TBD Meeting (5444-24)

STOCKHOLM — An artificial intelligence (AI)–assisted image-enhanced endoscopy system accurately assessed vascular healing and predicted long-term clinical relapse in patients with ulcerative colitis (UC), according to data from the study of a novel investigational tool. 

Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.

In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said. 

Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said. 

“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.” 

Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.

Stratifying the Relapse Risk

Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC. 

The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes. 

“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.

In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1). 

Patient characteristics were similar between both groups with an average disease duration of 10 years. 

In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.

In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.

Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.

The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI. 

“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.

They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience. 

Still in the Early Stages

AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria. 

We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said. 

The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.

Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — An artificial intelligence (AI)–assisted image-enhanced endoscopy system accurately assessed vascular healing and predicted long-term clinical relapse in patients with ulcerative colitis (UC), according to data from the study of a novel investigational tool. 

Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.

In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said. 

Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said. 

“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.” 

Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.

Stratifying the Relapse Risk

Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC. 

The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes. 

“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.

In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1). 

Patient characteristics were similar between both groups with an average disease duration of 10 years. 

In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.

In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.

Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.

The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI. 

“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.

They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience. 

Still in the Early Stages

AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria. 

We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said. 

The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.

Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — An artificial intelligence (AI)–assisted image-enhanced endoscopy system accurately assessed vascular healing and predicted long-term clinical relapse in patients with ulcerative colitis (UC), according to data from the study of a novel investigational tool. 

Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.

In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said. 

Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said. 

“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.” 

Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.

Stratifying the Relapse Risk

Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC. 

The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes. 

“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.

In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1). 

Patient characteristics were similar between both groups with an average disease duration of 10 years. 

In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.

In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.

Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.

The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI. 

“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.

They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience. 

Still in the Early Stages

AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria. 

We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said. 

The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.

Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — Eight live bacterial strains have been identified as having the potential to regulate the inflammatory imbalance in the gut microbiome of patients with mild to moderate ulcerative colitis (UC). 

The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.

In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product. 

In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.

On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).

 Calming Inflammation With Specific Bacteria 

To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.

The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.

“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”

Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response. 

“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.

Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule. 

The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions. 

The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation. 

The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages. 

And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.

Moving in the Right Direction

Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.

“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.

“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.

“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.

Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — Eight live bacterial strains have been identified as having the potential to regulate the inflammatory imbalance in the gut microbiome of patients with mild to moderate ulcerative colitis (UC). 

The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.

In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product. 

In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.

On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).

 Calming Inflammation With Specific Bacteria 

To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.

The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.

“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”

Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response. 

“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.

Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule. 

The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions. 

The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation. 

The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages. 

And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.

Moving in the Right Direction

Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.

“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.

“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.

“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.

Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — Eight live bacterial strains have been identified as having the potential to regulate the inflammatory imbalance in the gut microbiome of patients with mild to moderate ulcerative colitis (UC). 

The eight-strain live biotherapeutic product (MB310, Microbiotica) is due to enter its first clinical trial later this year.

In patients with UC who showed clinical benefit after fecal microbiota transplantation (FMT), these eight specific bacterial strains were shown to be consistently elevated, reported Ron Carter, MD, chief medical officer at Microbiotica, Cambridge, UK, the company developing the product. 

In addition, “in lab studies, we’ve found they exhibit anti-inflammatory effects when incubated with different cells of the immune system,” he explained. With the biotherapeutic product, “we want to prompt the immune system to realign the gut inflammation” in UC.

On February 23, at the annual congress of the European Crohn’s and Colitis Organisation, Dr. Carter presented the work-to-date and the near-term plans for a phase 1b randomized, placebo-controlled, double-blind trial to be conducted across roughly 20 sites in Europe (Abstract DOP 67). The trial, COMPOSER-1, will investigate the engraftment and initial signs of clinical activity of MB310 in 30 patients with active, mild to moderate UC (modified Mayo score 4-7; endoscopic subscore ≥ 2).

