Thyroiditis and immune check point inhibitors: the post-marketing experience using the French National Pharmacovigilance database.

Fiche publication

Date publication

octobre 2018

Journal

Fundamental & clinical pharmacology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GILLET Pierre

Tous les auteurs :
Garon-Czmil J, Petitpain N, Rouby F, Sassier M, Babai S, Yelehe-Okouma M, Weryha G, Klein M, Gillet P

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30308083

Résumé

Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, are seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database. This database was queried for nivolumab, pembrolizumab and ipilimumab-induced adverse drug reactions reported before 30 April 2017. Both a pharmacologist and an endocrinologist have reviewed each case to select only those of peripheral thyroiditis (thyrotoxicosis and hypothyroidism). During this period, 110 thyroiditis following ICI therapy were reported. Sex/ratio was around one. Most of the cases (47·2%) were asymptomatic. Although some thyrotoxicosis cases were severe, no orbitopathy was reported. Hypothyroidism and thyrotoxicosis were equally described. Antithyroid antibodies were positive in only 16% patients. The ultrasonography was informative in 19% patients. Levothyroxine supplementation was necessary in 57% patients, leading to 19% recovery. With a dedicated optimized management, most of the cases did not require immunotherapy discontinuation. Finally, immune-mediated related thyroiditis are increasing due to a wider prescription of ICI therapy in various cancer conditions and systematic screening. Often asymptomatic, they lead to a local activation accompanied by hormonal deficiency in the long run. It is necessary to carry out an early and sustained multidisciplinary screening to allow immunotherapy continuation.