Our study aims at providing evidence on patterns of use of biologic drugs for psoriasis in Tuscany, Italy. We conducted a drug-utilization study based on administrative databanks of Tuscany (EUPAS45365) from 2011 to 2019. We selected new users of etanercept, infliximab, adalimumab, ustekinumab, or secukinumab between 1 January 2011 and 31 December 2016. We considered subjects with psoriasis and followed subjects until the end of the study period (three years after the first dispensation of biologic drug for psoriasis) or the patient’s death, whichever came first. We censored subjects for pregnancy or neoplasia. For each subject, we defined the state as the weekly coverage of one of the biologic drugs of interest. We then defined the switch as the change from a state to another one. A total of 7062 subjects with a first dispensation of a PSObio drug in the inclusion period was identified, and 1839 (52.9% female, 51.6 mean age) patients were included in the analysis. Among new users of adalimumab (N = 770, 41.9%), one third showed a continuous behaviour whereas the others moved to etanercept and ustekinumab. New users of etanercept (N = 758, 41.2%), had the highest proportion of switchers, with adalimumab most often being the second choice. New users of infliximab (N = 159, 8.6%) experienced the highest proportion of treatment discontinuation. The present study suggests that the majority of patients treated with PSObio drugs do not switch from one active ingredient to another. However, patients who started biological therapy with etanercept had the highest frequency of switching to other PSObio drugs, whereas those who started with secukinumab or ustekinumab had the lowest.

Psoriasis is one of the most common immune-mediated inflammatory diseases (IMIDs). Living in a rural environment during childhood is associated with a decreased risk of certain IMIDs, like asthma, in adulthood. However, its role in other IMIDs, such as psoriasis is still unclear. To evaluate the relationships between different factors related to the environment during childhood and the risk of psoriasis in adulthood we conducted a study in E3N, a French prospective cohort composed of 98 995 women. During the 1990-2018 follow-up of 72 154 study participants, we identified 1967 incident cases of psoriasis from self-reports in self-administered structured questionnaires. During the 2004-2018 follow-up of 67 917 study participants, 188 moderate-to-severe cases of psoriasis were identified through self-reports and from data from a drug reimbursement database. We fitted Cox proportional hazards regression models with age as the time scale and adjusted for putative confounders (aHRs). We found inverse associations with risk of psoriasis for rural birthplace [aHR: 0.89 (95%CI: 0.79-0.96)] and for having farming parents [aHR: 0.84 (95%CI: 0.72-0.97)]. For moderate-to-severe psoriasis we found a nominally similar inverse association with rural birthplace but not with having farming parents. Our results suggest that an exposure to a rural environment during childhood may be associated with a reduced risk of psoriasis. These findings may help to improve our understanding of the pathogenesis of psoriasis.

Background and aim: The involvement of mucosa associated lymphoid tissues (MALT) in the development of an autoimmune response in the skin is unclear and unstudied. In this study we sought to assess the relationship between removal of MALT tissues (MALTectomy) and the risk of development of psoriasis (overall or moderate-to-severe). Methods: We conducted a prospective observational study based on E3N, a French cohort composed of 98 995 women born between 1925 and 1950 and insured by the health insurance of the national education system (MGEN). The study population included the 90 119 women that completed the 1990 baseline questionnaire with available information on MALTectomy and a valid incident diagnostic date for psoriasis. During the 1990–2018 follow-up period 2 433 incident cases of psoriasis were identified through self-reports while during the period for which drug reimbursement data were available from the MGEN database (2004–2018), 120 cases of moderate-to-severe psoriasis were identified. Hazard ratios (HR) and their 95% confidence intervals were estimated by Cox proportional hazards models and adjusted for known or putative psoriasis risk factors. Results: Appendectomy was associated with an increased risk of psoriasis both in the univariate [HR: 1.17 (95% CI: 1.08–1.27)] and multivariable models [HR: 1.14 (95% CI: 1.05–1.24)]. A suggestive association with appendectomy was observed for moderate-to-severe psoriasis risk [univariate HR: 1.40 (95%CI: 0.97–2.02); multivariable HR: 1.36 (95%CI: 0.94–1.96)]. No association was observed between tonsillectomy or adenoidectomy both for overall and moderate-to-severe psoriasis. Conclusions: The observed association between appendectomy and risk of psoriasis warrants further investigations as they may help to elucidate the disease etiology and improve risk prediction.

Étude des facteurs de risque de psoriasis liés à l'inflammation et à l'immunité dans la cohorte E3N: Le psoriasis est une maladie cutanée à médiation immunitaire qui touche des millions de personnes dans le monde, avec des coûts sociaux et économiques importants. Le psoriasis reste une maladie incurable en raison d'un manque de compréhension de sa pathogenèse, qui semble impliquer une interaction complexe entre des facteurs génétiques et environnementaux qui provoquent une activation aberrante du système immunitaire. Des données expérimentales suggèrent que les expositions environnementales contribuent à la pathogenèse du psoriasis en modulant l'immunité et l'inflammation, à la fois en agissant directement sur la maturation des cellules immunitaires innées et adaptatives impliquées et en agissant indirectement sur le microbiome, qui à son tour stimule l'acquisition de la tolérance immunitaire ou, à l'inverse, provoque une activation immunitaire. Cependant, pour de nombreux facteurs environnementaux soupçonnés de jouer un rôle dans la modulation de l'immunité et de l'inflammation et leur relation avec le risque de psoriasis, les études dans la littérature sont rares et peu concluantes. L'objectif général de ce projet de doctorat était d'étudier le rôle de l'environnement dans le développement du psoriasis. Le concept d'"environnement" adopté dans cette thèse est large et englobe le réseau complexe de facteurs externes et le mode de vie qui peuvent influencer le risque de psoriasis par le biais de réponses immunitaires et inflammatoires. L'objectif spécifique de la thèse était de tester l'association avec le psoriasis pour trois groupes de facteurs de risque supposés : L'ablation du MALT (tissu lymphoïde associé aux muqueuses - appendicectomie, adénoïdectomie, amygdalectomie), l'environnement de l'enfance (comme le fait de vivre dans un lieu de naissance urbain ou rural, d'avoir des parents agriculteurs et de vivre avec des animaux domestiques) et l'exposition au soleil en milieu résidentiel. Nous avons testé ces associations à l'aide de la cohorte prospective française E3N, établie en 1990 et composée de 98 995 femmes nées entre 1925 et 1950 et affiliées à la Mutuelle Générale de l'Éducation Nationale (MGEN). Nous avons effectué les analyses statistiques à l'aide des modèles de risques proportionnels de Cox et de régression logistique. Les résultats suggèrent que l'appendicectomie augmente le risque de psoriasis, alors qu'aucune association n'est observée avec l'adénoïdectomie ou l'amygdalectomie. En outre, une association inverse a été observée entre le lieu de naissance rural, le fait d'avoir des parents agriculteurs et le risque de psoriasis. Enfin, une association inverse a été observée entre l'exposition solaire résidentielle et le psoriasis. Les associations identifiées dans nos analyses, si elles sont reproduites dans d'autres populations, permettront de mieux comprendre la pathogenèse de la maladie psoriasique et pourraient ouvrir des voies prometteuses pour le développement de programmes de prévention ciblant les populations à haut risque de psoriasis.