 Calming Inflammation With Specific Bacteria 

To date, the researchers have focused on identifying bacterial species that correlate with clinical outcomes in individual patients with UC after treatment with FMT. Dr. Carter and colleagues worked in collaboration with Sam Costello, MBBS, gastroenterologist at The Queen Elizabeth Hospital in Adelaide, Australia.

The initial research involved analyzing stool samples from a round 70 patients diagnosed with mild to moderate UC, who were randomly assigned to receive either pooled, anaerobically prepared, healthy donor FMT, or their own autologous FMT as a comparative control. FMT was delivered via colonoscopy and two enemas over 7 days. The primary endpoint of the study was achieving steroid-free remission of UC on the basis of specific Mayo scores, at the end of week 8.

“Results indicated that the group receiving the pooled donor FMT showed a 32% success rate with respect to the primary outcome compared with only 9% of the control group,” said Dr. Carter. “This suggested a promising therapeutic strategy.”

Based on these outcomes, Microbiotica then decided to conduct a local study in which they analyzed fecal samples from FMT donors and from pre-FMT and post-FMT recipients in order to precisely identify which bacterial species were associated with clinical response. 

“With our precision microbiome analysis platform, we determined eight bacterial species that were consistently elevated in FMT responders, but absent or not elevated in non-responders,” reported Dr. Carter.

Next, they carried out subspecies-level bioinformatic analysis and identified one bacterial strain from each of the eight species, which were then cultured individually, freeze-dried, and combined into a custom delayed-release capsule. 

The researchers tested the resulting live biotherapeutic product in cellular assays using human cell lines to confirm that they effectively modulated immune functions. 

The cellular assays showed that in epithelial cell monolayer tests, MB310 not only enhanced barrier integrity but also protected the cellular barrier from inflammation. 

The eight bacterial strain combination also exhibited anti-inflammatory effects when incubated with different primary innate immune cells, dendritic cells, and M1 macrophages. 

And, Dr. Carter emphasized, the specific MB310 bacterial strains were found to regulate T-cells directly or via metabolites.

Moving in the Right Direction

Julien Kirchgesner, MD, Saint-Antoine Hospital and Sorbonne University, Paris, France, who co-moderated the session where the research was presented, welcomed the work.

“Many more trials need to be done before we see this enter the clinic, but this is moving in the right direction,” Dr. Kirchgesner noted.

“We need to find only the functionally active bacterial strains, rather than just take the fecal transplant alone [as is done with FMT],” he said. That is what is being done here.

“The researchers want to identify which bacterial strains will impact the effectiveness in patients, and to select for these strains before industrializing the process and producing them at the optimal strength, at scale,” Dr. Kirchgesner said.

Dr. Carter is chief medical officer at Microbiotica and Dr Kirshgensner has no financial disclosures.

A version of this article appeared on Medscape.com.

STOCKHOLM — Long-term data on risankizumab (Skyrizi) in moderate to severe Crohn’s disease (CD) show that clinical remission and endoscopic response rates remain stable for up to 3 years, according to results of the FORTIFY extension study.

“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”

Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents. 

Ferrante_Marc_BELGIUM_web.jpg

“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”

Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”

“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.

Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
 

Open-Label Extension up to 152 Weeks

The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD. 

These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.

Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months. 

Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population. 

For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.

The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said. 

Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
 

‘Effective and Durable Option’

Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.

“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.” 

But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.

In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine. 

“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted. 

“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”

Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.

A version of this article appeared on Medscape.com.

STOCKHOLM — Long-term data on risankizumab (Skyrizi) in moderate to severe Crohn’s disease (CD) show that clinical remission and endoscopic response rates remain stable for up to 3 years, according to results of the FORTIFY extension study.

“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”

Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents. 

Ferrante_Marc_BELGIUM_web.jpg

“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”

Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”

“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.

Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
 

Open-Label Extension up to 152 Weeks

The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD. 

These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.

Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months. 

Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population. 

For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.

The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said. 

Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
 

‘Effective and Durable Option’

Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.

“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.” 

But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.

In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine. 

“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted. 

“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”

Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.

A version of this article appeared on Medscape.com.

STOCKHOLM — Long-term data on risankizumab (Skyrizi) in moderate to severe Crohn’s disease (CD) show that clinical remission and endoscopic response rates remain stable for up to 3 years, according to results of the FORTIFY extension study.

“For me, most striking are the endoscopic endpoints,” Marc Ferrante, MD, PhD, AGAF, said in an interview. In the most conservative analysis, “you see a benefit the longer you follow the patients ... We haven’t seen this with many — if any — other compounds before.”

Dr. Ferrante, from University Hospitals Leuven in Belgium, added that patients showed less antibody formation in response to risankizumab, an anti-interleukin (IL)–23 p19 inhibitor, compared with anti–tumor necrosis factor agents. 

Ferrante_Marc_BELGIUM_web.jpg

“Most patients seemed to continue on treatment without the formation of antibodies to risankizumab becoming a problem,” he said. Also, for patients who achieve a good response to risankizumab, the effects were the same whether “they received this biologic first line, or only after failing other compounds.”

Generally, “I think we all have the impression that the IL-23 inhibitors have good efficacy, probably even better than other compounds available,” said Dr. Ferrante. “And, importantly, this is true without any increased adverse effects.”

“Now, with these new long-term data in risankizumab, we see the benefit-risk ratio continues to be favorable,” he added.

Dr. Ferrante presented the data (Abstract DOP 53) on February 23 at the annual congress of the European Crohn’s and Colitis Organisation.
 

Open-Label Extension up to 152 Weeks

The ongoing FORTIFY maintenance open-label extension study is evaluating the long-term efficacy and safety of risankizumab in patients with moderate to severe CD. 

These data follow the initial 52-week study published in 2022 showing that subcutaneous risankizumab was a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active CD. Dr. Ferrante also led that study.

Participants in this open-label extension study who had already completed 52-weeks maintenance dosing received 180-mg subcutaneous risankizumab every 8 weeks (n = 872) at week 56. Those who had received prior rescue therapy, a single 1200-mg intravenous risankizumab dose followed by 360-mg subcutaneously every 8 weeks, continued with this latter regimen (n = 275). Data for analysis were pooled from both treatment groups (risankizumab 180 mg and 360 mg), and clinical outcomes were evaluated every 6 months. 

Data for the population, after patients who received rescue treatment were imputed as nonresponders, showed Clinical Disease Activity Index (CDAI) clinical response of 84.9% at week 56 and 52.7% at week 152. CDAI clinical remission was 66.7% at week 56 and 47.2% at week 152 for this population. 

For endoscopic outcomes, additional benefit was seen over time. Endoscopic response, considered to be the best available predictor of long-term outcomes, was 50.8% at week 56 and 52.5% at week 152. Endoscopic remission was 35.8% at week 56 and 41.8% at week 152, and ulcer-free endoscopy was seen in 28.6% patients at week 56 and 35.5% at week 152.

The safety profile of risankizumab is consistent and supports long-term treatment, Dr. Ferrante said. 

Treatment emergent adverse events included major adverse cardiovascular events in five patients on risankizumab and 50 serious infections.
 

‘Effective and Durable Option’

Providing comment, Tim Raine, MD, a consultant gastroenterologist & IBD lead at Cambridge University Hospitals, United Kingdom, remarked on the value of long-term extension studies for understanding the impact of continued drug administration beyond the typical 1-year time horizon of registrational clinical trials given that CD is currently incurable.

“However, there are limitations with long-term extension studies,” he said in an interview. In particular, the patients who remain in the study tend to be “those who have had a good experience with the drug and remain motivated to take part in ongoing monitoring.” 

But “patients will drop out of a long-term extension study for reasons that may or may not reflect loss of benefit from the drug, and this can be problematic with handling of missing data,” he explained.

