Long-term Outcomes of Paediatric Patients Admitted With Acute Severe Colitis— A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN

Krauthammer, Alex; Tzivinikos, Christos; Assa, Amit; Miele, Erasmo; Strisciuglio, Caterina; Urlep, Darja; Serban, Daniela Elena; Singh, Avantika; Winter, Harland S.; Russell, Richard K.; Hojsak, Iva; Malham, Mikkel; Navas-López, Víctor Manuel; Croft, Nicholas M.; Lee, Huey Miin; Ledder, Oren; Shamasneh, Ibrahim; Hussey, Séamus; Huynh, Hien Q.; Wine, Eytan; Shah, Neil; Sładek, M.; Meij, Tim G. de; Romano, Claudio; Dipasquale, Valeria; Lionetti, Paolo; Afzal, Nadeem; Aloi, Marina; Lee, Kwangyang; Martín-de-Carpi, Javier; Yerushalmy‐Feler, Anat; Subramanian, Sreedhar; Weiss, Batia; Shouval, Dror S.

doi:10.1093/ecco-jcc/jjz092

Cited by 16 publications

(9 citation statements)

References 39 publications

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“…The colectomy among patients with no flares differed substantially from that among patients with several flares during follow-up (3-40%) [2]. A recent multi-centre study of pediatric patients admitted with ASUC reported a colectomy rate of 36.4% at 5-year follow-up [15]. The colectomy rate of 26% in our series was lower than that reported in those studies.…”

Section: Discussioncontrasting

confidence: 77%

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids

Eronen

Ilus

Jussila

et al. 2021

Scandinavian Journal of Gastroenterology

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Background and aims: Every fifth patient with ulcerative colitis (UC) experiences severe acute flare at some point in the course of the disease. Corticosteroids (Cs) remain the treatment of choice in acute flare. Data on the efficacy of first intravenous Cs in the long-term prognosis of UC are scarce and were investigated here. Materials and methods: All episodes of patients with acute UC admitted to Tampere University Hospital and treated with intravenous Cs between January 2007 and January 2016 were identified from patient records and reviewed. The risks for colectomy and for continuous use of Cs were evaluated. Predictive factors were analysed. Results: The study comprised 217 patients of whom 184 (85%) responded to intravenous Cs at index flare. Of the 33 non-responders, 31 (94%) were treated with intravenous cyclosporine A and 28 responded. Five (2.3%) patients needed emergency colectomy. Twenty-six (12%) patients underwent colectomy within 1 year of index flare. Overall colectomy rate was 56 (26%) during follow-up (median 7.5 years, range 0.1-10.5). Six months after index flare 66 (30%) patients were still on steroids. In this series 149 (69%) required further Cstherapy and 104 (48%) needed rehospitalization for new flare at some point during follow-up. Overall 155 patients were treated with thiopurines, of whom 72% within the first year after admission. A total of 36 patients had infliximab as a first-line biological treatment, nine needed second-line therapy with adalimumab or vedolizumab after infliximab failed. Conclusion: Although intravenous Cs were efficient in inducing clinical response in patients with severe acute UC, only one fifth maintained remission in the long term. Two-thirds of patients required further Cs and the overall colectomy rate remained at 26%. High relapse rate indicates the need for closer monitoring of these patients. Enhancement of maintenance therapy should be considered at early stage after acute flare.

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Section: Discussioncontrasting

confidence: 77%

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids

Eronen

Ilus

Jussila

et al. 2021

Scandinavian Journal of Gastroenterology

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“…26 Colectomy-free rates were 71.3%, 66.4%, and 63.6% after one, three, and five years, respectively, demonstrating that despite the introduction of anti-TNFs, the clinical outcomes of children with ASC are still poor. 26 In our cohort, children with severe UC at IFX initiation developed poorer long-term outcomes, including a higher rate of IFX failure and a higher colectomy rate, than those with moderate UC. Specifically, the Kaplan-Meier curve detected a two-year cumulative colectomy rate of 15.38% in children with severe UC versus 3.92% in patients with moderate UC.…”

Section: Discussionmentioning

confidence: 99%

“…IFX optimization strategies are particularly needed in the setting of ASC. Recently, Krauthammer et al reported the follow‐up of a multicenter cohort of children admitted for an ASC flare in the biologics era 26 . Colectomy‐free rates were 71.3%, 66.4%, and 63.6% after one, three, and five years, respectively, demonstrating that despite the introduction of anti‐TNFs, the clinical outcomes of children with ASC are still poor 26 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Krauthammer et al reported the follow‐up of a multicenter cohort of children admitted for an ASC flare in the biologics era 26 . Colectomy‐free rates were 71.3%, 66.4%, and 63.6% after one, three, and five years, respectively, demonstrating that despite the introduction of anti‐TNFs, the clinical outcomes of children with ASC are still poor 26 . In our cohort, children with severe UC at IFX initiation developed poorer long‐term outcomes, including a higher rate of IFX failure and a higher colectomy rate, than those with moderate UC.…”

Section: Discussionmentioning

confidence: 99%

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Post‐induction infliximab trough levels and disease activity in the clinical evolution of pediatric ulcerative colitis

