Ruben J Colman, MD, PhD

All Publications

• Operating Properties of Disease Activity Indices in Pediatric Inflammatory Bowel Disease: A Systematic Review. Inflammatory bowel diseases Colman, R. J., Solitano, V., MacDonald, J. K., Ma, C., Griffiths, A. M., Jairath, V., Crowley, E. 2024

  Abstract

  Accurate, reliable, and responsive disease activity indices are important to streamline drug approval and treatment modalities for pediatric inflammatory bowel disease (pIBD). We aimed to identify all scoring indices used in pIBD randomized controlled trials (RCTs) and to evaluate their operating properties.MEDLINE, EMBASE, and CENTRAL were searched on December 6, 2022, to identify studies evaluating clinical, endoscopic, imaging, or patient-reported outcome measures (PROMs) in pIBD including Crohn's disease (CD) and ulcerative colitis (UC). Validity, reliability, responsiveness, and feasibility were summarized.Seventy RCTs evaluating pIBD indices were identified. Forty-one studies reported on the operating properties of 14 eligible indices (n = 9 CD, n = 5 UC). The Pediatric Crohn's Disease Activity Index (PCDAI) varied widely in terms of validity and reliability and was less feasible overall. In contrast, the Mucosal Inflammation Noninvasive Index, which includes fecal calprotectin, had better operating properties than the PCDAI. The Simplified Endoscopic Mucosal Assessment of Crohn's Disease appears more feasible and had similar operating properties than the longer Simple Endoscopic Score for Crohn's Disease. The Pediatric Ulcerative Colitis Activity Index was feasible, valid, and reliable, but responsiveness needs to be evaluated further. The Endoscopic Mayo score and the Ulcerative Colitis Endoscopic Index of Severity were reliable, but validity and responsiveness need to be evaluated further. Imaging and PROMs/quality of life indices need further evaluation.The operating properties of pIBD clinical trial end points varied widely. These results highlight the need for further validation and development of novel indices.

  View details for DOI 10.1093/ibd/izae060

  View details for PubMedID 38547511

• Precise infliximab exposure and pharmacodynamic control to achieve deep remission in paediatric Crohn's disease (REMODEL-CD): study protocol for a multicentre, open-label, pragmatic clinical trial in the USA. BMJ open Minar, P. P., Colman, R. J., Zhang, N., Mizuno, T., Vinks, A. A. 2024; 14 (3): e077193

  Abstract

  The only biologic therapy currently approved to treat moderate to severe Crohn's disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically important to develop novel strategies that maximise treatment effectiveness in this population. There is growing evidence that rates of sustained corticosteroid-free clinical remission, endoscopic healing and drug durability considerably improve when patients receive early anti-TNF dose optimisations guided by reactive or proactive therapeutic drug monitoring and pharmacodynamic monitoring. In response, our team has developed a personalised and scalable infliximab dosing intervention that starts with dose selection and continues throughout maintenance to optimise drug exposure. We hypothesise that a precision dosing strategy starting from induction and targeting dose-specific pharmacokinetic and pharmacodynamic endpoints throughout therapy will significantly improve outcomes compared with a conventional dosing strategy.Conduct a clinical trial to assess rates of deep remission between Crohn's disease patients receiving infliximab with precision dosing (n=90) versus conventional care (n=90). Patients (age 6-22 years) will be recruited from 10 medical centres in the USA. Each centre has been selected to provide either precision dosing or conventional care dosing. Precision dosing includes the use of a clinical decision support tool (RoadMAB) from the start of infliximab to achieve specific (personalised) trough concentrations and specific pharmacodynamic targets (at doses 3, 4 and 6). Conventional care includes the use of a modified infliximab starting dose (5 or 7.5 mg/kg based on the pretreatment serum albumin) with a goal to achieve maintenance trough concentrations of 5-10 µg/mL. The primary endpoint is year 1 deep remission defined as a combination of clinical remission (paediatric Crohn's disease activity index<10 (child) or a Crohn's disease activity index<150 (adults)), off prednisone>8 weeks and endoscopic remission (simple endoscopic severity-Crohn's disease≤2).). The study protocol has been approved by the Cincinnati Children's Hospital Medical Centre Institutional Review Board. Study results will be disseminated in peer-reviewed journals and presented at scientific meetings.NCT05660746.

  View details for DOI 10.1136/bmjopen-2023-077193

  View details for PubMedID 38531570

• Infliximab Monotherapy vs Combination Therapy for Pediatric Crohn's Disease Exhibit Similar Pharmacokinetics. Inflammatory bowel diseases Colman, R. J., Vuijk, S. A., Mathôt, R. A., Van Limbergen, J., Jongsma, M. M., Schreurs, M. W., Minar, P., de Ridder, L., D'Haens, G. R. 2024

  Abstract

  The use of concomitant azathioprine may improve efficacy and pharmacokinetic (PK) properties of infliximab (IFX) but is also associated with an increased risk of adverse events. Proactive therapeutic drug monitoring (pTDM) of IFX monotherapy is an alternative strategy to improve PK. The aim of this study was to evaluate whether IFX with an immunomodulator (combo) has PK benefits over IFX-pTDM (mono) in pediatric Crohn's disease (CD).This PK analysis included pediatric CD patients who started either IFX combo (TISKids study) or IFX mono with pTDM (REFINE cohort). Combo and mono IFX trough levels (TLs) and antibodies-to-infliximab were assessed at infusion 3, 4, and 5. A population PK model was built to compare IFX PK outcomes (clearance [CL], TLs and cumulative exposure) between combo and mono groups at infusion 4 and 5. Clinical response and steroid-free clinical remission (SFCR) was assessed at infusion 4 and 5.This study included 128 pediatric CD patients (66 mono and 62 combo). At infusion 5, there was no significant difference between mono and combo median TLs 4.1 µg/mL (2.1, 7.8) vs 5.9 µg/mL (3.2, 9.4; P = .14) or median CL 0.26 L/d (0.21, 0.32) vs 0.26 L/d (0.21, 0.33; P = .81). Mono patients had a lower SFCR rate at infusion 5 (53% [31 of 59] vs 80% [32 of 40]; P = .01). Clinical response rates were significantly higher among combo than mono patients at both infusion 4 and 5.This study suggests that there are no PK differences (TLs and CL) between combo and mono therapy in pediatric CD patients who started IFX.

