Biologics, small molecule therapies and surgery in small bowel Crohn's disease.

PURPOSE OF REVIEW: The terminal ileum and small bowel (SB) are involved in 30-45% of patients with Crohn's disease, while 20% have both small and large bowel involvement. Ileal Crohn's is associated with higher risk of progression to stricturing and penetrating disease 1 , hence it's imperative to utilize effective therapies to induce and maintain clinical and endoscopic remission and prevent intestinal complications. We review the available data of biologics and upadacitinib in small bowel disease, and the emerging data on the role of surgery as first line therapy for isolated Crohn's ileitis. RECENT FINDINGS: Most trials assessing drug efficacy do not report efficacy by disease location, and robust data on efficacy of therapies in isolated small bowel Crohn's is sparse. Several studies indicate that small bowel disease is generally less responsive to biologics, and could require higher drug trough levels to achieve endoscopic healing. SUMMARY: Current therapies for induction and maintenance of remission in moderate to severe Crohn's disease include several classes of monoclonal antibodies and a Janus Kinase inhibitor, upadacitinib. While small bowel Crohn's disease is generally less responsive to treatment, anti-TNFs are still preferred as first line therapy, and the option of early ileocecal resection in early limited ileal disease is gaining interest.

Pregnancy and medications for inflammatory bowel disease: An updated narrative review.

Inflammatory bowel disease (IBD) is often diagnosed during the peak reproductive years of young women. Women with active IBD around conception are at a significantly increased risk of disease relapse during pregnancy, which is associated with poor pregnancy and neonatal outcomes. Given these substantial risks, it is prudent that disease remission should ideally be achieved before conception. Unfortunately, some patients may experience a disease flare-up even if they are in a state of remission before pregnancy. Patients must continue their IBD medications to reduce the risk of disease flare and subsequent poor outcomes during the gestational and postpartum periods. When treating IBD flare-ups during pregnancy, the management is quite similar to the therapeutic approach for non-pregnant patients with IBD, including 5-aminosalicylate, steroids, calcineurin inhibitors (CNIs), and biologic therapies. While the data regarding the safety of CNIs in pregnant women with IBD is limited, the findings in our recent meta-analysis suggest that CNIs may be safer to use in those with IBD than in solid organ transplant recipients. There are several types of biologics and small-molecule therapies currently approved for IBD, and physicians should thoroughly understand their clinical benefits and safety profiles when utilizing these treatments in the context of pregnancy. This review highlights recent studies, including our systematic review and meta-analysis, and discusses the clinical advantages and safety considerations of biologics and small molecules for pregnant women with IBD.

Endo-histologic Normalization Is Achievable with Tofacitinib and Is Associated with Improved Clinical Outcomes.

BACKGROUND: Recent real-world effectiveness studies investigating tofacitinib have been encouraging. Questions remain regarding the long-term effectiveness and safety of tofacitinib, effect on endoscopic remission rates, histologic changes, and alterations in fecal calprotectin levels. METHODS: This retrospective study includes consecutive patients with inflammatory bowel disease (IBD) who initiated tofacitinib therapy. We reviewed electronic medical records for demographic and clinical data, as well as all adverse events and hospitalizations. All patients receiving tofacitinib were included in the safety analysis and only patients with ulcerative colitis (UC) were included in the effectiveness analysis. RESULTS: 119 patients with IBD (97 UC, 12 CD, and 10 pouchitis) seen at our center between 2014 and 2020 were included in this study. Median follow-up was 32 weeks (interquartile range (IQR) 3-252). Clinical response and remission were observed in 70% and 21%, 59% and 33%, and 49%, and 37% at weeks 8, 24, and 52, respectively. Endo-histologic healing was achieved by 11%, 25%, and 37.5% of patients at weeks 8, 24, and 52, respectively. Histologic normalization occurred as early as 24 weeks in this cohort and was achieved by 26% of patients in endoscopic remission. Overall, there were 27 (25%) adverse events with 6 (5%) resulting in treatment discontinuation. There were 11 (10%) infections, none required treatment discontinuation. Ten (10.3%) patients underwent colectomy during the follow-up period. There were no cardiovascular adverse events in the cohort during follow-up. CONCLUSION: This study demonstrates the effectiveness and long-term safety of tofacitinib in patients with UC. Importantly, we show that the endpoint of endo-histologic healing is achievable with tofacitinib and can occur as early as week 8 of therapy.

Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases.

