In which patients the best efficacy of secukinumab? Update of a real-life analysis after 136 weeks of treatment with secukinumab in moderate-to-severe plaque psoriasis.

ABSTRACTBackground: There is limited long-term, real-world evidence on the efficacy and safety in patients with plaque psoriasis treated with secukinumab. We present results at 136 weeks in a real-..

Treating a Multidrug-Resistant Psoriatic HLA-C*18:01 Allele Carrier with Combination Ustekinumab Apremilast Therapy

Nowadays, even though several biologic therapies are available to treat psoriasis, multidrug-resistant disease continues to be a therapeutic challenge. Combination therapy has therefore become increasingly important. In this context, apremilast, according to its safety profile, could easily be combined with biologics in patients with comorbidities and/or recalcitrant multidrug-resistant psoriasis

Secukinumab in moderate-to-severe plaque psoriasis: a multi-center, retrospective, real-life study up to 52 weeks observation

To evaluate efficacy and safety of the anti-IL-17 drug secukinumab in a real-life large cohort of patients with moderate-to-severe plaque psoriasis in Central Italy. METHODS: Multicenter, retrospective study with an observation period of up to 52 weeks. Efficacy was assessed by Psoriasis Area and Severity Index (PASI) score; clinical and laboratory examinations were performed at baseline and at weeks 4, 12, 24, 36, and 52. RESULTS: A 90% and a 100% PASI score reduction (PASI90 and PASI100) were reported in 67.5% and 55% of patients at week 12, respectively. A rapid improvement of skin lesions was observed particularly in young patients and in patients naïve to biologics: at week 4, the achievement of PASI90 and PASI100 was higher in younger patients (odds ratio [OR] 0.95, and 0.95; p = 0.003, and 0.005, respectively); PASI90 was achieved by 42.0% of patients naïve to biologics and by 17.0% of patients with prior exposure to biologics (PBT) (OR 0.24; p = 0.001); and PASI100 was reached by 25.5% of naïve patients and 9.8% of PBT (OR 0.28; p = 0.015).The drug was well tolerated. CONCLUSION: Secukinumab was effective in this real-life analysis, with rapid clinical improvement and long-term maintenance of results

Guselkumab for the treatment of psoriasis: a 60-week real-life multicenter retrospective experience

Background: Real-world data for guselkumab, the first interleukin-23 inhibitor approved to treat moderate-to-severe psoriasis, are scarce. This study represents the first 60-week, real-life, multicenter, retrospective experience to investigate the effectiveness, safety, tolerability, and drug retention of guselkumab in psoriatic patients. Research design and methods: Clinical information was collected at baseline and at weeks 12, 24, 36, 48, and 60. Results: The mean baseline Psoriasis Activity Severity Index (PASI) reduced from 14.2 to 3.1 at week 12 and decreased to around 0 at weeks 36, 48, and 60. PASI 75, PASI 90, and PASI 100 were 100%, 96.8%, and 83.9% at week 60, respectively. Multiple logistic regression analysis showed that neither body mass index >30, smoking, ≥3 comorbidities, difficult-to-treat areas, nor a failure to ≥2 prior biologic treatments significantly influenced PASI reduction (p > 0.05). Conclusions: Our findings confirm guselkumab as an appropriate therapeutic option in routine clinical practice, especially when dealing with complex patients with comorbidities or previous failure to biologic treatments

Clinical and histopathological characterization of eczematous eruptions occurring in course of anti IL-17 treatment: a case series and review of the literature

Background: Real-life data often highlight the side effects of certain drugs not previously reported in randomized controlled trials (RCTs).Objective: To describe cutaneous inflammatory eruptions in psoriatic patients treated with an anti IL-17A agent (secukinumab or ixekizumab).Methods: Retrospective analysis of a cohort of patients with chronic plaque psoriasis who started an anti IL-17A agent between September 2016-February 2019 and who developed cutaneous inflammatory eruptions during treatment. A systematic review of similar events reported in the literature was performed.Results: Data of 468 patients were reviewed and 27 cutaneous inflammatory eruptions of 27 (5.8%) patients were collected. The eruptions appeared after a mean of 16.9 ± 17.0 weeks of therapy showing a classical acute eczema in 11 patients (40.7%), an atopic dermatitis-like rash in 11 patients (40.7%) and a psoriasiform eruption in 5 patients (18.5%). Histopathology of 12/27 cases showed epidermal spongiosis in all these variants.Conclusion: We described the clinic-pathologic features of some eczematous eruptions occurring in psoriatic patients, 3-4 months after treatment initiation with an anti IL-17A agent. Further investigations are needed to explain this phenomenon, that might be defined a paradoxical adverse event, based upon the role of IL17 in eczema pathogenesis

Use of apremilast in the psoriasis treatment: a real-life multicentre Italian experience

Background: Apremilast is the first small molecule approved for the treatment of moderate-to-severe psoriasis in adult patients; however, real-life data are still limited. We investigated the effectiveness and safety of this drug in a multicentre real-world setting. Methods: We retrospectively reviewed data from all psoriatic patients who received at least one dose of apremilast, collecting demographic data and medical history, at baseline and periodically until 36 months. Results: A total of 111 patients entered in the study. The mean drug survival duration was 21.8±10.6 months, significantly shorter when comorbidities were≥3 and if biologic drugs were previously administered.ΔPASI90 was achieved in 29% of patients and ΔPASI50 in 68% at T4;the rate of ΔPASI improvement increased progressively at T12, T24, T36 in patients who continued to receive apremilast.At the end of the study 50 patients discontinued the treatment because of adverse events (19.8%), primary failure(19%) or secondary failure(6.3%). Conclusions: Apremilast proved to be an effective, safe, and manageable drug, showing effectiveness also in difficult-to-treat patients with psoriasis, with a favourable tolerability profile and a potentially valid weight loss effect. We believe that treating patients with few comorbidities who are naive to biological therapy may result in higher response rates and longer mean drug survival

Glucocorticoid-induced Leucine Zipper (GILZ) and Long GILZ Inhibit Myogenic Differentiation and Mediate Anti-myogenic Effects of Glucocorticoids*

Myogenesis is a process whereby myoblasts differentiate and fuse into multinucleated myotubes, the precursors of myofibers. Various signals and factors modulate this process, and glucocorticoids (GCs) are important regulators of skeletal muscle metabolism. We show that glucocorticoid-induced leucine zipper (GILZ), a GC-induced gene, and the newly identified isoform long GILZ (L-GILZ) are expressed in skeletal muscle tissue and in C2C12 myoblasts where GILZ/L-GILZ maximum expression occurs during the first few days in differentiation medium. Moreover, we observed that GC treatment of myoblasts, which increased GILZ/L-GILZ expression, resulted in reduced myotube formation, whereas GILZ and L-GILZ silencing dampened GC effects. Inhibition of differentiation caused by GILZ/L-GILZ overexpression correlated with inhibition of MyoD function and reduced expression of myogenin. Notably, results indicate that GILZ and L-GILZ bind and regulate MyoD/HDAC1 transcriptional activity, thus mediating the anti-myogenic effect of GCs