Efficacy of Secukinumab in Psoriasis: Post Hoc Gender-Wise Analysis of the SUPREME Study.

Purpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24. Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test. Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P<0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P=0.0779) and 24 (83.2% vs 79.7%; P=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (-10.9 vs -8.1, respectively, in females vs males; P=0.0004). Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender.

Management of psoriatic arthritis in rheumatology and dermatology settings: sub-analysis of the Italian population from the international LOOP study.

Psoriatic arthritis (PsA) patients are often treated by dermatology and rheumatology specialities and may receive different treatments. To evaluate the impact of dermatology/rheumatology specialist settings on diagnosis and therapeutic approach in PsA patients. This cross-sectional multicounty study in Italy involved twenty-eight rheumatology or dermatology clinics. Patients with suspected or confirmed PsA were examined by both a dermatologist and a rheumatologist. A total of 413 patients were enrolled and 347 (84%) were diagnosed with PsA. The majority of patients were enrolled from a rheumatology setting (N = 224, 64.6%). Patients with PsA in the dermatology settings had significantly higher disease activity, including skin involvement and musculoskeletal symptoms. Time from PsA onset to diagnosis was 22.3 ± 53.8 vs. 39.4 ± 77.5 months (p = 0.63) in rheumatology and dermatology settings; time from diagnosis to initiation of csDMARD was 7.3 ± 27.5 vs. 19.5 ± 50.6 months, respectively (p < 0.001). In contrast, time from diagnosis to bDMARD use was shorter in dermatology settings (54.9 ± 69 vs. 44.2 ± 65.6 months, p = 0.09, rheumatology vs. dermatology), similar to the time taken from first csDMARDs and bDMARDs (48.7 ± 67.9 vs. 35.3 ± 51.9 months, p = 0.34). The choice to visit a rheumatologist over a dermatologist was positively associated with female gender and swollen joints and negatively associated with delay in time from musculoskeletal symptom onset to PsA diagnosis. This study highlights a diagnostic delay emerging from both settings with significantly different therapeutic approaches. Our data reinforce the importance of implementing efficient strategies to improve early identification of PsA that can benefit from the integrated management of PsA patients. Key Points • A diagnostic delay was observed from both dermatology and rheumatology settings with significantly different therapeutic approaches. • Shared dermatology and rheumatology clinics offer the combined expertise to improve in the early identification and management of PsA.

Long-term safety and efficacy of adalimumab in psoriasis: a multicentric study focused on infections (connecting study).

INTRODUCTION: This Italian multicenter retrospective study evaluated safety and efficacy of the anti-TNF drug, adalimumab, in a cohort of patients affected by tuberculosis (TB), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Psoriasis is an autoimmune disease affecting around 3% of the Italian population and associated with several comorbidities, including arthritis, cardio-metabolic diseases and depression. In its moderate-to-severe form, psoriasis profoundly impairs quality of life of patients. AIM: Therefore, these patients deserve systemic treatments including conventional DMARDS (disease modifying anti-rheumatic drugs) and biologics. Management of moderate and severe psoriasis patients affected by relevant infections such as TB, HBV, HCV and HIV may be difficult because of the toxicity of the conventional systemic treatment. MATERIAL AND METHODS: The CONNECTING study analysed 28 moderate to severe psoriasis patients infected by TB, HBV, HCV and HIV who were treated with adalimumab for up to 96 weeks together with respective prophylactic treatment. RESULTS: We observed a rapid decrease in PASI (psoriasis area severity index) reaching a 75% improvement in 91% of patients. Some of these patients (n = 9) were also affected by arthritic comorbidity. The patients experienced a rapid decrease in pain, measured by pain VAS (visual analogic scale) that reached 0 in all of them. Monitoring of the respective infection did not show any worsening or reactivation of infection or any severe adverse events during the entire observation period. CONCLUSIONS: Adalimumab is effective and safe in patients affected by these important infections.

Treatment of severe psoriasis with ixekizumab in a liver transplant recipient with concomitant hepatitis B virus infection.

Treatment of severe psoriasis (PsO) in organ transplant (OT) patients is difficult. In fact, systemic drugs used for PsO therapy can be detrimental to transplanted organs and/or can increase the risk of serious infections in subjects already taking antireject medicines. Current guidelines fail to give indications on how to manage PsO OT subjects. Moreover, only a few cases of patients with the above-cited characteristics treated with systemic therapies have been published so far. Here, we report our experience concerning a liver transplant patient successfully treated with ixekizumab for his psoriasis throughout 1 year.

Ultrasound assessment of enthesis thickness in psoriasis and psoriatic arthritis: A cross-sectional study.

