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Papers by Marc Ferrante

Research paper thumbnail of What are the Unmet Needs and Most Relevant Treatment Outcomes According to Patients with Inflammatory Bowel Disease? A Qualitative Patient Preference Study

Journal of Crohn's and Colitis

Background and Aims As more therapeutic options with their own characteristics become available f... more Background and Aims As more therapeutic options with their own characteristics become available for inflammatory bowel disease [IBD], drug development and individual treatment decision-making needs to be tailored towards patients’ preferences and needs. This study aimed to understand patient preferences among IBD patients, and their most important treatment outcomes and unmet needs. Methods This qualitative study consisted of [1] a scoping literature review, [2] two focus group discussions [FGDs] with IBD patients [n = 11] using the nominal group technique, and [3] two expert panel discussions. Results IBD patients discussed a multitude of unmet needs regarding their symptoms, side-effects, and psychological and social issues for which they would welcome improved outcomes. In particular, IBD patients elaborated on the uncertainties and fears they experienced regarding the possible need for surgery or an ostomy, the effectiveness and onset of action of their medication, and the medic...

Research paper thumbnail of What are the Unmet Needs and Most Relevant Treatment Outcomes According to Patients with Inflammatory Bowel Disease? A Qualitative Patient Preference Study

Journal of Crohn's and Colitis

Background and Aims As more therapeutic options with their own characteristics become available f... more Background and Aims As more therapeutic options with their own characteristics become available for inflammatory bowel disease [IBD], drug development and individual treatment decision-making needs to be tailored towards patients’ preferences and needs. This study aimed to understand patient preferences among IBD patients, and their most important treatment outcomes and unmet needs. Methods This qualitative study consisted of [1] a scoping literature review, [2] two focus group discussions [FGDs] with IBD patients [n = 11] using the nominal group technique, and [3] two expert panel discussions. Results IBD patients discussed a multitude of unmet needs regarding their symptoms, side-effects, and psychological and social issues for which they would welcome improved outcomes. In particular, IBD patients elaborated on the uncertainties and fears they experienced regarding the possible need for surgery or an ostomy, the effectiveness and onset of action of their medication, and the medic...

Research paper thumbnail of Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn’s Disease: Results from the Phase 2 Open-Label Extension Study

Journal of Crohn's and Colitis

Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptabl... more Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. Methods Enrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks. Results Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The ra...

Research paper thumbnail of Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn’s Disease: Results from the Phase 2 Open-Label Extension Study

Journal of Crohn's and Colitis

Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptabl... more Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. Methods Enrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks. Results Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The ra...

Research paper thumbnail of Patient-reported continuous clinical response to golimumab in adults with moderately to severely active ulcerative colitis: results from GO OBSERVE, a real-world European observational study

European Journal of Gastroenterology & Hepatology

BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcera... more BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcerative colitis (UC). We assessed whether remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores is an effective real-world outcome measure for assessing maintenance of GLM-induced clinical response. METHODS This was a 54-week prospective, observational cohort study conducted at 43 European outpatient clinics in adults with moderate-to-severe UC who were biologic naïve or had received a maximum of one other biological therapy. Patients were treated according to European GLM UC label/local practice. Clinical response (based on partial or full Mayo score) was assessed at week 6, 10, or 14 of induction, depending on local practice. Investigators remotely monitored scores every 4 weeks. The primary endpoint was the proportion of induction responders in patient-reported continuous clinical response (pCCR) at week 54, defined as absence of UC flare based on combined patient-reported Mayo stool frequency and rectal bleeding scores every 4 weeks and full or partial Mayo score. A key secondary endpoint was the proportion of induction responders in clinical remission at week 54. RESULTS Among 109 patients, 37 (34.0%) received at least two GLM induction doses and completed induction in clinical response (induction responders). At week 54, 15/37 (40.5%) induction responders were in pCCR, and 21/37 (56.8%) were in clinical remission. CONCLUSION In daily clinical practice, regular remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores appears to be a meaningful real-world outcome measure for monitoring maintenance of GLM-induced clinical response in UC.