Patients with inflammatory bowel disease (IBD) are more likely to have concurrent immune-mediated inflammatory diseases (IMIDs) than those without IBD. IMIDs have been observed to alter the phenotype and outcomes of IBD in recent studies. Several studies have found that IBD patients with concurrent IMIDs may have more extensive or severe disease phenotypes, and are considered to be at increased risk of requiring biologics and IBD-related surgeries, suggesting that having multiple IMIDs is a poor prognostic factor for IBD. Furthermore, IBD patients with primary sclerosing cholangitis and Takayasu arteritis are reported to have unique endoscopic phenotypes, suggesting concurrent IMIDs can influence IBD phenotype with specific intestinal inflammatory distributions. In this review, we discuss the pathogenesis, disease phenotypes, and clinical outcomes in IBD patients with concomitant IMIDs.

Evolving roles of magnifying endoscopy and endoscopic resection for neoplasia in inflammatory bowel diseases.

Magnifying endoscopy is a useful technique to differentiate neoplasia from non-neoplastic lesions. Data regarding the clinical utility of magnifying endoscopy for neoplasia in patients with inflammatory bowel disease (IBD) has been emerging. While Kudo's pit pattern types III-V are findings suggestive of neoplasia in non-IBD patients, these pit patterns are predictive of IBD-associated neoplasia as well. However, active chronic inflammatory processes, particularly regenerative changes, can mimic neoplastic pit patterns and may affect a meticulous evaluation of pit pattern diagnosis in patients with IBD. The clinical evidence regarding the utility of magnifying endoscopy with narrow band imaging or endocytoscopy has also been evolving in regard to the diagnosis of IBD-associated neoplasia. These advanced endoscopic techniques are promising for multiple reasons; not only for making an accurate diagnosis of neoplasia, but also in determining if endoscopic resection is appropriate for such lesions in patients with IBD. In this review, we discuss the diagnostic accuracy and limitations of magnifying endoscopy in assessing IBD-associated neoplasia and examine the feasibility and outcomes of endoscopic resection for these lesions.

Hepatotoxicty of Agents Used in the Management of Inflammatory Bowel Disease: a 2020 Update.

PURPOSE OF REVIEW: As treatment options for inflammatory bowel disease (IBD) continue to expand, the opportunity for hepatotoxicity remains a clinical concern. This review looks to update the current literature on drug-induced liver injury (DILI) and liver-related complications from current and emerging treatments for Crohn's disease (CD) and ulcerative colitis (UC). RECENT FINDINGS: An extensive literature review on currently used medications to treat IBD and their liver-related side effects that includes mesalamine, thiopurines, certain antibiotics, methotrexate, anti-TNF agents including recently introduced biosimilars, anti-integrin therapy, anti-IL 12/IL 23 therapy, and small molecule JAK inhibitors. Hepatotoxicity remains an important clinical issue when managing patients with IBD. Clinicians need to remain aware of the potential for liver-related adverse events with various medication classes and adjust their clinical monitoring as appropriate based on the agents being used.

The Management Approach to the Adolescent IBD Patient: Health Maintenance and Medication Considerations.

PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) is often diagnosed during adolescence and can have a deep impact on the physical, hormonal, developmental, and psychosocial changes associated with this life period. The purpose of this review is to address the particular manifestations of IBD (such as growth and pubertal delay), health maintenance issues, and treatment considerations in the adolescent. RECENT FINDINGS: The need for a multidisciplinary approach to recognize and address growth and pubertal delay, bone health, as well as the psychosocial impact of IBD on the adolescent has been increasingly recognized as an integral part of IBD care in this population. Vaccinations schedule, preventive health measures, and promoting compliance with care are particularly important during adolescence. Replacing nutrients deficits is also crucial: in particular, vitamin D has been shown to play a role in the gut immune system, and adequate vitamin D levels might promote IBD remission. Iron replacement should be done by intravenous route since oral iron is poorly absorbed in chronic inflammatory states. Finally, recent data have shed light on the increased risk of particular types of lymphoma in adolescent on thiopurines, whereas biologic therapies, in particular, anti-TNF, now are positioned as a preferred and effective steroid-sparing agents in moderate to severe IBD. Management of adolescents with IBD is not without significant challenges. An early implementation of steroid-sparing therapies, a multidisciplinary treatment approach, and a dynamic physician-patient relationship are essential to achieve remission, prevent disease-related complications but also optimize developmental, physical, and psychosocial health, and encourage compliance and transition to adult care.

Post-endoscopic procedure satisfaction scores: Can we improve?

