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Noncompliance in use of anti-tumor necrosis factor (anti-TNF) therapy in patients with moderate-to-severe inflammatory bowel disease (IBD) can be a factor in medication failure. Few studies have evaluated the contribution of depressive symptoms to medication noncompliance in anti-TNF therapies. A retrospective chart review was performed in a single-center tertiary care IBD center for patients with Crohn’s disease and ulcerative colitis starting anti-TNF therapy over a 2-year period. Medication noncompliance was defined as interruption of medication (not filling anti-TNF prescription if injectable or not getting infliximab infusion for 30 days beyond needed date for continuation) due to patient-driven circumstances. Depressive symptoms were evaluated at baseline using the well-validated Patient Health Questionnaire-9 (PHQ-9), with PHQ-9 ≥ 10 indicative of at least moderate depressive symptoms. Statistical analysis was performed using Cox proportional hazards regression controlling for age, sex, psychiatric history, and disease. A total of 246 patients (75 with ulcerative colitis, 171 with Crohn’s disease) were started on anti-TNF therapy. Seventy-nine patients (32%) had a prior psychiatric diagnosis reported in the medical record. Thirty-three patients (13%) were noncompliant in follow-up. Sixty patients (24%) had at least moderate depressive symptoms at baseline (PHQ ≥ 10). Depressive symptoms at baseline were significantly associated with noncompliance in follow-up (hazards ratio 2.28, CI 1.1–4.6, p

Background The safety of inflammatory bowel disease (IBD) medications during lactation is of significant interest and relevance to female patients of childbearing potential. Available data regarding the safety and transfer of biologic agents via breast milk are limited to case reports. Vedolizumab has a well-established, positive benefit-risk profile in adult IBD patients. Literature data show that vedolizumab is detectable in human milk. Methods A prospective, postmarketing, phase 4, open-label, milk-only lactation study was conducted to assess vedolizumab concentrations in breast milk from lactating women with IBD who were on an established vedolizumab maintenance regimen (300 mg intravenous [IV] every 8 weeks [Q8W] or an alternative dose frequency). Maternal milk samples were serially collected throughout the dosing interval on Days 1 (predose and 1 h after the end of vedolizumab infusion), 4, 8, 15, 29, and 57 to allow the estimation of drug excreted in milk relative to the maternal dosage. Maternal safety data were also collected. Results A total of 11 patients were enrolled in the study. Vedolizumab was detectable in the majority of milk samples collected on Days 1 and 57, and in all samples collected at other time points. Following receipt of vedolizumab 300 mg IV on Day 1, the vedolizumab milk concentration increased with a median time to peak concentration (Cmax) of 3–4 days, and subsequently decreased exponentially. For the 9 patients on the Q8W regimen, median Cmax was 0.213 µg/ml (range, 0.098–0.561 µg/ml); the geometric mean daily infant dosage, calculated using average concentration over 8-week dosing interval (0.13 µg/ml), was 0.02 mg/kg/day with a corresponding geometric mean percentage of maternal dosage consumed in breast milk by infants of 21%. The maternal safety profile was acceptable and similar to that observed in previous adult studies. Leveraging the mean trough serum concentration of 11.2 µg/ml from historical studies of vedolizumab, the ratio of mean milk concentration (trough, 0.05 µg/ml; peak, 0.25 µg/ml) to serum concentration was approximately 0.4%-2.2%, which is consistent with published data for vedolizumab and comparable with several other monoclonal antibody therapeutics for IBD. Published vedolizumab studies also showed no increase in general or gastrointestinal tract infections in the infants exposed to vedolizumab in breast milk, and exposed infants reached their acceptable development milestones through up to 10 months of follow-up. Conclusion Vedolizumab was found to be present in human breastmilk at a low level. The impact of vedolizumab IV administration during breastfeeding is expected to be minimal.