Research paper thumbnail of Patient-reported continuous clinical response to golimumab in adults with moderately to severely active ulcerative colitis: results from GO OBSERVE, a real-world European observational study

European Journal of Gastroenterology & Hepatology

BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcera... more BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcerative colitis (UC). We assessed whether remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores is an effective real-world outcome measure for assessing maintenance of GLM-induced clinical response. METHODS This was a 54-week prospective, observational cohort study conducted at 43 European outpatient clinics in adults with moderate-to-severe UC who were biologic naïve or had received a maximum of one other biological therapy. Patients were treated according to European GLM UC label/local practice. Clinical response (based on partial or full Mayo score) was assessed at week 6, 10, or 14 of induction, depending on local practice. Investigators remotely monitored scores every 4 weeks. The primary endpoint was the proportion of induction responders in patient-reported continuous clinical response (pCCR) at week 54, defined as absence of UC flare based on combined patient-reported Mayo stool frequency and rectal bleeding scores every 4 weeks and full or partial Mayo score. A key secondary endpoint was the proportion of induction responders in clinical remission at week 54. RESULTS Among 109 patients, 37 (34.0%) received at least two GLM induction doses and completed induction in clinical response (induction responders). At week 54, 15/37 (40.5%) induction responders were in pCCR, and 21/37 (56.8%) were in clinical remission. CONCLUSION In daily clinical practice, regular remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores appears to be a meaningful real-world outcome measure for monitoring maintenance of GLM-induced clinical response in UC.

Research paper thumbnail of Introduction of Subcutaneous Infliximab CT-P13 and Vedolizumab in Clinical Practice: A Multi-Stakeholder Position Statement Highlighting the Need for Post-Marketing Studies

Journal of Crohn's and Colitis, 2022

Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are r... more Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are registered for treating moderate-to-severe inflammatory bowel disease [IBD], many questions on their use remain unanswered. We set up a multi-stakeholder initiative resulting in a position statement. Methods Based on publicly available data, statements on subcutaneous infliximab and vedolizumab were developed and reviewed by 45 Belgian IBD physicians in a three-round modified Delphi process. During a consensus meeting, input from 16 IBD patients, nine IBD nurses and two clinical pharmacologists was provided and statements were further discussed, modified and scored. Statements achieving agreement by at least 70% of the IBD physicians were accepted. Results The Delphi process resulted in 79 agreed statements. In patients initiating intravenous therapy, IBD physicians would only consider switching to subcutaneous formulations in patients achieving both clinical and biological response [for ...

Research paper thumbnail of Introduction of Subcutaneous Infliximab CT-P13 and Vedolizumab in Clinical Practice: A Multi-Stakeholder Position Statement Highlighting the Need for Post-Marketing Studies

Journal of Crohn's and Colitis, 2022

Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are r... more Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are registered for treating moderate-to-severe inflammatory bowel disease [IBD], many questions on their use remain unanswered. We set up a multi-stakeholder initiative resulting in a position statement. Methods Based on publicly available data, statements on subcutaneous infliximab and vedolizumab were developed and reviewed by 45 Belgian IBD physicians in a three-round modified Delphi process. During a consensus meeting, input from 16 IBD patients, nine IBD nurses and two clinical pharmacologists was provided and statements were further discussed, modified and scored. Statements achieving agreement by at least 70% of the IBD physicians were accepted. Results The Delphi process resulted in 79 agreed statements. In patients initiating intravenous therapy, IBD physicians would only consider switching to subcutaneous formulations in patients achieving both clinical and biological response [for ...

Research paper thumbnail of Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis

Cells, 2020

Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopath... more Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 36 ulcerative colitis patients (7 active, with Mayo endoscopic subscore ≥2, and 29 inactive) as compared to 15 non-inflammatory bowel disease controls. Differential gene expression analysis with DESeq2 showed distinct expression patterns depending on disease activity and maximal disease extent. We found 84 dysregulated genes in patients with active extensive colitis and 20 in inactive extensive colitis, compared to controls. There was an overlap of 5 genes: REG1B, REG1A, MUC4, GRAMD2, and CASP10. In patients with left-sided colitis, ileal gene expression levels were similar to controls. Based on gene co-expression analysis, ileal changes in active ulcerative colitis pati...

Research paper thumbnail of Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis

Cells, 2020

Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopath... more Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 36 ulcerative colitis patients (7 active, with Mayo endoscopic subscore ≥2, and 29 inactive) as compared to 15 non-inflammatory bowel disease controls. Differential gene expression analysis with DESeq2 showed distinct expression patterns depending on disease activity and maximal disease extent. We found 84 dysregulated genes in patients with active extensive colitis and 20 in inactive extensive colitis, compared to controls. There was an overlap of 5 genes: REG1B, REG1A, MUC4, GRAMD2, and CASP10. In patients with left-sided colitis, ileal gene expression levels were similar to controls. Based on gene co-expression analysis, ileal changes in active ulcerative colitis pati...

