Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide

Marzia Lazzerini, Vincenzo Villanacci, Maria Chiara Pellegrin, Stefano Martelossi, Giuseppe Magazzù, Salvatore Pellegrino, Maria Cristina Lucanto, Arrigo Barabino, Angela Calvi, Serena Arrigo, Paolo Lionetti, Massimo Fontana, Giovanna Zuin, Giuseppe Maggiore, Matteo Bramuzzo, Massimo Maschio, Marianna Salemme, Stefania Manenti, Luisa Lorenzi, Giuliana DecortiMarcella Montico, Alessandro Ventura

Research output: Contribution to journalArticle

Abstract

BACKGROUND & AIMS: Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long-term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings.

METHODS: We collected data from 2 multicenter trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileocolonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD; and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, respectively, for patients with UC. Patients with a clinical response to 8 weeks' treatment with thalidomide underwent endoscopic examination with biopsy collection at study weeks 12 and 52. Severity of inflammation in patients with UC was assessed by Mayo score and in patients with CD by 4-grade system. Biopsies were assessed for signs of active inflammation, erosion or ulceration, and crypt abscesses and assigned a histologic score.

RESULTS: Clinical remission was observed in 42 patients (60.0%) and clinical response in 45 patients (64.2%) at Week 8. At Week 52, a total of 38 patients (54.3%) were still in clinical remission or still had a clinical response; 29 patients (41.4%) had mucosal healing, defined as complete healing of erosions or ulcerations, and 20 patients (27.7%) had histologic healing, defined as complete absence of markers of inflammation. Of patients with clinical remission or clinical response, 75.3% also had mucosal healing and 52.6% also had histologic healing. The probability of achieving mucosal healing decreased significantly with increasing values of erythrocyte sedimentation rate (adjusted odds ratio, 0.96; 95% CI, 0.93-0.98; P = .006).

CONCLUSIONS: In a long-term analysis of data from 2 clinical trials of pediatric patients with CD or UC, 52 weeks' treatment with thalidomide led to clinical remission in 54.3% of patients with ileocolonic or colonic disease; of these patients, 75.3% had mucosal healing and 52.6% also had histologic healing. Further studies are needed to determine how thalidomide therapy affects long-term progression of inflammatory bowel diseases. (ClinicalTrials.gov number NCT00720538).

Original languageEnglish
Pages (from-to)1382-1389.e1
JournalClinical Gastroenterology and Hepatology
Volume15
Issue number9
DOIs
Publication statusPublished - Sep 2017

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Thalidomide
Inflammatory Bowel Diseases
Ulcerative Colitis
Crohn Disease
Colonic Diseases
Inflammation
Endoscopy
Biopsy
Blood Sedimentation
Therapeutics
Abscess
Multicenter Studies

Keywords

  • Journal Article

Cite this

Lazzerini, M., Villanacci, V., Pellegrin, M. C., Martelossi, S., Magazzù, G., Pellegrino, S., ... Ventura, A. (2017). Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide. Clinical Gastroenterology and Hepatology, 15(9), 1382-1389.e1. https://doi.org/10.1016/j.cgh.2017.02.029

Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide. / Lazzerini, Marzia; Villanacci, Vincenzo; Pellegrin, Maria Chiara; Martelossi, Stefano; Magazzù, Giuseppe; Pellegrino, Salvatore; Lucanto, Maria Cristina; Barabino, Arrigo; Calvi, Angela; Arrigo, Serena; Lionetti, Paolo; Fontana, Massimo; Zuin, Giovanna; Maggiore, Giuseppe; Bramuzzo, Matteo; Maschio, Massimo; Salemme, Marianna; Manenti, Stefania; Lorenzi, Luisa; Decorti, Giuliana; Montico, Marcella; Ventura, Alessandro.

In: Clinical Gastroenterology and Hepatology, Vol. 15, No. 9, 09.2017, p. 1382-1389.e1.