  View details for DOI 10.1093/ibd/izad307

  View details for PubMedID 38167922

• HLA-DQA1*05 Genotype and Immunogenicity to Tumor Necrosis Factor-alpha Antagonists: A Systematic Review and Meta-analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Solitano, V., Facciorusso, A., McGovern, D. P., Nguyen, T., Colman, R. J., Zou, L., Boland, B. S., Syversen, S. W., Jorgensen, K. K., Ma, C., Armuzzi, A., Wilson, A., Jairath, V., Singh, S. 2023

  Abstract

  BACKGROUND AND AIMS: Identifying patients at high risk of immunogenicity is important when selecting tumor necrosis factor-(TNF)alpha antagonists in patients with immune-mediated inflammatory diseases (IMIDs). We evaluated the association HLA-DQA1*05 genotype and risk of immunogenicity with TNFalpha antagonists.METHODS: Through a systematic review till 14 July, 2022, we identified studies in patients with IMIDs treated with TNFalpha antagonists, which reported the risk of immunogenicity and/or secondary loss of response in patients with HLA-DQA1*05 variants. Primary outcome was risk of immunogenicity. We performed random effects meta-analysis and used GRADE to appraise certainty of evidence.RESULTS: On meta-analysis of 13 studies (3,756 patients, median follow-up, 12m; 41% with variants), HLA-DQA1*05 variants were associated with 75% higher risk of immunogenicity compared to wild type [relative risk (RR), 1.75 (95% CI, 1.37-2.25)] with considerable heterogeneity (I2=62%) (low certainty evidence). Positive and negative predictive value of HLA-DQA1*05 variants for predicting immunogenicity was 30% and 80%, respectively. Proactive therapeutic drug monitoring, but not concomitant use of IMMs, IMIDs- and TNFalpha antagonist-type, modified this association. Patients with HLA-DQA1*05 variants experienced 2.2-fold higher risk of secondary loss of response [six cohorts; RR, 2.24 (1.67-3.00), I2=0%] (moderate certainty evidence).CONCLUSION: Variants in HLA-DQA1*05 are associated with an increased risk in immunogenicity and secondary loss of response in patients with IMIDs treated with TNFalpha antagonists. However, the positive and negative predictive value is moderate, and decisions on concomitant use of IMMs to prevent immunogenicity should be individualized based on all factors that influence drug clearance.

  View details for DOI 10.1016/j.cgh.2023.03.044

  View details for PubMedID 37061107

• Editorial: achievements and unresolved questions in improving the pharmacokinetics of vedolizumab in adolescents with inflammatory bowel disease-authors' reply. Alimentary pharmacology & therapeutics Colman, R. J., Minar, P. 2023; 57 (5): 567-568

  View details for DOI 10.1111/apt.17337

  View details for PubMedID 36786467

• Model-informed Precision Dosing for Biologics Is Now Available at the Bedside for Patients With Inflammatory Bowel Disease INFLAMMATORY BOWEL DISEASES Colman, R. J., Samuels, A., Mizuno, T., Punt, N., Vinks, A. A., Minar, P. 2022

  View details for DOI 10.1093/ibd/izac237

  View details for Web of Science ID 000891988200001

  View details for PubMedID 36413113

• Real world population pharmacokinetic study in children and young adults with inflammatory bowel disease discovers novel blood and stool microbial predictors of vedolizumab clearance ALIMENTARY PHARMACOLOGY & THERAPEUTICS Colman, R. J., Mizuno, T., Fukushima, K., Haslam, D. B., Hyams, J. S., Boyle, B., Noe, J. D., D'Haens, G. R., Van Limbergen, J., Chun, K., Yang, J., Denson, L. A., Ollberding, N. J., Vinks, A. A., Minar, P. 2022

  Abstract

  Vedolizumab for inflammatory bowel disease (IBD) is often intensified based on distinct pharmacokinetics in children. Prior adult-specific population pharmacokinetic models have identified limited covariates of drug clearance.To establish a population pharmacokinetic model for children and young adults to identify novel covariates of drug clearance to better account for paediatric-specific inter-patient variability in vedolizumab pharmacokinetics; a key secondary exploratory aim was to identify microbial signatures of pharmacokinetic outcomes in a subset of patients.The study included data from 463 observed vedolizumab concentrations (59 peaks and 404 troughs) from 74 patients with IBD (52 with Crohn's disease and 22 with ulcerative colitis or unclassified IBD, median age 16 years). Pharmacokinetic analysis was conducted with non-linear mixed effects modelling. For the evaluation of the exposure-response relationship, clinical outcomes were evaluated by trough levels, clearance and vedolizumab exposure. Whole-genome metagenomic sequencing was conducted at baseline and week 2.A two-compartment population pharmacokinetic model was identified with a clear correlation between CL and weight, erythrocyte sedimentation rate, and hypoalbuminemia. Trough concentrations before infusion 3 (37 μg/ml) and before infusion 4 (20 μg/ml) best predicted steroid-free clinical remission at infusion 4. Using faecal metagenomics, we identified an early (baseline and week 2) abundance of butyrate-producing species and pathways that were associated with an infusion 4 trough concentration >20 μg/ml.This novel paediatric vedolizumab pharmacokinetic model could inform precision dosing. While additional studies are needed, an abundance of faecal butyrate producers is associated with early response to vedolizumab, suggesting that microbial analysis may be beneficial to biological selection.

  View details for DOI 10.1111/apt.17277

  View details for Web of Science ID 000876329200001

  View details for PubMedID 36314265

• BIOMARKERS OF DRUG CLEARANCE IN PEDIATRIC IBD - A REALWORLD VEDOLIZUMAB PHARMACOKINETIC STUDY Colman, R. J., Mizuno, T., Hyams, J. S., Noe, J. D., Boyle, B. M., Denson, L. A., Vinks, A. A., Minar, P. P. W B SAUNDERS CO-ELSEVIER INC. 2022: S642

  View details for Web of Science ID 000826446202341

• Antibodies-to-infliximab accelerate clearance while dose intensification reverses immunogenicity and recaptures clinical response in paediatric Crohn's disease ALIMENTARY PHARMACOLOGY & THERAPEUTICS Colman, R. J., Xiong, Y., Mizuno, T., Hyams, J. S., Noe, J. D., Boyle, B., D'Haens, G. R., van Limbergen, J., Chun, K., Yang, J., Rosen, M. J., Denson, L. A., Vinks, A. A., Minar, P. 2021

