Service de Pharmacosurveillance - Centre Régional de Pharmacovigilance et d'Information sur le Médicament Centre Val de Loire - Unité de Vigilance des recherches biomédicales CHRU Tours
Contact Université de tours : Hervé Watier
“Secukinumab a monoclonal antibody targeting interleukin (IL) 17-A, is registred in adults for the treatment of plaque psoriasis, psoriatic arthritis and active ankylosing spondylitis. Secukinumab was recently marketed and there is very little data on its safety profile. Based on the biological function of IL-17A, fungal infections were anticipated as a possible side-effect (SE) of secukinumab. The aim of this study was to assess the safety profile of secukinumab and to determine which unexpected SE could be explained by its biological effects.
All cases of SE reported with secukinumab to the French Regional Pharmacovigilance Centers or to the firm since marketing (2016) to December 2017, were analyzed. The incidence of SE was estimated using sales of secukinumab. For each type of new SE, a literature review about biological effects of IL 17A was performed.
During the 18 months of the study, 690 cases of SE were reported, of which 521 provided useful information: 182 serious and 339 non-serious. The incidence of SE reported was estimated at 4%. Il-17A a T cell-derived proinflammatory cytokine, has been shown to be mostly beneficial against infection caused by extracellular bacteria and fungi. So,the most SE reported were bacterial infections (Staphylococcus, Pneumococcus) (n=48) and Candida infections (n=33). Among digestive SE, Crohn’s disease (CD) (new or exacerbation) (n=15) and ulcerative colitis (n=9) were common. IL-17A plays a role in inflammatory bowel disease but in a study on the treatment of CD, secukinumab demonstrated more relapse than placebo. IL-17 /23 axis is a key player in CD pathogenesis, witch could result from an inappropriate inflammatory response to intestinal microorganisms as C.albicans. Finally, 10 arterial thromboembolisms (myocardial infarction, unstable angina and transient ischemic attack) were reported, always in patients with cardiovascular (CV) risk factors. So, in some trials studying IL17 inhibitors, serious cardiovascular events were more frequent in patients with CR risk factors and IL-17 can have both protective and exacerbating effect on atherosclerosis.
Most of new secukinumab SE may be explained by its biological effects. However pharmocoepidemiological studies are needed to confirm this fact, because these diseases could be associated with the initial pathology”.