Recent research suggests a relationship of inflammatory bowel disease (IBD) and depression. Our objective was to evaluate for improvement of depressive symptoms with treatment of IBD using immunosuppressive medications.A retrospective study of consecutive patients with IBD started on immunosuppressive agents [anti-tumor necrosis factor (anti-TNF) or immunomodulator therapy] was conducted. Patients were evaluated if disease activity indices using Harvey Bradshaw Index for Crohn's disease (CD) and Simple Clinical Colitis Disease Activity Index for ulcerative colitis (UC) and depressive indices using Patient Health Questionnaire-9 (PHQ-9) scores were obtained before and at least 30 days after initiation of therapy.Sixteen patients with UC and 53 patients with CD (all with active disease symptoms) were evaluated over a 60 day median follow-up evaluation (range 30, 140 days). Twenty-two patients started on immunomodulator therapy, and 47 patients started on anti-TNF therapy. Crohn's disease patients had significantly decreased PHQ-9 scores at follow-up [median 9 (range 3, 14) to 4 (1, 8)], with significant decreases only in those started on anti-TNF therapy. Changes in PHQ-9 and CRP were correlated (ρ = 0.38, p0.05). In patients with UC, PHQ-9 scores [5 (3, 9) to 2 (0, 5)] were significantly decreased. Percentage at risk of moderate to severe depression (PHQ-9 scores ≥10) was lower after treatment [Crohn's disease 51-18 % (p0.05), ulcerative colitis 18-0 %].Depressive scores decreased significantly in patients with IBD treated with immunosuppressive therapy and the number at risk for moderate to severe depression improved significantly.

This manuscript is a secondary analysis of a large multicenter randomized controlled trial. The primary study is Cross RK et al., A Randomized Controlled Trial of TELEmedicine for patients with Inflammatory Bowel Disease (TELE-IBD). Am J Gastroenterol, 2019 Mar.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), affects over 1 million Americans and 2 million Europeans, and the incidence is increasing worldwide. While these diseases require unique medical care, the differentiation between UC and CD lacks a gold standard, and therefore relies on long term follow up, success or failure of existing treatment, and recurrence of the disease. Here, we present colonoscopy-coupled fiber optic probe-based Raman spectroscopy as a minimally-invasive diagnostic tool for IBD of the colon (UC and Crohn’s colitis). This pilot in vivo study of subjects with existing IBD diagnoses of UC (n = 8), CD (n = 15), and normal control (n = 8) aimed to characterize spectral signatures of UC and CD. Samples were correlated with tissue pathology markers and endoscopic evaluation. The collected spectra were processed and analyzed using multivariate statistical techniques to identify spectral markers and discriminate IBD and disease classes. Confounding factors including the presence of active inflammation and the particular colon segment measured were investigated and integrated into the devised prediction algorithm, reaching 90% sensitivity and 75% specificity to CD from this in vivo data set. These results represent significant progress towards improved real-time classification for accurate and automated in vivo detection and discrimination of IBD during colonoscopy procedures.

Background L-arginine (L-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. L-Arg is actively transported into cells by means of cationic amino acid transporter (SLC7) proteins. We have linked L-Arg and arginase 1 activity to epithelial restitution. Our aim was to determine if L-Arg, related amino acids, and metabolic enzymes are altered in ulcerative colitis (UC). Methods Serum and colonic tissues were prospectively collected from 38 control subjects and 137 UC patients. Dietary intake, histologic injury, and clinical disease activity were assessed. Amino acid levels were measured by high-performance liquid chromatography. Messenger RNA (mRNA) levels were measured by real-time PCR. Colon tissue samples from 12 Crohn's disease patients were obtained for comparison. Results Dietary intake of arginine and serum L-Arg levels were not different in UC patients versus control subjects. In active UC, tissue L-Arg was decreased, whereas L-citrulline (L-Cit) and the L-Cit/L-Arg ratio were increased. This pattern was also seen when paired involved (left) versus uninvolved (right) colon tissues in UC were assessed. In active UC, SLC7A2 and ARG1 mRNA levels were decreased, whereas ARG2 and NOS2 were increased. Similar alterations in mRNA expression occurred in tissues from Crohn's disease patients. In involved UC, SLC7A2 and ARG1 mRNA levels were decreased, and NOS2 and ARG2 increased, when compared with uninvolved tissues. Conclusions Patients with UC exhibit diminished tissue L-Arg, likely attributable to decreased cellular uptake and increased consumption by NOS2. These findings combined with decreased ARG1 expression indicate a pattern of dysregulated L-Arg availability and metabolism in UC.

