Efficacy and safety of canakinumab in Schnitzler syndrome: A multicenter randomized placebo-controlled study - 19/04/17
, Athanasios Tsianakas, MD c, Nicola Wagner, MD d, Jörg Fischer, MD e, Karsten Weller, MD a, Martin Metz, MD a, Martin K. Church, PhD a, Marcus Maurer, MD a, bAbstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : Autoinflammatory, canakinumab, IL-1, Schnitzler syndrome, urticaria
Abbreviations used : CAPS, CRP, DLQI, IL-1Ra, PGA, SAA, SF-36
Plan
| This study was financially supported by Novartis Pharma GmbH and intramural grants. |
|
| Disclosure of potential conflict of interest: K. Krause has received grants from Regeneron and Novartis; has consultant arrangements with Novartis; and has received payment for lectures from Roche and Novartis. K. Weller has received grants, payment for lectures, and travel support from Novartis; has worked on different projects funded by Novartis during the past 3 years outside the submitted work; has a board membership and consultant arrangements with Novartis; and has received honoraria for educational lectures from Dr R. Pfleger, Essex Pharma (now MSD), Uriach, UCB, Novartis, Shire, Viropharma, and Moxie. In addition, he received honoraria for consulting from Novartis and he is or was involved in clinical research projects of Dr R. Pfleger, Essex Pharma (now MSD), Faes, Uriach, Novartis, Shire, and Viropharma. M. Metz has received payment for lectures from Bayer, Dr R. Pfleger, GlaxoSmithKline, Moxie, Nerre, Novartis, Roche, and Sanofi. M. Maurer has received grants from Novartis and Regeneron and has received a consulting fee or honorarium and travel support from Novartis. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 4
P. 1311-1320 - avril 2017 Retour au numéro
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