Real-world retention rates and effectiveness of secukinumab in psoriasis: Results from a multicenter cohort study (RAILWAY).

Psoriasis is a chronic, immune-mediated inflammatory skin disease with a high negative impact on patient's quality of life. Secukinumab, the first interleukin 17A inhibitor, has been used for the systemic treatment of psoriasis, but its long-term, real-world retention rates in Japan have not been fully investigated. In this multicenter, noninterventional, retrospective chart review study, the retention rate of secukinumab and its effectiveness among patients with psoriasis in Japan was evaluated up to 5 years. Data of patients who received secukinumab after December 26, 2014, were collected from medical charts obtained from seven sites, all certified for biologics use by the Japanese Dermatological Association. Patient characteristics, secukinumab retention, factors affecting secukinumab retention, reason for drug discontinuation, and effectiveness data were collected. The primary end point was secukinumab retention rate at week 52. A total of 123 patients were included in the analysis. Of these, 27 patients discontinued secukinumab by week 52, yielding a 78.0% (95% confidence interval, 69.6-84.4) retention rate at week 52. For patients whose Psoriasis Area and Severity Index (PASI) score was available, mean ± standard deviation PASI at baseline and at week 52 were 9.21 ± 7.37 and 1.4 ± 2.6, respectively. During the entire study period, "insufficient response" was the most common reason for discontinuation, and "history of biologics use" was a factor significantly associated with secukinumab discontinuation (hazard ratio, 1.72; p = 0.018). This study demonstrates the real-world retention rate and effectiveness of secukinumab in patients with psoriasis in Japan for up to 5 years and provides clinical insights into psoriasis treatment strategies.

Effectiveness of Long-Term Treatment with Brodalumab on Anxiety or Depressive Symptoms in Japanese Patients with Psoriasis: The ProLOGUE Study.

INTRODUCTION: Evidence on treatment effectiveness in patients with psoriasis having anxiety or depressive symptoms helps shared decision-making. This single-arm, open-label, prospective study-ProLOGUE-was conducted to assess the effectiveness of brodalumab on self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. METHODS: Patients aged ≥ 18 years with plaque psoriasis without peripheral arthritis symptoms who had responded inadequately to current therapies were enrolled at 15 Japanese facilities and received brodalumab 210 mg subcutaneously. RESULTS: A total of 73 patients were enrolled (male, 82%; median age, 54 years). The proportion of patients without anxiety symptoms changed significantly from baseline (72.6%) to weeks 12 (88.9%, p = 0.008) and 48 (87.7%, p = 0.02); the proportion of patients without depressive symptoms did not change significantly. The Generalized Anxiety Disorder-7 score (median [quartile(Q)1-Q3], 1.0 [0.0-5.0] at baseline; 0.0 [0.0-2.0] at week 12, p = 0.008; and 0.0 [0.0-1.0] at week 48, p = 0.007) and Patient Health Questionnaire-8 score (median [Q1-Q3], 2.0 [0.0-4.0] at baseline; 1.0 [0.0-4.0] at week 12, p = 0.03; and 0.0 [0.0-2.0] at week 48, p = 0.004) significantly decreased after treatment. The median Psoriasis Area and Severity Index scores after treatment were < 1, irrespective of the presence of baseline anxiety or depressive symptoms. At week 12, the health-related quality of life was more impaired in patients with versus without baseline depressive symptoms, which largely resolved at week 48. CONCLUSIONS: Brodalumab treatment resulted in the reduction of the levels of self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. Unlike anxiety symptoms, depressive symptoms did not resolve completely with brodalumab treatment. Patients with psoriasis having depressive symptoms may require long-term treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000027783, Japan Registry of Clinical Trials identifier: jRCTs031180037.

Clinical characteristics of patients with psoriasis with family history: A multicenter observational study.

Previous studies on family history of psoriasis showed that patients with a family history have an earlier onset of the disease, but such studies in Japan are still limited. To elucidate the characteristics of patients with familial psoriasis, we studied the family history of patients with psoriasis using the West Japan Psoriasis Registry, a multi-institutional registry operated by 26 facilities in the western part of Japan, including university hospitals, community hospitals, and clinics. This study enrolled 1847 patients registered between September 2019 and December 2021, with 199 (10.8%) having a family history of psoriasis. Patients with a family history of psoriasis had significantly earlier onset of the disease than those without a family history. Furthermore, patients with a family history of psoriasis had significantly longer disease duration. Psoriatic arthritis (PsA) was significantly more common in patients with a family history (69/199, 34.7%) than in those without a family history (439/1648, 26.6%) (adjusted P = 0.023). A subanalysis of patients with PsA revealed a significant difference in the patient global assessment (PaGA) score in Fisher's exact test and adjusted test. The numbers of patients with PaGA 0/1 were 29 (43.3%) and 172 (39.9%) in patients with PsA with and without family history of psoriasis, respectively, whereas the numbers of patients with PaGA 3/4 were 13 (19.4%) and 145 (33.6%) in patients with PsA with and without family history of psoriasis, respectively. Other disease severity variables did not show a difference between the two groups. Our findings suggest that genetics play a larger role in the development of PsA than in the development of psoriasis vulgaris. Most cases of PsA occur in patients who already have psoriasis, therefore dermatologists should pay attention to joint symptoms, especially in patients with psoriasis who have a family history of psoriasis.

