Risk Factors and Outcomes of Thalidomide-induced Peripheral Neuropathy in a Pediatric Inflammatory Bowel Disease Cohort

Matteo Bramuzzo, Gabriele Stocco, Marcella Montico, Serena Arrigo, Angela Calvi, Paola Lanteri, Stefano Costa, Salvatore Pellegrino, Giuseppe Magazzù, Jacopo Barp, Silvia Ghione, Paolo Lionetti, Giovanna Zuin, Massimo Fontana, Teresa Di Chio, Giuseppe Maggiore, Marzia Lazzerini, Marianna Lucafò, Chiara Udina, Maria Chiara PellegrinAndrea Chicco, Marco Carrozzi, Giuliana Decorti, Giuliana Decorti, Alessandro Ventura, Alessandro Ventura, Stefano Martelossi

Research output: Contribution to journalArticle

Abstract

© Copyright 2017 Crohn's & Colitis Foundation. Background: Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease. Methods: Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors. Results: One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio 2.62; 95% confidence interval [CI], 1.31-5.21; 100-149 mg/d adjusted hazard ratio 6.16; 95% CI, 20.9-13.06; > 150 mg/d adjusted hazard ratio 9.57; 95% CI, 2.6-35.2). Single nucleotide polymorphisms in ICAM1 (rs1799969) and SERPINB2 (rs6103) genes were found to be protective against TiPN (odds ratio 0.15; 95% CI, 0.03-0.82 and 0.36; 95% CI, 0.14-0.88, respectively). TiPN was the cause of drug suspension in 41.8% of patients. Clinical symptoms resolved in 89.2% of cases, whereas instrumental alteration persisted in more than half of the patients during a short follow-up. Conclusions: In children with inflammatory bowel disease, TiPN is common but mild and generally reversible. Cumulative dose seems to be the most relevant risk factor, whereas polymorphisms in genes involved in neuronal inflammation may be protective.
Original languageEnglish
Pages (from-to)1810-1816
Number of pages7
JournalInflammatory Bowel Diseases
Volume23
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

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Thalidomide
Peripheral Nervous System Diseases
Inflammatory Bowel Diseases
Pediatrics
Confidence Intervals
Colitis
Therapeutics
Causality
Genes
Multicenter Studies
Single Nucleotide Polymorphism
Suspensions
Cohort Studies
Odds Ratio

Keywords

  • inflammatory bowel disease
  • peripheral neuropathy
  • thalidomide

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Risk Factors and Outcomes of Thalidomide-induced Peripheral Neuropathy in a Pediatric Inflammatory Bowel Disease Cohort. / Bramuzzo, Matteo; Stocco, Gabriele; Montico, Marcella; Arrigo, Serena; Calvi, Angela; Lanteri, Paola; Costa, Stefano; Pellegrino, Salvatore; Magazzù, Giuseppe; Barp, Jacopo; Ghione, Silvia; Lionetti, Paolo; Zuin, Giovanna; Fontana, Massimo; Di Chio, Teresa; Maggiore, Giuseppe; Lazzerini, Marzia; Lucafò, Marianna; Udina, Chiara; Pellegrin, Maria Chiara; Chicco, Andrea; Carrozzi, Marco; Decorti, Giuliana; Decorti, Giuliana; Ventura, Alessandro; Ventura, Alessandro; Martelossi, Stefano.

In: Inflammatory Bowel Diseases, Vol. 23, No. 10, 01.10.2017, p. 1810-1816.