Research paper thumbnail of Long-term outcome of IBD patients with primary non-response to anti-TNF therapy

Journal of Crohns & Colitis, 2015

Research paper thumbnail of Long-term outcome of IBD patients with primary non-response to anti-TNF therapy

Journal of Crohns & Colitis, 2015

Research paper thumbnail of A phase III randomised controlled trial of Cx601, expanded allogeneic adipose-derived mesenchymal stem cells (eASC), for complex perianal fistulas in Crohn's disease

Journal of Crohns & Colitis, 2016

Research paper thumbnail of A phase III randomised controlled trial of Cx601, expanded allogeneic adipose-derived mesenchymal stem cells (eASC), for complex perianal fistulas in Crohn's disease

Journal of Crohns & Colitis, 2016

Research paper thumbnail of S754 Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study

American Journal of Gastroenterology, 2021

Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease ... more Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study Remo Panaccione, MD, FRCP1, Stefan Schreiber, MD2, Laurent Peyrin-Biroulet, MD3, Edward V. Loftus, MD, FACG4, Marla Dubinsky, MD5, Marc Ferrante, MD6, Alexandra Song, PhD7, Bidan Huang, PhD8, Xiaomei Liao, PhD8, Sofie Berg, PhD8, Weijiang R Duan, PhD8, Kori Wallace, PhD8, Brian Feagan, MD9. Inflammatory Bowel Disease Clinic, Gastrointestinal Research, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; University Hospital Schleswig-Holstein, Kiel University, Kiel, Schleswig-Holstein, Germany; University Hospital of Nancy, Lorraine University, Nancy, Lorraine, France; Mayo Clinic, Rochester, MN; Icahn School of Medicine at Mount Sinai, New York, NY; University Hospitals Leuven, Leuven, Luxembourg, Belgium; AbbVie, Inc., North Chicago, IL; AbbVie Inc., North Chicago, IL; Robarts Clinical Trials, Robarts Research Institute, Western University, London, ON, Canada.

Research paper thumbnail of S754 Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study

American Journal of Gastroenterology, 2021

Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease ... more Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study Remo Panaccione, MD, FRCP1, Stefan Schreiber, MD2, Laurent Peyrin-Biroulet, MD3, Edward V. Loftus, MD, FACG4, Marla Dubinsky, MD5, Marc Ferrante, MD6, Alexandra Song, PhD7, Bidan Huang, PhD8, Xiaomei Liao, PhD8, Sofie Berg, PhD8, Weijiang R Duan, PhD8, Kori Wallace, PhD8, Brian Feagan, MD9. Inflammatory Bowel Disease Clinic, Gastrointestinal Research, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; University Hospital Schleswig-Holstein, Kiel University, Kiel, Schleswig-Holstein, Germany; University Hospital of Nancy, Lorraine University, Nancy, Lorraine, France; Mayo Clinic, Rochester, MN; Icahn School of Medicine at Mount Sinai, New York, NY; University Hospitals Leuven, Leuven, Luxembourg, Belgium; AbbVie, Inc., North Chicago, IL; AbbVie Inc., North Chicago, IL; Robarts Clinical Trials, Robarts Research Institute, Western University, London, ON, Canada.

Research paper thumbnail of Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD

Journal of Crohn's and Colitis, 2020

The gut microbiota appears to play a central role in health, and alterations in the gut microbiot... more The gut microbiota appears to play a central role in health, and alterations in the gut microbiota are observed in both forms of inflammatory bowel disease [IBD], namely Crohn’s disease and ulcerative colitis. Yet, the mechanisms behind host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not yet fully understood. Dissecting the role of host-microbiota interactions in disease onset and progression is pivotal, and requires representative models mimicking the gastrointestinal ecosystem, including the intestinal epithelium, the gut microbiota, and immune cells. New advancements in organoid microfluidics technology are facilitating the study of IBD-related microbial-epithelial cross-talk, and the discovery of novel microbial therapies. Here, we review different organoid-based ex vivo models that are currently available, and benchmark their suitability and limitations for specific research questions. Organoid applications, such as patient-derived o...

