Limited efficacy of thalidomide in the treatment of febrile attacks of thehyper-IgD and periodic fever syndrome: A randomized, double-blind, placebo-controlled trial

Hyper-IgD and periodic fever syndrome (HIDS) is an autosomal recessive diso rder featured by recurrent febrile attacks. Previous unpublished experience (J. van der Meer and R. Powell) suggested that thalidomide may prevent feb rile attacks. Six HIDS patients (5 male and 1 female) who had at least one febrile attack every 6 weeks, entered a randomized, double-blind, placebo-c ontrolled crossover trial to explore the efficacy of a daily 200-mg thalido mide dose in the treatment of recurrent febrile attacks of HIDS. The patien ts received either thalidomide, 200-mg daily, or placebo for 16 weeks, foll owed by a 4-week washout period and another 16-week treatment (crossover) w ith either thalidomide or placebo. Patients completed a weekly diary card n oting attacks and side effects. During the study, C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6, tumor necrosis factor (TNF)-alp ha, IL-1 receptor antagonist, soluble TNF receptor p55 and p75, and lipopol ysaccharide-stimulated IL-1 beta and TNF-alpha production were measured at six different points, whereas urine neopterin levels were measured weekly. During the active treatment with thalidomide, there were 10 attacks compare d with 13 attacks with placebo. Thalidomide resulted in a nonsignificant de crease of CRP and SAA, but the concentrations of other inflammatory mediato rs, including urine neopterin, remained unchanged. One patient developed se nsory polyneuropathy, but this resolved when thalidomide administration was stopped. The effect of thalidomide in HIDS is limited to a decrease in acu te phase protein synthesis without an effect on the attack rate.