BACKGROUND: The inflammatory involvement of the enthesis in the course of psoriasis is accompanied by structural abnormalities detectable by ultrasound. The most common of these abnormalities is the thickening of the tendon at the insertion site. AIMS: The aim of the present study was to compare the thickness of entheses of patients with psoriatic arthritis, only skin psoriasis, and healthy controls. METHODS: A cross-sectional study was conducted in a cohort of patients affected with either only skin psoriasis or psoriatic arthritis as well as in a control group. Eight entheses sites were scanned by ultrasound bilaterally. The following entheseal characteristics were collected and recorded in a predefined database: entheseal thickness, bone erosions, enthesis calcifications (enthesophytes), presence of blood flow, and presence of bursitis. All the detected entheseal changes were scored, and the data was statistically analyzed. RESULTS: The major differences in enthesis thickness between only skin psoriasis and psoriatic arthritis patients were found at the following sites: (i) olecranon tuberosity, (ii) superior pole of the patella, and (iii) medial epicondyle of femur. The thickness of the medial collateral ligament at the site of the femoral origin was increased in psoriatic arthritis, but not in both only skin psoriasis and healthy controls. The score obtained by adding the thickness of all the 8 examined entheses for each patient showed significant differences among the three groups (psoriatic arthritis: 81.3; only skin psoriasis 74.4; Controls: 67.6; P < 0.0001). Interestingly, we found that in psoriatic arthritis patients, the highest enthesis thickening was seen in entheses affected by bone erosions. LIMITATIONS: The small sample of patients studied is a limiting factor in this study. CONCLUSIONS: Our data demonstrated that the ultrasound measurement of the enthesis thickness enables a distinction between patients with psoriatic arthritis from those with only skin psoriasis. It is a useful method to improve diagnostic accuracy, especially in patients without clear clinical signs of enthesitis.

Reflectance confocal microscopy features of seborrheic dermatitis for plaque psoriasis differentiation.

BACKGROUND: Plaque psoriasis (PP) and seborrheic dermatitis (SD) are chronic inflammatory skin diseases with similar clinical and pathological features. Differential diagnosis can be difficult, especially when particular skin areas of the face are involved. Reflectance confocal microscopy (RCM) has been demonstrated to be useful for 'real-time' diagnosis of skin inflammatory diseases. OBJECTIVE: To define distinctive confocal criteria of SD and to evaluate the usefulness of this technique for noninvasive differential diagnosis with PP. METHODS: A total of 40 patients affected by PP and 19 patients by SD involving the face were recruited and subjected to RCM evaluation. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot ROC curves. RESULTS: The results disclosed specific patterns for SD and PP. The following distinctive confocal features for SD have been identified: spongiosis, dermal inflammation and horizontal orientation of dilated blood vessels. CONCLUSION: SD has a specific and easily recognizable confocal pattern supporting clinical differentiation with PP.

Biologic therapies for psoriasis.

Psoriasis is a common chronic inflammatory skin disease that may lead to disability and significant effects on patients' quality of life. A challenge in psoriasis management is to use an effective therapy early in the disease course in order to achieve a safe and well tolerated maintenance of remission with an improvement of both skin and joint manifestations. Recent advances in knowledge of the pathogenesis of psoriasis helped develop targeted treatment options that may be effective and well tolerated over long periods of administration, thus improving the patient's quality of life. These novel "biologic" agents specifically target tumor necrosis factor-alpha (infliximab, etanercept, and adalimumab) or T cells (efalizumab).

Griscelli syndrome type 2: long-term follow-up after unrelated donor bone marrow transplantation.

Griscelli syndrome (GS) is a rare autosomal recessive disease characterized by silvery hair ('partial albinism'). Three forms exist; GS type 2 (GS2), the most common one, is characterized by severe primary immunodeficiency with acute episodes of hemophagocytic lymphohistiocytosis (HLH) which may be fatal in the absence of hematopoietic stem cell transplantation. A 5-year-old boy with HLH was referred to us because of silvery-gray hair present since birth. Abnormal pigment clumps were observed in the medulla of hair shafts on light microscopy. Electron microscopy of a skin biopsy revealed melanosomes in melanocytes, but not in keratinocytes. Leukocytes were devoid of intracytoplasmic granules on blood smear. Neurological signs were absent. Genotyping revealed a homozygous haplotype for polymorphic markers linked to the RAB27A locus, but no RAB27A mutation. A diagnosis of GS2 was established. The patient received bone marrow transplantation (BMT) from an unrelated donor, and after 72 months he did not show relapse of HLH. The long, uneventful follow-up supports the use of BMT from an unrelated donor if transplantation from a relative is not possible.

