Use of Upadacitinib as Salvage Therapy for Ulcerative Colitis in Pregnancy: A Case Report.

Upadacitinib, a selective JAK-1 inhibitor, was used as rescue therapy for ulcerative colitis in the setting of pregnancy following use of mesalamine, vedolizumab, infliximab, and corticosteroids. This resulted in an uncomplicated live full birth without need for surgical intervention.

Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease.

Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.

Saddle Nose Deformity in a Patient With Crohn's Disease.

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, frequently presenting with extraintestinal manifestations. Granulomatosis with polyangiitis is a systemic vasculitis primarily affecting the respiratory tract and kidneys. Extraintestinal Crohn's disease and granulomatosis with polyangiitis may have similar clinical presentations and, in rare occurrences, can coexist. This case report highlights the diagnostic and therapeutic complexities of this uncommon overlap syndrome.

Neoplasia Diagnosis After Multi-target Stool DNA Is Enhanced Among Lowest Baseline Detectors.

BACKGROUND AND AIMS: Variation in colorectal neoplasia detection limits the effectiveness of screening colonoscopy. By evaluating neoplasia detection rates of individual colonoscopists, we aimed to quantify the effects of pre-procedural knowledge of a positive (+) multi-target stool DNA (mt-sDNA) on colonoscopy quality metrics. METHODS: We retrospectively identified physicians who performed a high volume of + mt-sDNA colonoscopies; colorectal neoplasia at post-mt-sDNA colonoscopy was recorded. These colonoscopists were stratified into quartiles based on baseline adenoma detection rates. Baseline colonoscopy adenoma detection rates and sessile serrated lesion detection rates were compared to post-mt-sDNA colonoscopy neoplasia diagnosis rates among each quartile. Withdrawal times were measured from negative exams. RESULTS: During the study period (2014-17) the highest quartile of physicians by volume of post-mt-sDNA colonoscopies were evaluated. Among thirty-five gastroenterologists, their median screening colonoscopy adenoma detection rate was 32% (IQR, 28-39%) and serrated lesion detection rate was 13% (8-15%). After + mt-sDNA, adenoma diagnosis increased to 47% (36-56%) and serrated lesion diagnosis increased to 31% (17-42%) (both p < 0.0001). Median withdrawal time increased from 10 (7-13) to 12 (10-17) minutes (p < 0.0001) and was proportionate across quartiles. After + mt-sDNA, lower baseline detectors had disproportionately higher rates of adenoma diagnosis in female versus male patients (p = 0.048) and higher serrated neoplasia diagnosis rates among all patients (p = 0.0092). CONCLUSIONS: Knowledge of + mt-sDNA enriches neoplasia diagnosis compared to average risk screening exams. Adenomatous and serrated lesion diagnosis was magnified among those with lower adenoma detection rates. Awareness of the mt-sDNA result may increase physician attention during colonoscopy. Pre-procedure knowledge of a positive mt-sDNA test improves neoplasia diagnosis rates among colonoscopists with lower baseline adenoma detection rates, independent of withdrawal time.

Decreased Risk of Preeclampsia in Women with Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy.

BACKGROUND: Evidence suggests that upregulation of tumor necrosis factor-alpha (TNF-α) plays a role in immune dysregulation in both preeclampsia and inflammatory bowel disease (IBD). AIMS: We aimed to investigate whether anti-TNF therapy during pregnancy decreases the risk of preeclampsia in women with IBD. METHODS: The study population included women with IBD and pregnancies who were followed at a tertiary care center from 2007 to 2021. Cases of preeclampsia were compared with controls with a normotensive pregnancy. Data on patient demographics, disease type and activity, pregnancy complications, and additional risk factors for preeclampsia were collected. The association between anti-TNF therapy and preeclampsia was analyzed using univariate analysis and multivariate logistic regression. RESULTS: Women with preeclampsia were more likely to have a preterm delivery (44% vs. 12%, p < 0.001). More women without preeclampsia were exposed to anti-TNF therapy during pregnancy than women with preeclampsia (55% vs. 30%, p = 0.029). The majority of women (32/44) on anti-TNF therapy, either adalimumab or infliximab, continued to have some degree of exposure during the third trimester. Though not significant, multivariate analysis showed a trend towards a protective effect of anti-TNF therapy against developing preeclampsia if exposed during the third trimester (OR 0.39; 95% CI 0.14-1.12, p = 0.08). CONCLUSIONS: In this study, anti-TNF therapy exposure was higher in IBD patients who did not develop preeclampsia than in those who did. While not significant, there was a trend towards a protective effect of anti-TNF therapy against preeclampsia if exposed during the third trimester.

