions of the colon, respectively, with a risk ratio (RR) of 0.74 (95% CI, 0.72-0.84), meaning that CADx accuracy was significantly lower in the proximal colon than in the distal colon.
“According to the optical diagnosis strategy, we can use the leave-in-situ approach for the distal colon because the performance is adequate, but for the rest of the colon, CADx requires further enhancement,” Rizkala said.
Sensitivity values were 0.89 (95% CI, 0.83-0.93) and 0.87 (95% CI, 0.80-0.92) for the proximal and distal regions, respectively, with an RR of 1.00 (95% CI, 0.97-1.03).
Regarding the secondary outcomes, the NPV was 0.64 vs 0.93 for the proximal vs distal colon, with an RR of 0.71 (95% CI, 0.64-0.79), and accuracy was 0.81 vs 0.86, with an RR of 0.95 (95% CI, 0.91-0.99).
With the higher prevalence of neoplastic lesions in the proximal colon than in the distal colon, a lower NPV was observed in the proximal colon, Rizkala noted.
The PPV was 0.87 vs 0.76 for the proximal vs distal colon, with an RR of 1.11 (95% CI, 1.06-1.17), so the two parts of the colon were comparable, he reported.
In the future, CADx systems should focus on using lesions from the proximal colon to train more accurately because currently CADx systems are trained on the available endoscopic data in which most of those polyps are from the rectosigmoid colon, Rizkala said.
We would also “like manufacturers of CADx systems to provide public access to data balanced between the proximal and distal regions of the colon,” he added.
Diagnosis More Challenging Than Detection With CADx
Commenting on the study, comoderator David G. Graham, MD, consultant gastroenterologist at University College London Hospital in England, remarked: “The key questions here relate to why are these systems underperforming in the proximal colon, and how can we improve this?”
Are these results “due to the very different appearance of adenomas in the distal colon vs the proximal colon on CADx (which is not what we see as endoscopists but seems to be what the systems are seeing), or is it due to a different characterization of polyps,” that is, more sessile serrated lesions in the proximal colon than in the distal colon, he asked.
Also commenting on the study was Raf Bisschops, MD, head of endoscopy at KU Leuven in Belgium. He remarked that the review underscores the fact that optical diagnosis by artificial intelligence is a more challenging task than detection.
It is “not entirely clear” what would explain the difference in performance of CADx between the distal colon and proximal colon, he said. It can’t be excluded that the inclusion of different CADx systems, some of which clearly underperformed, may account for the difference.
He went on to suggest that the differences might be down to location beyond proximal and distal.
“The difference in performance between the right and left colon is also interesting, since recent insights in the molecular and morphological features of hyperplastic polyps indicates that there are different classes with more goblet cell–rich hyperplastic polyps in the right colon, and more microvesicular hyperplastic polyps in the left.”
These have “distinct microscopic and endoscopic appearances” that could account for a difference in performance of a CADx system if not included in the training and validation sets, he explained.
Rizkala and Graham reported no relevant disclosures. Bisschops reported receiving research grants and speaker fees from Medtronic, Fujifilm, and Pentax.
A version of this article first appeared on Medscape.com.
FROM UEG 2024