Effectiveness and Safety of Tildrakizumab in Psoriasis Patients Who Failed Anti-IL17 Treatment: A 28-Week Real-Life Study.

Tildrakizumab is a humanised IgG1/k-type monoclonal antibody that targets the p19 protein subunit of IL23. Despite its effectiveness and safety have been widely reported by clinical trials and real-life experiences, data regarding its use on patients who previously failed anti-IL17 (brodalumab, ixekizumab, bimekizumab and/or secukinumab) are scant. Therefore, further studies on this topic would be beneficial for clinicians in guiding the selection of biologic shifting, considering that anti-IL23, -12/23, and -IL17 partially share their therapeutic targets. In this context, we performed a 28-week, single-center, real-life, retrospective study, with the aim of assessing the efficacy and safety of tildrakizumab in patients who previously failed anti-IL17, also focusing the attention on psoriasis located in difficult-to-treat areas (scalp, palms or soles, fingernails, genitals). A total of 23 patients (12 male, 52.2%; mean age 52.8 ± 12.4 years) were enrolled. Of these, 11 (47.8%) failed secukinumab, 7 (30.4%) ixekizumab, 3 (13.0%) brodalumab, 1 (4.3%) both secukinumab and ixekizumab and 1 (4.3%) bimekizumab. At baseline, mean PASI and BSA were 12.8 ± 5.9 and 18.7 ± 9.6, respectively. At W16 PASI75 and PASI90 response were achieved by 15 (65.2%), and 9 (39.1%) patients, respectively, whereas 19 (82.6%) and 13 (56.6%) subjects reached these scores at W28. One (4.3%) case of primary inefficacy and 1 (4.3%) case of secondary inefficacy were assessed. Finally, no severe adverse events were collected. Tildrakizumab seems to be a valuable option in selected patients with psoriasis unresponsive to anti-IL17, suggesting that prior exposure to biological therapies seem not directly affect its effectiveness.

Real-Life Effectiveness and Safety of Guselkumab in Patients with Psoriasis Who Have an Inadequate Response to Ustekinumab: A 3-Year Multicenter Study.

Background: Guselkumab is the first approved human IgG1λ monoclonal antibody selectively targeting the p19 subunit of IL23. Its effectiveness and safety were widely reported by clinical trials. However, these results must be confirmed in real life since its safety deals with more complicated subjects with respect to trials. Currently, real-life data on the use of guselkumab following treatment failure with ustekinumab are limited, and existing studies usually show a small cohort and/or a reduced follow-up period. In this context, the aim of our study was to evaluate the use of guselkumab in patients who previously did not respond to ustekinumab after up to 3 years of treatment. Methods: A multicenter retrospective study was performed. The study enrolled patients affected by moderate-to-severe plaque psoriasis undergoing treatment with guselkumab who were attending the Psoriasis Center of nine different centers in the Campania region of Italy. Demographic and clinical features were collected for each patient at baseline. Moreover, data on psoriasis severity and adverse events (AEs) were collected at each follow-up visit (week (W)16-W36-W52-W104-W156). Results: A total of 112 patients (70 male, 62.5%; mean age 54.8 ± 11.7 years old) were enrolled. Of these, 48 (42.9%), 34 (30.4%), and 16 (14.3%) reached 1, 2, and 3 years, respectively, of follow-up under guselkumab. A statistically significant clinical improvement was observed since W16, and sustained effectiveness was reported at each timepoint up to W156. No serious AEs were collected. Moreover, a sub analysis on the body mass index, involvement of difficult-to-treat areas, and presence of psoriatic arthritis (PsA) showed that the presence of PsA or palmoplantar psoriasis was associated with a reduced clinical improvement at W16 and W36, without differences from W52. In contrast, the efficacy of guselkumab does not seem to be affected by the BMI, involvement of fingernails, or location in the genital or scalp area. Conclusions: To sum up, our long-term real-life multicenter retrospective study confirmed the efficacy and safety of guselkumab following ustekinumab discontinuation up to 156 weeks of treatment.

Biological Therapy for Psoriasis in Cancer Patients: An 8-Year Retrospective Real-Life Study.

