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: Linda Rossi-Semerano, Bruno Fautrel, Daniel Wendling, Eric Hachulla, Caroline Galeotti, Luca Semerano, Isabelle Touitou, Isabelle Koné-Paut, MAIL1 (Maladies Auto-inflammatoires et Anti-IL-1) study Group on behalf of CRI (Club Rhumatisme et Inflammation)
• Journal: Orphanet journal of rare diseases (Orphanet J Rare Dis) Vol. 10 Pg. 19 (Feb 15 2015) ISSN: 1750-1172 [Electronic] England
• PMID: 25758134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1
• canakinumab

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Autoimmune Diseases (drug therapy, immunology)
• Child
• Child, Preschool
• Cross-Sectional Studies
• Female
• France
• Humans
• Infant
• Inflammation (drug therapy, immunology)
• Interleukin 1 Receptor Antagonist Protein (administration & dosage, adverse effects, therapeutic use)
• Interleukin-1 (antagonists & inhibitors)
• Male
• Middle Aged
• Off-Label Use (statistics & numerical data)
• Young Adult