Limited Efficacy of Thalidomide in the Treatment of Febrile Attacks of the Hyper-IgD and Periodic Fever Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

• Published in: The Journal of pharmacology and experimental therapeutics 2001-09, Vol.298 (3), p.1221
• Main Authors: Drenth, J P, Vonk, A G, Simon, A, Powell, R, van der Meer, J W
• Format: Article
• Language: English
• Subjects: Acute-Phase Reaction; Adult; Cross-Over Studies; Cytokines - metabolism; DNA Mutational Analysis; Double-Blind Method; Female; Fever - drug therapy; Humans; Immune System Diseases - blood; Immune System Diseases - drug therapy; Immune System Diseases - immunology; Immunoglobulin D; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Male; Middle Aged; Neopterin - urine; Recurrence; Syndrome; Thalidomide - adverse effects; Thalidomide - therapeutic use; Treatment Outcome
• ISSN: 0022-3565; 1521-0103

Hyper-IgD and periodic fever syndrome (HIDS) is an autosomal recessive disorder featured by recurrent febrile attacks. Previous unpublished experience (J. van der Meer and R. Powell) suggested that thalidomide may prevent febrile attacks.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-controlled crossover trial to explore the efficacy of a daily 200-mg thalidomide dose in the treatment of recurrent febrile attacks of HIDS. The patients received either thalidomide, 200-mg daily, or placebo for 16 weeks, followed by a 4-week washout period and another 16-week treatment (crossover) with either thalidomide or placebo. Patients completed a weekly diary card noting attacks and side effects. During the study, C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist, soluble TNF receptor p55 and p75, and lipopolysaccharide-stimulated IL-1β and TNF-α production were measured at six different points, whereas urine neopterin levels were measured weekly. During the active treatment with thalidomide, there were 10 attacks compared with 13 attacks with placebo. Thalidomide resulted in a nonsignificant decrease of CRP and SAA, but the concentrations of other inflammatory mediators, including urine neopterin, remained unchanged. One patient developed sensory polyneuropathy, but this resolved when thalidomide administration was stopped. The effect of thalidomide in HIDS is limited to a decrease in acute phase protein synthesis without an effect on the attack rate.