In light of this issue, “the investigators have used the most stringent way of handling these patients, regarding all who drop out as instances of failure of the drug. This offers the most robust assessment of durability of response that may slightly underestimate the true long-term efficacy,” said Dr. Raine. 

“Nevertheless, the response and remission rates for clinical endpoints suggest good durability of effect out to 3 years of follow-up. The endoscopic data are also encouraging,” he asserted. 

“Taken together, these data suggest that risankizumab can offer an effective and durable option for some patients with Crohn’s disease and is associated with a favorable safety profile.”

Dr. Ferrante disclosed ties with AbbVie, Agomab Therapeutics, Amgen, Biogen, Boehringer Ingelheim, Celgene, Celltrion, EG, Eli Lilly, Falk, Ferring, Janssen, Janssen-Cilag, Lamepro, Medtronic, MRM, MSD, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Takeda, ThermoFisher, Truvion Healthcare, and Viatris. Dr. Raine disclosed ties with AbbVie, Arena, Aslan, AstraZeneca, Boehringer-Ingelheim, BMS, Celgene, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, Mylan, MSD, Novartis, Pfizer, Sandoz, Takeda, and UCB.

A version of this article appeared on Medscape.com.

STOCKHOLM — A proactive treat-to-target strategy in patients with Crohn’s disease (CD) who are in remission but are considered to be high risk as determined by video capsule endoscopy was superior for prevention of clinical flare within the next 2 years compared with continued standard care, a new study showed.

Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification. 

The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.

Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus. 

He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse. 

The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months. 

A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic. 

The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care. 

Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months. 
 

A Nearly Threefold Difference

Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20). 

By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported. 

The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).

In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy. 

“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.” 

It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained. 

The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out. 

“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”

Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes. 

She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”

“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted. 

Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm. 

Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

STOCKHOLM — A proactive treat-to-target strategy in patients with Crohn’s disease (CD) who are in remission but are considered to be high risk as determined by video capsule endoscopy was superior for prevention of clinical flare within the next 2 years compared with continued standard care, a new study showed.

Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification. 

The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.

Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus. 

He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse. 

The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months. 

A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic. 

The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care. 

Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months. 
 

A Nearly Threefold Difference

Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20). 

By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported. 

The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).

In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy. 

“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.” 

It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained. 

The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out. 

“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”

Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes. 

She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”

“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted. 

Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm. 

Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.

STOCKHOLM — A proactive treat-to-target strategy in patients with Crohn’s disease (CD) who are in remission but are considered to be high risk as determined by video capsule endoscopy was superior for prevention of clinical flare within the next 2 years compared with continued standard care, a new study showed.

Capsule endoscopy reveals small-intestinal inflammation in over 70% of patients with CD who are in clinical remission, said Shomron Ben-Horin, MD, from Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel. The question remains however, which patients would benefit from treatment intensification. 

The randomized controlled CURE-CD trial showed that patients who have high inflammatory activity — a Lewis score ≥ 350 as seen in video capsule endoscopy findings — experienced statistically significantly fewer relapses during the 2-year follow-up vs patients with the same amount of inflammation who continued their standard treatment, he said.

Dr. Ben-Horin presented the results at the annual congress of the European Crohn’s and Colitis Organisation on behalf of the Israeli IBD Research Nucleus. 

He and his colleagues aimed to examine the value of video capsule endoscopy to guide proactive treat-to-target strategy in patients with CD who are in clinical remission, adding onto their previous work published in 2019 that established the benefit of video capsule endoscopy over calprotectin in predicting relapse. 

The prospective randomized controlled trial recruited 60 patients with CD involving the small bowel who were in clinical remission (Crohn’s Disease Activity Index [CDAI] < 150). Patients underwent clinical, biomarker, and imaging checks as well as video capsule endoscopies at baseline and every 6 months thereafter for up to 24 months. 