Efficacy of adalimumab in plaque psoriasis: experience on 28 patients.

Psoriasis is a common, chronic inflammatory skin disease with arthritis that may occur in a percentage of patients that varies between 5% and 42%. Many systemic agents as cyclosporine, methotrexate, acitretin, and photochemotherapy have been used for the treatment of patients affected by moderate-to-severe plaque psoriasis although they present side effects (ie, cumulative organ toxicity and lack of efficacy over time) that limit long-term use. Significant therapeutical improvement has been obtained introducing biological therapies, designed to modify and regulate immunological processes by targeting specific molecules involved in the immunopathogenesis of psoriasis. Adalimumab is a fully human recombinant antibody against tumor necrosis factor-alpha (TNF-alpha). To date, there is not much data available on the efficacy and safety of adalimumab in patients affected by moderate-to-severe plaque psoriasis. The authors report our first experience on the efficacy and safety of adalimumab in monotherapy at a dose of 40 mg every-other-week for the treatment of plaque psoriasis in patients with or without arthritis. Twenty-eight patients were treated for a period of 48 months. It was observed an improvement of the psoriasis condition as well as of patients' quality of life and mood state.

Monochromatic excimer light (308 nm) in the treatment of prurigo nodularis.

Three hundred and eight nanometre excimer light has been reported to be safe and effective in the treatment of chronic skin diseases, but the range of potential applications has not been fully explored. Our objective was to assess the efficacy of monochromatic excimer light (MEL) in the treatment of prurigo nodularis (PN). Eleven patients were enrolled in this pilot study. Patients were treated weekly and an average of eight sessions of MEL was given. Follow-up was 4 months. Partial or complete clinical and histological remission was observed in all patients who completed the study (81%).

Biological markers in the etiology of psoriasis: Targeted treatment options.

Psoriasis is a common chronic and disabling inflammatory disease that has an enormous physical, functional and psychosocial impact on patients' quality of life. To date several conventional therapies are available for the treatment of this condition (eg, cyclosporine, methotrexate, retinoids, and psoralen plus ultraviolet A) which, although providing clinical response, do not maintain long-lasting disease remission and at times show poor tolerability with potential toxicity thus limiting their use. A challenge in psoriasis management is to utilize precociously an adequate therapy and to achieve effective and safe maintenance of its clearance by improving both skin and joint manifestations as well as to prevent joint destruction and disability. Recent improvement in the knowledge of the pathogenesis of this disease was fundamental for the development of novel targeted treatment options that may be effective, safer and well tolerated on long-term administration periods, thus improving patient's quality of life. These novel agents, which are called "biologics", target specifically tumor necrosis factor-alpha (infliximab, etanercept and adalimumab) or T cells (alefacept and efalizumab).

High-dose initiation of etanercept in psoriatic arthritis and plaque psoriasis: efficacy, safety and impact on patients' quality of life.

BACKGROUND: Etanercept is a human recombinant protein that functions as a competitive inhibitor of tumour necrosis factor-alpha (TNF-alpha), a pro-inflammatory molecule exerting a key role in the pathogenesis of psoriatic arthritis (PsA). METHODS: Seventy-one patients affected by PsA with variable skin involvement, refractory to conventional anti-rheumatic drugs, were treated with 50 mg etanercept subcutaneous injections twice-weekly for 12 weeks, followed by a maintenance dose regimen of 25 mg twice-weekly for an additional 12 weeks. Efficacy and safety were assessed at 12-24 weeks. Efficacy criteria was the global assessment of a patient's joint symptoms expressed by the Ritchie index (RI), while skin symptoms were assessed by the psoriasis area and severity index (PASI). The impact of etanercept on patients' quality of life (QoL) was measured by four validated QoL instruments. RESULTS: At week 12, all patients showed a reduction of symptoms with improvement of mean RI (mRI) of 66.1% from baseline and a reduction of mean PASI (mPASI) from 8.8 to 3.2. At week 24, there was a mRI reduction of 78.4% as well as a mPASI reduction to 1.7. Psoriasis-specific QoL measures improved throughout therapy. CONCLUSIONS: A high-dose regimen of etanercept is a highly effective and tolerable treatment for PsA with variable skin involvement, although a larger study population group and a longer trial would be needed to draw strong conclusions about the safety of the higher dose.

Treatment of lentigo maligna with tazarotene 0.1% gel.

We report 2 elderly patients with facial lentigo maligna who experienced complete regression, both clinically and histopathologically, after once-daily topical treatment with tazarotene 0.1% gel for 6 to 8 months. After a follow-up period of 18 and 30 months, no recurrence was observed. We believe that tazarotene might be considered as an alternative medical approach in selected patients with lentigo maligna.