AIM: To organize post-procedure satisfaction data into a useful reference and analyze patient-centered parameters to find trends that influence patient satisfaction. METHODS: A robust database of two cohorts of outpatients that underwent an endoscopic procedure at Georgetown University Hospital at two separate three-month intervals ranging from November 2012 to January 2013 and November 2015 to January 2016 was compiled. Time of year was identical to control for weather/seasonal issues that may have contributed to the patient experience. The variables recorded included age, sex, body mass index (BMI), type of procedure, indication for procedure, time of the procedure, length of the procedure, type of prep used, endoscopist, satisfactory score, and comments/reasons for score. For continuous variables, differences in averages were tested by two sample t-test, Wilcoxon rank sum test, and ANOVA as appropriate. For categorical variables, differences in proportions between two groups were tested by χ2 test. Correlation test and linear regression analyses were conducted to examine relationships between length of procedure and continuous predictors. A P value < 0.05 used to indicate statistically significant relationship. RESULTS: The primary outcome of this study was to assess if telephone outreach after an endoscopic intervention was a satisfactory method of obtaining post-procedure satisfaction scores from patients at a tertiary care center. With the addition of post-procedure calls, instilled in January 2014, the response rate was 40.5% (508/1256 patients) from a prior completion rate of 3.4% (31/918) with the mail out survey initially. There was a statistically significant improved response rate pre and post intervention with P < 0001. The secondary outcome of this study was to assess if we could use predictive analytics to identify independent predictors of procedure length, such as gender, age, type of procedure, time of procedure, or BMI. The combined pre and post intervention data was used in order to optimize the power to identify independent predictors of procedure length. The total number of patient's data analyzed was 2174. There was no statistically significant difference in procedure length between males and females with P value 0.5282. However, there was a small (1 min), but statistically significant difference (P = 0.0185) in procedure length based on the time of day the procedure took place, with afternoon procedures having a longer duration than morning procedures. The type of procedure was an independent predictor of procedure length as demonstrated with P value < 0.0001. There is a statistically significant correlation between age and procedure length, although it is only a weak relationship with a correlation coefficient < 0.3. Contrary to patient age, BMI did not have a statistically significant correlation with procedure length (P = 0.9993), which was also confirmed by linear regression analysis. CONCLUSION: Our study proves calling patients after endoscopy improves post-procedure satisfaction response rates and changing procedural time allotment based on patient characteristics would not change endoscopic workflow.

Drug-Induced Liver Injury: Highlights from a Review of the 2015 Literature.

Numerous publications contributed to the expanding knowledge base about drug-induced liver injury (DILI) in 2015. New findings from the US Drug Induced Liver Injury Network (DILIN) in their most recently updated registry include a 1- to 3-week delay in the appearance of acute DILI from short-course antibiotics such as cefazolin. They corroborated the finding that acute DILI in patients with underlying liver disease was far more severe and potentially fatal than in patients without liver disease. The only drug that seemed to have an increased risk of hepatotoxicity in these patients was azithromycin. While nearly one in six patients with acute DILI had persistently elevated liver tests at 6 months, and results for 75 % of these patients continued to be abnormal at 12 months, most of these "chronic" injury cases were relatively minor and the result of cholestatic hepatotoxins. Newly described DILI agents include tolvaptan, as well as some new direct-acting antiviral protease inhibitors for chronic hepatitis C. The latter have been associated with serious acute hepatitis, hyperbilirubinemia, and decompensation. Herbal hepatotoxicity continues to be increasingly reported, although applying causality assessment to these cases can, in fact, be more challenging than with prescription drugs. As important as cases with DILI, the class of PCSK9 inhibitors used to lower low-density lipoprotein (LDL) cholesterol have not been associated with significant liver injury, in contrast with other lipid-lowering agents. With respect to pharmacologic DILI risk factors, new data show that drugs metabolized by cytochrome P450 enzymes had a nearly four times higher likelihood of causing DILI. Interestingly, high lipophilicity, which was previously felt to be a risk factor for DILI, was not found to be associated, although more study is needed to confirm this observation. While human leukocyte antigen (HLA) genotypes have been linked to several specific agents, the role of such testing in the general population remains undefined due to the currently low positive and negative predictive values of the available tests. New DILI biomarkers, specifically microRNA-122 and keratin-18, among others, appear to have the necessary predictive value to determine the prognosis and outcome of patients with paracetamol (acetaminophen [AAP])-induced acute liver failure (ALF), and may be of great benefit in deciding who requires N-acetylcysteine (NAC), and for what duration. Treatment options for other forms of DILI remain limited; no firm conclusions can currently be drawn for the use of NAC in non-AAP ALF.