Research paper thumbnail of Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD

Journal of Crohn's and Colitis, 2020

The gut microbiota appears to play a central role in health, and alterations in the gut microbiot... more The gut microbiota appears to play a central role in health, and alterations in the gut microbiota are observed in both forms of inflammatory bowel disease [IBD], namely Crohn’s disease and ulcerative colitis. Yet, the mechanisms behind host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not yet fully understood. Dissecting the role of host-microbiota interactions in disease onset and progression is pivotal, and requires representative models mimicking the gastrointestinal ecosystem, including the intestinal epithelium, the gut microbiota, and immune cells. New advancements in organoid microfluidics technology are facilitating the study of IBD-related microbial-epithelial cross-talk, and the discovery of novel microbial therapies. Here, we review different organoid-based ex vivo models that are currently available, and benchmark their suitability and limitations for specific research questions. Organoid applications, such as patient-derived o...

Research paper thumbnail of Chronic Antibiotic-Refractory Pouchitis: Management Challenges

Clinical and Experimental Gastroenterology, 2021

Background: Pouchitis is the most common long-term complication in patients with ulcerative colit... more Background: Pouchitis is the most common long-term complication in patients with ulcerative colitis who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. The incidence of acute pouchitis is 20% after 1 year and up to 40% after 5 years. Chronic antibiotic-refractory pouchitis develops in approximately 10% of patients. Aim: To present a narrative review of published literature regarding the management of chronic antibiotic-refractory pouchitis. Methods: Current relevant literature was summarized and critically evaluated. Results: Clear definitions should be used to classify pouchitis into acute versus chronic, and responsive versus dependent versus refractory to antibiotics. Before treatment is started for chronic antibiotic-refractory pouchitis, secondary causes should be ruled out. There is a need for validated scoring systems to measure the severity of the disease. Because chronic antibiotic-refractory pouchitis is a rare condition, only small studies with often a poor study design have been performed. Treatments with antibiotics, aminosalicylates, steroids, immunomodulators and biologics have shown to be effective and safe for chronic antibioticrefractory pouchitis. Also, treatments with AST-120, hyperbaric oxygen therapy, tacrolimus enemas, and granulocyte and monocyte apheresis suggested some efficacy. Conclusion: The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.

Research paper thumbnail of Chronic Antibiotic-Refractory Pouchitis: Management Challenges

Clinical and Experimental Gastroenterology, 2021

Background: Pouchitis is the most common long-term complication in patients with ulcerative colit... more Background: Pouchitis is the most common long-term complication in patients with ulcerative colitis who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. The incidence of acute pouchitis is 20% after 1 year and up to 40% after 5 years. Chronic antibiotic-refractory pouchitis develops in approximately 10% of patients. Aim: To present a narrative review of published literature regarding the management of chronic antibiotic-refractory pouchitis. Methods: Current relevant literature was summarized and critically evaluated. Results: Clear definitions should be used to classify pouchitis into acute versus chronic, and responsive versus dependent versus refractory to antibiotics. Before treatment is started for chronic antibiotic-refractory pouchitis, secondary causes should be ruled out. There is a need for validated scoring systems to measure the severity of the disease. Because chronic antibiotic-refractory pouchitis is a rare condition, only small studies with often a poor study design have been performed. Treatments with antibiotics, aminosalicylates, steroids, immunomodulators and biologics have shown to be effective and safe for chronic antibioticrefractory pouchitis. Also, treatments with AST-120, hyperbaric oxygen therapy, tacrolimus enemas, and granulocyte and monocyte apheresis suggested some efficacy. Conclusion: The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.

Research paper thumbnail of What are the Unmet Needs and Most Relevant Treatment Outcomes According to Patients with Inflammatory Bowel Disease? A Qualitative Patient Preference Study

Journal of Crohn's and Colitis

Background and Aims As more therapeutic options with their own characteristics become available f... more Background and Aims As more therapeutic options with their own characteristics become available for inflammatory bowel disease [IBD], drug development and individual treatment decision-making needs to be tailored towards patients’ preferences and needs. This study aimed to understand patient preferences among IBD patients, and their most important treatment outcomes and unmet needs. Methods This qualitative study consisted of [1] a scoping literature review, [2] two focus group discussions [FGDs] with IBD patients [n = 11] using the nominal group technique, and [3] two expert panel discussions. Results IBD patients discussed a multitude of unmet needs regarding their symptoms, side-effects, and psychological and social issues for which they would welcome improved outcomes. In particular, IBD patients elaborated on the uncertainties and fears they experienced regarding the possible need for surgery or an ostomy, the effectiveness and onset of action of their medication, and the medic...

