Erythrodermic psoriasis (EP) is a dermatological emergency and its treatment with secukinumab is still controversial. Furthermore, no data exist regarding the prognostic value of drug abuse in such a condition. We performed a multi-center, international, retrospective study, enrolling a sample of EP patients (body surface area > 90%) who were treated with secukinumab (300 mg) during the study period from December 2015 to December 2018. Demographics and clinical data were collected. Drug abuses were screened and, specifically, smoking status (packages/year), cannabis use (application/week) and alcoholism—tested with the Alcohol Use Disorders Identification Test (AUDIT)—were assessed. All patients were followed for up to 52 weeks. We enrolled 13 EP patients, nine males, and four females, with a median age of 40 (28–52) years. Patients naïve to biologic therapy were 3/13. Regarding drug use, seven patients had a medium-high risk of alcohol addiction, three used cannabis weekly, and seven were smokers with a pack/year index of 295 (190–365). The response rate to secukinumab was 10/13 patients with a median time to clearance of three weeks (1.5–3). No recurrences were registered in the 52-week follow-up and a Psoriasis Area Severity Index (PASI) score of 90 was achieved. The entire cohort of non-responders (n = 3) consumed at least two drugs of abuse (alcohol, smoking or cannabis). Non-responders were switched to ustekinumab and obtained a PASI 100 in 24 weeks. However, given our observed number of patients using various drugs in combination with secukinumab in EP, further studies are needed to ascertain drug abuse prevalence in a larger EP cohort. Secukinumab remains a valid, effective and safe therapeutic option for EP.