Effectiveness of guselkumab in patients with facial and/or genital psoriasis: Interim analysis results at Week 12 from the GULLIVER study.

BACKGROUND: Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on these difficult-to-treat areas. Guselkumab is an interleukin (IL)-23 inhibitor which has been proven effective in treating patients with moderate-to-severe plaque psoriasis. OBJECTIVES: The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. MATERIALS AND METHODS: GULLIVER is a 52-week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real-life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate-to-severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. RESULTS: Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty-four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. CONCLUSIONS: Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult-to-treat areas.

Successful treatment of severe recalcitrant vernal keratoconjunctivitis and atopic dermatitis associated with elevated IgE levels with omalizumab.

We report the clinical case of an atopic patient with important manifestations impacting the quality of life at the cutaneous and ocular site. The condition resisted conventional treatments, and omalizumab had to be used to treat the disease successfully.

Mortality and prognostic factors in patients with bullous pemphigoid: a retrospective multicenter Italian study.

INTRODUCTION: Bullous pemphigoid is the most common autoimmune bullous dermatosis. In recent years several studies have tried to identify the main factors of the disease related with an increased risk of death. The aim of this multicenter Italian study was to assess the risk score of death considering epidemiologic, clinical, immunological, and therapeutic factors in a cohort of patients affected by bullous pemphigoid and try to identify the cumulative survival up to 120 months. METHODS: We retrospectively reviewed the medical records of patients with bullous pemphigoid who were diagnosed between 2005 and 2020 in the 12 Italian centers. Data collected included sex, age at the time of diagnosis, laboratory findings, severity of disease, time at death/censoring, treatment, and multimorbidity. RESULTS: A total of 572 patients were included in the study. The crude mortality rate was 20.6%, with an incidence mortality rate of 5.9 × 100 person/year. The mortality rate at 1, 3, 5, and 10 years was 3.2%, 18.2%, 27.4% and 51.9%, respectively. Multivariate model results showed that the risk of death was significantly higher in patients older than 78 years, in presence of multimorbidity, anti-BP180 autoantibodies >72 U/mL, or anti-BP230 > 3 U/mL at diagnosis. The variables jointly included provided an accuracy (Harrel's Index) of 77% for predicting mortality. CONCLUSION: This study represents the first nationwide Italian study to have retrospectively investigated the mortality rates and prognostic factors in patients with bullous pemphigoid. A novel finding emerged in our study is that a risk prediction rule based on simple risk factors (age, multimorbidity, steroid-sparing drugs, prednisone use, and disease severity) jointly considered with two biomarkers routinely measured in clinical practice (anti-BP230 and anti-BP180 autoantibodies) provided about 80% accuracy for predicting mortality in large series of patients with this disease.

Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience.

BACKGROUND: Brodalumab was efficacious and safe in moderate-to-severe plaque-type psoriasis in the AMAGINE trials; published reports under real-life conditions are limited. OBJECTIVES: To evaluate the effectiveness and safety of brodalumab in patients with moderate-to-severe plaque-type psoriasis in a real-world setting. METHODS: This observational, retrospective study enrolled adult patients (≥18 years) with moderate-to-severe plaque-type psoriasis who underwent 24 weeks of treatment with brodalumab at 17 Italian dermatological centres. Baseline data included demographics, comorbidities, age of onset and duration of psoriasis and previous treatments. Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), static PGA of Genitalia, Dermatology Life Quality Index and patient satisfaction were assessed at weeks 0, 4, 12 and 24; adverse events were recorded. RESULTS: Seventy-eight patients (mean age 47.9 years, 71.8% male, average disease duration 16.8 years) were enrolled. A rapid and significant reduction in mean PASI score was observed after 4 weeks of treatment, decreasing further at weeks 12 and 24 (all P < 0.0001 vs. baseline). A higher number of cardiometabolic comorbidities and previous therapies were negatively associated with the achievement of PASI 90 at all assessments. Brodalumab was effective in bio-experienced patients, including those who had failed on anti-interleukin (IL)-17 therapies. Quality of life and patient satisfaction increased significantly during treatment (P < 0.0001 and P < 0.01 vs. baseline, respectively). Treatment was interrupted in 9 (11.5%) patients due to adverse events (n = 4), lack of efficacy (n = 3), lost to follow-up (n = 1) and surgical procedure (n = 1). CONCLUSIONS: Brodalumab is effective and safe in the treatment of moderate-to-severe psoriasis in a real-world setting, including in patients with failure to anti-IL17 therapies.

Elderly psoriatic patients under biological therapies: an Italian experience.

BACKGROUND: The number of elderly patients with psoriasis is steadily increasing in the Western world; nevertheless, they are frequently excluded from biological clinical trials and described as a high-risk group for adverse events. Thus, there is lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biological systemic drugs. OBJECTIVE: Our aim was to describe our experience with all biological therapies currently used in the elderly (>65 years) psoriatic patients. METHODS: A retrospective multicentric review of clinical records of all psoriatic patient aged 65 years or older actually receiving biological drugs (etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab or secukinumab) was undertaken. RESULTS: Our study population included 266 elderly psoriatic patients actually receiving any biological therapy (adalimumab 31.2%, ustekinumab 28.9%, etanercept 20.3%, secukinumab 15%, infliximab 3%, golimumab 1% and certolizumab pegol 0.6%). The PASI score at the baseline (week 0) ranged from 4 to 54; mean ± SD, 16.5 ± 7.1, which changed after biological administration to 3.7 ± 8 at week 16, 1.6 ± 2.1 at week 28 and 1.2 ± 2.1 at week 52. Among 266 elderly psoriatic patients, 25 adverse events were reported during the observation period. The most frequent events were infections with 12 (48%) reports, followed by malignancies with four (16%) reports. CONCLUSIONS: To date, our study represents the widest experience on the use of biological drugs in elderly psoriatic patients. We found that all biologics for psoriasis showed a great efficacy also in elderly people, and the rate and the type of adverse effects were similar to the younger patients. In conclusion, the age alone should not limit our therapeutic options. Further observational study using multiple data sources is needed to evaluate long-term effectiveness and safety for elderly psoriatic patients.