Moore

Dolce²,

Devas

et al. 2020

UEG Journal

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Background and aims Recent adult evidence suggests that infliximab (IFX) trough levels (TL) in patients with severe ulcerative colitis (UC) may be decreased. The aims of our study were to compare post-induction IFX TL of children with severe versus moderate UC and to evaluate short- and long-term outcomes. Methods In this single-center retrospective study, children with a diagnosis of UC starting IFX with a Pediatric Ulcerative Colitis Activity Index (PUCAI) ≥35 and with available post-induction TL were recruited. UC characteristics, IFX dosage and interval, primary non-response, IFX failure, and surgery after 24 months were collected. Post induction TL, anti-IFX antibodies, and laboratory evaluations at the time of starting IFX were also acquired. Results A total of 90 children were enrolled, of whom 39 (43.3%) were classified as severe UC and 51 (56.6%) as moderate UC. Median post-induction IFX TL were lower in severe UC versus moderate group (5.5 vs 10.3; p = 0.03), despite a more frequently intensified IFX regimen. Children in the higher TL quartiles showed increased rates of clinical, biological, and combined remission ( p = 0.04, p < 0.001, and p = 0.01, respectively). In a multivariate analysis, a PUCAI ≥65 and time interval from last IFX infusion were the only predictors associated with IFX TL. At 24 months, children in the higher TL quartiles had a decreased risk of IFX failure ( p = 0.002). The severe UC group showed a higher risk of IFX failure at 24 months (16/23 (41%) vs. 11/40 (21.6%); p = 0.05). Kaplan–Meier methods demonstrated a trend toward statistical significance, with a two-year cumulative colectomy rate of 15.38% (95% confidence interval (CI) 8.1–15.6%) in children with severe UC and 3.92% (95% CI 2.9–10.8%) in patients with moderate UC (logrank test p = 0.06). Conclusions Children starting IFX with severe UC showed lower post-induction TL and poor disease outcomes. Achieving adequate TL was associated with better efficacy outcomes.

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“…Historical data report that between 4% and 17% [1][2][3] of children with UC have a colectomy by 1 year after diagnosis, rising to 20% to 26% by 5 years. 4,5 Universal or extensive colitis at diagnosis and an initial Pediatric Ulcerative Colitis Activity Index (PUCAI) score ≥ 65 1,3,6,7 have been associated with a higher risk of colectomy, as have hypoalbuminemia, 3 elevated C-reactive protein, 8 elevated erythrocyte sedimentation rate (ESR), 9 and anemia. 2,10 Early requirements for antitumor necrosis factor (TNF) α therapy 1,8,10 and a lack of complete response by 6 weeks after anti-TNFα therapy have been associated with a higher risk of colectomy.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis

Hyams

Brimacombe

Haberman

et al. 2021

Inflammatory Bowel Diseases

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Background Develop a clinical and biological predictive model for colectomy risk in children newly diagnosed with ulcerative colitis (UC). Methods This was a multicenter inception cohort study of children (ages 4-17 years) newly diagnosed with UC treated with standardized initial regimens of mesalamine or corticosteroids (CS) depending upon initial disease severity. Therapy escalation to immunomodulators or infliximab was based on predetermined criteria. Patients were phenotyped by clinical activity per the Pediatric Ulcerative Colitis Activity Index (PUCAI), disease extent, endoscopic/histologic severity, and laboratory markers. In addition, RNA sequencing defined pretreatment rectal gene expression and high density DNA genotyping by the Affymetrix UK Biobank Axiom Array. Coprimary outcomes were colectomy over 3 years and time to colectomy. Generalized linear models, Cox proportional hazards multivariate regression modeling, and Kaplan-Meier plots were used. Results Four hundred twenty-eight patients (mean age 13 years) started initial theapy with mesalamine (n = 136), oral CS (n = 144), or intravenous CS (n = 148). Twenty-five (6%) underwent colectomy at ≤1 year, 33 (9%) at ≤2 years, and 35 (13%) at ≤3 years. Further, 32/35 patients who had colectomy failed infliximab. An initial PUCAI ≥ 65 was highly associated with colectomy (P = 0.0001). A logistic regression model predicting colectomy using the PUCAI, hemoglobin, and erythrocyte sedimentation rate had a receiver operating characteristic area under the curve of 0.78 (95% confidence interval [0.73, 0.84]). Addition of a pretreatment rectal gene expression panel reflecting activation of the innate immune system and response to external stimuli and bacteria to the clinical model improved the receiver operating characteristic area under the curve to 0.87 (95% confidence interval [0.82, 0.91]). Conclusions A small group of children newly diagnosed with severe UC still require colectomy despite current therapies. Our gene signature observations suggest additional targets for management of those patients not responding to current medical therapies.

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Long-term Outcomes of Paediatric Patients Admitted With Acute Severe Colitis— A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN

Cited by 16 publications

References 39 publications

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids

Long-term outcome of patients with acute ulcerative colitis after first course of intravenous corticosteroids

Post‐induction infliximab trough levels and disease activity in the clinical evolution of pediatric ulcerative colitis

Clinical and Host Biological Factors Predict Colectomy Risk in Children Newly Diagnosed With Ulcerative Colitis

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