Guselkumab in moderate to severe psoriasis in routine clinical care: an Italian 44-week real-life experience.

OBJECTIVES: We aimed to evaluate the effectiveness, safety and tolerability of guselkumab in a real-life setting. METHODS: A prospective, observational, single-center, real-life study including patients under guselkumab treatment from October 2018 to January 2020 was conducted. RESULTS: Twenty-three patients with moderate-to-severe psoriasis were enrolled and twenty-two continued the treatment until week 44. One patient discontinued for increase in liver enzymes. At baseline, mean PASI score was 15.1 ± 6.1, which reduced up to 3.2 ± 1.9 at week 12 (p < .001) and 0.8 ± 0.7 at week 44 (p < .001). BSA reduced from 36.4 ± 13.6 at baseline, to 8.3 ± 7.4 at week 12 (p < .001), up to 2.2 ± 1.4 at week 44 (p < .001). A total of 4 patients (17.4%) experienced mild blood tests alterations and 6 subjects (26%) experienced potential adverse events (AEs). No AEs required guselkumab discontinuation. No cases of serious AEs, injection site reaction, candida, malignancy, cardiovascular events were reported. CONCLUSIONS: Patients under guselkumab therapy reach an optimal clinical response, even in a real-life and long-term setting.

Risankizumab in real life: preliminary results of efficacy and safety in psoriasis during a 16-week period.

No data on real-life experiences of risankizumab efficacy and safety are reported, apart from two isolated case reports. We carried out a single-centre, prospective study to assess the efficacy and safety of risankizumab. Fourteen patients were included (mean age 44.5 ± 14.2 years). Mean PASI decreased from 12.3 ± 5.2 (baseline) to 4.4 ± 2.7 at week 4 (p < 0.01), and to 2.7 ± 1.7 at week 16 (p < 0.001). A similar trend was observed for BSA. In patients previously treated with biologics (71.4%, n = 10) versus the naïve ones, mean baseline PASI was similar (12.7 ± 5.8 vs 11.3 ± 3.8). Mean BSA was higher in multifailure (23.5 ± 11.8 vs 15.5 ± 11.8). At 4 and 16 weeks, a significant improvement in PASI and BSA was observed in both groups. An improvement in NAPSI score, mean scalp, and palmo-plantar area reduction was noticed during follow-up. No AEs were reported up to week 16 and few and mild grade laboratory tests were reported. Our initial data confirm the promising results on efficacy and safety of Risankizumab, even in a more challenging and "real" population, composed of a high percentage of multi-failure psoriatic patients who have benefitted from a new class agent.

Real world practice indirect comparison between guselkumab and risankizumab: Results from an Italian retrospective study.

IL-23-inhibitors, such as guselkumab and risankizumab, represent the newest class of biologics approved for psoriasis. Phase III trials have shown their efficacy and safety. However, real life data are still scant. to indirectly compare the effectiveness, safety and tolerability of guselkumab and risankizumab in real world practice. An Italian single-center retrospective cohort study enrolling moderate-to-severe psoriasis patients from September 1, 2018 and December 31, 2020 was performed to indirectly compare guselkumab and risankizumab efficacy and safety. Sixty eight patients were included (36 received guselkumab and 32 risankizumab). The groups were comparable for all analyzed characteristics, except for mean psoriasis duration (p < 0.01) which was higher for guselkumab. In guselkumab group, mean PASI reduced from 16.1 ± 6.4 (baseline) 2.1 ± 0.9 (week-28) (p < 0.001) up to 0.9 ± 0.8 (week-44) (p < 0.001). In risankizumab group mean PASI decreased from 13.5 ± 4.9 (baseline) 1.9 ± 0.8 (p < 0.001), (week-28) (p < 0.001) up to 0.9 ± 0.4 (week-40) (p < 0.001). No significant difference in mean PASI and BSA were observed between the treatments. No cases of serious AEs, injection site reaction, candida, malignancy, cardiovascular events were reported in both groups. Guselkumab and risankizumab showed favorable efficacy and safety profile, being comparable in terms of PASI90 and PASI100 responses as well as in AEs frequency and discontinuation rates.

Ocular Manifestations in Psoriasis Screening (OcMaPS) Questionnaire: A Useful Tool to Reveal Misdiagnosed Ocular Involvement in Psoriasis.

