Thalidomide Use and Outcomes in Pediatric Patients With Crohn Disease Refractory to Infliximab and Adalimumab

Abstract

Thalidomide is a potentially effective rescue therapy for severe refractory CD in children who fail to respond to anti-TNF medications.

Effect of Thalidomide on Clinical Remission in Children and Adolescents with Ulcerative Colitis Refractory to Other Immunosuppressives

“…Fourth, both in Crohn's disease 13,29 and in UC, thalidomide was effective even in children with previous failure or intolerance to infliximab. This supports the hypothesis that although both thalidomide and infliximab have an anti-tumor necrosis factor a effect, their action is mediated by different mechanisms.…”

“…Based on the very limited available data existing on the efficacy of on thalidomide in treating patients with UC, [14][15][16][17] and Crohn's disease, [13][14][15][25][26][27][28][29] our a priori hypothesis was that the remission rate at 8 weeks would be 55% in the thalidomide group, compared with 20% in the placebo group. Additionally, because of major uncertainty around this estimate and the risk associated with conducting a placebo-controlled trial (e.g., possible disease progression due to placebo assignment), we predefined stopping rules to guide the final sample size; 3 interim analyses were anticipated, and cutoffs of statistical significance were predefined according to Peto group sequential stopping method, which preserve both an alpha level of 0.05 and a power of at least 80%.…”

Mucosal Healing With Thalidomide in Refractory Crohn’s Disease Patients Intolerant of Anti-TNF-α Drugs

“…29 A further US study reported the efficacy of thalidomide for severe CD in 12 children who failed to respond to anti-TNF-a drugs. 31 Thus far, however, randomized, controlled trials on the efficacy of thalidomide in adult CD patients are lacking. 32,33 Recently, a pediatric placebo-controlled trial has been published.…”

“…[16][17][18] Given this broad spectrum of immunomodulatory and anti-inflammatory properties, thalidomide has been used in pediatric and adult CD patients who are refractory to other therapies, with positive results. [19][20][21][22][23][24][25][26][27][28][29][30][31][32] On the basis of these observations and study results, we have employed thalidomide to treat several patients with active CD who failed to respond to conventional therapies and to anti-TNF-a agents. Here, we report the cases of 3 patients with moderate-to-severe CD refractory to anti-TNF-a drugs who obtained clinical remission and endoscopic healing of all mucosal ulcerative lesions on thalidomide treatment.…”

Peripheral neuropathy: An underreported neurologic manifestation of inflammatory bowel disease

“…The underlying mechanisms of nerve damage induced by thalidomide remain obscure; however, capillary damage, secondary hypoxemia in nerve fibers and acceleration of neuronal cell death secondary to downregulation of TNF-α have been proposed. Given the potential neurotoxicity, patients treated with thalidomide should undergo regular clinical examination and NS to detect presymptomatic or progressive PN [54][55][56][57][58][59][60][61][62][63][64][65].…”