  Abstract

  Antibodies to infliximab (ATI) are associated with secondary loss of response and increased risk for drug reactions. Limited studies have associated ATI with increased infliximab clearance.We assessed the impact of ATI on infliximab clearance and loss of response in an inception paediatric Crohn's disease cohort with 1-year follow-up.This multi-centre prospective cohort study collected peak and trough serum infliximab/ATI concentrations from 660 infusions (78 patients) during the first year of therapy. Clinicians were blinded to these research labs. The primary outcome was the difference in infliximab clearance between ATI-positive (ATI) and ATI-negative (no-ATI) patients. Secondary outcomes included pre-treatment predictors of ATI (including HLA-DQA1 genotyping). Clinical remission, loss of response and infliximab clearance were compared between pre-ATI, during ATI and following ATI resolution with MANOVA. Time to ATI was calculated by Cox proportional Hazards model.ATI were detected in 68% (53/78) patients with a median concentration of 76 ng/mL (range 23-1828). Maximum ATI concentration was <200 ng/mL in 73.6% (39/53). Median clearance in ATI patients was higher (with higher clearance if loss of response), compared to no-ATI patients (P < 0.001). Neutrophil CD64 ratio >6 and starting dose <7.5 mg/kg independently predicted ATI in multivariable regression, while HLA-DQA1*05 presence did not. Dose adjustment resolved ATI in 37.5% (12/32) patients with concomitant infliximab concentration and clearance recovery. A maximum ATI level of ≤99 ng/mL predicted ATI resolution (area under the receiver operating curve 0.80 [95% CI 0.64-0.96]).In this real-world cohort, ATI as low as 23 ng/mL impacted drug clearance. Our data suggest that dose optimisation for low-level ATI can improve infliximab clearance and prevent loss of response.

  View details for DOI 10.1111/apt.16733

  View details for Web of Science ID 000732588600001

  View details for PubMedID 34935161

• Achieving Target Infliximab Drug Concentrations Improves Blood and Fecal Neutrophil Biomarkers in Crohn's Disease INFLAMMATORY BOWEL DISEASES Colman, R. J., Tsai, Y., Jackson, K., Boyle, B. M., Noe, J. D., Hyams, J. S., D'Haens, G. M., van Limbergen, J., Rosen, M. J., Denson, L. A., Minar, P. 2021; 27 (7): 1045-1051

  Abstract

  The neutrophil fecal biomarkers, calprotectin (FCP) and lactoferrin (LCT), and peripheral blood neutrophil CD64 surface receptor (nCD64) are biomarkers for mucosal inflammation in inflammatory bowel disease (IBD). Although FCP has been evaluated as a biomarker for mucosal healing, cut points for LCT and nCD64 are less known. We aimed to identify the cut points for LCT and nCD64 that were associated with FCP remission, with a secondary aim to evaluate the relationship between biochemical outcomes and infliximab (IFX) trough concentrations.We analyzed FCP, LCT, and nCD64 before and after IFX induction in a pediatric Crohn's disease (CD) cohort study. Week-14 FCP biomarker remission was defined as FCP <250 µg/g, with clinical response defined as a weighted Pediatric Crohn's Disease Activity Index <12.5 or Δ>17.5 improvement. Predictive outcomes were calculated by receiver operating characteristics (ROCs).Among 56 CD patients, ROC analysis identified an infusion 4 LCT <8.06 (area under the receiver operator characteristics [AUROC], 0.934, P < 0.001) and nCD64 <6.12 (AUROC, 0.76, P = 0.02) as the ideal cut points for week-14 FCP biomarker remission. End of induction IFX-trough of >9.4 µg/mL (AUROC, 0.799, P = 0.002) and >11.5 µg/mL (AUROC, 0.835, P = 0.003) were associated with a FCP <250 and FCP <100, respectively. We found patients achieving end of induction trough >5 µg/mL had a median FCP improvement (dose 1 to dose 4) of 90% compared with a median of 35% with levels <5 µg/mL (P = 0.024) with a similar median reduction in nCD64 (48% vs 20%, P = 0.031).This study establishes cut points in neutrophil stool and blood biomarkers for both biochemical remission and therapeutic trough levels following induction therapy. Further studies that evaluate pharmacodynamic biomarker targets for endoscopic and histologic healing are warranted.

  View details for DOI 10.1093/ibd/izaa241

  View details for Web of Science ID 000670937700013

  View details for PubMedID 32944769

  View details for PubMedCentralID PMC8205636

• SHOTGUN METAGENOMICS IDENTIFIES MICROBIAL SIGNATURE CHANGES ASSOCIATED WITH INDUCTION INFLIXIMAB CLEARANCE IN CROHN'S DISEASE Colman, R. J., Tadesse, D., Xiong, Y., Haslam, D., Hyams, J. S., Noe, J. D., Boyle, B. M., van Limbergen, J., D'Haens, G. R., Rosen, M. J., Denson, L. A., Vinks, A. A., Ollberding, N., Minar, P. P. W B SAUNDERS CO-ELSEVIER INC. 2021: S723-S724

  View details for Web of Science ID 000649085002417

• Favorable Outcomes and Anti-TNF Durability After Addition of an Immunomodulator for Anti-Drug Antibodies in Pediatric IBD Patients INFLAMMATORY BOWEL DISEASES Colman, R. J., Portocarrero-Castillo, A., Chona, D., Hellmann, J., Minar, P., Rosen, M. J. 2021; 27 (4): 507-515

  Abstract

  Anti-drug antibodies (ADAs) to anti-tumor necrosis factor alpha (anti-TNF) drugs are associated with increased drug clearance and loss of response. We aimed to assess the effectiveness of starting an immunomodulator (IM) drug in patients with newly detected ADAs on anti-TNF monotherapy.We reviewed the medical records of pediatric patients with inflammatory bowel disease on infliximab or adalimumab monotherapy with first-time detection of significant ADAs between 2014 and 2018. Patients who started an IM within 3 months of ADA detection were compared with those who did not (No-IM). Outcomes included steroid-free clinical and biochemical remission on the same anti-TNF , anti-TNF durability, and ADA reversal.We identified 89 patients with ADAs: 30 IM patients and 59 No-IM patients. The initial anti-TNF was stopped shortly after ADA detection in 36% of the No-IM patients vs none of the IM patients, driving longer survival on the initial anti-TNF in the IM group (P = 0.005). At 12 months, steroid-free clinical and biochemical remission on the same anti-TNF occurred in 53.9% of the IM group vs 26.8% in the No-IM group (P = 0.025). Drug levels rose higher (P = 0.003) and ADA levels fell farther (P = 0.037) in the IM group than in the No-IM group. Baseline ADA level predicted ADA reversal in the No-IM patients with an area under the receiver operating characteristic of 0.79 (P = 0.006). An ADA level <329 ng/mL had a 76.2% sensitivity and an 83.3% specificity for ADA reversal without IM.Pediatric patients with inflammatory bowel disease on anti-TNF monotherapy who started an IM for significant ADA levels exhibited longer anti-TNF durability and a higher likelihood of steroid-free clinical and biochemical remission on the same anti-TNF. Patients not treated with an IM were unlikely to reverse ADAs >329 ng/mL.