Psoriasis is an immune-mediated, chronic inflammatory disease, which mainly affects the skin, although it has systemic pathological effects. Comorbidities of psoriasis include ocular disorders, which are often nonspecific or mildly symptomatic. The aim of this study was to show the importance of ocular-disease screening in psoriatic patients using the Ocular Manifestations in Psoriasis Screening (OcMaPS) questionnaire. Patients suffering from moderate-to-severe psoriasis referring at our outpatient-clinic were consecutively enrolled. Each patient was asked to complete a screening questionnaire (OcMaPS). Patients reporting ocular symptoms were referred for an ophthalmological examination. A total of 372 patients were enrolled in the study. Ocular symptoms were detected in 39 patients (10.5%), and 37 patients were referred to ophthalmological examination which confirmed the presence of ocular manifestation in 30 patients. There were three cases (10%) of uveitis, 14 (46.6%) of dry eye and 13 (43.3%) of cataract, in progress or already treated with surgery. In the remaining seven patients, no ocular manifestations were found. Ocular manifestations in psoriatic patients are not rare. It is important to be aware of ocular symptoms in psoriatic patients, screening patients (with a consultation or OcMaPS questionnaire), which leads to earlier diagnosis and treatment.

Psoriasis awareness among general population: preliminary results of an online survey.

BACKGROUND: Psoriasis represents one of the most common skin diseases in Italy, with a prevalence of 2.9%. It has been defined as a noncommunicable disease, due to its high burden and impact on patients' quality of life. The aim of our observational study was to assess the actual knowledge and perception of psoriasis in Italian population by administering an online 10-question survey to a representative sample general population. METHODS: An online 10-question survey was administered to a representative sample general population from September 2019 to December 2019. A representative sample of general population (age ≥18 years) was enrolled by promoting the online survey through multiple means of communication such as social sites (Facebook, Instagram) or delivering a questionnaire link in public spaces (outpatient clinic, pharmacy). All results were then collected and analyzed in graphs by the Google form platform. RESULTS: One hundred fifty-one individuals participated in the survey. Results showed that 7.3% (N.=11) of general population were not familiar with the term psoriasis; 4.6% (N.=7) thought to psoriasis as an infectious disease and 6% (N.=9) thought that psoriasis was contagious. Interestingly, 39.1% (N.=59) of participants have never heard about targeted/biologic therapy. Our study is limited by the small sample size as well as lack of data regarding sex, age and education level of the study participant. CONCLUSIONS: There is still lack of knowledge of psoriasis among general population, representing an obstacle for patients' everyday activities and quality of life. Future studies to investigate the details of this impaired knowledge and new psoriasis campaign on large scale should fill this gap are required.

Therapeutic update of biologics and small molecules for scalp psoriasis: a systematic review.

Scalp psoriasis represents the most common difficult-to-treat area in psoriasis patients. Its presence is linked to severe discomfort and impairment of quality of life given the associated symptoms (most of all, scaling and pruritus) and the location in a highly visible area, thus a prompt treatment is required. Its management may be challenging as the scalp is quite sensitive to long-term treatment with topical corticosteroids and usually resistant to topical and systemic agents. Likely, the currently available therapeutic armamentarium has been enriched with biologicals and small molecules that revolutionized psoriasis treatment and that of scalp psoriasis. Nevertheless, the lack of international dedicated guidelines pushed us to perform a comprehensive review on the efficacy and safety of biologics and small molecules on scalp psoriasis with the aim to put the basis for a therapeutic algorithm. After reviewing all the available evidence on the short-term and long-term efficacy of biologics and small molecules on scalp psoriasis the use of the newest biologics (anti-IL-17 and anti-IL-23) seems to be linked to the highest clinical performances in controlling scalp psoriasis. However, head-to-head comparisons between different biologics or biologics and small molecules are lacking. Hence, treatment selection should always be individualized.

Efficacy and safety of guselkumab in psoriasis patients who failed ustekinumab and/or anti-interleukin-17 treatment: A real-life 52-week retrospective study.