Research output: Contribution to journalArticle

Lazzerini, M, Villanacci, V, Pellegrin, MC, Martelossi, S, Magazzù, G, Pellegrino, S, Lucanto, MC, Barabino, A, Calvi, A, Arrigo, S, Lionetti, P, Fontana, M, Zuin, G, Maggiore, G, Bramuzzo, M, Maschio, M, Salemme, M, Manenti, S, Lorenzi, L, Decorti, G, Montico, M & Ventura, A 2017, 'Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide', Clinical Gastroenterology and Hepatology, vol. 15, no. 9, pp. 1382-1389.e1. https://doi.org/10.1016/j.cgh.2017.02.029
Lazzerini, Marzia ; Villanacci, Vincenzo ; Pellegrin, Maria Chiara ; Martelossi, Stefano ; Magazzù, Giuseppe ; Pellegrino, Salvatore ; Lucanto, Maria Cristina ; Barabino, Arrigo ; Calvi, Angela ; Arrigo, Serena ; Lionetti, Paolo ; Fontana, Massimo ; Zuin, Giovanna ; Maggiore, Giuseppe ; Bramuzzo, Matteo ; Maschio, Massimo ; Salemme, Marianna ; Manenti, Stefania ; Lorenzi, Luisa ; Decorti, Giuliana ; Montico, Marcella ; Ventura, Alessandro. / Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide. In: Clinical Gastroenterology and Hepatology. 2017 ; Vol. 15, No. 9. pp. 1382-1389.e1.
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abstract = "BACKGROUND & AIMS: Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long-term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings.METHODS: We collected data from 2 multicenter trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileocolonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50{\%} from baseline, respectively, for patients with CD; and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, respectively, for patients with UC. Patients with a clinical response to 8 weeks' treatment with thalidomide underwent endoscopic examination with biopsy collection at study weeks 12 and 52. Severity of inflammation in patients with UC was assessed by Mayo score and in patients with CD by 4-grade system. Biopsies were assessed for signs of active inflammation, erosion or ulceration, and crypt abscesses and assigned a histologic score.RESULTS: Clinical remission was observed in 42 patients (60.0{\%}) and clinical response in 45 patients (64.2{\%}) at Week 8. At Week 52, a total of 38 patients (54.3{\%}) were still in clinical remission or still had a clinical response; 29 patients (41.4{\%}) had mucosal healing, defined as complete healing of erosions or ulcerations, and 20 patients (27.7{\%}) had histologic healing, defined as complete absence of markers of inflammation. Of patients with clinical remission or clinical response, 75.3{\%} also had mucosal healing and 52.6{\%} also had histologic healing. The probability of achieving mucosal healing decreased significantly with increasing values of erythrocyte sedimentation rate (adjusted odds ratio, 0.96; 95{\%} CI, 0.93-0.98; P = .006).CONCLUSIONS: In a long-term analysis of data from 2 clinical trials of pediatric patients with CD or UC, 52 weeks' treatment with thalidomide led to clinical remission in 54.3{\%} of patients with ileocolonic or colonic disease; of these patients, 75.3{\%} had mucosal healing and 52.6{\%} also had histologic healing. Further studies are needed to determine how thalidomide therapy affects long-term progression of inflammatory bowel diseases. (ClinicalTrials.gov number NCT00720538).",
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TY - JOUR

T1 - Endoscopic and Histologic Healing in Children With Inflammatory Bowel Diseases Treated With Thalidomide