  View details for DOI 10.1093/ibd/izaa108

  View details for Web of Science ID 000637281600015

  View details for PubMedID 32426829

  View details for PubMedCentralID PMC7957223

• Predicting Therapeutic Response in Pediatric Ulcerative Colitis-A Journey Towards Precision Medicine FRONTIERS IN PEDIATRICS Colman, R. J., Dhaliwal, J., Rosen, M. J. 2021; 9: 634739

  Abstract

  Ulcerative colitis (UC) is a disabling disease, characterized by chronic inflammation of the colon, with a rising prevalence worldwide in the pediatric age group. Although UC presents in children with varying severity, disease extent, and comorbidities, initial treatment is essentially uniform, consisting of 5-aminosalicylate drugs with corticosteroid induction for those with moderately to severely active disease. With the advent of anti-tumor necrosis factor (TNF) biologic therapy and several new biologics and small-molecule drugs for UC, precision medicine approaches to treatment are needed to more rapidly achieve sustained remission, restore quality of life, normalize development, and limit exposure to toxic corticosteroids in children with UC. Here, we review available data on clinical, biochemical, histopathologic, and molecular predictors of treatment response in UC. We also address known predictors and special treatment considerations in specific relevant scenarios such as very-early-onset UC, acute severe UC, ileal pouch anal anastomosis, and UC with concomitant primary sclerosing cholangitis. The review concludes with a prediction of how machine learning will integrate multimodal patient data to bring precision medicine to the bedside of children with UC in the future.

  View details for DOI 10.3389/fped.2021.634739

  View details for Web of Science ID 000624511300001

  View details for PubMedID 33681110

  View details for PubMedCentralID PMC7925616

• Real-World Infliximab Pharmacokinetic Study Informs an Electronic Health Record-Embedded Dashboard to Guide Precision Dosing in Children with Crohn's Disease CLINICAL PHARMACOLOGY & THERAPEUTICS Xiong, Y., Mizuno, T., Colman, R., Hyams, J., Noe, J. D., Boyle, B., Tsai, Y., Dong, M., Jackson, K., Punt, N., Rosen, M. J., Denson, L. A., Vinks, A. A., Minar, P. 2021; 109 (6): 1639-1647

  Abstract

  Standard-of-care infliximab dosing regimens were developed prior to the routine use of therapeutic drug monitoring and identification of target concentrations. Not surprisingly, subtherapeutic infliximab concentrations in pediatric Crohn's disease (CD) are common. The primary aim was to conduct a real-world pharmacokinetic (PK) evaluation to discover blood biomarkers of rapid clearance, identify exposure targets, and a secondary aim to translate PK modeling to the clinic. In a multicenter observational study, 671 peak and trough infliximab concentrations from 78 patients with CD were analyzed with a drug-tolerant assay (Esoterix; LabCorp, Calabasas, CA). Individual area under the curve (AUC) estimates were generated as a measure of drug exposure over time. Population PK modeling (nonlinear mixed-effect modeling) identified serum albumin, antibody to infliximab, erythrocyte sedimentation rate (ESR), and neutrophil CD64 as biomarkers for drug clearance. Week 14 and week 52 biochemical remitters (fecal calprotectin < 250 µg/g) had higher infliximab exposure (AUC) throughout induction. The optimal infliximab AUC target during induction for week 14 biochemical remission was 79,348 µg*h/mL (area under the receiver operating characteristic curve (AUROC) 0.77, [0.63-0.90], 85.7% sensitive, and 64.3% specific) with those exceeding the AUC target more likely to achieve a surgery-free week 52 biochemical remission (OR 4.3, [1.2-14.6]). Pretreatment predictors for subtherapeutic week 14 AUC included neutrophil CD64 > 6 (OR 4.5, [1.4-17.8]), ESR > 30 mm/h (OR 3.8, [1.4-11]), age < 10 years old (OR 4.2, [1.2-20]), and weight < 30 kg (OR 6.6, [2.1-25]). We created a decision-support PK dashboard with an iterative process and embedded the modeling program within the electronic health record. Model-informed precision dosing guided by real-world PKs is now available at the bedside in real-time.

  View details for DOI 10.1002/cpt.2148

  View details for Web of Science ID 000605586500001

  View details for PubMedID 33354765

  View details for PubMedCentralID PMC8159860

• An 11-Month-Old With Vomiting, Altered Mental Status, and Hypoventilation CLINICAL PEDIATRIC EMERGENCY MEDICINE Rudloff, J., Lipshaw, M. J., McKee, C., Colman, R. J., Vukovic, A. A. 2020; 21 (1)

  View details for Web of Science ID 000547567400002

• CHANGE IN FECAL CALPROTECTIN AND LACTOFERRIN PREDICT CLINICAL REMISSION FOLLOWING INDUCTION THERAPY WITH INFLIXIMAB IN PEDIATRIC CROHN'S DISEASE (CD) Colman, R., Boyle, B., Noe, J., Hyams, J., Minar, P. OXFORD UNIV PRESS INC. 2020: S68-S69

  View details for DOI 10.1093/ibd/zaa010.175

  View details for Web of Science ID 000518532600177

• Upper Gastrointestinal Endoscopy in Adolescents With Severe Obesity Before Vertical Sleeve Gastrectomy JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Colman, R. J., Baidal, J., Zitsman, J. L., Mencin, A. A. 2019; 69 (3): 287-291

  Abstract

  Esophagogastroduodenoscopy (EGD) is often performed to evaluate for mucosal and anatomical abnormalities before vertical sleeve gastrectomy (SG). Little is known, however, about how prebariatric EGD in adolescents influences clinical management or outcome. Our aim was to assess if an abnormal prebariatric EGD resulted in interventions or modification of bariatric surgery.We performed a retrospective cohort study of adolescents undergoing evaluation for bariatric surgery. We obtained demographic and anthropometric data in addition to EGD findings, biopsy pathology, gastrointestinal symptoms, and surgical outcomes. An EGD was considered abnormal if either abnormal gross findings or abnormal pathology was reported. Patients were followed until a 6-week postop visit.Of 134 patients presenting for evaluation, 94 (70%) underwent preoperative EGD. Fifty-one (54%) had a normal EGD and 43 (46%) had EGD abnormalities including 7 with an anatomical abnormality and 36 with mild mucosal abnormalities. Among patients with EGD abnormalities, 22% received medical intervention including proton pump inhibitor (PPI) administration (n = 10) and Helicobacter pylori eradication (n = 11). GI symptoms were the only predictor of EGD abnormalities (odds ratio [OR] 4.9: 95% confidence interval [CI] 1.6-15.0; P < 0.001). No factors predicted likelihood of a post-EGD intervention. An abnormal EGD did not correlate with any postoperative complications.In this cohort of adolescents undergoing evaluation for SG, 46% had an abnormal EGD, of which 22% received a medical intervention. Symptoms were the only predictor of EGD abnormalities. Abnormal EGD findings were not associated with modification of the surgery or any adverse outcome.

