ORIGINAL ARTICLE AUTOIMMUNE DISEASES Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study K. Krause 1 , K. Weller 1 , R. Stefaniak 1 , H. Wittkowski 2 , S. Altrichter 1 , F. Siebenhaar 1 , T. Zuberbier 1 & M. Maurer 1 1 Department of Dermatology and Allergy, Allergie-Centrum-Charite ´ , Charite ´ – Universita ¨ tsmedizin Berlin, Berlin; 2 Department of Pediatrics, Universita ¨ tsklinikum Mu ¨ nster, Mu ¨ nster, Germany To cite this article: Krause K, Weller K, Stefaniak R, Wittkowski H, Altrichter S, Siebenhaar F, Zuberbier T, Maurer M. Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study. Allergy 2012; 67: 943–950. Keywords cryopyrin-associated periodic syndrome; interleukin-1; rilonacept; Schnitzler syndrome. Correspondence Marcus Maurer, MD, Department of Dermatology and Allergy, Allergie-Centrum- Charite ´ , Charite ´ – Universita ¨ tsmedizin Berlin, Charite ´ platz 1, 10117 Berlin, Germany. Tel.: + 49-30-450 518 043 Fax: + 49-30-450 518 972 E-mail: marcus.maurer@charite.de Accepted for publication 05 April 2012 DOI:10.1111/j.1398-9995.2012.02843.x Edited by: Hans-Uwe Simon Abstract Background: Schnitzler syndrome (SchS) is a rare disease with suspected autoin- flammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin-associ- ated periodic syndromes (CAPS). Cryopyrin-associated periodic syndromes respond to treatment with interleukin-1 antagonists, and single case reports of Schnitzler syndrome have shown improvement following treatment with the inter- leukin-1 blocker anakinra. This study evaluated the effects of the interleukin-1 antagonist rilonacept on the clinical signs and symptoms of SchS. Methods: Eight patients with SchS were included in this prospective, single-center, open-label study. After a 3-week baseline, patients received a subcutaneous load- ing dose of rilonacept 320 mg followed by weekly subcutaneous doses of 160 mg for up to 1 year. Efficacy was determined by patient-based daily health assess- ment forms, physician’s global assessment (PGA), and measurement of inflamma- tory markers including C-reactive protein (CRP), serum amyloid A (SAA), and S100 calcium-binding protein A12 (S100A12). Results: Treatment with rilonacept resulted in a rapid clinical response as demon- strated by significant reductions in daily health assessment scores and PGA scores compared with baseline levels (P < 0.05). These effects, which were accompanied by reductions in CRP and SAA, continued over the treatment duration. Rilona- cept treatment was well tolerated. There were no treatment-related severe adverse events and no clinically significant changes in laboratory safety parameters. Conclusion: Rilonacept was effective and well tolerated in patients with SchS and may represent a promising potential therapeutic option (NCT01045772 [Clinical- Trials.gov Identifier]; EudraCT #2006-004290-97). Schnitzler syndrome (SchS) is a rare condition with slightly more than 100 cases identified. However, it is likely that SchS is underdiagnosed, especially because its clinical presentation may overlap with common disorders such as chronic urticaria and patients commonly experience a delay in diagnosis that can exceed 5 years (1). Patients with SchS are characterized by the hallmark symptoms of chronic urticarial rash and monoclonal gamm- opathy that is usually IgM but may also be IgG. These symptoms are required for a diagnosis along with the concur- rent presence of at least two other characteristic symptoms including recurrent fever, arthralgia or arthritis, bone pain, lymphadenopathy, hepato- or splenomegaly, leukocytosis, elevated erythrocyte sedimentation rate, and abnormal bone morphology (1). However, a diagnosis of SchS can only be Abbreviations ADA Antidrug antibodies; AE adverse event; CAPS cryopyrin- associated periodic syndromes; DHAF Daily health assessment form; ETP extended treatment phase; hs-CRP high-sensitivity C- reactive protein; ITP initial treatment phase; MWS Muckle–Wells syndrome; PGA physician’s global assessment; SAA serum amyloid A; SchAS Schnitzler syndrome activity score; SchS Schnitzler syndrome; S100A12 S100 calcium-binding protein A12. Allergy 67 (2012) 943–950 © 2012 John Wiley & Sons A/S 943 Allergy