Background: Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. Methods: This was a retrospective, observational study of CD patients treated with maintenance infliximab beyond 3 years. Maintenance infliximab infusion regimens were categorized as scheduled maintenance (SM) (maintenance infusions q ≤8 weeks after loading) or prior irregular (PI) (no loading, gap in therapy >8 weeks prior to or during maintenance therapy). We examined differences in need for medical and surgical hospitalizations as well as associated healthcare costs between the 2 groups. Results: In all, 104 CD patients met criteria for 3-year maintenance infliximab treatment (SM n = 64; PI n = 40). The rates of CD-related surgeries (60.9% and 55.0%, P = not significant [N.S.]) and medical hospitalizations (35.9% and 37.5%, P = N.S.) prior to infliximab initiation was similar between the 2 groups. However, the rate of medical (26.5% versus 47.5%, P = 0.035) and surgical hospitalizations (21.8% versus 48.7%, P = 0.009) were significantly lower in the SM compared to the PI group. During the third year of treatment the excess costs per patient for the PI group compared to the SM group amounted to $11,464 in spite of both cohorts being on SM therapy. Conclusions: Patients who begin and continue an uninterrupted maintenance dosing regimen had a lower incidence of hospitalization and surgery than those who received an irregular or interrupted regimen prior to beginning an SM regimen. (Inflamm Bowel Dis 2010)

Background: Patients who require hospitalization for the management of ulcerative colitis (UC) may represent a subset with severe disease. These patients may be more likely to require future colectomy. There are limited data examining whether medical hospitalization is predictive of subsequent colectomy. Methods: This was a retrospective case–control study utilizing the inflammatory bowel disease center database at our academic referral center. Cases comprised UC patients who underwent colectomy for disease refractory to medical management. The control population was comprised of all patients with UC who had not undergone colectomy. Multivariate logistic regression was used to identify independent predictors of requiring colectomy. Results: There were a total of 246 UC patients included in our study, with 103 being hospitalized sometime in their disease course (41.9%). A total of 27 patients underwent colectomy (11%). Colectomy patients were significantly more likely to have been on infliximab therapy (51.8% versus 22.4%, P = 0.001) but no more likely to have been on immunomodulator therapy (74.1% versus 59.4%, P = 0.14). Patients who required medical hospitalization for UC were more likely to require future colectomy (20.4% versus 4.2%, P < 0.001) than those who had not required hospitalization. On multivariate analysis, requiring medical hospitalization for management of UC (odds ratio [OR] 5.37, 95% confidence interval [CI] 2.00–14.46) and ever requiring infliximab therapy (OR 3.12, 95% CI 1.21–8.07) were independent predictors of colectomy. Conclusions: Requiring medical hospitalization for the management of disease activity in UC is an independent predictor of the need for colectomy. Future studies will determine whether aggressive medical management may modify the need for colectomy in this cohort. (Inflamm Bowel Dis 2008)

Background: There is no standard approach for the medical management of Crohn's disease (CD) during pregnancy and there is limited data regarding safety and efficacy of the treatments. Budesonide (Entocort® EC, AstraZeneca) is an enteric coated locally acting glucocorticoid preparation whose pH- and time-dependent coating enables its release into the ileum and ascending colon for the treatment of mild to moderate Crohn's disease. There is no available data on the safety of using oral budesonide in pregnant patients. Methods: We reviewed our Inflammatory Bowel Disease (IBD) center database to identify patients with CD who received treatment with budesonide for induction and/or maintenance of remission during pregnancy and describe the maternal and fetal outcomes in a series of eight mothers and their babies. Results: The mean age of the patients was 27.7 years. All patients had small bowel involvement with their CD. The disease pattern was stricturing in 6 patients, fistulizing in 1 and inflammatory in 1 patient. Budesonide was used at the 6 mg/day dose in 6 patients and 9 mg/day dose in 2 patients. The average treatment duration ranges from 1-8 months. There were no cases of maternal adrenal suppression, glucose intolerance, ocular side effects, hypertension or fetal congenital abnormalities. Conclusion: Budesonide may be a safe option for treatment of CD during pregnancy. (Inflamm Bowel Dis 2008)