Research paper thumbnail of What are the Unmet Needs and Most Relevant Treatment Outcomes According to Patients with Inflammatory Bowel Disease? A Qualitative Patient Preference Study

Journal of Crohn's and Colitis

Background and Aims As more therapeutic options with their own characteristics become available f... more Background and Aims As more therapeutic options with their own characteristics become available for inflammatory bowel disease [IBD], drug development and individual treatment decision-making needs to be tailored towards patients’ preferences and needs. This study aimed to understand patient preferences among IBD patients, and their most important treatment outcomes and unmet needs. Methods This qualitative study consisted of [1] a scoping literature review, [2] two focus group discussions [FGDs] with IBD patients [n = 11] using the nominal group technique, and [3] two expert panel discussions. Results IBD patients discussed a multitude of unmet needs regarding their symptoms, side-effects, and psychological and social issues for which they would welcome improved outcomes. In particular, IBD patients elaborated on the uncertainties and fears they experienced regarding the possible need for surgery or an ostomy, the effectiveness and onset of action of their medication, and the medic...

Research paper thumbnail of Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn’s Disease: Results from the Phase 2 Open-Label Extension Study

Journal of Crohn's and Colitis

Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptabl... more Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. Methods Enrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks. Results Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The ra...

Research paper thumbnail of Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn’s Disease: Results from the Phase 2 Open-Label Extension Study

Journal of Crohn's and Colitis

Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptabl... more Background and Aims Risankizumab, an interleukin-23 antibody, demonstrated efficacy and acceptable safety in a phase 2 study of patients with moderate-to-severe refractory Crohn’s disease. This open-label extension investigated the long-term safety, pharmacokinetics, immunogenicity and efficacy of risankizumab in responders to risankizumab in the parent phase 2 study. Methods Enrolled patients had achieved clinical response [decrease in Crohn’s Disease Activity Index from baseline ≥100] without clinical remission [Crohn’s Disease Activity Index <150] at Week 26, or clinical response and/or remission at Week 52 in the parent phase 2 study and received open-label subcutaneous risankizumab 180 mg every 8 weeks. Results Sixty-five patients were enrolled, including four who had lost response in the parent study and were first reinduced with risankizumab 600 mg every 4 weeks [three infusions]. Patients received risankizumab for a median of 33 months [total: 167.0 patient-years]. The ra...

Research paper thumbnail of Patient-reported continuous clinical response to golimumab in adults with moderately to severely active ulcerative colitis: results from GO OBSERVE, a real-world European observational study

European Journal of Gastroenterology & Hepatology

BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcera... more BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcerative colitis (UC). We assessed whether remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores is an effective real-world outcome measure for assessing maintenance of GLM-induced clinical response. METHODS This was a 54-week prospective, observational cohort study conducted at 43 European outpatient clinics in adults with moderate-to-severe UC who were biologic naïve or had received a maximum of one other biological therapy. Patients were treated according to European GLM UC label/local practice. Clinical response (based on partial or full Mayo score) was assessed at week 6, 10, or 14 of induction, depending on local practice. Investigators remotely monitored scores every 4 weeks. The primary endpoint was the proportion of induction responders in patient-reported continuous clinical response (pCCR) at week 54, defined as absence of UC flare based on combined patient-reported Mayo stool frequency and rectal bleeding scores every 4 weeks and full or partial Mayo score. A key secondary endpoint was the proportion of induction responders in clinical remission at week 54. RESULTS Among 109 patients, 37 (34.0%) received at least two GLM induction doses and completed induction in clinical response (induction responders). At week 54, 15/37 (40.5%) induction responders were in pCCR, and 21/37 (56.8%) were in clinical remission. CONCLUSION In daily clinical practice, regular remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores appears to be a meaningful real-world outcome measure for monitoring maintenance of GLM-induced clinical response in UC.

