Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSIONS: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

[Autoimmune bullous diseases in children]. / Dermatoses bulleuses auto-immunes chez les enfants.

Auto-immune bullous diseases (AIBD) are rare in children. Although their pathogenesis is similar to their adult counterpart, there are differences in the clinical presentation. Moreover certain AIBD prevail at certain ages. There are no guidelines for the treatment of AIBD specific for children. In this review the recent literature is summarised with attention to recent data including diagnostic criteria. We also propose a treatment algorithm.

Les maladies bulleuses auto-immunes (MBAI) sont rares chez les enfants. Bien que la pathogenèse soit similaire à celle de l'adulte, il existe des différences concernant la présentation clinique et la prévalence des MBAI selon l'âge. À ce jour, il n'y a pas de recommandations spécifiques pour leur prise en charge chez l'enfant. Dans cet article, nous présentons une revue des données actuelles, des critères diagnostiques et proposons un algorithme de prise en charge.

[Anti-IL17 induced eczema and the yin-yang of Th2 and Th17]. / Eczéma induit par les anti-IL-17 et le yin-yang Th2/Th17.

Biologics targeting specific cytokines and pathways have revolutionized the management of patients with chronic inflammatory diseases. However, these treatments have their limitations and, surprisingly, can induce novel inflammatory diseases. Here, we present a case of a psoriasis patient developing anti-IL17 induced eczema, an intriguing side effect of IL-17 blockade. The coexistence of psoriasis and eczema in a single patient is uncommon given their distinct and opposing immune mechanisms. Psoriasis is mainly driven by Th17 cells, whereas atopic dermatitis is Th2-dominated. In this article, we propose the yin yang of Th2 and Th17 with IL-4 and IL17 as principal antipodal vectors that control each other. Thus, blocking one of these cytokines can tip the balance between Th2 and Th17 and lead to the induction of the opposing inflammatory pathway via lifting the controlling mediator.

Les biologiques ciblant des cytokines spécifiques ont révolutionné la prise en charge des maladies inflammatoires chroniques. Cependant, ces thérapies possèdent leurs propres limites et peuvent ­ de manière surprenante ­ induire de nouvelles pathologies inflammatoires. Nous présentons le cas d'un patient psoriasique avec un eczéma induit par anti-IL-17. La coexistence du psoriasis et de l'eczéma atopique chez un même patient est rare, du fait de leurs mécanismes inflammatoires distincts. Le psoriasis est médié par la voie Th17, tandis que l'eczéma atopique est dominé par la voie Th2. Nous proposons un modèle yin-yang entre la voie Th17 et Th2, avec respectivement l'IL-17 et l'IL-4 comme vecteurs opposés. Le blocage de l'une de ces deux cytokines peut perturber cet équilibre dynamique et induire l'expression de la voie inflammatoire opposée par levée du médiateur de contrôle.

[Paradoxical psoriasis induced by anti-TNF - a clinical challenge]. / Psoriasis paradoxal induit par anti-TNF ­ un challenge en clinique.

Anti-TNFs have revolutionized the management of numerous chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. Although anti-TNF drugs are highly effective, 2-5 % of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. Paradoxical psoriasis is specific to anti-TNFs and it is, despite clinically resembling classical psoriasis, immunologically distinct. As it frequently requires cessation of the anti-TNF therapy, paradoxical psoriasis is a critical drug side effect and a challenge in the management of patients with chronic inflammatory diseases. In this review, we discuss the clinical, histological and pathogenic distinctions between the two entities and the management of patients developing paradoxical psoriasis.

Les thérapies anti-TNF ont révolutionné la prise en charge de nombreuses maladies inflammatoires chroniques telles que la polyarthrite rhumatoïde, les maladies inflammatoires chroniques de l'intestin et le psoriasis. Bien que les anti-TNF soient hautement efficaces, 2 à 5 % des patients traités développent des lésions cutanées psoriasiformes appelées psoriasis paradoxal. Le psoriasis paradoxal est spécifique aux anti-TNF et, malgré sa ressemblance clinique au psoriasis classique, il est immunologiquement distinct. Toutefois, il représente un challenge et un événement clé dans la prise en charge des patients sous anti-TNF étant donné qu'il nécessite fréquemment un arrêt de la thérapie. Dans cet article, nous discutons les distinctions cliniques, histologiques et pathogéniques des deux entités et la prise en charge des patients présentant un psoriasis paradoxal.

Drug Survival of Interleukin (IL)­17 and IL­23 Inhibitors for the Treatment of Psoriasis: A Retrospective Multi­country, Multicentric Cohort Study.

BACKGROUND: Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. OBJECTIVE: The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. METHODS: This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. CONCLUSION: The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab.

Secukinumab demonstrates improvements in absolute and relative psoriasis area severity indices in moderate-to-severe plaque psoriasis: results from a European, multicentric, retrospective, real-world study.

Objective: This European, multicentric, retrospective study aimed to collect data on secukinumab effectiveness in a real-world setting.Research design and methods: All psoriatic patients starting secukinumab between January 2016 and February 2017 in 11 European centers were followed until February 2018 and retrospectively evaluated.Main outcome measures: Secukinumab effectiveness was assessed by relative improvement from baseline of the Psoriasis Area Severity Index (PASI) and absolute PASI score modifications throughout 52 weeks of therapy. Additionally measures assessing effectiveness were used, including improvements of body surface area (BSA) and Dermatology Life Quality Index (DLQI).Results: Out of the 330 patients with potentially 52-week treatment duration, naïve to biologics patients showed greater probability to achieve PASI score of ≤1, ≤2, ≤3, and ≤5 at week 12, compared to bio-experienced patients (45.86% vs. 27.17%, 62.42% vs. 42.42%, 73.89% vs. 57.80%, and 84.08% vs. 74.57%, respectively). The greater effectiveness of secukinumab treatment in bio-naïve patients was confirmed at week 24 and 52.Conclusions: In this real-world experience, secukinumab was proven effective in treating psoriasis patients throughout a 52-weeks observation period, with higher response in bio-naïve patients. This study may contribute to defining the clinical profile of secukinumab best-responders.