Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response

Turner, Dan; Mack, David R.; LeLeiko, Neal S.; Walters, Thomas D.; Uusoue, Krista; Leach, Steven T.; Day, Andrew S.; Crandall, Wallace; Silverberg, Mark S.; Markowitz, James; Otley, Anthony; Keljo, David J.; Mamula, Petar; Kugathasan, Subra; Hyams, Jeffrey S.; Griffiths, Anne M.

doi:10.1053/j.gastro.2010.02.047

Cited by 227 publications

(218 citation statements)

References 34 publications

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“…In this study, the disease extent (10-13), disease duration (14,15), gender (16,17) and endoscopic findings (14,15,18,19) were not significant predictive factors for a colectomy as well as CNI non-responsiveness, although previous reports have identified these factors to predict the outcome. Most of these previous reports investigated the prognostic factors of patients treated with corticosteroids.…”

Section: Discussioncontrasting

confidence: 67%

Prognostic factors for colectomy in refractory ulcerative colitis treated with calcineurin inhibitors

Bamba

Andoh

Imaeda

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. Calcineurin inhibitors (CNIs) such as cyclosporin A (CSA) and tacrolimus (FK506) are efficacious in patients with steroid-refractory or steroid-dependent ulcerative colitis (UC). We retrospectively investigated patients with refractory UC treated with CNIs to elucidate the prognostic factors for a colectomy. Data from 59 patients (35 men and 24 women) were analyzed. CSA and FK506 were administered by intravenous infusion and peroral administration, respectively. The efficacy of the CNIs was assessed using Seo's complex integrated disease activity index. Categorical data analyses were also conducted. The results revealed that the response rates for CSA and FK506 were similar (CSA, 66.6%; FK506, 63.6%). However, oral FK506 had a slower onset of action than intravenous CSA. The risk factors for CNI non-responsiveness were: i) more than 10,000 mg of prednisolone used prior to CNI treatment; and ii) positivity for cytomegalovirus antigenemia (C7-HRP). The factors affecting the rate of colectomy were: i) CNI non-responsiveness; ii) more than 10,000 mg of prednisolone used prior to the initiation of CNI treatment; and iii) positivity for C7-HRP. The addition of azathioprine (AZA) following CNI treatment significantly reduced the incidence of colectomy. Our results revealed the prognostic factors affecting the efficacy of CNI therapy and the need for colectomy in patients with refractory UC. Importantly, some of these factors may be obtained prior to or shortly following the start of CNI treatment. Furthermore, AZA is an important agent for averting colectomy once a patient responds to CNIs.

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Section: Discussioncontrasting

confidence: 67%

Prognostic factors for colectomy in refractory ulcerative colitis treated with calcineurin inhibitors

Bamba

Andoh

Imaeda

et al. 2012

Experimental and Therapeutic Medicine

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“…PUCAI >65 on day 5 of IV CS predicts nonresponse to therapy with a specificity of 94% and a positive predictive value of 100%, representing an indication to start second-line therapy. 33 In patients with PUCAI scores between 35 and 64 on day 5 of treatment with IV CS, rescue therapy should always be considered; however, many clinicians wait another 2 to 3 days before assessing response to IV steroid therapy. Those with PUCAI <35 points on day 5 are unlikely to require second-line therapy by discharge 26 (Fig 1).…”