  View details for DOI 10.1097/MPG.0000000000002371

  View details for Web of Science ID 000502025700011

  View details for PubMedID 31436669

• Safety and Efficacy of Combination Treatment With Calcineurin Inhibitors and Vedolizumab in Patients With Refractory Inflammatory Bowel Disease CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Christensen, B., Gibson, P. R., Micic, D., Colman, R. J., Goeppinger, S. R., Kassim, O., Yarur, A., Weber, C. R., Cohen, R. D., Rubin, D. T. 2019; 17 (3): 486-493

  Abstract

  Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohn's disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors.We collected data on patients with CD (n = 9) or UC (n = 11) who began treatment with vedolizumab from May 20, 2014, through March 30, 2015, and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy. Clinical activity scores and inflammatory markers were measured at baseline and at weeks 14, 30, and 52 of vedolizumab treatment. Clinical remission was defined as a Harvey-Bradshaw index score ≤4 or short clinical colitis activity index score ≤2; steroid-free clinical remission was defined as clinical remission without corticosteroids.By week 14 of treatment, 44% of the patients with CD and 55% of the patients with UC achieved steroid-free clinical remission; after 52 weeks of treatment, 33% of the patients with CD and 45% of the patients with UC were in steroid-free clinical remission. Seven patients received salvage therapy with a calcineurin inhibitor after primary nonresponse to vedolizumab-1 of the 2 patients with UC and 2 of 5 patients with CD stopped taking the calcineurin inhibitors and achieved steroid-free remission at week 52. In total, 16 patients (59%) received 52 weeks of treatment with vedolizumab. Three serious adverse events were associated with calcineurin inhibitors.Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow-up evaluation. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted.

  View details for DOI 10.1016/j.cgh.2018.04.060

  View details for Web of Science ID 000456339200026

  View details for PubMedID 29751166

  View details for PubMedCentralID PMC7034423

• Efficacy and Follow-up of Segmental or Subtotal Colectomy in Patients With Colitis-Associated Neoplasia CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Cleveland, N., Ollech, J. E., Colman, R. J., Rodriquez, D., Hirsch, A., Cohen, R. D., Hanauer, S. B., Hart, J., Hurst, R., Rubin, D. T. 2019; 17 (1): 205-206

  Abstract

  The historical approach to neoplasia in the setting of chronic colitis was to perform a total proctocolectomy. Recent consensus and society guidelines1-3 suggest that when dysplastic lesions can be removed endoscopically, continued surveillance is appropriate. This is based on improvements in optical technologies and the low risk of metachronous colorectal carcinoma in these patients.4-6 We hypothesized that if a lesion was completely removed surgically and followed up endoscopically, metachronous colorectal carcinoma would be a rare occurrence. Thus, segmental resection may be offered as a definitive surgery in patients with chronic colitis and localized colorectal neoplasia in whom endoscopic resection is not feasible. Retention of the distal colon/rectum is expected to result in an overall improved quality of life compared with permanent ileostomy or an ileoanal J-pouch. Here, we report our experience and follow-up evaluation of segmental resections for preoperative neoplasia in patients with Crohn's disease (CD) or ulcerative colitis (UC).

  View details for DOI 10.1016/j.cgh.2018.04.061

  View details for Web of Science ID 000453252900038

  View details for PubMedID 29751167

  View details for PubMedCentralID PMC7034413

• Methotrexate for the Treatment of Pediatric Crohn's Disease: A Systematic Review and Meta-analysis INFLAMMATORY BOWEL DISEASES Colman, R. J., Lawton, R. C., Dubinsky, M. C., Rubin, D. T. 2018; 24 (10): 2135-2141

  Abstract

  Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature.A systematic literature search was performed using MEDLINE and the Cochrane library from inception until March 2016. Synonyms for 'pediatric', 'methotrexate' and 'IBD' were utilized as both free text and MESH search terms. The studies included contained clinical remission (CR) rates for MTX treatment of pediatric IBD patients 18 yrs old, as mono- or combination therapy. Case studies with <10 patients were excluded. Quality assessment was performed with the Newcastle-Ottawa Scale. Meta-analysis calculated pooled CR rates. A random-effects meta-analysis with forest plots was performed using R.Fourteen (11 monotherapy, 1 combination therapy, 2 both; n = 886 patients) observational studies were eligible out of 202 studies. No interventional studies were identified. The pooled achieved CR rate for pediatric CD patients on monotherapy within 3-6 months was 57.7% (95% CI 48.2-66.6%), (P =0.22; I2 = 29.8%). The CR was 37.1% (95% CI 29.5-45.5%), (P = 0.20; I2 = 37.4%) for maintenance therapy at 12 months. Sub-analysis could not identify CR differences between MTX administration types, thiopurine exposure.This meta-analysis demonstrated that, over 50% of pediatric Crohn's disease patients induced with methotrexate achieved clinical remission, while 12-month remission rate was only 37%. Prospective controlled interventional trials should assess treatment efficacy among patient subgroups. 10.1093/ibd/izy078_video1izy078.video15774883936001.