Nail involvement as a negative prognostic factor in biological therapy for psoriasis: a retrospective study.

BACKGROUND: Psoriasis (Pso) has a strong impact on quality of life and a positive association has been reported between nail psoriasis (NP) and more severe disease, together with a longer duration of skin lesions. The treatment of NP represents a challenge and biological therapy can be recommended for severe disease. OBJECTIVE: The first end point of this retrospective study was to evaluate the time to achieve Psoriasis Area Severity Index (PASI) 75 in patients with and without NP treated with biological therapy. The second end point was to evaluate the efficacy of biological therapy to improve NP. METHODS: A total of 127 patients (88 men and 39 women) with moderate to severe Pso referring to our Service between 2007 and 2014 were included. Inclusion criteria were age ≥18 years and a 24 week treatment. The outcome variable was achievement of PASI 75 at 24 weeks with and without NP. All patients were treated with topical therapy and one of four different biological treatments: adalimumab (44.09%), etanercept (18.11%), infliximab (13.39%) and ustekinumab (24.41%). Physical examinations were performed every 4 weeks, and at each visit, the clinician assessed the PASI and Nail Psoriasis Severity Index (NAPSI). RESULTS: At multivariate Cox regression analysis, a smaller proportion of patients with NP achieved PASI 75 at 24 weeks than patients without NP when adjusted for the epidemiological, clinical features and biological treatment received. With all biological drugs, the NAPSI score began to improve already after 8 weeks (from 18.53 at week 0-2.83 at week 24). CONCLUSION: Patients with NP reach PASI 75 more slowly than patients without NP. Clinicians should therefore consider that treatment with a biological agent may require a longer period before reaching a satisfying therapeutical goal. Nevertheless, adalimumab, infliximab, ustekinumab and etanercept demonstrated their equal effectiveness in reducing the NAPSI score.

Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis.

Psoriasis is a common disease, which has a considerable impact on the healthcare system. Therefore, appropriate use of therapeutic resources is very important. Management of psoriasis in daily clinical practice is highly variable because many issues are still debated and not definitely addressed by the evidence-based medicine. Moreover, the different availability and reimbursability of drugs in each country justifies national guidelines. Expert consensus can provide helpful guidelines for optimizing patient care. A total of 20 dermatologists from different areas of Italy and with large experience in the treatment of psoriasis agreed to participate in the guidelines expert panel who aimed to reach consensus on the factors influencing psoriasis severity, the indications for systemic treatments, the parameters to be considered in the choice of treatment, and the factors to be considered in the choice of biological treatment. The recommendations for the use, screening and monitoring of systemic therapies were based on the 2015 S3 European Dermatology Forum/European Academy of Dermatology and Venereology psoriasis guidelines. Recommendations on the treatment of psoriasis in special patient populations were also agreed. The final document was discussed in a meeting moderated by a facilitator with participation of the entire group and adopting a nominal group technique to reach consensus. A statement was regarded as consented when agreement was achieved by at least 75% of the voting experts according to the Delphi procedure.

Sex and the PASI: patients affected by a mild form of psoriasis are more predisposed to have a more severe form of erectile dysfunction.

BACKGROUND: Psoriasis is a multi-systemic disease involving the skin and joints, but it is also characterized by endothelial dysfunction, which may cause sexual impotence and erectile dysfunction (ED), an embarrassing disease frequently neglected by dermatologists. OBJECTIVE: The principal objective was assessing the relationship between the severity of psoriasis and the severity of ED. We also investigated whether severity of psoriasis was related to International Index of Erectile Function-5 (IIEF-5) score, whether genital lesions worsened the IIEF-5 score, whether ED was related to factors such as diabetes, smoking and hypertension, and finally the overall the psychological factors felt by the patient. METHODS: We administered two questionnaires (one of which was the IIEF-5, a validated score to assess erectile dysfunction) to three groups of patients: 60 with mild psoriasis, 60 with severe psoriasis (assessed by Psoriasis Area Severity Index, PASI) and a control group including 60 patients without the disease. RESULTS: In the group of mild psoriasis, the patients who suffered from ED were the 56.67%, while in the group of severe psoriasis, ED affected the 46.68% of subjects. In the control group, ED was reported by the 23.33% of patients. The average IIEF-5 score was 18.81 for patients with mild psoriasis and 20.31 for patients with severe form. The difference in the average IIEF-5 scores between psoriatic (mild and severe cases) and control group was not statistically significant. Most patients with sexual dysfunction had also genital lesions; diabetes, smoking and hypertension were not related to lower IIEF-5 scores. The overall psychological profile of psoriatic patients was worse than that of the controls. CONCLUSION: We concluded that ED was related to psoriasis, in particular to mild forms. Moreover, since ED is a marker of cardiovascular events, also related to negative impact on the quality of life, physicians should always investigate the presence of ED in clinical practice.