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

Orphanet Journal of Rare Diseases

Isabelle Koné-Paut¹  Isabelle Touitou³  Luca Semerano²  Caroline Galeotti¹  Eric Hachulla⁶  Daniel Wendling⁴  Bruno Fautrel⁵  Linda Rossi-Semerano¹ 

[1] 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, Le Kremlin, 94270, Bicêtre, France;Department of Rheumatology, Hôpital Avicenne, APHP, INSERM UMR 1125, Paris 13 University, Bobigny, France;Maladies Auto-inflammatoires, Laboratoire de Génétique, Hôpital A de Villeneuve, CHRU Montpellier, Montpellier, France;Department of Rheumatology, University Teaching Hospital, CHRU Besançon, and University of Franche-Comté, Besançon, France;Department of Rheumatology, Hôpital La Pitié Salpêtrière, APHP; UPMC, GRC 08, Institut Pierre Louis d’Epidémiologie et Santé Publique, Paris, France;Centre de Référence des Maladies Autoimmunes et systémiques Rares, Service de Médecine Interne, Hôpital Claude Huriez, Université Lille Nord-de-France, Lille Cedex, France

关键词: Off-label;    Tolerance;    Canakinumab;    Anakinra;    IL-1;    Auto-inflammatory diseases;   

Others  :  1135281
DOI  :  10.1186/s13023-015-0228-7

 received in 2014-10-29, accepted in 2015-01-18,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Rossi-Semerano et al.; licensee BioMed Central.

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