  View details for DOI 10.1093/ibd/izy078

  View details for Web of Science ID 000449182600006

  View details for PubMedID 29688409

  View details for PubMedCentralID PMC6994018

• Prevalence of functional GI disorders among pediatric patients with persistent asthma JOURNAL OF DIGESTIVE DISEASES Colman, R. J., Rosario, N. S., Gutierrez Bonilla, A., Benavidez Alvarez, G., Benavidez Alvarez, J., Uy, V. P., Pina, P. R., Rubin, D. H. 2018; 19 (9): 522-528

  Abstract

  Functional gastrointestinal (GI) disorders (FGIDs), such as irritable bowel syndrome, functional abdominal pain and dyspepsia, are common causes of chronic GI symptoms in children. Prior studies found high comorbidity of FGID and asthma. This study aimed to assess the prevalence and comorbidities of FGID among pediatric patients with asthma at a university-affiliated urban community hospital.This prospective, cross-sectional study assessed FGID prevalence, asthma control and symptoms of anxiety among pediatric patients with persistent asthma. The pediatric ROME III questionnaire was used to assess FGID. The Asthma Control Test assessed asthma control. The Beck Anxiety Inventory assessed symptoms of anxiety.Of the 110 enrolled patients, 18 (16.4%) met the diagnostic criteria for FGID, of which 10 were consistent with the diagnosis of functional abdominal pain disorder. Patients with FGID had a significantly lower mean asthma control score than patients without FGID (11.5 ± 4.9 vs 14.8 ± 5.3, P = 0.03; Cohen's d = 0.6) and higher mean anxiety scores than those without FGID (P < 0.01). Asthma control predicted the presence of FGID (OR 0.90, 95% CI 0.80-0.99, P = 0.03). However, after adjusted for anxiety, asthma control no longer predicted FGID presence (adjusted OR 0.90, 95% CI 0.83-1.05, P = 0.23).This study suggests a high prevalence of FGID among patients with persistent asthma. Moreover, patients with FGID had poor asthma control and increased anxiety. Clinicians should consider FGID in patients with poor asthma control and assess them for anxiety.

  View details for DOI 10.1111/1751-2980.12653

  View details for Web of Science ID 000446989200002

  View details for PubMedID 30094945

• Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety INFLAMMATORY BOWEL DISEASES Christensen, B., Colman, R. J., Micic, D., Gibson, P. R., Goeppinger, S. R., Yarur, A., Weber, C. R., Cohen, R. D., Rubin, D. T. 2018; 24 (4): 849-860

  Abstract

  Vedolizumab is approved for moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease.Consecutive patients receiving vedolizumab for treatment of UC or CD with at least 14 weeks of follow-up, regardless of outcome, were included. Patients had clinical activity scores (Harvey-Bradshaw Index [HBI] or Simple Clinical Colitis Activity Index [SCCAI]) and inflammatory markers prospectively measured at baseline and weeks 14, 30, and 52. Clinical response was defined as a reduction ≥3 in HBI or SCCAI, clinical remission as HBI ≤4 or SCCAI ≤2, steroid-free remission as clinical remission without the need for corticosteroids, and mucosal healing (assessed at 6 months) as a Mayo endoscopic subscore of 0 or 1 or CD-SES <3.A total of 132 patients were included: 61 (45%) male, 94 (71%) with CD, 42 (29%) with UC; 22% and 34% of CD and UC patients, respectively, achieved steroid-free remission by week 14. This increased to 31% in CD patients and plateaued at 35% in UC patients at 12 months. Increasing remission rates to 6 months were seen in patients with CD, but minimal improvements after 3 months of therapy occurred in those with UC. Mucosal healing was achieved in 52% of UC and 30% of CD patients. Most adverse events were minor; 74% remained on vedolizumab at 12 months.In this real-world study, vedolizumab demonstrated similar efficacy and safety seen in pivotal trials, with sustained clinical response in the majority of patients. Similar rates of response were seen in UC and CD patients. 10.1093/ibd/izx067_video1izx067_Video5754037470001.

  View details for DOI 10.1093/ibd/izx067

  View details for Web of Science ID 000428546400018

  View details for PubMedID 29562271

  View details for PubMedCentralID PMC6196763

• Histological inflammation increases the risk of colorectal neoplasia in ulcerative colitis: a systematic review INTESTINAL RESEARCH Colman, R. J., Rubin, D. T. 2016; 14 (3): 202-210

  Abstract

  Ulcerative colitis (UC) patients are at greater risk for the development of colorectal neoplasia. Several individual studies have demonstrated associations between severity of histologic inflammation and colorectal neoplasia. However, a comprehensive systematic review has not been completed. We performed a systematic review and meta-analysis to explore the relationship between histologic inflammation and risk for neoplasia among available observational studies.Three databases (EMBASE, MEDLINE and the Cochrane Library) were systematically searched. Studies were included if they included UC patients who underwent colonoscopic assessment and when histologic inflammation and colorectal neoplasia were both reported. Colorectal neoplasia rates were compared. Quantitative meta-analysis was attempted.Four of 1,422 records found were eligible. Results from 2 case-control studies reported a 3.5-fold increased risk for colorectal neoplasia associated with a single point increase in histologic inflammation. This result was further corroborated by one cohort study that demonstrated increased hazard ratios. The second cohort study reported outcomes for patients with normal gross endoscopy, but had increased histological inflammation when neoplasia was assessed. Finally, this study reported increased risk for neoplastic progression by histological inflammation among patients who were normal by gross endoscopic evaluation. Quantitative meta-analysis was unsuccessful due to heterogeneity between study measures.There is strong evidence that histologic inflammation among patients with UC increases the risk of colorectal neoplasia. The depth and nature of assessment of additional clinical variables was varied and may have resulted in greater outcome discrepancy. Additional study related to mechanisms of inflammation-related neoplasia and therapeutic modification is needed.

  View details for DOI 10.5217/ir.2016.14.3.202

  View details for Web of Science ID 000405284800002

  View details for PubMedID 27433141

  View details for PubMedCentralID PMC4945523

• Antibodies to Infliximab are Frequently Present when Infliximab Levels are Detectable in an ECLIA-based Assay Colman, R. J., Rubin, D. W B SAUNDERS CO-ELSEVIER INC. 2016: S420

  View details for DOI 10.1016/S0016-5085(16)31458-5

  View details for Web of Science ID 000391764900406

• Segmental and Total Abdominal Colectomies are Safe Management Strategies for Colitis-Associated Neoplasia Cleveland, N., Colman, R., Rodriquez, D., Hirsch, A., Cohen, R., Hanauer, S., Hurst, R., Hartk, J., Rubin, D. LIPPINCOTT WILLIAMS & WILKINS. 2016: S19

  View details for DOI 10.1097/01.MIB.0000480122.74166.7f

  View details for Web of Science ID 000393896400057

• Surveillance of IBD Using High Definition Colonoscopes Does Not Miss Adenocarcinoma in Patients with Low-grade Dysplasia INFLAMMATORY BOWEL DISEASES Cleveland, N., Colman, R. J., Rodriquez, D., Hirsch, A., Cohen, R. D., Hanauer, S. B., Hart, J., Rubin, D. T. 2016; 22 (3): 631-637

