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.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Creation of a severity index for hidradenitis suppurativa that includes a validated quality-of-life measure: the HIDRAscore.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, debilitating disease with a considerable effect on patient quality of life. Its clinical severity can be measured using different scoring systems; however, few of them include patient-centred parameters. OBJECTIVE: To create a new scoring system for HS that includes a quality-of-life instrument, the HIDRAdisk. METHODS: This post hoc analysis was carried out within the framework of a multicentre, longitudinal, epidemiologic study conducted over 9 months on quality-of-life aspects of HS. The new severity score was created using as reference a question from the Subject Satisfaction Questionnaire (SSQ) concerning the severity of HS as evaluated by the patient. Associated variables were selected using univariable and multivariable logistic regression models. The discriminant capabilities of the final model and of the final score were evaluated by the area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The study population included 308 patients with HS of any severity grade. According to the results of the regression models, the variables associated with the reference SSQ measure were number of inflammatory nodules, abscesses and draining fistulas; the HIDRAdisk score; and the number of subumbilical lesions. The HIDRAscore is obtained by the sum of the scores associated with the number of these parameters. Possible scores range from 0 to 10. CONCLUSION: The HIDRAscore is a new scoring system for HS severity which, in addition to the clinical evaluation by the physician, includes a validated patient-reported outcome measure, the HIDRAdisk.

Tuscan consensus on the diagnosis and treatment of hidradenitis suppurativa.

BACKGROUND: A rationalized model of clinical and therapeutic management of hidradenitis suppurativa (HS) should place the patients at the heart of the process, facilitating their access to diagnostic tests and treatments, providing the appropriate care for each grade of disease severity and optimizing the use of healthcare resources, both in economic and human terms. MATERIAL AND METHODS: This paper reports the results of a Consensus of the Tuscany HS working group for a rationalized model of diagnosis and management of HS. RESULTS: The diagnostic and therapeutic protocols, the available technological equipments and the management models, are presented in the light of today's scientific evidence. CONCLUSION: The goal of the Consensus is to bring the issue of HS management to the attention of the Tuscan regional government, in order to create unanimously accepted diagnostic and therapeutic protocols.

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.

HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland-bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. OBJECTIVE: The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. METHODS: A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). RESULTS: A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS-PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test-retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. CONCLUSION: Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.

The role of the dermatologist in Raynaud's phenomenon: a clinical challenge.

Raynaud's phenomenon (RP) is a functional vascular disorder involving extremities. In his practice, the dermatologist may frequently encounter RP which affects mainly women and is categorized into a primary benign form and a secondary form associated with different diseases (infections, drugs, autoimmune and vascular conditions, haematologic, rheumatologic and endocrinologic disorders). Still today, the differential diagnosis is a clinical challenge. Therefore, a careful history and a physical examination, together with laboratory tests and nailfold capillaroscopy, is mandatory. RP is generally benign, but a scheduled follow-up for primary RP patients should be established, due to risk of evolution to secondary RP. A combination of conservative measures and medications can help in the management of RP. The importance of avoiding all potential physical, chemical and emotional triggers, as well as quitting smoking, should be strongly suggested to the patient. As first-line treatment, dihydropyridine calcium channel blockers should be used. If this approach is not sufficient, prostacyclin derivatives, phosphodiesterases inhibitors and endothelin receptor antagonists can be considered as second-line treatment. In cases of acute ischaemia, nifedipine and intravenous prostanoids are helpful. In refractory cases, botulinum injections have shown a significant benefit. The approach to the RP patients requires therefore a coordinated care of specialists together with the primary care physician.

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.

Circulating T cells to infliximab are detectable mainly in treated patients developing anti-drug antibodies and hypersensitivity reactions.

