Pub Date : 2023-06-28DOI: 10.58931/cibdt.2023.1213
Jennifer Lipson
As clinicians’ knowledge about the relationship between inflammatory bowel diseases (IBDs) and the integumentary system continues to expand, gastroenterologists and dermatologists need to know about the disease associations involved and understand the impact of treatments on these immune conditions in order to provide care to these medically complex patients.
{"title":"Cutaneous manifestations of inflammatory bowel disease","authors":"Jennifer Lipson","doi":"10.58931/cibdt.2023.1213","DOIUrl":"https://doi.org/10.58931/cibdt.2023.1213","url":null,"abstract":"As clinicians’ knowledge about the relationship between inflammatory bowel diseases (IBDs) and the integumentary system continues to expand, gastroenterologists and dermatologists need to know about the disease associations involved and understand the impact of treatments on these immune conditions in order to provide care to these medically complex patients.","PeriodicalId":104720,"journal":{"name":"Canadian IBD Today","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126548279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-11DOI: 10.58931/cibdt.2023.1s0510
Christopher Ma
Targeting Th17-mediated inflammatory pathways through inhibition of interleukin (IL)-23 has emerged as an important therapeutic mechanism for patients with inflammatory bowel disease. Ustekinumab, a monoclonal antibody blocking both IL-12 and IL-23, was the first agent approved by Health Canada with this mechanism of action, initially for Crohn’s disease (CD) in 2016 and subsequently for ulcerative colitis (UC) in 2020. Over the past decade, there has been increasing attention focused on selectively blocking IL-23, as the key activator of pathogenic Th17 inflammatory cells. Several monoclonal antibodies that target the unique p19 subunit of IL-23 (IL23p19 antagonists) have been developed for psoriasis and psoriatic arthritis, where IL-23 specific blockade results in substantially greater efficacy compared to targeting IL-12/23. The first IL23p19 antagonist, risankizumab, has recently been approved in Canada for the treatment of moderate-to-severely active CD. Here, we describe the mechanism of action of risankizumab and how it differentiates from ustekinumab; review the pivotal clinical trial data that demonstrates the ability of risankizumab to achieve relevant clinical and endoscopic endpoints in both biologic treatment naïve and exposed patients; and summarize key safety data that helps inform decisions about the benefit-risk profile of this novel therapy.
{"title":"Targeting IL23p19 using risankizumab for the management of moderate-to-severely active Crohn's disease","authors":"Christopher Ma","doi":"10.58931/cibdt.2023.1s0510","DOIUrl":"https://doi.org/10.58931/cibdt.2023.1s0510","url":null,"abstract":"\u0000\u0000\u0000Targeting Th17-mediated inflammatory pathways through inhibition of interleukin (IL)-23 has emerged as an important therapeutic mechanism for patients with inflammatory bowel disease. Ustekinumab, a monoclonal antibody blocking both IL-12 and IL-23, was the first agent approved by Health Canada with this mechanism of action, initially for Crohn’s disease (CD) in 2016 and subsequently for ulcerative colitis (UC) in 2020. Over the past decade, there has been increasing attention focused on selectively blocking IL-23, as the key activator of pathogenic Th17 inflammatory cells. Several monoclonal antibodies that target the unique p19 subunit of IL-23 (IL23p19 antagonists) have been developed for psoriasis and psoriatic arthritis, where IL-23 specific blockade results in substantially greater efficacy compared to targeting IL-12/23. The first IL23p19 antagonist, risankizumab, has recently been approved in Canada for the treatment of moderate-to-severely active CD. Here, we describe the mechanism of action of risankizumab and how it differentiates from ustekinumab; review the pivotal clinical trial data that demonstrates the ability of risankizumab to achieve relevant clinical and endoscopic endpoints in both biologic treatment naïve and exposed patients; and summarize key safety data that helps inform decisions about the benefit-risk profile of this novel therapy.\u0000\u0000\u0000","PeriodicalId":104720,"journal":{"name":"Canadian IBD Today","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133964401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Inflammatory bowel disease (IBD) affects over 6.8 million people worldwide and is highly associated with the development of malnutrition. Malnutrition in patients with Crohn’s disease (CD) and ulcerative colitis (UC) is often due to the following: decreased oral intake; food avoidance; side effects of medications; malabsorption; chronic enteric losses; altered anatomy from luminal surgery; and increased nutritional needs in the setting of active inflammation and a high catabolic state. Approximately 20%-80% of patients with IBD are estimated to be malnourished at some point during their disease course; this wide range is likely secondary to significant heterogeneity in the definition of malnutrition in the literature, and due to the lack of robust, validated tools to identify individuals who are malnourished. While malnutrition is traditionally thought of as under- nutrition or protein calorie malnutrition, there are other nutrition phenotypes of significance in patients with IBD including micronutrient deficiencies, sarcopenia and obesity (over-nutrition). Malnutrition is associated with poor outcomes in patients with IBD, including a high number of disease flares; impaired response to biologics; increased surgical complications; hospitalizations; and impaired quality of life, independent of disease activity. Given the significant prevalence of malnutrition, the impact it can have in patients with IBD, and its responsiveness to therapeutic interventions, it is crucial to accurately assess the nutritional status of patients at the time of diagnosis and regularly thereafter.