Clinical advances: pregnancy in gastroenterologic and hepatic conditions.

The fields of gastroenterology and hepatology, along with endoscopic practice, have seen significant changes and innovations to practice in just the past few years. These practice changes are not limited to gastroenterology, but maternal fetal medicine and the care of the pregnant person have become increasingly more sophisticated as well. Gastroenterologists are frequently called on to provide consultative input and/or perform endoscopy during pregnancy. To be able to provide the best possible care to these patients, gastroenterologists need to be aware of (and familiar with) the various nuances and caveats related to the care of pregnant patients who either have underlying gastrointestinal (GI) conditions or present with GI and liver disorders. Here, we offer a clinical update with references more recent than 2018, along with a few words about SARS-CoV-2 infection and its relevance to pregnancy.

Interobserver agreement of the modified Paris classification and histology prediction of colorectal lesions in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: SCENIC (International Consensus Statement on Surveillance and Management of Dysplasia in IBD) guidelines recommend that visible dysplasia in patients with longstanding inflammatory bowel disease (IBD) should be endoscopically characterized using a modified Paris classification. This study aimed to determine the interobserver agreement (IOA) of the modified Paris classification and endoscopists' accuracy for pathology prediction of IBD visible lesions. METHODS: One hundred deidentified endoscopic still images and 30 videos of IBD visible colorectal lesions were graded by 10 senior and 4 trainee endoscopists from 5 tertiary care centers. Endoscopists were asked to assign 4 classifications for each image: the standard Paris classification, modified Paris classification, pathology prediction, and lesion border. Agreement was measured using Light's kappa coefficient. Consensus of ratings was assessed according to strict majority. RESULTS: The overall Light's kappa for all study endpoints was between .32 and .49. In a subgroup analysis between junior and senior endoscopists, Light's kappa continued to be less than .6 with a slightly higher agreement among juniors. Lesions with the lowest agreement and no consensus were mostly classified as Is, IIa, and mixed Paris classification and sessile and superficial elevated for modified Paris classification. Endoscopist accuracy for prediction of dysplastic, nondysplastic, and serrated pathology was 77%, 56%, and 30%, respectively. There was a strong association (P < .001) between the given morphology classification and the predicted pathology with Ip lesions carrying a much lower expectation of dysplasia than Is/IIc/III and mixed lesions. The agreement for border prediction was .5 for junior and .3 for senior endoscopists. CONCLUSIONS: This study demonstrates very low IOA for Paris and modified Paris classifications and low accuracy and IOA for lesion histopathology prediction. Revisions of these classifications are required to create a clinically useful risk stratification tool and enable eventual application of augmented intelligence tools.

Multicentre Real-world Experience of Upadacitinib in the Treatment of Crohn's Disease.

BACKGROUND: Upadacitinib is a selective Janus kinase inhibitor approved for the management of ulcerative colitis and is under evaluation for the management of Crohn's disease [CD] in Phase 3 clinical trials. AIMS: Our goal was to describe our real-world experience with upadacitinib in CD. METHODS: This is a two-centre retrospective cohort study of adult patients with moderate to severe CD on upadacitinib. The primary outcome was clinical response and remission as determined by stool frequency and abdominal pain scores. Secondary endpoints included endoscopic response and remission as determined by change in Simple Endoscopic Score for CD. Outcomes were assessed at 3 months after starting upadacitinib and at the patient's most recent follow-up. We further evaluated adverse events and dose-related response. RESULTS: A total of 45 CD patients received upadacitinib and were included in the safety analysis. Thirty-six patients received upadacitinib for CD, whereas nine received it for inflammatory arthritis [n = 8] or pyoderma [n = 1]. Thirty-three patients received upadacitinib for 3 months or longer and were included in the efficacy analysis. At the 3-month follow-up, 21 patients achieved clinical response [63.6%] and nine achieved clinical remission [27.2%]. At time of last follow-up, 23 patients had clinical response [69.7%], ten achieved clinical remission [30.3%] and four [28.6%] achieved endoscopic remission. Adverse events occurred in 12 patients [26.7%]. Two patients had a serious adverse event [4.5%] without associated mortality. CONCLUSION: In this real-world cohort of highly refractory CD patients, upadacitinib was effective in inducing remission and had an acceptable safety profile.