Background: It is now recognized that psoriasis plays a key role in the development of several comorbidities, such as cardiovascular disease, and metabolic syndrome. Some authors have hypothesized that patients with psoriasis may have an increased risk of developing certain types of cancer. The efficacy and safety of biologic drugs are well-documented in clinical trials and in real-life studies. However, there is limited evidence on the safety of the use of biologic treatments in cancer patients with psoriasis, and the use of this therapeutic class in patients with a pre-existing or concomitant malignancy is still debated. Methods: We have conducted a retrospective observational study of a group of oncology patients with moderate-to-severe psoriasis treated with biologic therapy at the Dermatology Clinic of the University of Naples Federico II, during the period from 2016 to 2024. We included 20 adult patients; in 15 of them the diagnosis of neoplasm preceded the start of treatment biologic, while four of these patients had been diagnosed with cancer during the course of therapy biologics. Results: The most represented neoplasms in our population were breast carcinoma, prostate carcinoma, thyroid carcinoma, and chronic lymphatic leukemia. Anti-IL17 drugs were the most frequently prescribed (47.7%), followed by anti-IL23p19 (36.8%), anti-IL-12/23 (10.5%) and anti-TNF alpha (5.26%). All patients showed improvement of psoriasis after starting the therapy. Conclusions: Our experience supports the effectiveness and safety of biological therapy for psoriasis in patients with a history of cancer or recent onset neoplasia.

Very low-calorie ketogenic diet (VLCKD): a therapeutic nutritional tool for acne?

BACKGROUND: Acne, a chronic inflammatory disease impacting the pilosebaceous unit, is influenced significantly by inflammation and oxidative stress, and is commonly associated with obesity. Similarly, obesity is also associated with increased inflammation and oxidation. The role of diet in acne remains inconclusive, but the very low-calorie ketogenic diet (VLCKD), known for weight loss and generating anti-inflammatory ketone bodies, presents promising potential. Despite this, the effects of VLCKD on acne remain underexplored. This study aimed to investigate the efficacy of a 45-day active phase of VLCKD in reducing the clinical severity of acne in young women with treatment-naïve moderate acne and grade I obesity. METHODS: Thirty-one women with treatment-naïve moderate acne, grade I obesity (BMI 30.03-34.65 kg/m2), aged 18-30 years, meeting inclusion/exclusion criteria, and consenting to adhere to VLCKD were recruited. Baseline and post-intervention assessments included anthropometric measurements, body composition, phase angle (PhA), trimethylamine N-oxide (TMAO) levels, and reactive oxygen metabolite derivatives (dROMs) as markers of inflammation, dysbiosis, and oxidative stress, respectively. A comprehensive dermatological examination, incorporating the Global Acne Grading System (GAGS) and the Dermatology Life Quality Index (DLQI), was conducted for all women. RESULTS: VLCKD resulted in general improvements in anthropometric and body composition parameters. Significantly, there were significant reductions in both the GAGS score (Δ%: - 31.46 ± 9.53, p < 0.001) and the DLQI score (Δ%: - 45.44 ± 24.02, p < 0.001) after the intervention. These improvements coincided with significant decreases in TMAO (p < 0.001) and dROMs (p < 0.001) levels and a significant increase in PhA (Δ%: + 8.60 ± 7.40, p < 0.001). Changes in the GAGS score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjusting for Δ% FM. Changes in the DLQI score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjustment for Δ% FM. CONCLUSION: Given the side effects of drugs used for acne, there is an increasing need for safe, tolerable, and low-cost treatments that can be used for acne disease. The 45-day active phase of VLCKD demonstrated notable improvements in acne severity, and these improvements seemed to be attributable to the known antioxidant and anti-inflammatory effects of VLCKD.

The Past, the Present and the Future of Teledermatology: A Narrative Review.

Teledermatology may be defined as the application of telemedicine to dermatology. According to published data, teledermatology is more widespread in Europe and North America, probably where resources for health care are greater than in other areas of the world. Indeed, teledermatology requires advanced technology to be efficient, as high image quality is necessary to allow the dermatologist to make correct diagnoses. Thanks to the recent advances in this field, teledermatology is become routinary in daily clinical practice. However, its use has been improved over time, overcoming several challenges. The aim of this narrative review is to retrace the almost 30-year history of teledermatology, to address the new challenges posed by advancing technologies such as artificial intelligence and the implications it may have on healthcare.

Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study.