Antibodies recognizing infliximab (IFX) may develop in a proportion of treated patients, leading to loss of response or hypersensitivity reactions (HRs). T cell response to IFX has been poorly investigated. This paper was addressed to detect IFX-specific T cells in treated patients with inflammatory diseases developing, or not, anti-drug antibodies (ADA) and to correlate the presence of specific T cells with the clinical outcomes of the treatment. A co-culture system of IFX-loaded dendritic cells and purified autologous CD4+ T cells was used to detect memory T cells in 32 ADA+ and 39 ADA- IFX-treated patients and control groups. The cytokine profile of IFX-specific T cells was also studied in culture supernatants. IFX-specific cell proliferation was detected mainly in cells from ADA+ patients, irrespective of their different diseases. HR patients displayed higher T cell proliferation than non-responder and tolerant patients. A mixed [interferon (IFN)-γ, interleukin (IL)-13, IL-10] cytokine profile was shown in cells from ADA+ patients, while IL-10 was the most frequently detected cytokine in the supernatants of cultures from ADA- patients. Immunoglobulin (Ig)E+ ADA+ patients with previous HRs exhibited a more pronounced type 2 profile than IgE- ADA+ patients. This work provides evidence that IFX-specific circulating T cells are detectable mainly in ADA+ patients with HRs, regardless of their disease. The IFX-induced cytokine pattern partially correlates with the ADA isotype.

PSOCUBE, a multidimensional assessment of psoriasis patients as a both clinically/practically sustainable and evidence-based algorithm.

BACKGROUND: There is increasing awareness of the clinical relevance of psoriasis comorbidities and of the importance of timely and effective screening for such comorbidities in the management of psoriatic patients. Previous works have focused on assessing evidence for prevalence of comorbidities and on the best available evidence for sensitivity in diagnosing suspected comorbidities. No algorithms are available, which have been tested on large numbers of physicians concerning the acceptance of such algorithms both by practicing clinical dermatologists and by their consulting specialists from other fields. OBJECTIVE: To propose a multidimensional assessment algorithm for psoriasis comorbidities which may prove at the same time enough sensitive and practically sustainable in daily clinical practice. METHODS: After an exhaustive literature search, we performed a Delphi procedure involving 50 dedicated dermatological centres to obtain a standardized assessment algorithm, which would meet requirements of sustainability and acceptability both from the point of view of Evidence-Based Medicine as well as from the point of view of practical and clinical feasibility: to meet both requirements, results from the Delphi procedure were elaborated and modified by a restricted panel of experts. RESULTS: The procedure has yielded PSOCUBE, a three-dimensional table comprising 14 clinical examination and history taking items, 32 screening laboratory and instrumental exams and 11 clinimetric scores. CONCLUSION: PSOCUBE, a simple algorithm, may be employed by practising dermatologists to perform standardized assessment procedures on psoriatic patients raising the chances of early recognition of patients at risk for comorbidities, thus fostering more effective prevention; PSOCUBE may therefore contribute to reduce the overall impact of this chronic, widespread disease.

An innovative three-dimensional model of normal human skin to study the proinflammatory psoriatic effects of tumor necrosis factor-alpha and interleukin-17.

BACKGROUND: Among all cytokines involved in the pathogenesis and in the progression of psoriasis, Tumor Necrosis Factor (TNF)-alpha and interleukin (IL)-17 play a pivotal role. OBJECTIVE: The aim of the present study was to mimic a psoriatic microenvironment and to investigate the early effects of TNF-alpha and IL-17 in a three-dimensional model of organotypic normal human skin. METHODS: Human skin explants were obtained from plastic aesthetic surgery of healthy young women 20-40years old (n=7). The study was approved by the Institutional Review Board and written informed consent was obtained from all subjects. Bioptic fragments were cultured at the air-liquid interface overnight in a Transwell system and further divided before adding either 50ng/ml IL-17 or 100ng/ml TNF-alpha or a combination of both cytokines. For each subject, a control sample was cultured without any cytokine. Samples were harvested 24 or 48h after cytokine incubation. At both time points and for all cytokine treatments a bioptic fragment obtained from each patient was processed. Epidermal proliferation, expressions of terminal differentiation (keratin 10, K10, and 14, K14) and of intercellular adhesion (occludin for tight junctions and E-cadherin for adherens junctions) biomarkers were investigated by indirect immunofluorescence. RESULTS: IL-17 and TNF-alpha induced an early and statistically significant inhibition of keratinocyte proliferation (more than 80% compared with their respective controls). At 24h, the combination of both cytokines did not further reduce cell proliferation. Starting from 24h of incubation, a non-continuous occludin expression in the granular layer was observed after both IL-17 and TNF-alpha exposure. Immunolabelling for E-cadherin in adherens junctions, for K10 in the suprabasal layers, and for K14 in the basal layer was similar in all experimental groups and unaffected after cytokine treatment. CONCLUSIONS: These results suggest that in this experimental model IL-17 and TNF-alpha induced an early alteration of the homeostasis of the inner proliferative layer and of the upper granular layer, as shown by cell proliferation inhibition and occludin expression.