BACKGROUND Ustekinumab is a new biologic therapy targeting interleukin-12 and interleukin -23. It is currently approved for the treatment of psoriasis, but clinical trials have shown that it can induce and maintain remission in Crohn's disease (CD). We aim to evaluate effectiveness of ustekinumab in the treatment of CD. METHODS A retrospective chart review was performed including patients (pts) from 2 academic medical centers with complicated, refractory CD started on ustekinumab between June 2011 and June 2014. Pts were treated based on a novel subcutaneous dosing schedule designed to simulate the intravenous load used in clinical trials. RESULTS Forty-five pts were treated with ustekinumab during this study period. Of the pts who had clinical parameters available before and after medication start, 46% achieved clinical response (Harvey-Bradshaw index decrease ≥ 3) and 35% achieved clinical remission (Harvey-Bradshaw index ≤ 3). Short inflammatory bowel disease questionnaire scores increased significantly (46 [20, 68] to 55 [32, 70], P < 0.05). Erythrocyte sedimentation rate decreased significantly (20 [3, 54] to 12 [0, 42] mm/h, P < 0.05). C-reactive protein decreased significantly (4.9 [0.3, 111] to 3.3 [0.2, 226] mg/L, P < 0.05). Seventy-six percent of patients demonstrated an endoscopic response and 24% achieved complete endoscopic remission. Twelve patients (26%) were hospitalized for IBD-related issues. Four pts had infection-related complications. Six pts (13%) underwent surgery for IBD-related issues. Three pts stopped ustekinumab, 1 for pt preference and 2 for the lack of response. CONCLUSIONS Using a novel subcutaneous dosing schedule, ustekinumab was successful in improving clinical, laboratory, and endoscopic markers of disease activity in patients with severe, refractory CD.

Therapeutics blocking the activity of tumor necrosis factor (anti-TNF) are a risk factor for invasive fungal infections; however, infectious risks to infants born to mothers receiving anti-TNF therapy are not well defined. We report a case of vertical transmission of disseminated histoplasmosis in a mother-infant pair exposed to anti-TNF therapy.

Background Perianal disease is a manifestation of Crohn's disease (CD) that has poor long-term treatment outcomes. The aim was to determine if rectal endoscopic ultrasound (EUS)-guided therapy with adalimumab (ADA) can improve outcomes for patients with perianal fistulizing CD. Methods This is a randomized prospective study comparing serial EUS guidance of fistula treatment versus standard of care in fistulizing perianal CD. At enrollment, all patients underwent a rectal EUS and an EUA with seton placement and/or I&D. Treatment was maximized with immunomodulators, antibiotics, and ADA induction. Surgical interventions were determined by the surgeon's discretion in the control group and assisted by every 12th week EUS in the intervention group. Primary and secondary endpoints where complete drainage cessation at week 48 was fistula status per EUS, respectively. Results Twenty patients were enrolled: 11 control and 9 EUS guidance. At 24 weeks, 7/9 (78%) in EUS group and 3/11 (27%) in control group had drainage cessation (P = 0.04). This significant difference was lost at week 48 (P = 0.44). Three patients in the EUS and 1 in the control group had additional surgical intervention. Those in the EUS group had more rapid escalation of ADA dosing (P = 0.003). There was no difference in the change in PDAI at week 48 versus baseline (P = 0.81). Conclusions Rectal EUS-guided ADA therapy for CD perianal fistulas showed an initial benefit at 24 weeks, which was lost at week 48. This is likely due to small sample size and higher fistula closure in the controls. However, the faster rate of fistula resolution is a clinically significant finding.

Fertility is an important issue for both women and men. Studies thus far have not revealed a great difference in the capacity to conceive or induce conception in a patient with IBD when compared to the non-IBD patient. In general, IBD patients have normal fertility except in a certain subgroup of populations: women after surgical resection with ileal pouch-anal anastomosis (IPAA), men on sulfasalazine, and the use methotrexate (MTX). Subfertility or the inability to conceive has been seen in patients with active CD.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), affects over 1 million Americans and 2 million Europeans, and the incidence is increasing worldwide. While these diseases require unique medical care, the differentiation between UC and CD lacks a gold standard, and therefore relies on long term follow up, success or failure of existing treatment, and recurrence of the disease. Here, we present colonoscopy-coupled fiber optic probe-based Raman spectroscopy as a minimally-invasive diagnostic tool for IBD of the colon (UC and Crohn's colitis). This pilot in vivo study of subjects with existing IBD diagnoses of UC (n = 8), CD (n = 15), and normal control (n = 8) aimed to characterize spectral signatures of UC and CD. Samples were correlated with tissue pathology markers and endoscopic evaluation. The collected spectra were processed and analyzed using multivariate statistical techniques to identify spectral markers and discriminate IBD and disease classes. Confounding factors including the presence of active inflammation and the particular colon segment measured were investigated and integrated into the devised prediction algorithm, reaching 90% sensitivity and 75% specificity to CD from this in vivo data set. These results represent significant progress towards improved real-time classification for accurate and automated in vivo detection and discrimination of IBD during colonoscopy procedures.