Research paper thumbnail of Patient-reported continuous clinical response to golimumab in adults with moderately to severely active ulcerative colitis: results from GO OBSERVE, a real-world European observational study

European Journal of Gastroenterology & Hepatology

BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcera... more BACKGROUND In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcerative colitis (UC). We assessed whether remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores is an effective real-world outcome measure for assessing maintenance of GLM-induced clinical response. METHODS This was a 54-week prospective, observational cohort study conducted at 43 European outpatient clinics in adults with moderate-to-severe UC who were biologic naïve or had received a maximum of one other biological therapy. Patients were treated according to European GLM UC label/local practice. Clinical response (based on partial or full Mayo score) was assessed at week 6, 10, or 14 of induction, depending on local practice. Investigators remotely monitored scores every 4 weeks. The primary endpoint was the proportion of induction responders in patient-reported continuous clinical response (pCCR) at week 54, defined as absence of UC flare based on combined patient-reported Mayo stool frequency and rectal bleeding scores every 4 weeks and full or partial Mayo score. A key secondary endpoint was the proportion of induction responders in clinical remission at week 54. RESULTS Among 109 patients, 37 (34.0%) received at least two GLM induction doses and completed induction in clinical response (induction responders). At week 54, 15/37 (40.5%) induction responders were in pCCR, and 21/37 (56.8%) were in clinical remission. CONCLUSION In daily clinical practice, regular remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores appears to be a meaningful real-world outcome measure for monitoring maintenance of GLM-induced clinical response in UC.

Research paper thumbnail of Introduction of Subcutaneous Infliximab CT-P13 and Vedolizumab in Clinical Practice: A Multi-Stakeholder Position Statement Highlighting the Need for Post-Marketing Studies

Journal of Crohn's and Colitis, 2022

Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are r... more Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are registered for treating moderate-to-severe inflammatory bowel disease [IBD], many questions on their use remain unanswered. We set up a multi-stakeholder initiative resulting in a position statement. Methods Based on publicly available data, statements on subcutaneous infliximab and vedolizumab were developed and reviewed by 45 Belgian IBD physicians in a three-round modified Delphi process. During a consensus meeting, input from 16 IBD patients, nine IBD nurses and two clinical pharmacologists was provided and statements were further discussed, modified and scored. Statements achieving agreement by at least 70% of the IBD physicians were accepted. Results The Delphi process resulted in 79 agreed statements. In patients initiating intravenous therapy, IBD physicians would only consider switching to subcutaneous formulations in patients achieving both clinical and biological response [for ...

Research paper thumbnail of Introduction of Subcutaneous Infliximab CT-P13 and Vedolizumab in Clinical Practice: A Multi-Stakeholder Position Statement Highlighting the Need for Post-Marketing Studies

Journal of Crohn's and Colitis, 2022

Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are r... more Background and Aims Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are registered for treating moderate-to-severe inflammatory bowel disease [IBD], many questions on their use remain unanswered. We set up a multi-stakeholder initiative resulting in a position statement. Methods Based on publicly available data, statements on subcutaneous infliximab and vedolizumab were developed and reviewed by 45 Belgian IBD physicians in a three-round modified Delphi process. During a consensus meeting, input from 16 IBD patients, nine IBD nurses and two clinical pharmacologists was provided and statements were further discussed, modified and scored. Statements achieving agreement by at least 70% of the IBD physicians were accepted. Results The Delphi process resulted in 79 agreed statements. In patients initiating intravenous therapy, IBD physicians would only consider switching to subcutaneous formulations in patients achieving both clinical and biological response [for ...

Research paper thumbnail of Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis

Cells, 2020

Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopath... more Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 36 ulcerative colitis patients (7 active, with Mayo endoscopic subscore ≥2, and 29 inactive) as compared to 15 non-inflammatory bowel disease controls. Differential gene expression analysis with DESeq2 showed distinct expression patterns depending on disease activity and maximal disease extent. We found 84 dysregulated genes in patients with active extensive colitis and 20 in inactive extensive colitis, compared to controls. There was an overlap of 5 genes: REG1B, REG1A, MUC4, GRAMD2, and CASP10. In patients with left-sided colitis, ileal gene expression levels were similar to controls. Based on gene co-expression analysis, ileal changes in active ulcerative colitis pati...