{"title":"Malnutrition assessment in patients with inflammatory bowel disease","authors":"Stephanie L Gold, M. Raman","doi":"10.58931/cibdt.2023.119","DOIUrl":"https://doi.org/10.58931/cibdt.2023.119","url":null,"abstract":"\u0000 \u0000 \u0000Inflammatory bowel disease (IBD) affects over 6.8 million people worldwide and is highly associated with the development of malnutrition. Malnutrition in patients with Crohn’s disease (CD) and ulcerative colitis (UC) is often due to the following: decreased oral intake; food avoidance; side effects of medications; malabsorption; chronic enteric losses; altered anatomy from luminal surgery; and increased nutritional needs in the setting of active inflammation and a high catabolic state. Approximately 20%-80% of patients with IBD are estimated to be malnourished at some point during their disease course; this wide range is likely secondary to significant heterogeneity in the definition of malnutrition in the literature, and due to the lack of robust, validated tools to identify individuals who are malnourished. While malnutrition is traditionally thought of as under- nutrition or protein calorie malnutrition, there are other nutrition phenotypes of significance in patients with IBD including micronutrient deficiencies, sarcopenia and obesity (over-nutrition). Malnutrition is associated with poor outcomes in patients with IBD, including a high number of disease flares; impaired response to biologics; increased surgical complications; hospitalizations; and impaired quality of life, independent of disease activity. Given the significant prevalence of malnutrition, the impact it can have in patients with IBD, and its responsiveness to therapeutic interventions, it is crucial to accurately assess the nutritional status of patients at the time of diagnosis and regularly thereafter. \u0000 \u0000 \u0000","PeriodicalId":104720,"journal":{"name":"Canadian IBD Today","volume":"29 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"117145895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Biologics have revolutionized the management of patients with inflammatory bowel disease (IBD), in both ulcerative colitis (UC) and Crohn’s disease (CD). There are several classes of biologics used to treat IBD, including monoclonal antibodies directed against TNF, integrin, IL12/23, and IL-23 monoclonal antibodies. Despite the effectiveness of anti-TNF medications, approximately 30% of patients are primary non-responders (PNR), and another 50% lose response over time (secondary loss of response [SLR]). Therapeutic drug monitoring (TDM) provides a tool for biologic dose optimization by measuring drug trough concentrations and anti-drug antibodies (ADA). Drug concentrations are positively correlated to therapeutic benefits, but questions remain on how, when and for whom to perform TDM. Successful implementation is challenged by several factors such as variations in optimal drug targets, different types of drug detection assays, individual pharmacokinetics, and disease severity. Over recent years, various expert groups have provided guidelines on reactive TDM of anti-TNF therapies; however, a knowledge gap still exists on the role of proactive TDM, as well as reactive TDM for non-anti-TNF biologics. The most recent and comprehensive expert consensus statement published in the American Journal of Gastroenterology (AJG), attempted to fill this gap by advocating for the use of reactive TDM for anti-TNF medications, as well as for proactive TDM in certain scenarios.
