Schnitzler's Syndrome Clinical Trial
Official title:
A Pilot Open-label Study to Assess the Efficacy and Safety of Tocilizumab in Patients With Active Schnitzler's Syndrome
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 very effective,
well-tolerated and safe in other acquired autoinflammatory disorders, systemic juvenile
idiopathic arthritis (sJIA) and adult-onset Still's disease that share many clinical features
(rash, fever, joint involvement, lymphadenopathy, fatigue) and excessive cytokine production
with SchS. The study consists of a run-in baseline period of 1-4 weeks followed by an
open-label 20-week TCZ treatment phase with weekly s.c. injections (TCZ 162mg), followed by
an optional study extension up to a total of 1 year with ongoing once weekly TCZ 162mg
injections and a 4 week period of follow-up.
n/a
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT00442182 -
The Efficacy and Safety of ITF2357 in AIS
|
Phase 2 |