Long-term drug survival of risankizumab in psoriasis: insights from a real-life multicenter study on hard-to-treat areas.

Psoriasis, a chronic inflammatory condition, often presents challenges in treatment, particularly in areas such as nails, palms/soles, scalp/face, and genitalia. Monoclonal antibodies (mAb) like risankizumab targeting interleukin-23 (IL-23) have emerged as promising treatments, yet data on long-term efficacy remain limited. This multicenter retrospective study aimed to evaluate the drug survival at 12 and 36 months of 191 psoriasis patients treated with risankizumab, focusing on critical areas. Patients, previously unresponsive to first-line therapies, were treated according to Italian Guidelines. Survival analysis revealed a 97.6% one-year and 95% three-year drug survival rate. Secondary ineffectiveness was the primary reason for discontinuation, particularly in palmoplantar involvement cases. Factors such as BMI, gender, age, disease duration, baseline severity, and previous biologic exposure did not significantly impact drug survival, except for palmoplantar psoriasis (HR 4.72). Risankizumab demonstrated prolonged response with low treatment switch requirements, especially notable in challenging areas. Understanding such factors can aid in optimizing therapeutic approaches for improved patient care and long-term outcomes in managing psoriasis. Further research is warranted to refine treatment strategies in difficult-to-treat areas.

Efficacy and Safety of bimekizumab in elderly patients: real-world multicenter retrospective study - IL PSO (Italian Landscape Psoriasis).

Purpose of the article: The aim of this multicenter observational study is to report data from real world on the use of bimekizumab in patients aged ≥ 65 years with moderate-to-severe plaque psoriasis. Elderly patients are poorly represented in clinical trials on bimekizumab for plaque psoriasis, and real-world studies are important to guide clinical choices.Materials and methods: A retrospective multicenter study was conducted in 33 dermatological outpatient clinics in Italy. Patients aged ≥ 65 years, with moderate-to-severe plaque psoriasis and treated with bimekizumab were enrolled. No exclusion criteria were applied. Bimekizumab was administered following the Italian Guidelines for the management of plaque psoriasis and according to the summary of product characteristics, in adult patients who were candidates for systemic treatments. Overall, 98 subjects were included, and received bimekizumab up to week 36. Clinical and demographic data were collected before the initiation of treatment with bimekizumab. At baseline and each dermatological examination (4, 16, and 36 weeks), clinical outcomes were measured by the following parameters: (1) PASI score; (2) site-specific (scalp, palmoplantar, genital, nail) Psoriasis Global Assessment (PGA). At each visit, the occurrence of any adverse events (AEs) was recorded, including serious AEs and AEs leading to bimekizumab discontinuation.Results: The mean PASI score was 16.6 ± 9.4 at baseline and significantly decreased to 4.3 ± 5.2 after 4 weeks (p < 0.001), and 1.1 ± 1.7 after 16 week (p < 0.001). This level of improvement was maintained after 36 weeks (p < 0.001). PASI ≤2 was recorded in 36 (36.7%) at week 4, 68% and 69.4% at week 16 and 36, respectively. By week 16, 86/98 (87.8%) patients reached PASI75, 71/98 (72.4%) obtained PASI90, and 52/98 (53.1%) PASI100. Binary logistic regression tests showed a significant association of PASI100 by week 4 with lower PASI at baseline. PASI 100 at 16 or 36 weeks was not associated with baseline PASI, obesity, age, gender, previously naïve state, and presence of psoriatic arthritis. Patients naïve to biologics at baseline had similar response to bimekizumab as non-naïve subjects.Conclusions: Bimekizumab is a suitable option for elder patients as it is effective, tolerated and has a convenient schedule.