The Correlation between the Vascular Calcification Score of the Coronary Artery and the Abdominal Aorta in Patients with Psoriasis.

Psoriasis is known as an independent risk factor for cardiovascular disease due to its chronic inflammation. Studies have been conducted to evaluate the progress of atherosclerotic plaques in psoriasis. However, inadequate efforts have been made to clarify the relationship between atherosclerosis progress in coronary arteries and other important blood vessels. For that reason, we investigated the correlation and development of the coronary artery calcification score (CACS) and the abdominal aortic calcification score (AACS) during a follow-up examination. Eighty-three patients with psoriasis underwent coronary computed tomography angiography (CCTA) for total CACS and abdominal computed tomography (AbCT) for total AACS. PASI score, other clinical features, and blood samples were collected at the same time. The patients' medical histories were also retrieved for further analysis. Linear regression was used to analyze the CACS and AACS associations. There was a moderate correlation between CACS and AACS, while both calcification scores relatively reflected the coronary plaque number, coronary stenosis number, and stenosis severity observed with CCTA. Both calcification scores were independent of the PASI score. However, a significantly higher CACS was found in psoriatic arthritis, whereas no similar phenomenon was recorded for AACS. To conclude, both CACS and AACS might be potential alternative tests to predict the presence of coronary lesions as confirmed by CCTA.

A case of palisaded neutrophilic and granulomatous dermatitis associated with systemic lupus erythematosus presenting with pustules.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a relatively rare skin disease that is characterized by a reactive granulomatous histopathological pattern and is often associated with systemic autoimmune diseases. We encountered a case of PNGD that presented with pustules, although the prototypical clinical presentation of PNGD is mainly erythema and papules. Here, this rare case of PNGD with pustules is presented and discussed in relation to the relevant literature.

Effectiveness of brodalumab in improving itching and skin pain in Japanese patients with psoriasis: The ProLOGUE study.

Itching and skin pain are bothersome symptoms of psoriasis, but evidence is limited regarding the treatment effectiveness on these symptoms in daily clinical settings. We assessed the changes in the levels of itching and skin pain after brodalumab treatment in Japanese patients with psoriasis using patient-reported outcomes (PROs). Patients with psoriasis who have inadequate response to existing treatments were enrolled in the single-arm, open-label, multicenter, prospective ProLOGUE study and received brodalumab 210 mg subcutaneously in daily clinical practice. Psoriasis Area and Severity Index (PASI) and PRO assessments were performed at baseline and weeks 12 and 48. Seventy-three patients (men, 82.2%; median age, 54.0 years) were enrolled. The Itch Numeric Rating Scale (NRS; p < 0.0001 at weeks 12 and 48) and Skin Pain NRS (week 12, p = 0.0004; week 48, p < 0.0001) scores significantly decreased from baseline. The Itch NRS score was significantly higher in patients with a Dermatology Life Quality Index (DLQI) score of ≥2 (vs. 0/1; p < 0.0001 at weeks 12 and 48) and in patients with a Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) global satisfaction domain score of ≤70% (vs. >70%; week 12, p = 0.0120; week 48, p = 0.0348). The Itch NRS score cutoff value for achieving a PASI score of ≤2, DLQI score of 0/1, and TSQM-9 global satisfaction domain score of >70% was 1 at week 12 and 0 at week 48. Brodalumab treatment was associated with improvement in itching and skin pain in Japanese patients with psoriasis. An Itch NRS score of 0 can be a long-term treatment goal for psoriasis (Japan Registry of Clinical Trials identifier: jRCTs031180037).

Relationship between Psoriasis and Prevalence of Cardiovascular Disease in 88 Japanese Patients.

