title: Tolerance and efficacy of off-label anti-interleukin-1 treatments in France: a nationwide survey.
abstract: BACKGROUND
  Despite their limited licensed indications, anti-interleukin-1 (anti-IL-1) agents are often used in clinical practice for an increasing number of auto-inflammatory diseases. We conducted a national cross-sectional observational study from January 2011 to January 2013 to record the off-label use of such agents in France. We aimed to estimate the off-label use of anti-IL-1 treatments in France, assess their efficacy in rare diseases, and increase the reporting of their possible side effects.
  
  
  METHODS
  Physicians answered a questionnaire that covered patient and disease data, anti-IL-1 agent use, efficacy and adverse events. The study involved adult or paediatric patient who had received an anti-IL-1 agent after January 2005 in France.
  
  
  RESULTS
  In total, 189 patients from 38 centres were included. The main diseases were adult-onset Still's disease (AOSD) (35), gout (28), systemic juvenile idiopathic arthritis (27), cryopyrin-associated periodic syndrome (CAPS) (21), familial Mediterranean fever (14) and mevalonate kinase deficiency (12). The main off-label used agent was anakinra, used at least once for 185 patients, with canakinumab used for 25. Anakinra was effective in most patients (90%), with higher complete clinical response rates for Schnitzler's syndrome, gout, CAPS and AOSD. Overall, 58% of patients showed at least one adverse event, mainly minor injection-site reactions. The main reported serious adverse event was severe infection. Injection-site reactions and liver toxicity were significantly more frequent in children than adults. The main non-cutaneous adverse event was liver toxicity, significantly associated with treatment duration. Weight gain was reported in about 10% of patients and was associated with treatment duration and CAPS. Canakinumab was rarely used and showed better cutaneous tolerance than anakinra but similar rates of non-cutaneous and severe adverse events.
  
  
  CONCLUSIONS
  Anakinra was well tolerated and effective in most patients with various inflammatory diseases. The main adverse events were mild injection-site reactions, especially in children. The survey allowed for collecting limited information on the off-label use of canakinumab.
authors.affiliation: Department of Paediatric Rheumatology, Hôpital de Bicêtre, APHP, National Reference Centre for Auto-inflammatory Diseases, Le Kremlin-Bicêtre, University of Paris Sud, CHU de Bicêtre. 78 Rue du Général Leclerc, 94270, Le Kremlin, Bicêtre, France. linda.rossi@bct.aphp.fr.
authors.forename: Linda
authors.initials: L
authors.lastname: Rossi-Semerano
authors.affiliation: Department of Rheumatology, Hôpital La Pitié Salpêtrière, APHP; UPMC, GRC 08, Institut Pierre Louis d'Epidémiologie et Santé Publique, Paris, France. bruno.fautrel@psl.aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fautrel
authors.affiliation: Department of Rheumatology, University Teaching Hospital, CHRU Besançon, and University of Franche-Comté, Besançon, France. dwendling@chu-besancon.fr.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wendling
authors.affiliation: Centre de Référence des Maladies Autoimmunes et systémiques Rares, Service de Médecine Interne, Hôpital Claude Huriez, Université Lille Nord-de-France, Lille Cedex, France. eric.hachulla@chru-lille.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Department of Paediatric Rheumatology, Hôpital de Bicêtre, APHP, National Reference Centre for Auto-inflammatory Diseases, Le Kremlin-Bicêtre, University of Paris Sud, CHU de Bicêtre. 78 Rue du Général Leclerc, 94270, Le Kremlin, Bicêtre, France. caroline.galeotti@bct.aphp.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Galeotti
authors.affiliation: Department of Rheumatology, Hôpital Avicenne, APHP, INSERM UMR 1125, Paris 13 University, Bobigny, France. luca.semerano@avc.aphp.fr.
authors.forename: Luca
authors.initials: L
authors.lastname: Semerano
authors.affiliation: Maladies Auto-inflammatoires, Laboratoire de Génétique, Hôpital A de Villeneuve, CHRU Montpellier, Montpellier, France. isabelle.touitou@inserm.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Touitou
authors.affiliation: Department of Paediatric Rheumatology, Hôpital de Bicêtre, APHP, National Reference Centre for Auto-inflammatory Diseases, Le Kremlin-Bicêtre, University of Paris Sud, CHU de Bicêtre. 78 Rue du Général Leclerc, 94270, Le Kremlin, Bicêtre, France. isabelle.kone-paut@bct.aphp.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Koné-Paut
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005602:France; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; C541220:canakinumab