title: Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: a French multicenter study.
abstract: The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.
authors.affiliation: CHU de Nantes, Service de Médecine Interne, F 44093 Nantes, France. Electronic address: antoine.neel@univ-nantes.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Néel
authors.affiliation: CHU de Nantes, Service de Médecine Interne, F 44093 Nantes, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Henry
authors.affiliation: CHU de Nantes, Service de Dermatologie, F 44093 Nantes, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Barbarot
authors.affiliation: CHU de Nantes, Service de Médecine Interne, F 44093 Nantes, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Masseau
authors.affiliation: CHU de Nantes, Service de Médecine Interne, F 44093 Nantes, France.
authors.forename: François
authors.initials: F
authors.lastname: Perrin
authors.affiliation: CHU de Nantes, Service de Dermatologie, F 44093 Nantes, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Bernier
authors.affiliation: CH de Valenciennes, Service de Médecine Interne-Néphrologie, F 59322 Valenciennes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Kyndt
authors.affiliation: CHU Cochin (AP-HP), Département de Médecine Interne, F 75014 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Puechal
authors.affiliation: CHU la Timone (AP-HM; Aix-Marseille Université), Service de Médecine Interne, F 13385 Marseille, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Weiller
authors.affiliation: CHU de Rennes, Service de Médecine Interne, F 35033 Rennes, France; Université Rennes 1, UMR CNRS 6290 IGRD, 35042 Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Decaux
authors.affiliation: CHU Edouard Herriot (HCL), Service de Médecine Interne, F 69437 Lyon, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Ninet
authors.affiliation: CHU Edouard Herriot (HCL), Service de Médecine Interne, F 69437 Lyon, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Hot
authors.affiliation: CHU Antoine Béclère (AP-HP), Service de Médecine Interne et Immunologie Clinique, F 92140 Clamart, France.
authors.forename: Achille
authors.initials: A
authors.lastname: Aouba
authors.affiliation: CHU de Toulouse, Service de Médecine Interne, F 31059 Toulouse, France.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Astudillo
authors.affiliation: CHU de Nantes, Service de Rhumatologie, F 44093 Nantes, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Berthelot
authors.affiliation: CHU de Bordeaux, Service de Médecine Interne et Maladies Infectieuses, F 33075 Bordeaux, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bonnet
authors.affiliation: CHU de Nantes, Service de Médecine Interne, F 44093 Nantes, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Brisseau
authors.affiliation: CHU de Rennes, Service de Médecine Interne, F 35033 Rennes, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Cador
authors.affiliation: CH du Mans, Service de Médecine Polyvalente, F 72037 Le Mans, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Closs-Prophette
authors.affiliation: CHU de Nantes, Laboratoire de Biochimie, F 44093 Nantes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dejoie
authors.affiliation: CHU de Nancy, Service de Médecine Interne-Médecine Générale, F 54035 Nancy, France.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: de Korwin
authors.affiliation: CHU Avicenne (AP-HP), Service de Médecine Interne, F 93009 Bobigny, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Dhote
authors.affiliation: CHU Antoine Béclère (AP-HP), Service de Médecine Interne et Immunologie Clinique, F 92140 Clamart, France.
authors.forename: Renato
authors.initials: R
authors.lastname: Fior
authors.affiliation: CHU de Rennes, Service de Médecine Interne, F 35033 Rennes, France; Université Rennes 1, UMR CNRS 6290 IGRD, 35042 Rennes, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Grosbois
authors.affiliation: CHRU de Lille, Service de Médecine Interne et Immunologie Clinique, F 59037 Lille, France; Faculté de Médecine, Université Lille Nord de France, F59037 Lille, France; EA2686, IMPRT IFR 114, F 59037 Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: CHRU de Lille, Service de Médecine Interne et Immunologie Clinique, F 59037 Lille, France; Faculté de Médecine, Université Lille Nord de France, F59037 Lille, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Hatron
authors.affiliation: CH Bretagne Atlantique, Service de Médecine Interne, F 56017 Vannes, France.
authors.forename: Henry
authors.initials: H
authors.lastname: Jardel
authors.affiliation: CHRU de Lille, Service de Médecine Interne et Immunologie Clinique, F 59037 Lille, France; Faculté de Médecine, Université Lille Nord de France, F59037 Lille, France; EA2686, IMPRT IFR 114, F 59037 Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.affiliation: CH Bretagne Sud, Service de Médecine Interne et Maladies Infectieuses, F 56100 Lorient, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Lorleac'h
authors.affiliation: CHU de Nantes, Service de Médecine Interne, F 44093 Nantes, France; Faculté de Médecine, Université de Nantes, F44093 Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pottier
authors.affiliation: CHU d'Amiens, Service de Médecine Interne, F 80054 Amiens, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Moulis
authors.affiliation: CHU la Timone (AP-HM; Aix-Marseille Université), Service de Médecine Interne, F 13385 Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Serratrice
authors.affiliation: CHU d'Amiens, Service de Médecine Interne, F 80054 Amiens, France.
authors.forename: Amar
authors.initials: A
authors.lastname: Smail
authors.affiliation: CHU de Nantes, Service de Médecine Interne, F 44093 Nantes, France; Faculté de Médecine, Université de Nantes, F44093 Nantes, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
mesh_terms: D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000009:adverse effects*; D008297:Male; D011788:Quality of Life; D012074:Remission Induction; D012189:Retrospective Studies; D019873:Schnitzler Syndrome / Q000188:drug therapy*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein
keywords: Autoinflammatory disease; Gammopathy; IL-1 receptor antagonist; Schnitzler's syndrome; Urticaria