AU - Lazzerini, Marzia

AU - Villanacci, Vincenzo

AU - Pellegrin, Maria Chiara

AU - Martelossi, Stefano

AU - Magazzù, Giuseppe

AU - Pellegrino, Salvatore

AU - Lucanto, Maria Cristina

AU - Barabino, Arrigo

AU - Calvi, Angela

AU - Arrigo, Serena

AU - Lionetti, Paolo

AU - Fontana, Massimo

AU - Zuin, Giovanna

AU - Maggiore, Giuseppe

AU - Bramuzzo, Matteo

AU - Maschio, Massimo

AU - Salemme, Marianna

AU - Manenti, Stefania

AU - Lorenzi, Luisa

AU - Decorti, Giuliana

AU - Montico, Marcella

AU - Ventura, Alessandro

N1 - Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2017/9

Y1 - 2017/9

N2 - BACKGROUND & AIMS: Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long-term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings.METHODS: We collected data from 2 multicenter trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileocolonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD; and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, respectively, for patients with UC. Patients with a clinical response to 8 weeks' treatment with thalidomide underwent endoscopic examination with biopsy collection at study weeks 12 and 52. Severity of inflammation in patients with UC was assessed by Mayo score and in patients with CD by 4-grade system. Biopsies were assessed for signs of active inflammation, erosion or ulceration, and crypt abscesses and assigned a histologic score.RESULTS: Clinical remission was observed in 42 patients (60.0%) and clinical response in 45 patients (64.2%) at Week 8. At Week 52, a total of 38 patients (54.3%) were still in clinical remission or still had a clinical response; 29 patients (41.4%) had mucosal healing, defined as complete healing of erosions or ulcerations, and 20 patients (27.7%) had histologic healing, defined as complete absence of markers of inflammation. Of patients with clinical remission or clinical response, 75.3% also had mucosal healing and 52.6% also had histologic healing. The probability of achieving mucosal healing decreased significantly with increasing values of erythrocyte sedimentation rate (adjusted odds ratio, 0.96; 95% CI, 0.93-0.98; P = .006).CONCLUSIONS: In a long-term analysis of data from 2 clinical trials of pediatric patients with CD or UC, 52 weeks' treatment with thalidomide led to clinical remission in 54.3% of patients with ileocolonic or colonic disease; of these patients, 75.3% had mucosal healing and 52.6% also had histologic healing. Further studies are needed to determine how thalidomide therapy affects long-term progression of inflammatory bowel diseases. (ClinicalTrials.gov number NCT00720538).

AB - BACKGROUND & AIMS: Mucosal healing, determined by endoscopic evaluation, is one of the most important prognostic markers for patients with inflammatory bowel diseases. Findings from histologic evaluation, however, could complement findings from endoscopy in assessing mucosal responses to treatment. We analyzed long-term results of children treated with thalidomide to determine the association between clinical response and histology and endoscopy findings.METHODS: We collected data from 2 multicenter trials of 70 children with refractory Crohn's disease (CD) or ulcerative colitis (UC) (2-18 years old; ileocolonic or colonic disease) given thalidomide or placebo (NCT00720538). Clinical remission and clinical response at 8 weeks were defined as a pediatric CD activity index scores 10 points or lower and a decrease of at least 50% from baseline, respectively, for patients with CD; and as a pediatric UC activity index score below 10 and a decrease of at least 20 points from baseline, respectively, for patients with UC. Patients with a clinical response to 8 weeks' treatment with thalidomide underwent endoscopic examination with biopsy collection at study weeks 12 and 52. Severity of inflammation in patients with UC was assessed by Mayo score and in patients with CD by 4-grade system. Biopsies were assessed for signs of active inflammation, erosion or ulceration, and crypt abscesses and assigned a histologic score.RESULTS: Clinical remission was observed in 42 patients (60.0%) and clinical response in 45 patients (64.2%) at Week 8. At Week 52, a total of 38 patients (54.3%) were still in clinical remission or still had a clinical response; 29 patients (41.4%) had mucosal healing, defined as complete healing of erosions or ulcerations, and 20 patients (27.7%) had histologic healing, defined as complete absence of markers of inflammation. Of patients with clinical remission or clinical response, 75.3% also had mucosal healing and 52.6% also had histologic healing. The probability of achieving mucosal healing decreased significantly with increasing values of erythrocyte sedimentation rate (adjusted odds ratio, 0.96; 95% CI, 0.93-0.98; P = .006).CONCLUSIONS: In a long-term analysis of data from 2 clinical trials of pediatric patients with CD or UC, 52 weeks' treatment with thalidomide led to clinical remission in 54.3% of patients with ileocolonic or colonic disease; of these patients, 75.3% had mucosal healing and 52.6% also had histologic healing. Further studies are needed to determine how thalidomide therapy affects long-term progression of inflammatory bowel diseases. (ClinicalTrials.gov number NCT00720538).

KW - Journal Article

U2 - 10.1016/j.cgh.2017.02.029

DO - 10.1016/j.cgh.2017.02.029

M3 - Article

C2 - 28286192

VL - 15

SP - 1382-1389.e1

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 9

ER -