Tolerance and efficacy of off-label anti-interleukin-1 treatments in France: a nationwide survey

• DOI: 10.1186/s13023-015-0228-7
• Publication Date: 2015-02-17T06:32:13Z
• Authors: Linda Rossi-Semerano; Bruno Fautrel; Daniel Wendling; Eric Hachulla; Caroline Galeotti; Luca Semerano; Isabelle Touitou; Isabelle Koné-Paut
• Keywords: Adult; Male; Adolescent; Canakinumab; Antibodies, Monoclonal, Humanized; Autoimmune Diseases; Humans; Genetics(clinical); Pharmacology (medical); Child; Aged; Medicine(all); Aged, 80 and over; Inflammation; [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology; Off-label; IL-1; Research; Antibodies, Monoclonal; Infant; Auto-inflammatory diseases; Off-Label Use; Middle Aged; 3. Good health; Interleukin 1 Receptor Antagonist Protein; Anakinra; Cross-Sectional Studies; Child, Preschool; Female; France; Tolerance; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; Interleukin-1

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.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.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.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.