Recent major research advancements have significantly expanded our understanding of psoriasis pathophysiology, resulting in the development of highly effective, targeted therapies. Guselkumab is the first interleukin (IL)-23 inhibitor approved for the treatment of moderate-to-severe-psoriasis, providing a new therapeutical option for psoriasis. The aim of our study was to evaluate the efficacy of guselkumab in psoriatic patients who previously failed anti-IL-12/23 and/or anti-IL-17 treatment. A 52-week single-center retrospective study was performed enrolling moderate-to-severe patients attending our Psoriasis Care Center from October 2018 to May 2020. Study population included 13 patients; 46.1% have been previously treated with ustekinumab, while 69.2% have previously failed an anti-IL-17 treatment (38.5% secukinumab, 30.8% ixekizumab, and 38.5% both). At baseline, mean Psoriasis Area and Severity Index was 13.2 ± 6.8, reducing up to 0.5 ± 0.7 at week 52 (P < .001). Body surface area reduced from 22.3 ± 10.5 (baseline) to 0.8 ± 1.1 at week 52 (P < .001). No statistically significant differences have been found between patients previously treated with anti-IL-12/23 compared to anti-IL-17 or both. Only one patient discontinued guselkumab at week 36 due to secondary inefficacy. This is a single institution study with a relatively small sample size. Our real-life data confirm trial results, showing guselkumab as a safe and effective option in patients with moderate-to-severe psoriasis even in those who previously failed ustekinumab and/or anti-IL-17 treatment.

Personalized and targeted mutational analysis of multiple second primary melanomas under kinase inhibitors.

BACKGROUND: Second primary melanomas (SPMs) are new developed primary melanomas occurring in a subset of patients affected by BRAF-mutated metastatic melanoma during treatment with BRAF-inhibitors. A drug-induced paradoxical activation of mitogen-activated protein kinase (MAPK) signaling pathway in BRAF-wild type/RAS-mutated cells have been proposed as a possible molecular mechanism but data on the mutational status of SPMs are lacking. In order to better understand genetic alterations affecting the biological mechanism of SPMs, we performed a personalized and targeted next-generation sequencing analysis of a patient affected by metastatic melanoma who developed multiple SPMs during treatment with encorafenib (LGX818). METHODS: Using a cancer panel of 50 genes for solid tumors enriched with a custom panel of 10 genes specifically involved in melanoma pathogenesis, we analyzed the primary melanoma, two SPMs, one benign compound nevus and the normal DNA extracted from blood lymphocytes of the patient. RESULTS: We identified HRAS Q61 somatic mutation in one SPM developed in a pre-existing nevus. In the primary melanoma, besides the BRAF mutation, we identified the clinically actionable IDH1 R132C somatic mutation. Both SPMs were BRAF wild type. The patient harbors the recently recognized pathogenetic germline variant KDR Q472. We observed that mutations detected in tumor samples involving genes related to melanoma pathogenesis (TP53, PIK3CA, FGFR3, ATF1, KIT, HRAS and MAP2K2) were present in heterozygosis in the germline status of the patient. CONCLUSIONS: Our results support the paradoxical mechanism of MAPK pathway for SPMs under BRAF inhibitors. Moreover, they suggest that targeted mutational assessment based on matching somatic and germline analysis represent a promising approach to detect the neoplastic landscape of the tumor and to identify most accurate treatment in metastatic melanoma patient.

QuantiFERON TB-gold conversion rate among psoriasis patients under biologics: a 9-year retrospective study.

BACKGROUND: Tuberculosis (TB) screening is mandatory for psoriasis biologic treatment. However, evidences regarding TB screening results during biologic treatment are conflicting. OBJECTIVES: The aim of this study is to evaluate the rate of QuantiFERON TB Gold test (QFT) conversion in psoriasis patients during biologics over time. METHODS: A 9-year single center retrospective study was performed in order to evaluate the rate of QFT conversion in patients affected by moderate-to-severe plaque psoriasis under available biological therapies (anti-TNF-α, IL-12/23, IL-17). For each patient, demographic data, age, gender, comorbidities, previous psoriasis therapy, as well as ongoing treatment type were registered. Five-hundred twenty-six patients (61.2% male, with a mean age of 52.6 ± 13.9 years) treated with biologics were enrolled. RESULTS: QFT conversion occurred in 6.5% of patients over a mean treatment duration of 3.2 years. On average, QFT conversion occurred after 34.05 months of treatment. Anti-TNF-α drugs, and among them, adalimumab above all (35.5% of all cases), were the most commonly involved treatment during QFT conversion, followed by anti-IL-12/23 (17.6%) and anti-IL-17 (14.7%). However, differences among biologics class or single biologics (adalimumab, etanercept, infliximab, golimumab, certolizumab, ustekinumab, ixekizumab, secukinumab) did not approach statistical significance. CONCLUSIONS: Annual TB screening is important in psoriasis patients under biologic treatment in order to avoid possible latent TB infection reactivation. Indeed, our data showed that even in a low TB prevalence country like Italy, QFT may convert over time in psoriasis patients under biologics in 6.5% of the cases.