  Abstract

  Historically, limits to the ability to detect dysplasia in chronic inflammatory bowel disease (IBD)-associated colitis resulted in the recommendation that neoplasia of any grade be treated by proctocolectomy. We hypothesized that with improved optical technologies, most neoplasia in colitis is now detectable and reassessed the prevalence of colitis-associated neoplasia.We retrospectively reviewed all our patients with IBD who had pathologist-confirmed neoplasia on surveillance colonoscopy and underwent a subsequent colectomy. We included patients whose index lesions were found between 2005 and 2014 (the dates of our high definition equipment) and recorded the location and grade of these lesions. These findings were compared to the surgical specimens, and in patients with partial colectomies, included follow-up.Thirty-six patients with IBD (19 [53%] ulcerative colitis and 17 [47%] Crohn's disease) were found to have neoplastic lesions on surveillance colonoscopy and underwent a subsequent partial colectomy or total proctocolectomy. Forty-four index lesions were identified by colonoscopy (29 white light and 7 methylene blue chromoscopy): 30 low-grade dysplasia, 6 high-grade dysplasia, and 8 adenocarcinoma. None of the low-grade dysplasia or adenocarcinoma index lesions were associated with synchronous carcinoma at colectomy. One of the patients with high-grade dysplasia had adenocarcinoma of the appendix.In this experience with high definition colonoscopes in chronic colitis, no synchronous adenocarcinomas were found when colectomy was performed for low-grade dysplasia or index adenocarcinoma, and only 1 adenocarcinoma in the appendix was found in the setting of high-grade dysplasia. These findings suggest that active surveillance or subtotal colectomy may be safe options for patients with IBD and some grades of neoplasia.

  View details for DOI 10.1097/MIB.0000000000000634

  View details for Web of Science ID 000371503700013

  View details for PubMedID 26658214

  View details for PubMedCentralID PMC5058785

• Can Baseline Histological Score Predict Subsequent Clinical Outcomes in Patients With Ulcerative Colitis? Colman, R. J., Ackerman, M. T., Rodriquez, D., Sadiq, F., Cleveland, N., Goeppinger, S., Hart, J., Turner, J. R., Raffals, L., Cohen, R., Hanauer, S. B., Rubin, D. T. NATURE PUBLISHING GROUP. 2015: S799

  View details for DOI 10.14309/00000434-201510001-01882

  View details for Web of Science ID 000363715904041

• Endoscopic and Histologic Response and Remission in Inflammatory Bowel Disease Patients Initiating Vedolizumab Christensen, B., Rubin, D. T., Goeppinger, S., Colman, R. J., Yarur, A., Hirsch, A., Bocheneck, A., Wichmann, A., Sakuraba, A., Cohen, R., Siddiqui, D. NATURE PUBLISHING GROUP. 2015: S783-S784

  View details for DOI 10.14309/00000434-201510001-01843

  View details for Web of Science ID 000363715904003

• Successful Treatment of Ulcerative Colitis With Vedolizumab in a Patient With an Infliximab-Associated Psoriasiform Rash ACG CASE REPORTS JOURNAL Hirsch, A., Colman, R. J., Lang, G. D., Rubin, D. T. 2015; 2 (4): 236-238

  Abstract

  Psoriatic skin lesions associated with anti-tumor necrosis factor (TNF) agents are well-described in the medical literature. However, the etiology and optimal management of this condition remain unclear. Vedolizumab is a novel, gut-specific, anti-integrin agent used for the treatment of inflammatory bowel disease (IBD). We report a case of infliximab-associated psoriasiform lesions in an ulcerative colitis patient. Transition to vedolizumab resulted in resolution of the cutaneous lesions without recurrence and remission of his ulcerative colitis.

  View details for DOI 10.14309/crj.2015.70

  View details for Web of Science ID 000215263600019

  View details for PubMedID 26203450

  View details for PubMedCentralID PMC4508952

• Vedolizumab in the Treatment of IBD: The University of Chicago Experience Christensen, B., Goeppinger, S. R., Colman, R. J., Siddiqui, D., Yarur, A., Bochenek, A. A., Wichmann, A., Hirsch, A., Kinnucan, J. A., Sakuraba, A., Cohen, R. D., Rubin, D. T. W B SAUNDERS CO-ELSEVIER INC. 2015: S866

  View details for Web of Science ID 000360120300073

• Crohn's Disease Patients Currently or Previously on Natalizumab Can Be Safely and Effectively Switched to Vedolizumab Christensen, B., Goeppinger, S. R., Colman, R. J., Siddiqui, D., Yarur, A., Hirsch, A., Wichmann, A., Bochenek, A. A., Sakuraba, A., Cohen, R. D., Rubin, D. T. W B SAUNDERS CO-ELSEVIER INC. 2015: S866-S867

  View details for Web of Science ID 000360120300074

• The Efficacy and Safety of Calcineurin Inhibitors in Inducing and Maintaining Clinical Remission in IBD Patients Commencing Vedolizumab Christensen, B., Goeppinger, S. R., Colman, R. J., Siddiqui, D., Yarur, A., Hirsch, A., Bochenek, A. A., Wichmann, A., Sakuraba, A., Cohen, R. D., Rubin, D. T. W B SAUNDERS CO-ELSEVIER INC. 2015: S866

  View details for Web of Science ID 000360120300072

• Revised Predictive Values for IBD Colitis-Associated Neoplasia in the Modern Era Cleveland, N., Colman, R. J., Rodriquez, D. M., Hart, A., Rubin, D. T. W B SAUNDERS CO-ELSEVIER INC. 2015: S575

  View details for Web of Science ID 000360117100597

• Assessment of Injection Site Reactions Related to Anti-TNF Therapies in Inflammatory Bowel Disease Colman, R. J., Goeppinger, S. R., Micic, D., Rodriquez, D. M., Ackerman, M. T., Sakuraba, A., Rubin, D. T. W B SAUNDERS CO-ELSEVIER INC. 2015: S238

  View details for Web of Science ID 000360115800115

• Optimal Doses of Methotrexate Combined with Anti-TNF Therapy to Maintain Clinical Remission in Inflammatory Bowel Disease JOURNAL OF CROHNS & COLITIS Colman, R. J., Rubin, D. T. 2015; 9 (4): 312-317