Research paper thumbnail of Molecular Changes in the Non-Inflamed Terminal Ileum of Patients with Ulcerative Colitis

Cells, 2020

Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopath... more Ulcerative colitis is a chronic inflammatory disease confined to the colon. Although the etiopathogenesis remains unknown, small bowel dysfunctions like histological and permeability alterations have been described in ulcerative colitis. We evaluated the molecular gene signature in the non-inflamed terminal ileum of 36 ulcerative colitis patients (7 active, with Mayo endoscopic subscore ≥2, and 29 inactive) as compared to 15 non-inflammatory bowel disease controls. Differential gene expression analysis with DESeq2 showed distinct expression patterns depending on disease activity and maximal disease extent. We found 84 dysregulated genes in patients with active extensive colitis and 20 in inactive extensive colitis, compared to controls. There was an overlap of 5 genes: REG1B, REG1A, MUC4, GRAMD2, and CASP10. In patients with left-sided colitis, ileal gene expression levels were similar to controls. Based on gene co-expression analysis, ileal changes in active ulcerative colitis pati...

Research paper thumbnail of Long-term outcome of IBD patients with primary non-response to anti-TNF therapy

Journal of Crohns & Colitis, 2015

Research paper thumbnail of Long-term outcome of IBD patients with primary non-response to anti-TNF therapy

Journal of Crohns & Colitis, 2015

Research paper thumbnail of A phase III randomised controlled trial of Cx601, expanded allogeneic adipose-derived mesenchymal stem cells (eASC), for complex perianal fistulas in Crohn's disease

Journal of Crohns & Colitis, 2016

Research paper thumbnail of A phase III randomised controlled trial of Cx601, expanded allogeneic adipose-derived mesenchymal stem cells (eASC), for complex perianal fistulas in Crohn's disease

Journal of Crohns & Colitis, 2016

Research paper thumbnail of S754 Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study

American Journal of Gastroenterology, 2021

Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease ... more Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study Remo Panaccione, MD, FRCP1, Stefan Schreiber, MD2, Laurent Peyrin-Biroulet, MD3, Edward V. Loftus, MD, FACG4, Marla Dubinsky, MD5, Marc Ferrante, MD6, Alexandra Song, PhD7, Bidan Huang, PhD8, Xiaomei Liao, PhD8, Sofie Berg, PhD8, Weijiang R Duan, PhD8, Kori Wallace, PhD8, Brian Feagan, MD9. Inflammatory Bowel Disease Clinic, Gastrointestinal Research, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; University Hospital Schleswig-Holstein, Kiel University, Kiel, Schleswig-Holstein, Germany; University Hospital of Nancy, Lorraine University, Nancy, Lorraine, France; Mayo Clinic, Rochester, MN; Icahn School of Medicine at Mount Sinai, New York, NY; University Hospitals Leuven, Leuven, Luxembourg, Belgium; AbbVie, Inc., North Chicago, IL; AbbVie Inc., North Chicago, IL; Robarts Clinical Trials, Robarts Research Institute, Western University, London, ON, Canada.

Research paper thumbnail of S754 Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study

American Journal of Gastroenterology, 2021

Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease ... more Risankizumab as Induction Therapy in Patients with Moderately to Severely Active Crohn’s Disease Who Failed 1 vs >1 Prior Biologic Treatment: Results From the MOTIVATE Study Remo Panaccione, MD, FRCP1, Stefan Schreiber, MD2, Laurent Peyrin-Biroulet, MD3, Edward V. Loftus, MD, FACG4, Marla Dubinsky, MD5, Marc Ferrante, MD6, Alexandra Song, PhD7, Bidan Huang, PhD8, Xiaomei Liao, PhD8, Sofie Berg, PhD8, Weijiang R Duan, PhD8, Kori Wallace, PhD8, Brian Feagan, MD9. Inflammatory Bowel Disease Clinic, Gastrointestinal Research, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; University Hospital Schleswig-Holstein, Kiel University, Kiel, Schleswig-Holstein, Germany; University Hospital of Nancy, Lorraine University, Nancy, Lorraine, France; Mayo Clinic, Rochester, MN; Icahn School of Medicine at Mount Sinai, New York, NY; University Hospitals Leuven, Leuven, Luxembourg, Belgium; AbbVie, Inc., North Chicago, IL; AbbVie Inc., North Chicago, IL; Robarts Clinical Trials, Robarts Research Institute, Western University, London, ON, Canada.