{"title":"Therapeutic drug monitoring of biologics in inflammatory bowel disease","authors":"W. Afif, Arti Wongcha-um","doi":"10.58931/cibdt.2023.117","DOIUrl":"https://doi.org/10.58931/cibdt.2023.117","url":null,"abstract":"\u0000 \u0000 \u0000Biologics have revolutionized the management of patients with inflammatory bowel disease (IBD), in both ulcerative colitis (UC) and Crohn’s disease (CD). There are several classes of biologics used to treat IBD, including monoclonal antibodies directed against TNF, integrin, IL12/23, and IL-23 monoclonal antibodies. Despite the effectiveness of anti-TNF medications, approximately 30% of patients are primary non-responders (PNR), and another 50% lose response over time (secondary loss of response [SLR]). Therapeutic drug monitoring (TDM) provides a tool for biologic dose optimization by measuring drug trough concentrations and anti-drug antibodies (ADA). Drug concentrations are positively correlated to therapeutic benefits, but questions remain on how, when and for whom to perform TDM. Successful implementation is challenged by several factors such as variations in optimal drug targets, different types of drug detection assays, individual pharmacokinetics, and disease severity. Over recent years, various expert groups have provided guidelines on reactive TDM of anti-TNF therapies; however, a knowledge gap still exists on the role of proactive TDM, as well as reactive TDM for non-anti-TNF biologics. The most recent and comprehensive expert consensus statement published in the American Journal of Gastroenterology (AJG), attempted to fill this gap by advocating for the use of reactive TDM for anti-TNF medications, as well as for proactive TDM in certain scenarios. \u0000 \u0000 \u0000","PeriodicalId":104720,"journal":{"name":"Canadian IBD Today","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133893039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ileal pouch anal anastomosis (IPAA) is a surgical procedure conducted in patients with ulcerative colitis (UC) with medically refractory disease; in patients with the autosomal dominant inherited disease familial adenomatous polyposis (FAP); or in patients who have experienced dysplasia/colon cancer. The procedure aids in the management of these diseases, improves patients’ quality of life, prevents the need for a permanent stoma, and reduces the risk of colorectal cancer. A common complication from IPAA is pouchitis, which is characterized as an idiopathic non-specific inflammation within the created pouch resulting in symptoms including increased frequency of bowel movements and abdominal pain. Pouchitis is much more common in patients treated for UC (up to 60%) than in those receiving treatment for other indications (0-10%). This might be due to immune activation or dysbiosis in these patients.
{"title":"Management of pouchitis: Clinical pearls for the gastroenterologist","authors":"N. Narula","doi":"10.58931/cibdt.2023.116","DOIUrl":"https://doi.org/10.58931/cibdt.2023.116","url":null,"abstract":"\u0000 \u0000 \u0000Ileal pouch anal anastomosis (IPAA) is a surgical procedure conducted in patients with ulcerative colitis (UC) with medically refractory disease; in patients with the autosomal dominant inherited disease familial adenomatous polyposis (FAP); or in patients who have experienced dysplasia/colon cancer. The procedure aids in the management of these diseases, improves patients’ quality of life, prevents the need for a permanent stoma, and reduces the risk of colorectal cancer. A common complication from IPAA is pouchitis, which is characterized as an idiopathic non-specific inflammation within the created pouch resulting in symptoms including increased frequency of bowel movements and abdominal pain. Pouchitis is much more common in patients treated for UC (up to 60%) than in those receiving treatment for other indications (0-10%). This might be due to immune activation or dysbiosis in these patients. \u0000 \u0000 \u0000","PeriodicalId":104720,"journal":{"name":"Canadian IBD Today","volume":"160 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132480588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The most common extraintestinal manifestation of inflammatory bowel disease (IBD) is arthropathy. These conditions have been reported in up to 50% of patients with IBD and are more common in Crohn’s’ disease (CD), particularly colonic disease, and in females. IBD-associated arthritis is classified as a type of spondyloarthritis (SpA). The treatment is dependent on the type of SpA involvement, which can be subdivided into peripheral and/or axial disease. The treatment approach consists of a combination of non-pharmacological and pharmacological therapies managed by a multidisciplinary team and is based on collaborative decisions between gastroenterology and rheumatology. In light of rapidly expanding therapeutic armamentaria for both immune-mediated arthritis and IBD, this paper will provide an overview of an approach to the treatment of arthritis associated with IBD, considering recommendations by recent guidelines and novel therapies.