BACKGROUND: Hidradenitis suppurativa (HS), an inflammatory-based dermatological condition often associated with obesity, poses significant challenges in management. The very low-calorie ketogenic diet (VLCKD) has shown efficacy in addressing obesity, related metabolic disorders, and reducing chronic inflammation. However, its effects on HS remain underexplored. In this prospective pilot study, we aimed to investigate the impact of a 28-day active phase of VLCKD on HS in a sample of treatment-naive women with HS and excess weight. METHODS: Twelve women with HS and overweight or obesity (BMI 27.03 to 50.14 kg/m2), aged 21 to 54 years, meeting inclusion/exclusion criteria and agreeing to adhere to VLCKD, were included. Baseline lifestyle habits were assessed. The Sartorius score was used to evaluate the clinical severity of HS. Anthropometric parameters (waist circumference, weight, height, and body mass index), body composition via bioelectrical impedance analysis, levels of trimethylamine N-oxide (TMAO), oxidized low-density lipoprotein (oxLDL), and derivatives of reactive oxygen metabolites (dROMs) were assessed at baseline and after 28 days of the active phase of VLCKD. RESULTS: VLCKD led to general improvements in anthropometric parameters and body composition. Notably, a significant reduction in the Sartorius score was observed after the intervention (Δ%: - 24.37 ± 16.64, p < 0.001). This reduction coincided with significant decreases in TMAO (p < 0.001), dROMs (p = 0.001), and oxLDL (p < 0.001) levels. Changes in the Sartorius score exhibited positive correlations with changes in TMAO (p < 0.001), dROMs (p < 0.001), and oxLDL (p = 0.002). CONCLUSION: The 28-day active phase of VLCKD demonstrated notable improvements in HS severity and associated metabolic markers, highlighting the potential utility of VLCKD in managing HS and its association with metabolic derangements in women with overweight or obesity.

Viral Reactivation Following COVID-19 Vaccination: a review of the current literature.

BACKGROUND: Currently, four vaccines for COVID-19 have been licensed by the European Medi-cines Agency: viral vector-based vaccines (AstraZeneca; AZD1222 and Johnson & Johnson; Ad26.COV2. and 2 mRNA-based vaccines (Pfizer/BioNTech; BNT162b2 and Moderna; mRNA-1273). Since their approval, several cutaneous reactions related to vaccination have been reported in the literature. Among these, viral reactivations are one of the most frequent. OBJECTIVES: The aim of this manuscript was to investigate current literature regarding viral reactivations following COVID-19 vaccination, focusing the attention on Pityriasis Rosea, Herpes Zoster and Herpes Simplex. METHODS: A comprehensive literature research using various databases, including metanalyses, re-views, letters to the editor, real-life studies, case series, and reports, was performed. RESULTS: A total of 47 articles involving about 2000 patients were selected. Of these, 32, 6 and 17 articles reported VZV reactivation (1,758 cases), HSV (238 cases) onset and PR (71 cases), respectively. CONCULSION: Possible pathogenetic mechanisms underlying viral reactivation are not still understood as well as the possible correlations between vaccination and viral reactivation should be clarified. Certainly, vaccination should not be discouraged.

Secukinumab in Hidradenitis Suppurativa Patients Who Failed Adalimumab: A 52-Week Real-Life Study.

Background: The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, adalimumab the only biologic drug approved for HS is adalimumab, an anti-tumor necrosis factor (TNF)-α drug, the approval of this drug dates to 2015, data provided by real life show an effectiveness rate of about 60% percent. Recently (31 October 2023) FDA approves secukinumab for moderate-severe HS. The treatment and management of HS is very challenging as available treatments are very limited and show very variable outcomes. Methods: We conducted a prospective monocentric study designed to evaluate the efficacy and safety of secukinumab treatment in HS patients in a real-life setting. Results: The initial cohort of patients recruited included 21 HS patients including 12 females and 9 males. About 57.1% of patients achieved the primary endpoint and recorded significant decrease in all the severity assessment scales (IHS4, DLQI and VAS pain scale) at week 16 and 52, when HiSCR reached 71.4%. Conclusion: The results of our study highlight that treatment with secukinumab in patients with severe HS who failed adalimumab may be a safe and effective therapeutic weapon.

Pityriasis Rosea and Pityriasis Rosea-Like Eruption Following COVID-19 Vaccination: A Narrative Review.