Section: Second-line or Rescue Therapymentioning

confidence: 99%

Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era

et al. 2016

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BACKGROUND AND OBJECTIVE: Approximately one-third of children with ulcerative colitis will experience at least 1 attack of acute severe colitis (ASC) before 15 years of age. Severe disease can be defined in children when Pediatric Ulcerative Colitis Activity Index is >65 and/or ≥6 bloody stools per day, and/or 1 of the following: tachycardia, fever, anemia, and elevated erythrocyte sedimentation rate with or without systemic toxicity. Our aim was to provide practical suggestions on the management of ASC in children. The goal of medical therapy is to avoid colectomy while preventing complications of disease, side effects of medications, and mortality. METHODS: A systematic search was carried out through Medline via PubMed to identify all articles published in English to date, based on the following keywords “ulcerative colitis,” “pediatric ulcerative colitis,” “biological therapy,” and “acute severe colitis.” Multidisciplinary clinical evaluation is recommended to identify early nonresponders to conventional treatment with intravenous corticosteroids, and to start, if indicated, second-line therapy or “rescue therapy,” such as calcineurin inhibitors (cyclosporine, tacrolimus) and anti–tumor necrosis factor molecules (infliximab). RESULTS: Pediatric Ulcerative Colitis Activity Index is a valid predictive tool that can guide clinicians in evaluating response to therapy. Surgery should be considered in the case of complications or rapid clinical deterioration during medical treatment. CONCLUSIONS: Several pitfalls may be present in the management of ASC, and a correct clinical and therapeutic approach is recommended to reduce surgical risk.

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“…In this study, the Pediatric Ulcerative Colitis Activity Index (an index based only on symptoms) was more able to identify patients who did not respond to intravenous corticosteroids than the Travis index, levels of fecal calprotectin, serum CRP level, M2-pyruvate kinase level, or S100A12 levels. It is important to consider that physicians in these studies who calculated the Pediatric Ulcerative Colitis Index could have used the data that was used to calculate the index to make therapeutic decisions ( 38,39 ). If this is the case, then it seems apparent why it would be diffi cult for the biomarkers to fare better than symptoms, particularly when making therapeutic decisions, such as the need for colectomy.…”

Section: Infl Ammatory Markers In Ucmentioning

confidence: 99%

“…Th e literature is lacking regarding randomized controlled trials focusing on this area. Th e majority of data are retrospective and unblinded (37)(38)(39) in nature, thus limiting its clinical utility.…”

Section: Fecal Calprotectin and Fecal Lactoferrinmentioning

confidence: 99%

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

Lichtenstein¹,

McGovern²

2016

Am J Gastroenterol Suppl

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Biomarkers, radiology fi ndings, and endoscopic studies, together with clinical assessment of patients with infl ammatory bowel disease, can be used to help determine prognosis, assess disease activity, and increasingly to inform treatment decision-making. This article reviews the current "state of the science" regarding the multitude of different tests that can be performed and how these can be used in the clinic to guide management. Initially, when patients present with symptoms suggestive of infl ammatory bowel disease (IBD), standard endoscopic studies and radiographic studies should be performed and the use of combinations of serologic and fecal markers may additionally be incorporated into patient assessment. Once the patient has a formal diagnosis, prognosis should be assessed and serologic evaluation may be used, but in conjunction with endoscopic and radiographic studies. Within the context of evaluating clinical predictors of disease (e.g., disease location, nutritional status, routine blood tests), early mucosal healing has been linked to better outcomes, and failure to heal the mucosa has been associated with poorer outcomes. Evaluation of response to therapy can be approximated with the use of biomarkers (e.g., C-reactive protein, fecal calprotectin, lactoferrin), and therapeutic drug monitoring has enabled us to assess levels of drug metabolites, drug levels, and antidrug antibodies to guide the ongoing management. Although there is not yet universal adoption of biomarkers to determine treatment choices (e.g., the use of anti-tumor necrosis factor therapy), biomarkers have enabled us to "fi ne tune" treatment of some patients with IBD. Establishing mechanisms of communicating these risks/benefi ts to patients will be a considerable challenge and remains a priority area of research.

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Severe Pediatric Ulcerative Colitis: A Prospective Multicenter Study of Outcomes and Predictors of Response

Cited by 227 publications

References 34 publications

Prognostic factors for colectomy in refractory ulcerative colitis treated with calcineurin inhibitors

Prognostic factors for colectomy in refractory ulcerative colitis treated with calcineurin inhibitors

Management of Acute Severe Colitis in Children With Ulcerative Colitis in the Biologics Era

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

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