Bruining, David H.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49–0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48–0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Abstract Background To describe response to therapy of small bowel (SB) Crohn’s disease (CD) at CT or MR enterography (CTE/MRE) in patients on vedolizumab. Methods Patients with SB CD who underwent CTE/MRE exams greater than 12 months apart on vedolizumab therapy were included. Length (in cm) and inflammation severity (EMBARK score) of inflamed SB segments were assessed. Changes in inflammation length of 3.4 cm or greater or inflammation severity of 2 EMBARK points or greater was categorized as response or progression, as appropriate, with development of newly inflamed segments, strictures, or penetrating complications also indicating progression. Patients not meeting the criteria for response or progression were categorized as having stable disease. Results Of 36 SB CD patients, the large majority had prior surgery (86%; 31), anti-TNF use (92%; 33), and internal penetrating (78%; 28) disease. Thirty-two patients had paired baseline and follow-up CTE/MRE exams without interval surgery, with clinical response observed in 24/32 (75%). Based on imaging response criteria, 22% (7/32; 95% CI: 9%–40%) had response, 50% (16/32; 95% CI: 32%–68%) were stable, and 28% (9/32; 95% CI: 14%–47%) had disease progression. Fifty-six percent of (18/32; 95% CI: 38%–74%) patients had clinical improvement with response or stable disease by imaging. Patients with stable disease had shorter median baseline lengths of SB inflammation (P = .012). Proportion of patients with colonic inflammation, perianal disease, or penetrating complications did not change. Conclusions Most patients on vedolizumab for over 12 months demonstrated response or stable SB disease when using objective cross-sectional radiologic imaging criteria using CTE/MRE.

Abstract Background We aimed to determine if patient symptoms and computed tomography enterography (CTE) and magnetic resonance enterography (MRE) imaging findings can be used to predict near-term risk of surgery in patients with small bowel Crohn’s disease (CD). Methods CD patients with small bowel strictures undergoing serial CTE or MRE were retrospectively identified. Strictures were defined by luminal narrowing, bowel wall thickening, and unequivocal proximal small bowel dilation. Harvey-Bradshaw index (HBI) was recorded. Stricture observations and measurements were performed on baseline CTE or MRE and compared to with prior and subsequent scans. Patients were divided into those who underwent surgery within 2 years and those who did not. LASSO (least absolute shrinkage and selection operator) regression models were trained and validated using 5-fold cross-validation. Results Eighty-five patients (43.7 ± 15.3 years of age at baseline scan, majority male [57.6%]) had 137 small bowel strictures. Surgery was performed in 26 patients within 2 years from baseline CTE or MRE. In univariate analysis of patients with prior exams, development of stricture on the baseline exam was associated with near-term surgery (P = .006). A mathematical model using baseline features predicting surgery within 2 years included an HBI of 5 to 7 (odds ratio [OR], 1.7 × 105; P = .057), an HBI of 8 to 16 (OR, 3.1 × 105; P = .054), anastomotic stricture (OR, 0.002; P = .091), bowel wall thickness (OR, 4.7; P = .064), penetrating behavior (OR, 3.1 × 103; P = .096), and newly developed stricture (OR: 7.2 × 107; P = .062). This model demonstrated sensitivity of 67% and specificity of 73% (area under the curve, 0.62). Conclusions CTE or MRE imaging findings in combination with HBI can potentially predict which patients will require surgery within 2 years.

Intestinal fibrosis is considered an inevitable complication of Crohn’s disease (CD) that results in symptoms of obstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.

INTRODUCTION: Vulvar involvement is a rare complication of Crohn's disease (CD). The optimal treatment of vulvar CD is unknown. METHODS: We conducted a 25-year retrospective cohort study of vulvar CD from 3 referral centers. Clinical features and outcomes were studied. RESULTS: Fifty patients were identified. The most common vulvar symptoms were pain (74%), edema (60%), ulcerations (46%), nodules (36%), and abscess (34%). Medical management leading to symptomatic improvement varied, and 5 patients ultimately required surgery. DISCUSSION: Vulvar CD manifests with a broad spectrum of symptoms. Aggressive medical management was frequently effective, although surgery was required in 10% of cases.

Background Due to their easy accessibility, CT scans have been increasingly used for investigation of gastrointestinal (GI) bleeding. Purpose To estimate the performance of a dual-phase, dual-energy (DE) GI bleed CT protocol in patients with overt GI bleeding in clinical practice and examine the added value of portal phase and DE images. Materials and Methods Consecutive patients with GI bleeding underwent a two-phase DE GI bleed CT protocol. Two gastroenterologists established the reference standard. Performance was estimated using clinical CT reports. Three GI radiologists rated confidence in GI bleeding in a subset of 62 examinations, evaluating first mixed kV arterial images, then after examining additional portal venous phase images, and finally after additional DE images (virtual non-contrast and virtual monoenergetic 50 keV images). Results 52 of 176 patients (29.5%) had GI bleeding by the reference standard. The overall sensitivity, specificity, and positive and negative predictive values of the CT GI bleed protocol for detecting GI bleeding were 65.4%, 89.5%, 72.3%, and 86.0%, respectively. In patients with GI bleeding, diagnostic confidence of readers increased after adding portal phase images to arterial phase images ( p = 0.002), without additional benefit from dual energy images. In patients without GI bleeding, confidence in luminal extravasation appropriately decreased after adding portal phase, and subsequently DE images ( p = 0.006, p = 0.018). Conclusion A two-phase DE GI bleed CT protocol had high specificity and negative predictive value in clinical practice. Portal venous phase images improved diagnostic confidence in comparison to arterial phase images alone. Dual-energy images further improved radiologist confidence in the absence of bleeding.