Psoriasis is a systemic inflammatory disease known to affect survival in the presence of cerebral or cardiovascular comorbidities. However, no clear guidelines have been defined regarding the extent of vascular lesion testing that should be performed in patients with psoriasis. We therefore performed coronary computed tomography angiography (CCTA) in 88 Japanese patients with psoriasis who visited Kansai Medical University Hospital between 2015 and 2019 and determined the ankle-brachial pressure index (ABI) for 44 of these patients. CCTA abnormalities were found in 39 of the 88 patients, and a need for treatment was identified in 14 patients. The prevalence of cardiovascular lesions in these patients was 15.9%, significantly higher than that in the healthy Japanese population (6.38% according to the Suita Study). In the 44 patients with results for both ABI and CCTA, the rates of CCTA vascular lesions were significantly higher in cases with ABIs indicating hard vessels or above than in cases with supple, normal, or slightly stiff vessels. This is the first report to show a correlation between CCTA and ABI in psoriasis patients. ABI was considered useful as a preliminary test before CCTA. The univariate analysis of the abnormal and normal CCTA groups showed that the prevalence differed significantly among patients with psoriatic arthritis, erythrodermic psoriasis, older age, pre-existing conditions, drinking, and hypertension. The multivariate analysis showed correlations with arthritic or erythrodermic psoriasis.

Abatacept for rheumatoid arthritis complicated by disseminated cryptococcosis: a case report.

A 78-year-old man developed disseminated cryptococcosis with central nervous system involvement as encapsulated yeast cells were detected in transbronchial biopsy and skin biopsy specimens, and cerebrospinal fluid. Cryptococcus neoformans was confirmed by culture. He had been treated with low-dose prednisolone and methotrexate for rheumatoid arthritis. He started receiving antifungal therapy with intravenous liposomal amphotericin B followed by oral fluconazole. Methotrexate was discontinued. Approximately 4 months after the course of intravenous liposomal amphotericin B was completed, he complained of pain and swelling of the right wrist, which suggested that rheumatoid arthritis was worsening. Abatacept therapy was initiated along with antifungal therapy, and his symptoms relieved. After 24 months of antifungal therapy, although he was still receiving oral fluconazole, he was doing well and the serum cryptococcal antigen had become negative. Disseminated cryptococcosis is an important opportunistic infection associated with low-dose methotrexate for rheumatoid arthritis. Abatacept therapy may be feasible in strictly selected patients with rheumatoid arthritis complicated with cryptococcosis concomitantly with intensive anti-fungal therapy.

Psoriasis: Comorbidities.

Psoriasis has long been known as a disease with many complications, but was attributed to diet and obesity. However, in recent years, psoriasis itself has been recognized as a series of systemic inflammatory diseases, and that the cytokines involved can induce a variety of other diseases. Individuals with psoriasis were also found to have higher incidences of cerebral and cardiovascular diseases and a younger age at death compared to healthy individuals. However, no clear guidelines have been defined regarding how much vascular lesion testing should be performed in patients with psoriasis. In this report, I attempt to unravel the objective data on psoriasis and its complications from various reviews and reports, and introduce the impact of biologics, which are currently the main treatment for psoriasis, on cardiac vascular disease.

Utility of the Dermatology Life Quality Index at initiation or switching of biologics in real-life Japanese patients with plaque psoriasis: Results from the ProLOGUE study.

BACKGROUND: Plaque psoriasis significantly affects patients' health-related quality of life. To aid treatment decisions, not only objective assessment by physicians but also subjective assessment by patients is important. OBJECTIVE: To assess the significance of Dermatology Life Quality Index (DLQI) evaluation at the time of biologics introduction in clinical practice in Japanese patients with plaque psoriasis. METHODS: This was a single-arm, open-label, multicenter study. At baseline, Psoriasis Area and Severity Index (PASI) and DLQI scores were measured and stratified based on DLQI scores ≥6/≤5 and PASI scores ≤10/>10. Other patient-reported outcomes assessed included EQ-5D-5L, itch numerical rating scale (NRS), skin pain NRS, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-8 (PHQ-8), Sleep Problem Index-II (SPI-II), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). RESULTS: Of the 73 enrolled patients, 23 had PASI scores ≤10. Those with PASI/DLQI scores >10/≥6 had a significantly higher median PASI score than those with PASI/DLQI scores >10/≤5 (p = 0.0125). Regardless of PASI scores (>10/≤10), median itch NRS and GAD-7 scores were significantly higher in patients with DLQI scores ≥6 than in those with DLQI scores ≤5 (itch NRS, p = 0.0361 and p = 0.0086, respectively; GAD-7, p = 0.0167 and p = 0.0273, respectively). Patients with PASI/DLQI scores ≤10/≥6 had significantly higher skin pain NRS (p = 0.0292) and PHQ-8 (p = 0.0255) scores and significantly lower median SPI-II scores (p = 0.0137) and TSQM-9 Effectiveness domain scores (p = 0.0178) than those with PASI/DLQI scores ≤10/≤5. CONCLUSION: DLQI may be useful for assessing patients' concerns that cannot be identified by PASI alone while initiating biologics or switching from other biologics in clinical practice.

Case of pityriasis rubra pilaris progressed to generalized erythroderma following blockade of interleukin-17A, but improved after blockade of interleukin-12/23 p40.