  Abstract

  Methotrexate (MTX) is sometimes used as part of combination therapy for the treatment of inflammatory bowel disease [IBD]; however, the optimal MTX dose for combination therapy has not been established. This study compared the efficacy of lower-dose and higher-dose MTX with anti tumor necrosis factor alpha (anti-TNF) therapy among IBD patients.Retrospective chart review was performed of 88 IBD patients at our center between 2010 and 2013. Low-dose MTX was defined as ≤ 12.5mg/week and high-dose MTX as 15-25mg/week. Patients who met the criteria for clinical remission [Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2] at baseline were followed for up to 42 months. Chart review occurred in 6-month intervals. The primary outcome was consecutive months in remission prior to relapse. Secondary outcomes included other indicators of worsening disease [endoscopic inflammation, steroid use, therapy escalation/addition, or surgery] and adverse events. Regression analysis and Kaplan-Meier survival analysis were completed.We identified 73 [83%] dual-therapy patients, of whom 32 low-dose and 14 high-dose individuals achieved remission. When compared with high-dose patients, low-dose patients were more likely to relapse [log-rank test, p < 0.01]. Secondary indicators of worsening disease occurred during 34.4% of low-dose review periods and 31.4% of high-dose review periods [p = 0.67]; 3/52 [6%] low-dose patients and 3/21 [14%] high-dose patients [p = 0.34] discontinued MTX therapy due to adverse events.When combined with anti-TNF therapy, MTX at doses of >12.5mg/week was more effective at maintaining clinical remission than lower doses. These findings will guide management of combination therapy in IBD patients.

  View details for DOI 10.1093/ecco-jcc/jjv027

  View details for Web of Science ID 000353814900003

  View details for PubMedID 25616487

  View details for PubMedCentralID PMC4621545

• De ziekte van Crohn: een controverse. Nederlands tijdschrift voor geneeskunde Colman, R. J. 2015; 159: A8220

  Abstract

  In 1932, the New York City-based gastroenterologist, Burril B. Crohn, published the manuscript 'Regional Ileitis' in The Journal of the American Medical Association (JAMA). This publication is responsible for the current designation of Crohn's disease. Despite the fact that this ground-breaking article lead to the improved description and recognition of this gastrointestinal disease, the choice for the name Crohn's disease was not always straightforward. This article discusses the controversy between Crohn and his colleagues Ginzburg and Oppenheimer, about the naming of the disease. In addition, it touches on the recognition of phenotypes that vary from Crohn's original depiction.

  View details for PubMedID 25761291

• Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis JOURNAL OF CROHNS & COLITIS Colman, R. J., Rubin, D. T. 2014; 8 (12): 1569-1581

  Abstract

  Fecal microbiota transplantation (FMT) has gained interest as a novel treatment option for inflammatory bowel diseases (IBD). While publications describing FMT as therapy for IBD have more than doubled since 2012, research that investigates FMT treatment efficacy has been scarce. We conducted a systematic review and meta-analysis to evaluate the efficacy of FMT as treatment for patients with IBD.A systematic literature search was performed through May 2014. Inclusion criteria required FMT as the primary therapeutic agent. Clinical remission (CR) and/or mucosal healing were defined as primary outcomes. Studies were excluded if they did not report clinical outcomes or included patients with infections.Eighteen studies (9 cohort studies, 8 case studies and 1 randomized controlled trial) were included. 122 patients were described (79 ulcerative colitis (UC); 39 Crohn's disease (CD); 4 IBD unclassified). Overall, 45% (54/119) of patients achieved CR during follow-up. Among the cohort studies, the pooled proportion of patients that achieved CR was 36.2% (95% CI 17.4%-60.4%), with a moderate risk of heterogeneity (Cochran's Q, P=0.011; I(2)=37%). Subgroup analyses demonstrated a pooled estimate of clinical remission of 22% (95% CI 10.4%-40.8%) for UC (P=0.37; I(2)=0%) and 60.5% (95% CI 28.4%-85.6%) for CD (P=0.05; I(2)=37%). Six studies performed microbiota analysis.This analysis suggests that FMT is a safe, but variably efficacious treatment for IBD. More randomized controlled trials are needed and should investigate frequency of FMT administration, donor selection and standardization of microbiome analysis.

  View details for DOI 10.1016/j.crohns.2014.08.006

  View details for Web of Science ID 000347019600001

  View details for PubMedID 25223604

  View details for PubMedCentralID PMC4296742

• Efficacy of High-Dose Versus Low-Dose Methotrexate in Combination Therapy for Inflammatory Bowel Disease Colman, R., Rubin, D. NATURE PUBLISHING GROUP. 2014: S489-S490

  View details for DOI 10.14309/00000434-201410002-01649

  View details for Web of Science ID 000344383102045

• Fecal Alpha 1-Antitrypsin as a Biomarker for Disease Activity in Ulcerative Colitis Colman, R., Rubin, D. NATURE PUBLISHING GROUP. 2014: S434

  View details for DOI 10.14309/00000434-201410002-01468

  View details for Web of Science ID 000344383101692

• Agreement Between Patient- and Physician-completed Pediatric Ulcerative Colitis Activity Index Scores JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Lee, J. J., Colman, R. J., Mitchell, P. D., Atmadja, M. L., Bousvaros, A., Lightdale, J. R. 2011; 52 (6): 708-713

  Abstract

  Currently validated ulcerative colitis (UC) activity measures are physician based, but incorporate patient reports of symptoms. We aimed to assess whether patient-completed Pediatric UC Activity Index (PUCAI) scores are comparable to those of physician scores.We performed a single-center prospective study to assess agreement between patient- and physician-completed PUCAI scores. Seventy patients with UC (ages 4-29) representative of all of the disease activity categories (inactive, mild, moderate, and severe) in the currently published physician-completed scoring system were recruited. Agreement was analyzed for PUCAI scores both as continuous and categorical measures. To ascertain validity, we compared both patient- and physician-completed PUCAI scores with the physician global assessment and serum inflammatory markers.Patient- and physician-completed PUCAI summary scores were identical 49% of the time, were different but within the minimal clinically important difference (MCID) of 20 points 48% of the time, and were at or beyond the MCID only 3% of the time. In general, patients reported higher mean disease severity on their questionnaires than did their physicians, with a mean difference in PUCAI scores of 3 ± 8 (95% confidence interval 2%-5%). A categorical comparison of the 2 sets of questionnaires using the disease activity groups demonstrated perfect agreement for 60 (86%) pairs (kappa coefficient 0.78; 95% confidence interval 0.65%-0.90%). Both patient- and physician-completed PUCAI scores also correlated well with the physician global assessment and serum inflammatory markers.Our data indicate strong agreement between PUCAI scores obtained directly from patients and those completed by physicians. Hence, a patient-based PUCAI could complement existing instruments in both clinical and research settings.

  View details for DOI 10.1097/MPG.0b013e3182099018

  View details for Web of Science ID 000290750500011

  View details for PubMedID 21593644