{"title":"Approach to management of inflammatory bowel disease-related arthritis","authors":"M. Choi, Dianne Mosher","doi":"10.58931/cibdt.2023.118","DOIUrl":"https://doi.org/10.58931/cibdt.2023.118","url":null,"abstract":"\u0000 \u0000 \u0000The most common extraintestinal manifestation of inflammatory bowel disease (IBD) is arthropathy. These conditions have been reported in up to 50% of patients with IBD and are more common in Crohn’s’ disease (CD), particularly colonic disease, and in females. \u0000IBD-associated arthritis is classified as a type of spondyloarthritis (SpA). The treatment is dependent on the type of SpA involvement, which can be subdivided into peripheral and/or axial disease. The treatment approach consists of a combination of non-pharmacological and pharmacological therapies managed by a multidisciplinary team and is based on collaborative decisions between gastroenterology and rheumatology. In light of rapidly expanding therapeutic armamentaria for both immune-mediated arthritis and IBD, this paper will provide an overview of an approach to the treatment of arthritis associated with IBD, considering recommendations by recent guidelines and novel therapies. \u0000 \u0000 \u0000","PeriodicalId":104720,"journal":{"name":"Canadian IBD Today","volume":"52 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128323300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the past decade, Janus kinase (JAK) inhibitors have been developed for the treatment of several immune-mediated inflammatory diseases, including ulcerative colitis (UC) and Crohn’s disease (CD). The JAK-signal transducer and activator of transcription (STAT) pathway plays an essential role in coordinating the human immune response. Phosphorylation and activation of the JAK family of tyrosine kinases results in subsequent activation of intracytoplasmic STAT pathways with upregulation of inflammatory gene transcription. Blocking this signalling results in broad-spectrum immunosuppression, which is effective in the treatment of rheumatoid arthritis (RA), psoriasis, atopic dermatitis, and inflammatory bowel disease (IBD). To date, three oral, small-molecule JAK inhibitors (tofacitinib, filgotinib, and upadacitinib) have received regulatory approval in various jurisdictions globally for the treatment of moderate-to-severely active UC. It is anticipated that upadacitinib will soon become the first novel, advanced oral small molecule therapy approved for moderate-to-severely active CD. While these agents are highly effective, emerging data has highlighted potentially relevant safety signals associated with JAK inhibitors, and that the therapeutic index of these therapies may be distinct from that of monoclonal antibodies. Therefore, JAK inhibitors have a unique position in the therapeutic armamentarium for IBD. Here, we summarize the evidence supporting the use of JAK inhibitors and provide an overview of their practical applications in clinical care.
{"title":"JAK inhibitors for the treatment of inflammatory bowel disease","authors":"Christopher Ma","doi":"10.58931/cibdt.2023.115","DOIUrl":"https://doi.org/10.58931/cibdt.2023.115","url":null,"abstract":"\u0000 \u0000 \u0000Over the past decade, Janus kinase (JAK) inhibitors have been developed for the treatment of several immune-mediated inflammatory diseases, including ulcerative colitis (UC) and Crohn’s disease (CD). The JAK-signal transducer and activator of transcription (STAT) pathway plays an essential role in coordinating the human immune response. Phosphorylation and activation of the JAK family of tyrosine kinases results in subsequent activation of intracytoplasmic STAT pathways with upregulation of inflammatory gene transcription. Blocking this signalling results in broad-spectrum immunosuppression, which is effective in the treatment of rheumatoid arthritis (RA), psoriasis, atopic dermatitis, and inflammatory bowel disease (IBD). To date, three oral, small-molecule JAK inhibitors (tofacitinib, filgotinib, and upadacitinib) have received regulatory approval in various jurisdictions globally for the treatment of moderate-to-severely active UC. It is anticipated that upadacitinib will soon become the first novel, advanced oral small molecule therapy approved for moderate-to-severely active CD. While these agents are highly effective, emerging data has highlighted potentially relevant safety signals associated with JAK inhibitors, and that the therapeutic index of these therapies may be distinct from that of monoclonal antibodies. Therefore, JAK inhibitors have a unique position in the therapeutic armamentarium for IBD. Here, we summarize the evidence supporting the use of JAK inhibitors and provide an overview of their practical applications in clinical care. \u0000 \u0000 \u0000","PeriodicalId":104720,"journal":{"name":"Canadian IBD Today","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130905538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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