A total of 40 patients with a Lewis score ≥ 350 and who were considered high-risk were randomized to either proactive treatment optimization (targeting video capsule endoscopy mucosal healing, n = 20) or to continued standard care (n = 20) for 24 months. Patients with a Lewis score < 350 who were considered to be low-risk continued standard care (n = 20) which may or may not have been biologic. 

The primary outcome was the rate of clinical relapse (disease exacerbation comprised of a CDAI increase > 70 points or hospitalization/surgery) by 24 months in high-risk patients who received standard care vs proactive care. 

Secondary outcomes included risk for flare in the low-risk group (all on standard care) vs the high-risk group also on standard care, predictive profiles for flare of calprotectin, MRI, intestinal ultrasound, and Lewis score over the 24 months. 
 

A Nearly Threefold Difference

Treatment intensification in the high-risk proactive strategy group was split between therapeutic drug monitoring–based biologic dose-escalation (n = 11 in 20), starting a biologic (8 in 20), or swapping a biologic (1 in 20). 

By 24 months, clinical flare occurred in 5 in 20 (25%) of the high-risk proactive group vs 14 (70%) of the high-risk standard-care group (odds ratio [OR], 0.14; 95% CI, 0.04-0.57; P = .006), Dr. Ben-Horin reported. 

The data also showed that low-risk patients had a lower incidence of clinical flare at approximately 45% compared with 70% in high-risk patients also on standard care (P = .11 by intention-to-treat analysis; P = .06 by per-protocol analysis).

In an interview, Dr. Ben-Horin said that despite the results, there remained a “big dilemma” about who should be treated if they show mucosal inflammation on video capsule endoscopy. 

“Crohn’s disease is a progressive disease, and we don’t want flares down the road in a patient that currently feels okay but has underlying inflammation,” he said. “On the other hand, it’s important to consider that our therapies are sometimes associated with adverse events, they can be very costly, and become a huge burden to our healthcare systems and to some of the patients.” 

It is important to ask whether we should or treat patients in remission more aggressively “because not everyone will progress and some of them may never flare,” he explained. 

The findings offer three layers of added evidence to the field, Dr. Ben-Horin said. First, it offers further support to the treat-to-target approach if tailored to a high-risk group. Second, the study suggests that treat-to-target studies should be looking only at the high-risk patients and not the entire study population. “This is the first study of its kind to take this approach,” he pointed out. 

“Thirdly, our results build on our preceding trial to show that using video capsule endoscopy enables us to stratify the risk of patients’ with small-bowel Crohn’s disease and tailor their treatment accordingly, probably more accurately than calprotectin or C-reactive protein.”

Asked to comment on the results, Maria Abreu, MD, AGAF, a gastroenterologist who specializes in inflammatory bowel disease at the University of Miami, Miami, Florida, said that though it was a small study, it highlights that patients need to be closely monitored with objective, quantifiable tests for the best outcomes. 

She continued: “Capsule endoscopy is certainly the most sensitive test we have and lends itself in short order to artificial intelligence interpretation and quantification to make it even more robust.”

“We now need to nuance who needs a capsule vs intestinal ultrasound vs a colonoscopy, and that is likely to depend on disease location and manifestations of the disease,” ie, mucosa-only or transmural-predominant disease, she noted. 

Dr. Ben-Horin has declared that the trial was funded by the Helmsley Charitable Trust. The VCE was partly provided by Medtronic. He disclosed advisory board fees and/or consulting and/or research support from Janssen, AbbVie, CellTrion, Takeda, Schering Plough, Pfizer, Ferring, Falk Pharma, GlaxoSmithKline, Novartis, Roche, Galmed, EviNature, Galmed, PredictaMed, NeoPharm. 

Dr. Abreu has served as a consultant and scientific advisory board member for AbbVie, Arena Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly Pharmaceuticals, Gilead, Janssen Biotech, and Prometheus Biosciences, University of California, Berkeley; a speaker for Alimentiv; and has had projects funded by Pfizer, Prometheus Laboratories, and Takeda Pharmaceuticals.

A version of this article appeared on Medscape.com.