Background Inflammatory bowel diseases, ulcerative colitis and Crohn’s disease are considered to be of autoimmune origin, but the etiology of irritable bowel syndrome remains elusive. Furthermore, classifying patients into irritable bowel syndrome and inflammatory bowel diseases can be difficult without invasive testing and holds important treatment implications. Our aim was to assess the ability of gene expression profiling in blood to differentiate among these subject groups. Methods Transcript levels of a total of 45 genes in blood were determined by quantitative real-time polymerase chain reaction (RT-PCR). We applied three separate analytic approaches; one utilized a scoring system derived from combinations of ratios of expression levels of two genes and two different support vector machines. Results All methods discriminated different subject cohorts, irritable bowel syndrome from control, inflammatory bowel disease from control, irritable bowel syndrome from inflammatory bowel disease, and ulcerative colitis from Crohn’s disease, with high degrees of sensitivity and specificity. Conclusions These results suggest these approaches may provide clinically useful prediction of the presence of these gastro-intestinal diseases and syndromes.

Objective The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8 −/− and Mtgr1 −/− mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity. Methods Baseline and stress induced colonic phenotypes were examined in Mtg16 −/− mice. To unmask phenotypes, we treated Mtg16 −/− mice with dextran sodium sulphate (DSS) or infected them with Citrobacter rodentium and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation. Results Mtg16 −/− mice have altered immune subsets, suggesting priming towards Th1 responses. Mtg16 −/− mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1 + , F4/80 + , CD11c + and MHCII + ; CD11c + ) and Th1 adaptive (CD4) immune cells in Mtg16 −/− colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in Mtg16 −/− colons. Compared with wild-type mice, Mtg16 −/− mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wild-type marrow into Mtg16 −/− recipients did not rescue the Mtg16 −/− injury phenotype. Isolated colonic epithelial cells from DSS-treated Mtg16 −/− mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. Mtg16 −/− mice infected with C rodentium had more severe colitis and greater bacterial colonisation. Last, MTG16 mRNA levels were reduced in human ulcerative colitis versus normal colon tissues. Conclusions These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury.

Crohn disease and ulcerative colitis commonly affect women in their childbearing years. Fortunately, advances in the field of inflammatory bowel disease have made successful pregnancy outcomes a reality for many women. These advances have led to family planning as a common discussion between gastroenterologists and inflammatory bowel disease patients. Common discussion topics are fertility, conception, medication safety, pregnancy, delivery, and breastfeeding although there are limited available data. Education and patient awareness have become vital factors in successful pregnancy outcomes.

Background: Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%–10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls. Methods: This was a retrospective, case–control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey–Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. Results: There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (−1.33, 95% confidence interval [CI] 95% CI −1.85 to −0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%). Conclusions: PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability. (Inflamm Bowel Dis 2010)

Clostridium difficile-associated disease has increased significantly in North American medical centers. The impact of C difficile on patients with IBD (Crohn's disease, ulcerative colitis) at the present time is unknown.A retrospective, observational study evaluating IBD patients followed in a referral center to evaluate the impact of C difficile was performed. Diagnosis was confirmed with stool toxin analysis. Demographic information, diagnosis, anatomic location, IBD therapy, antibiotic exposure, hospitalizations, and surgeries were recorded. Available endoscopic and histologic data were evaluated.Rate of C difficile infection increased from 1.8% of IBD patients in 2004 to 4.6% in 2005 (P.01). Proportion of IBD patients within the total number of C difficile infections at our institution increased from 7% in 2004 to 16% in 2005 (P.01). IBD colonic involvement was found in the majority of C difficile-infected patients in 2005 (91%), and the majority contracted infection as an outpatient (76%). Antibiotic exposure was identified in 61% of IBD patients with C difficile infection in 2005. Pseudomembranes and fibrinopurulent eruptions were not seen endoscopically or histologically. During 2004-2005 more than half of the infected IBD patients required hospitalization, and 20% required colectomy. Univariate and multivariate analysis identified maintenance immunomodulator use and colonic involvement as independent risk factors for C difficile infection in IBD.C difficile infection has increased significantly in IBD patients and negatively impacts clinical outcome. Increased vigilance regarding this infection in IBD patients with colitis activity is warranted.