COVID-19 pandemic completely changed every aspect of human life. Several measures were adopted to limit the spreading of the infection. Among these, vaccination was the main one. Globally, vaccination campaign was a success, showing to be efficient in controlling and preventing the SARS-Cov2 infection, reducing the risk of disease progression, hospitalization, and mortality. However, with the increasing number of vaccines administered, several cutaneous reactions were described, making dermatologists key players in their recognition and treatment. Among these, also viral reactivations have been described. In particular, cases of Pityriasis Rosea (PR) and PR-like reactivations have been collected. An early diagnosis is mandatory to avoid mistreatments. In this context, we conducted a review of the current literature investigating cases of PR following COVID-19 vaccination with the aim of understanding the possible pathogenetic mechanisms and causal correlation as well as to investigate the risk of this cutaneous eruption, to offer clinicians a wide perspective on the linkage between PR and COVID-19 vaccines.

Multi-failure psoriasis patients: characterization of the patients and response to biological therapy in a multicenter Italian cohort.

INTRODUCTION: Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi-failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi-failure when ≥4 biologics fail to achieve a good response. METHODS: Demographic characteristics and efficacy of anti-interleukin drugs in multi-failure patients were compared to a cohort of general psoriatic patients treated with IL-23 or IL-17 inhibitors. RESULTS: In total 97 multi-failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi-failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi-failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi-failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti-IL-17 agents showed clinical superiority over IL-23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL-23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121). CONCLUSIONS: The multi-failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians.

Herpes Zoster and COVID-19 Vaccination: A Narrative Review.

COVID-19 was a worldwide emergency, leading to a global health crisis, which completely revolutionized every aspect of human life. Several strategies were adopted to limit the spreading of the infection such as testing and contact tracing, quarantine and isolation, use of face mask, social distancing, lockdowns, travel restrictions, etc. Of these, vaccines were the most important measures to reduce the transmission of the virus and the severity of the infection, in order to overcome the pandemic. Fortunately, vaccination campaign was a success, showing to be efficient in controlling and preventing the COVID-19, reducing the risk of disease progression, hospitalization, and mortality. Monitoring and addressing vaccine-related adverse events have been essential for maintaining public confidence. Indeed, with the increasing number of vaccines administered, various cutaneous reactions have been reported, making dermatologists key players in their recognition and treatment. Particularly, several cutaneous diseases and cutaneous findings have been reported. Of note, also viral reactivations have been described following COVID-19 vaccination. Among these, varicella zoster virus (VZV) reactivation has been collected. Globally, an early diagnosis and an accurate treatment of herpes zoster (HZ) is mandatory to reduce possible complications. In this context, we conducted a review of the current literature investigating cases HZ following COVID-19 vaccination with the aim of understanding the possible causal correlation and underlying pathogenetic mechanisms to offer clinicians a wide perspective on VZV reactivation and COVID-19 vaccines.

JAK Inhibitors in Psoriatic Disease.

Psoriasis is now considered to be the cutaneous phenotype of a systemic inflammatory condition, recognized under the term Psoriatic Disease (PsD). PsD has several extracutaneous manifestations, such as inflammatory articular and entheseal involvement, leading to psoriatic arthritis (PsA), and the less frequent intestinal and ocular manifestations with colitis/inflammatory bowel disease and uveitis, respectively. There have also been several reports of an increased frequency of comorbidities such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular manifestations during the course of PsD. The link between psoriasis and related comorbidities is considered a long-term disease sequela, often characterized by an unhealthy lifestyle and a consequence of systemic inflammation; hence, psoriasis requires adequate and prompt treatment, with the aim of controlling not only cutaneous manifestations but also extracutaneous manifestations and systemic inflammation. Pharmacological strategies for PsD have significantly increased over recent years. Recently, the targeted synthetic DMARDs, Janus kinase (JAK) inhibitors, tofacitinib and upadacitinib, were added to the therapeutic armamentarium for treating PsA, and deucravacitinib for psoriasis. These oral agents act directly on inflammatory mechanisms underlining the disease, as antagonists of the intracellular JAK signal pathway and, by STAT phosphorylation, inhibit gene proinflammatory cytokine transcription. JAK inhibitors represent a recent additional treatment strategy for PsD management and, among these, tofacitinib and upadacitinib have recently been approved for PsA, and deucravacitinib for psoriasis. In this review we describe ongoing and recent phase II and III randomized controlled trials (RCTs) evaluating the efficacy and safety of investigational JAK inhibitors in psoriasis and PsA.

Effectiveness of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis Located in Difficult-to-Treat Areas.

Background: Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient's quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers. Methods: An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment. Results: Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52. Conclusion: Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation.