TY - JOUR T1 - Effect of Thalidomide on Clinical Remission in Children and Adolescents with Ulcerative Colitis Refractory to Other Immunosuppressives: Pilot Randomized Clinical Trial. JF - Inflamm Bowel Dis Y1 - 2015 A1 - Lazzerini, Marzia A1 - Martelossi, Stefano A1 - Magazzù, Giuseppe A1 - Pellegrino, Salvatore A1 - Lucanto, Maria Cristina A1 - Barabino, Arrigo A1 - Calvi, Angela A1 - Arrigo, Serena A1 - Lionetti, Paolo A1 - Lorusso, Monica A1 - Mangiantini, Francesca A1 - Fontana, Massimo A1 - Zuin, Giovanna A1 - Palla, Gabriella A1 - Maggiore, Giuseppe A1 - Bramuzzo, Matteo A1 - Pellegrin, Maria Chiara A1 - Maschio, Massimo A1 - Villanacci, Vincenzo A1 - Manenti, Stefania A1 - Decorti, Giuliana A1 - De Iudicibus, Sara A1 - Paparazzo, Rossella A1 - Montico, Marcella A1 - Ventura, Alessandro AB -

BACKGROUND: In a randomized controlled trial, thalidomide has shown to be effective in refractory Crohn's disease in children. This pilot study aimed at evaluating thalidomide in refractory pediatric ulcerative colitis (UC).

METHODS: Double-blind, placebo-controlled randomized clinical trial on thalidomide 1.5 to 2.5 mg/kg/day in children with active UC despite multiple immunosuppressive treatments. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks; all responders were followed up for a minimum of 52 weeks.

RESULTS: Twenty-six children with refractory UC were randomized to thalidomide or placebo. Clinical remission at week 8 was achieved by significantly more children treated with thalidomide {10/12 (83.3%) versus 2/11 (18.8%); risk ratio, 4.5 (95% confidence interval [CI], 1.2-16.4); P = 0.005; number needed to treat, 1.5}. Of the nonresponders to placebo who were switched to thalidomide, 8 of 11 (72.7%) subsequently reached remission at week 8 (risk ratio, 4.0 [95% CI, 1.1-14.7]; number needed to treat, 2.45; P = 0.01). Clinical remission in the thalidomide group was 135.0 weeks (95% CI, 32-238), compared with 8.0 weeks (95% CI, 2.4-13.6) in the placebo group (P < 0.0001). Cumulative incidence of severe adverse events was 3.1 per 1000 patient-weeks. Peripheral neuropathy and amenorrhea were the most frequent adverse events.

CONCLUSIONS: In this pilot randomized controlled trial on cases of UC refractory to immunosuppressive therapy, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and in longer term maintenance of remission. These findings require replication in larger clinical studies evaluating both thalidomide efficacy and safety.

VL - 21 IS - 8 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26185909?dopt=Abstract ER - TY - JOUR T1 - Genetic predictors of glucocorticoid response in pediatric patients with inflammatory bowel diseases. JF - J Clin Gastroenterol Y1 - 2011 A1 - De Iudicibus, Sara A1 - Stocco, Gabriele A1 - Martelossi, Stefano A1 - Londero, Margherita A1 - Ebner, Egle A1 - Pontillo, Alessandra A1 - Lionetti, Paolo A1 - Barabino, Arrigo A1 - Bartoli, Fiora A1 - Ventura, Alessandro A1 - Decorti, Giuliana KW - Adolescent KW - Child KW - Drug Resistance KW - Female KW - Follow-Up Studies KW - Genotype KW - Glucocorticoids KW - Humans KW - Inflammatory Bowel Diseases KW - Male KW - Multivariate Analysis KW - Polymorphism, Genetic KW - Receptors, Glucocorticoid KW - Regression Analysis KW - Retrospective Studies KW - Sex Factors KW - Treatment Outcome AB -

BACKGROUND: Glucocorticoids (GCs) are used in moderate-to-severe inflammatory bowel diseases (IBD) but their effect is often unpredictable.

AIM: To determine the influence of 4 polymorphisms in the GC receptor [nuclear receptor subfamily 3, group C, member 1 (NR3C1)], interleukin-1β (IL-1β), and NACHT leucine-rich-repeat protein 1 (NALP1) genes, on the clinical response to steroids in pediatric patients with IBD.

METHODS: One hundred fifty-four young IBD patients treated with GCs for at least 30 days and with a minimum follow-up of 1 year were genotyped. The polymorphisms considered are the BclI in the NR3C1 gene, C-511T in IL-1β gene, and Leu155His and rs2670660/C in NALP1 gene. Patients were grouped as responder, dependant, and resistant to GCs. The relation between GC response and the genetic polymorphisms considered was examined using univariate, multivariate, and Classification and Regression Tree (CART) analysis.

RESULTS: Univariate analysis showed that BclI polymorphism was more frequent in responders compared with dependant patients (P=0.03) and with the combined dependant and resistant groups (P=0.02). Moreover, the NALP1 Leu155His polymorphism was less frequent in the GC responsive group compared with resistant (P=0.0059) and nonresponder (P=0.02) groups. Multivariate analysis comparing responders and nonresponders confirmed an association between BclI mutated genotype and steroid response (P=0.030), and between NALP1 Leu155His mutant variant and nonresponders (P=0.033). An association between steroid response and male sex was also observed (P=0.034). In addition, Leu155His mutated genotype was associated with steroid resistance (P=0.034). Two CART analyses supported these findings by showing that BclI and Leu155His polymorphisms had the greatest effect on steroid response (permutation P value=0.046). The second CART analysis also identified age of disease onset and male sex as important variables affecting response.

CONCLUSIONS: These results confirm that genetic and demographic factors may affect the response to GCs in young patients with IBD and strengthen the importance of studying high-order interactions for predicting response.

VL - 45 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20697295?dopt=Abstract ER - TY - JOUR T1 - Usefulness of wireless capsule endoscopy for detecting inflammatory bowel disease in children presenting with arthropathy. JF - Eur J Pediatr Y1 - 2011 A1 - Taddio, Andrea A1 - Simonini, Gabriele A1 - Lionetti, Paolo A1 - Lepore, Loredana A1 - Martelossi, Stefano A1 - Ventura, Alessandro A1 - Cimaz, Rolando KW - Adolescent KW - Arthritis, Juvenile KW - Capsule Endoscopy KW - Child KW - Colitis, Ulcerative KW - Colon KW - Crohn Disease KW - Diagnosis, Differential KW - Follow-Up Studies KW - Humans KW - Inflammatory Bowel Diseases KW - Intestine, Small KW - Male KW - Predictive Value of Tests KW - Sensitivity and Specificity KW - Severity of Illness Index KW - Treatment Outcome AB -

Inflammatory bowel disease (IBD) is a cause of chronic intestinal inflammation in children. In a subset of patients affected by IBD, arthropathy may be the leading presenting sign. In the past years, remarkable advances in gastrointestinal endoscopy techniques have been achieved; recently, the development of capsule endoscopy (CE) provided a non-invasive method for the complete endoscopic evaluation, including small bowel assessment. We report three children suffering from IBD but presenting with articular complaints in whom CE was a useful tool for detecting gut inflammation. Patients were investigated with the wireless CE: PillCam SB2 (Given Imaging, Yoqneam, Israel) capsule, the second-generation capsule, was used in our paediatric patients. Three patients were initially evaluated for arthropathy. Enteropathic arthritis was suspected for gastrointestinal symptoms and/or persistence of inflammatory markers elevation. In one of these children, conventional endoscopy was refused by parents, while in the other two children, CE was proposed as first-line diagnostic tool. In all patients, CE revealed to be safe and provided information that led to diagnosis. Paediatric rheumatologists should consider CE as a valid, non-invasive tool, eventually first level diagnostic approach in order to evaluate the presence of IBD in children presenting with chronic articular complaints.

VL - 170 IS - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21643650?dopt=Abstract ER -