until used for cytokine determination. The concentration of intestine mucosa cytokines involved in the Th1 (IL-2, IL-12p70, IFN-γ), Th2 (IL-4), Th17 (IL-6, IL-17A, IL-23) and Treg (IL-10, TGF-β) cell commitment and IL-1 β and TNF-α (cytokines of the innate immune response) was assayed in duplicate by ELISA (Biosource, Camarillo, CA) and the results were expressed as picogram of cytokine per milligram of protein. Data were analyzed with SPSS. Comparisons between the groups were done by the two-tailed Mann-Whitney U-test. The ileal and colonic concentration of all proinflammatory cytokines was significantly higher in the patients with CD and also UC than in control group (p

Background Fistulizing disease occurs in up to 40% of patients with Crohn's disease (CD) . Symptoms, including anal pain, purulent discharge, and incontinence, are associated with high morbidity and impaired quality of life. Vedolizumab (VDZ) is a monoclonal antibody to alpha4beta7 integrin with demonstrated efficacy and safety in the treatment of patients with CD. The present exploratory analysis evaluated the efficacy of VDZ in the subpopulation of patients with fistulizing CD from a phase 3, randomized, placebo (PBO)-controlled trial (GEMINI 2).1 Methods In the GEMINI 2 study, patients who received 2 doses of VDZ during the induction phase and achieved a clinical response at week 6 received treatment with PBO or VDZ 300 mg every 8 weeks (Q8W) or every 4 weeks (Q4W) for an additional 46 weeks (maintenance intent-to-treat [ITT] population). Fistula closure, a prespecified exploratory endpoint, was assessed at each visit (2-6 week intervals) until week 52. The percentage of patients achieving fistula closure and mean time to fistula closure were calculated. Results Among the maintenance ITT population (N=461), 57 patients (12%) had 1 or more draining fistulae at study entry, with 74% of fistulae located perianally. Of these patients, 44-49% had failed prior anti-tumor necrosis factor therapy and 39-54% had prior surgery for CD. By week 14, 28% of patients treated with VDZ/VDZ (Q8W + Q4W combined) had achieved fistula closure versus 11% of those receiving VDZ/PBO (Table). This treatment difference was maintained up to week 52. Kaplan-Meier probabilities of fistula closure with VDZ treatment were 29.2% and 33.4% at 6 and 12 months, respectively; notably, the number of patients at risk was small (Figure). Conclusion In the GEMINI 2 maintenance ITT population, a greater percentage of patients with draining fistulae at study entry achieved fistula closure when they continued treatment with VDZ compared with those who were re-randomized to PBO. This effect was maintained through to week 52.These preliminary findings support the role of VDZ in the treatment of fistulizing disease and warrant further investigation in dedicated prospective studies in this population. Reference 1. Sandborn WJ, et al. N Engl J Med . 2013;369(8):711-721; NCT00783692. The clinical study was funded by Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.). Medical writing assistance was provided by inVentiv Medical Communications and supported by Takeda Pharmaceuticals International, Inc.

Introduction: IBD in the mother is associated with higher rates of adverse pregnancy outcomes. However, long-term effects of maternal IBD on childhood growth and development are not known. The aim of this study was to determine the impact of IBD medication exposure in utero on newborn developmental milestones. Methods: We created a prospective cohort of pregnant women at 30 US IBD centers to follow patients through pregnancy and first four years of a child's life. We ascertained IBD medications and disease activity during gestation, complications of pregnancy and delivery, and achievement of developmental milestones. Patients were classified by exposure to drugs taken between conception and delivery: 6MP/Azathioprine (Group A), infliximab, adalimumab, certolizumab (Group B), combination therapy (Group AB). We compared these groups to women who did not take any Group A or B drugs. Developmental milestones achieved by the infant, based on Denver Childhood Developmental Score, were measured by the mother at months 4, 9 and 12 and by the validated Ages and Stages Questionnaire at 1,2,3 and 4 years of age. Follow up is ongoing. Results: 1289 women are enrolled in the study as of Nov 12 2013: 1097 have completed pregnancy, 1039 with live births. There were 215 live births in Group A, 364 in Group B, 137 in Group AB and 323 to unexposed mothers. When compared to the unexposed infants, infants in Group A, B and AB always had equivalent or better achievement of milestones. These results were unchanged when controlled for maternal income and education level. Table 1 lists the milestones in which the exposed infants had better outcomes that the unexposed. Conclusions: Infants with in utero exposure to immunomodulator and biologic therapy did not exhibit developmental delay compared to infants not exposed to these agents, controlling for preterm birth. Overall, developmental scores were similar between exposed and unexposed infants, and scores of exposed infants were slightly higher in some categories. Significant Differences in Developmental Milestones by Drug Exposure