Research output: Contribution to journalArticle

Bramuzzo, M, Stocco, G, Montico, M, Arrigo, S, Calvi, A, Lanteri, P, Costa, S, Pellegrino, S, Magazzù, G, Barp, J, Ghione, S, Lionetti, P, Zuin, G, Fontana, M, Di Chio, T, Maggiore, G, Lazzerini, M, Lucafò, M, Udina, C, Pellegrin, MC, Chicco, A, Carrozzi, M, Decorti, G, Decorti, G, Ventura, A, Ventura, A & Martelossi, S 2017, 'Risk Factors and Outcomes of Thalidomide-induced Peripheral Neuropathy in a Pediatric Inflammatory Bowel Disease Cohort', Inflammatory Bowel Diseases, vol. 23, no. 10, pp. 1810-1816. https://doi.org/10.1097/MIB.0000000000001195
Bramuzzo, Matteo ; Stocco, Gabriele ; Montico, Marcella ; Arrigo, Serena ; Calvi, Angela ; Lanteri, Paola ; Costa, Stefano ; Pellegrino, Salvatore ; Magazzù, Giuseppe ; Barp, Jacopo ; Ghione, Silvia ; Lionetti, Paolo ; Zuin, Giovanna ; Fontana, Massimo ; Di Chio, Teresa ; Maggiore, Giuseppe ; Lazzerini, Marzia ; Lucafò, Marianna ; Udina, Chiara ; Pellegrin, Maria Chiara ; Chicco, Andrea ; Carrozzi, Marco ; Decorti, Giuliana ; Decorti, Giuliana ; Ventura, Alessandro ; Ventura, Alessandro ; Martelossi, Stefano. / Risk Factors and Outcomes of Thalidomide-induced Peripheral Neuropathy in a Pediatric Inflammatory Bowel Disease Cohort. In: Inflammatory Bowel Diseases. 2017 ; Vol. 23, No. 10. pp. 1810-1816.
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T1 - Risk Factors and Outcomes of Thalidomide-induced Peripheral Neuropathy in a Pediatric Inflammatory Bowel Disease Cohort

AU - Bramuzzo, Matteo

AU - Stocco, Gabriele

AU - Montico, Marcella

AU - Arrigo, Serena

AU - Calvi, Angela

AU - Lanteri, Paola

AU - Costa, Stefano

AU - Pellegrino, Salvatore

AU - Magazzù, Giuseppe

AU - Barp, Jacopo

AU - Ghione, Silvia

AU - Lionetti, Paolo

AU - Zuin, Giovanna

AU - Fontana, Massimo

AU - Di Chio, Teresa

AU - Maggiore, Giuseppe

AU - Lazzerini, Marzia

AU - Lucafò, Marianna

AU - Udina, Chiara

AU - Pellegrin, Maria Chiara

AU - Chicco, Andrea

AU - Carrozzi, Marco

AU - Decorti, Giuliana

AU - Decorti, Giuliana

AU - Ventura, Alessandro

AU - Ventura, Alessandro

AU - Martelossi, Stefano

PY - 2017/10/1

Y1 - 2017/10/1

N2 - © Copyright 2017 Crohn's & Colitis Foundation. Background: Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease. Methods: Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors. Results: One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio 2.62; 95% confidence interval [CI], 1.31-5.21; 100-149 mg/d adjusted hazard ratio 6.16; 95% CI, 20.9-13.06; > 150 mg/d adjusted hazard ratio 9.57; 95% CI, 2.6-35.2). Single nucleotide polymorphisms in ICAM1 (rs1799969) and SERPINB2 (rs6103) genes were found to be protective against TiPN (odds ratio 0.15; 95% CI, 0.03-0.82 and 0.36; 95% CI, 0.14-0.88, respectively). TiPN was the cause of drug suspension in 41.8% of patients. Clinical symptoms resolved in 89.2% of cases, whereas instrumental alteration persisted in more than half of the patients during a short follow-up. Conclusions: In children with inflammatory bowel disease, TiPN is common but mild and generally reversible. Cumulative dose seems to be the most relevant risk factor, whereas polymorphisms in genes involved in neuronal inflammation may be protective.

AB - © Copyright 2017 Crohn's & Colitis Foundation. Background: Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease. Methods: Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors. Results: One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio 2.62; 95% confidence interval [CI], 1.31-5.21; 100-149 mg/d adjusted hazard ratio 6.16; 95% CI, 20.9-13.06; > 150 mg/d adjusted hazard ratio 9.57; 95% CI, 2.6-35.2). Single nucleotide polymorphisms in ICAM1 (rs1799969) and SERPINB2 (rs6103) genes were found to be protective against TiPN (odds ratio 0.15; 95% CI, 0.03-0.82 and 0.36; 95% CI, 0.14-0.88, respectively). TiPN was the cause of drug suspension in 41.8% of patients. Clinical symptoms resolved in 89.2% of cases, whereas instrumental alteration persisted in more than half of the patients during a short follow-up. Conclusions: In children with inflammatory bowel disease, TiPN is common but mild and generally reversible. Cumulative dose seems to be the most relevant risk factor, whereas polymorphisms in genes involved in neuronal inflammation may be protective.

KW - inflammatory bowel disease

KW - peripheral neuropathy

KW - thalidomide

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