Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional
Official Title: A Pilot Open-label Study to Assess the Efficacy and Safety of Tocilizumab in Patients With Active Schnitzler's Syndrome
Brief Summary:
Schnitzler's Syndrome (SchS) is a late-onset multifactorial autoinflammatory disease characterized by chronic urticarial skin lesions and a monoclonal gammopathy usually belonging to the immunoglobulin M (IgM) or IgG class. Symptoms associated with SchS are recurrent fever attacks, bone and muscle pain, arthralgia or arthritis, fatigue and lymphadenopathy. SchS is a rare disease with approximately 300 cases reported in the literature. The nature of SchS is chronic without known reports about spontaneous remissions. Disease onset occurs around the age of 50. About 15% of patients eventually develop a lymphoproliferative disorder, most often Waldenström's macroglobulinemia. The pathogenesis of SchS is still not well defined. Functional ex vivo studies showed excessive cytokine production (IL-1ß, IL-6 and IL-18) of peripheral blood monocytes (PBMCs) in SchS as compared to healthy controls. In addition to excessive IL-6 secretion from PBMCs IL-6 has repeatedly been reported to be elevated in the serum of SchS patients too. As IL-6 plays a major role in the development of multiple myeloma, IL-6 may also be associated with the formation of lymphoproliferative disorders in SchS.
Until now, there is no approved standard therapy available for the treatment of SchS. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other immunosuppressive agents have been reported to provide variable relief from symptoms of bone pain and arthralgia. Case reports and small studies about successful treatment of SchS with anti-IL-1 blockers (anakinra, rilonacept and canakinumab) accumulate. However, there have been complete and partial treatment failures to anti-IL-1 blockade in SchS. In these patients, anti-IL-6 treatment (tocilizumab [TCZ]) demonstrated to be very effective in reducing the clinical symptoms and inflammation markers in SchS. TCZ treatment has proved to be