Research paper thumbnail of Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD

Journal of Crohn's and Colitis, 2020

The gut microbiota appears to play a central role in health, and alterations in the gut microbiot... more The gut microbiota appears to play a central role in health, and alterations in the gut microbiota are observed in both forms of inflammatory bowel disease [IBD], namely Crohn’s disease and ulcerative colitis. Yet, the mechanisms behind host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not yet fully understood. Dissecting the role of host-microbiota interactions in disease onset and progression is pivotal, and requires representative models mimicking the gastrointestinal ecosystem, including the intestinal epithelium, the gut microbiota, and immune cells. New advancements in organoid microfluidics technology are facilitating the study of IBD-related microbial-epithelial cross-talk, and the discovery of novel microbial therapies. Here, we review different organoid-based ex vivo models that are currently available, and benchmark their suitability and limitations for specific research questions. Organoid applications, such as patient-derived o...

Research paper thumbnail of Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD

Journal of Crohn's and Colitis, 2020

The gut microbiota appears to play a central role in health, and alterations in the gut microbiot... more The gut microbiota appears to play a central role in health, and alterations in the gut microbiota are observed in both forms of inflammatory bowel disease [IBD], namely Crohn’s disease and ulcerative colitis. Yet, the mechanisms behind host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not yet fully understood. Dissecting the role of host-microbiota interactions in disease onset and progression is pivotal, and requires representative models mimicking the gastrointestinal ecosystem, including the intestinal epithelium, the gut microbiota, and immune cells. New advancements in organoid microfluidics technology are facilitating the study of IBD-related microbial-epithelial cross-talk, and the discovery of novel microbial therapies. Here, we review different organoid-based ex vivo models that are currently available, and benchmark their suitability and limitations for specific research questions. Organoid applications, such as patient-derived o...

Research paper thumbnail of Chronic Antibiotic-Refractory Pouchitis: Management Challenges

Clinical and Experimental Gastroenterology, 2021

Background: Pouchitis is the most common long-term complication in patients with ulcerative colit... more Background: Pouchitis is the most common long-term complication in patients with ulcerative colitis who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. The incidence of acute pouchitis is 20% after 1 year and up to 40% after 5 years. Chronic antibiotic-refractory pouchitis develops in approximately 10% of patients. Aim: To present a narrative review of published literature regarding the management of chronic antibiotic-refractory pouchitis. Methods: Current relevant literature was summarized and critically evaluated. Results: Clear definitions should be used to classify pouchitis into acute versus chronic, and responsive versus dependent versus refractory to antibiotics. Before treatment is started for chronic antibiotic-refractory pouchitis, secondary causes should be ruled out. There is a need for validated scoring systems to measure the severity of the disease. Because chronic antibiotic-refractory pouchitis is a rare condition, only small studies with often a poor study design have been performed. Treatments with antibiotics, aminosalicylates, steroids, immunomodulators and biologics have shown to be effective and safe for chronic antibioticrefractory pouchitis. Also, treatments with AST-120, hyperbaric oxygen therapy, tacrolimus enemas, and granulocyte and monocyte apheresis suggested some efficacy. Conclusion: The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.

Research paper thumbnail of Chronic Antibiotic-Refractory Pouchitis: Management Challenges

Clinical and Experimental Gastroenterology, 2021

Background: Pouchitis is the most common long-term complication in patients with ulcerative colit... more Background: Pouchitis is the most common long-term complication in patients with ulcerative colitis who underwent restorative proctocolectomy with ileal pouch-anal anastomosis. The incidence of acute pouchitis is 20% after 1 year and up to 40% after 5 years. Chronic antibiotic-refractory pouchitis develops in approximately 10% of patients. Aim: To present a narrative review of published literature regarding the management of chronic antibiotic-refractory pouchitis. Methods: Current relevant literature was summarized and critically evaluated. Results: Clear definitions should be used to classify pouchitis into acute versus chronic, and responsive versus dependent versus refractory to antibiotics. Before treatment is started for chronic antibiotic-refractory pouchitis, secondary causes should be ruled out. There is a need for validated scoring systems to measure the severity of the disease. Because chronic antibiotic-refractory pouchitis is a rare condition, only small studies with often a poor study design have been performed. Treatments with antibiotics, aminosalicylates, steroids, immunomodulators and biologics have shown to be effective and safe for chronic antibioticrefractory pouchitis. Also, treatments with AST-120, hyperbaric oxygen therapy, tacrolimus enemas, and granulocyte and monocyte apheresis suggested some efficacy. Conclusion: The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.