Pregnancy and Crohn's disease: concerns and assurance of medical therapy.

Approximately 50% of patients with inflammatory bowel disease including both Crohn's disease and ulcerative colitis are female with many being diagnosed and treated during their reproductive years. It is important for women to be in remission prior to and during pregnancy. There have been many advances in the treatment of inflammatory bowel disease, including new therapies. In this review, we summarize the currently approved medications for Crohn's disease and their safety in pregnancy and postpartum. The totality of evidence suggests that the majority of therapies are low-risk before and during pregnancy, and should be continued to control maternal disease.

Inflammatory Bowel Disease and Cardiovascular Diseases.

BACKGROUND: Emerging data showed patients with chronic inflammatory disorders, including inflammatory bowel disease, are more likely to develop atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. This article aims to review the evidence of those associations. METHODS: PubMed was searched from inception to January 2022 using the keywords, including inflammatory bowel diseases, Crohn disease, ulcerative colitis, atherosclerotic cardiovascular disease, coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, and premature coronary artery disease. Relevant literature, including retrospective/prospective cohort studies, clinical trials, meta-analyses, and guidelines, were reviewed and summarized. RESULTS: Both ulcerative colitis and Crohn disease are associated with an increased risk of atherosclerotic cardiovascular diseases, cerebrovascular accidents, premature coronary artery disease, and atrial fibrillation. Ulcerative colitis is associated with an increased risk of heart failure. The increased atrial fibrillation occurred during inflammatory bowel disease flares and persistent activity but not during periods of remission. Hypotheses for the mechanism underlying the association of inflammatory bowel disease and atherosclerotic cardiovascular diseases include shared risk factors (ie, obesity, diabetes, smoking, diet) and pathophysiology (gut microbiome dysfunction) or adverse effects from inflammatory bowel disease itself or its treatment (ie, chronic inflammation, dyslipidemia, thrombocytosis, steroids). CONCLUSION: Inflammatory bowel disease is associated with an increased risk of atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. A multidisciplinary team with gastroenterologists and cardiologists is needed to optimize the care for patients with inflammatory bowel disease and associated cardiac diseases.

A Cohort Study of the Age at Menopause in Female Patients With and Without Inflammatory Bowel Disease.

Background: Menopause, defined by the complete cessation of menstrual cycles for 12 consecutive months, may occur at a younger age in women who have concomitant immune dysregulation. Our aim was to determine whether women with inflammatory bowel disease (IBD) experience an earlier onset of menopause compared to women without IBD. Methods: This was a retrospective cohort study using resources of the Rochester Epidemiology Project, a collaboration between clinics, hospitals, and medical facilities in Olmsted County, Minnesota. From these people, women who were diagnosed with IBD between 1970 and 2010 comprised the case cohort while the reference cohort included women with no diagnosis of IBD. Data including age, body mass index (BMI), ethnicity, smoking status, age at onset of menopause, and current use of hormone therapy were collected. Patients with history of hysterectomy or oophorectomy were excluded. Wilcoxon rank-sum test for numeric variables and Fisher's exact test for categorical variables were used to analyze the data. Results: A total of 171 women met criteria for inclusion (83 cases and 88 controls). Mean age of menopause in women with IBD was 50.0 years compared to 51.5 years in women with no IBD (P = .006). There was no difference in BMI of women with and without IBD (28.7 versus 28.2 kg m-2; P = .9), respectively. There were more former smokers (33.7%) and current (6%) smokers in the IBD group (P = .009) compared to the non-IBD group. Conclusions: IBD is associated with an earlier onset of menopause. Although it is unclear if this mean difference of 1.5 years is clinically relevant, it is known that early menopause is associated with an increased risk of osteoporosis and cardiovascular disease. Further research on the possible mechanisms is needed.

Management of pouch neoplasia: consensus guidelines from the International Ileal Pouch Consortium.

Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise.

Conventional Therapies for Crohn's Disease.

Crohn's disease is a chronic and progressive immune-mediated disease with increasing incidence worldwide. There are no curative therapies. The primary agents used in the treatment of Crohn's disease are aminosalicylates, corticosteroids, immunomodulators, and biologics. Each agent has different roles in the induction and maintenance of remission of disease. The biologics available include anti-TNF agents, anti-integrins, and anti-interleukins. The choice of initial biologic therapy should be determined through shared decision-making between the patient and provider.