Karoline Krause1, Athanasios Tsianakas2, Nicola Wagner3, Jörg Fischer4, Karsten Weller5, Martin Metz5, Martin K Church5, Marcus Maurer6. 1. Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany; Autoinflammation Reference Center Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address: karoline.krause@charite.de. 2. Department of Dermatology, Universitätsklinikum Münster, Münster, Germany. 3. Department of Dermatology, Klinikum Darmstadt, Darmstadt, Germany. 4. Department of Dermatology and Allergy, Universitätsklinik Tübingen, Tübingen, Germany. 5. Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany. 6. Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany; Autoinflammation Reference Center Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Abstract
BACKGROUND:Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available. OBJECTIVE: We assessed effects of the anti-IL-1β mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome. METHODS: In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey). RESULTS: The proportion of patients with complete clinical response at day 7 was significantly higher (P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markersC-reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension. CONCLUSIONS: In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease.
RCT Entities:
BACKGROUND:Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available. OBJECTIVE: We assessed effects of the anti-IL-1β mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome. METHODS: In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey). RESULTS: The proportion of patients with complete clinical response at day 7 was significantly higher (P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markers C-reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension. CONCLUSIONS: In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease.
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Authors: Mario Sánchez-Borges; Ignacio J Ansotegui; Ilaria Baiardini; Jonathan Bernstein; Giorgio Walter Canonica; Motohiro Ebisawa; R Maximiliano Gomez; Sandra González-Diaz; Bryan Martin; Mário Morais de Almeida; Jose Antonio Ortega Martell Journal: World Allergy Organ J Date: 2021-06-03 Impact factor: 4.084