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

Bramuzzo, Matteo MD*; Stocco, Gabriele PhD; Montico, Marcella MSc; Arrigo, Serena MD§; Calvi, Angela MD§; Lanteri, Paola MD, PhD; Costa, Stefano MD, PhD; Pellegrino, Salvatore MD, PhD; Magazzù, Giuseppe MD; Barp, Jacopo MD**; Ghione, Silvia MD**; Lionetti, Paolo MD, PhD**; Zuin, Giovanna MD††; Fontana, Massimo MD††; Di Chio, Teresa MD‡‡; Maggiore, Giuseppe MD‡‡; Lazzerini, Marzia MD, PhD; Lucafò, Marianna PhD§§; Udina, Chiara MD§§; Pellegrin, Maria Chiara MD§§; Chicco, Andrea BSc; Carrozzi, Marco MD‖‖; Decorti, Giuliana MD*,§§; Ventura, Alessandro MD*,§§; Martelossi, Stefano MD*

doi: 10.1097/MIB.0000000000001195
Original Clinical Articles

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.

Article first published online 16 August 2017.

*Pediatric Gastroenterology, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” Trieste, Italy;

Department of Life Sciences, University of Trieste, Trieste, Italy;

Clinical Epidemiology and Public Health Research Unit, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” Trieste, Italy;

§Pediatric Gastroenterology Unit, Institute “Giannina Gaslini,” Genoa, Italy;

Neuropsychiatry Unit, Institute “Giannina Gaslini,” Genoa, Italy;

Pediatric Gastroenterology and Cystic Fibrosis Unit, University of Messina, Messina, Italy;

**Department of Sciences for Woman and Child Health, University of Florence, Meyer Children Hospital, Florence, Italy;

††Pediatric Department, Children's Hospital “V. Buzzi” Milan, Italy;

‡‡Pediatric Gastroenterology and Hepatology, University of Pisa, Pisa, Italy;

§§Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy; and

‖‖Pediatric Neurology, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” Trieste, Italy.

Address correspondence to: Matteo Bramuzzo, MD, Pediatric Department, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,” Via dell' Istria 65, 34137 Trieste, Italy (e-mail: matteo.bramuzzo@burlo.trieste.it).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

The authors have no conflict of interest to disclose.

Received January 29, 2017

Accepted April 17, 2017

© Crohn's & Colitis Foundation
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