We report herein a case of a 72-year-old man with pityriasis rubra pilaris (PRP) that was refractory to conventional therapies. His skin lesions progressed to generalized erythroderma despite anti-interleukin (IL)-17A antibody therapy. Topical corticosteroids, emollients, systemic retinoid, methotrexate, cyclosporin and phototherapy yielded no therapeutic response. However, blockade of IL-12/23 p40 dramatically improved his cutaneous lesions. Complete remission was achieved 4 weeks after the first injection of ustekinumab and maintained for more than 48 weeks. Our data indicate that IL-12 was associated with the onset of PRP in this patient, rather than IL-23. IL-12 is critical for the differentiation of T-helper (Th)1 cells. Thus, the Th1 pathway may be associated with the onset of PRP.

Adalimumab treatment in Japanese patients with generalized pustular psoriasis: Results of an open-label phase 3 study.

A phase 3, multicenter, open-label, 52-week study investigated the efficacy and safety of adalimumab 80 mg at week 0 followed by adalimumab 40 mg every other week (option to escalate to 80 mg when necessary) in Japanese patients with generalized pustular psoriasis (GPP). Adults (aged 15-75 years) with GPP, total skin score (overall erythema area, erythema area with pustules, and edema area) of 3 or more, and erythema with pustules (skin score, ≥1) based on the 2014 Japanese Dermatological Association severity index of GPP were enrolled. The primary efficacy end-point was clinical response at week 16 (non-responder imputation), defined as achieving remission (total skin score, 0) or improvement from baseline (reduction of ≥1 point from a baseline total skin score of 3 or ≥2 points from a baseline total skin score of ≥4). Of 10 enrolled patients (mean disease duration, 10.6 years), seven patients, including three with the dose escalated to 80 mg every other week before week 15, achieved clinical response at week 16, and five achieved clinical response at week 52. Mean change from baseline total GPP score was -4.6 at week 16 (n = 8) and -6.0 at week 52 (n = 5); change in total skin score was -3.1 (n = 8) and -4.2 (n = 5), respectively. Nine patients experienced one or more adverse events and three experienced serious adverse events. The most common adverse events were nasopharyngitis, pruritus and hypoalbuminemia. In conclusion, adalimumab was effective and well tolerated for up to 52 weeks in the treatment of Japanese patients with GPP.

Up-regulated expression of CD86 on circulating intermediate monocytes correlated with disease severity in psoriasis.

BACKGROUND: The number of intermediate monocytes (CD14++CD16+) increases in many inflammatory conditions. However, it is not yet known which functional markers expressed by these populations are linked to the pathogenesis of psoriasis. OBJECTIVES: We evaluated the expression of functional markers on circulating intermediate monocytes. Our goal was to correlate specific populations and their markers with the clinical severity of psoriasis. METHODS: A cohort of 43 psoriatic patients was subjected to analysis. The proportion of intermediate monocytes with CD86 expression was evaluated by flow cytometry. Serum beta defensin-2 levels were measured by ELISA. Immunofluorescent staining was performed in order to identify the presence of CD14+CD16+ cells that co-expressed CD86 in affected skin tissues. RESULTS: Upregulated expression of CD86 on the intermediate subset (but not the number of intermediate monocytes) correlated with clinical severity as measured by PASI scores and serum beta defensin-2 levels. Immunostaining also showed the presence of CD86+CD14+CD16+ cells in the epidermis and dermis of psoriatic plaques, which was associated with increased epidermal proliferation. CONCLUSION: These results suggest that the expression of CD86 on circulating intermediate monocytes could be used as an index in clinical practice and provide novel insights into how these cells join a complex immune network under the pathological conditions of psoriasis.

Extraocular sebaceous carcinoma accompanied by invasive squamous cell carcinoma: The first case report and consideration of histogenesis.

A 61-year-old man presented with a dome-shaped nodule, 1.2 cm in size, with a central crater covered by keratinous material near the left lateral malleolus. Histological findings demonstrated a basophilic circular cone in the center, surrounded and sharply demarcated by a broad eosinophilic area. The central conical mass was composed mainly of atypical basaloid cells intermingled with scattered atypical sebaceous cells with scalloped nuclei and microvesicular cytoplasms, suggesting sebaceous carcinoma. The peripheral area consisted of atypical keratinizing squamoid cells without sebaceous cells, suggesting invasive squamous cell carcinoma. Atypical sebaceous cells were positive for adipophilin. Atypical basaloid cells were positive for 34ßE12 and CAM5.2. Peripheral squamoid cells were positive for 34ßB4 and 34ßE12 throughout, and were positive for LHP1 in the superficial layer. We herein describe the first case of extraocular sebaceous carcinoma accompanied by invasive squamous cell carcinoma, which might have arisen from biphasic differentiation of cancer stem cells.

Maintenance of sweat glands by stem cells located in the acral epithelium.

The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes.