High prevalence of dermatophytosis of the feet in acral melanoma of the foot.

The clinical characteristics and pathogenesis of acral melanoma of the foot (AMF) have not been sufficiently elucidated. Clinical or subclinical persistent inflammation of the feet is caused by dermatophytosis of the feet (DPF). Persistent inflammation is potentially associated with oncogenesis. Moreover, diabetes has been reported to be associated with the development of dermatophytosis and cancer. The present study aimed to elucidate the clinical association between DPF and AMF, with consideration of diabetes. The medical records of 114 Japanese patients were retrospectively examined and divided into an AMF group (n = 30) and a control group consisting of patients with foot diseases other than melanoma (n = 84). Microscopic DPF screening was performed on all patients who reported symptoms in the foot, with or without AMF. Patients underwent a microscopic test to detect the presence of dermatophytes, and the diagnosis of DPF was made based on a positive result. In the AMF group, 18 (60.0%) and eight (26.7%) patients had DPF and diabetes, respectively. Four patients (13.3%) had both DPF and diabetes. In the control group, 25 (29.8%) and 11 (13.1%) patients had DPF and diabetes, respectively. Five patients (6.0%) had both DPF and diabetes. Univariate analyses showed a significantly higher prevalence of DPF in the AMF group than in the control group (odds ratio, 3.540; p = 0.003, Pearson χ2 test). Furthermore, multivariate analyses of sex, body mass index, DPF, and diabetes revealed DPF as a significant factor associated with AMF (odds ratio, 4.285; p = 0.002, logistic regression analysis). The hyperkeratotic type of DPF was more frequently observed in patients with AMF than in control patients (odds ratio, 11.083; p < 0.001, Pearson χ2 test). In conclusion, the present study found a significantly higher prevalence of DPF, especially its hyperkeratotic type, in patients with AMF. DPF may be associated with AMF pathogenesis.

Generation of induced pluripotent stem cell (iPSC) from NY-ESO-I-specific cytotoxic T cells isolated from the melanoma patient with minor HLAs: The practical pilot study for the adoptive immunotherapy for melanoma using iPSC technology.

Melanoma is one of the most severe skin cancers, derived from melanocytes. Among various therapies for melanoma, adoptive immunotherapy using tumor-infiltrating lymphocytes/chimeric antigen receptor-T cells (TCs) is advanced in recent years; however, the efficacy is still limited, and major challenges remain in terms of safety and cell supply. To solve the issues of adoptive immunotherapy, we utilized induced pluripotent stem cells (iPSCs), which have an unlimited proliferative ability and various differentiation capability. First, we monoclonally isolated CD8+ TCs specifically reactive with NY-ESO-1, one of tumor antigens, from the melanoma patient's monocytes after stimulated with NY-ESO-1 peptide by manual procedure, and cultured NY-ESO-1-specific TCs until proliferated and formed colonies. iPSCs were consequently generated from colony-forming TCs by exogenous expression of reprogramming factors using Sendai virus vector. After the RAG2 gene in TC-derived iPSCs (T-iPSCs) was knocked out for preventing T-cell receptor (TCR) rearrangement, T-iPSCs were re-differentiated into rejuvenated cytotoxic TCs. We confirmed that TCR of T-iPSC-derived TC was maintained as the same of original TCs. In conclusion, T-iPSCs have a potential to be an unlimited cell source for providing cytotoxic TCs. Our study could be a "touchstone" to develop iPSC-based adoptive immunotherapy for the treatment of melanoma for the future clinical use.

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results.

INTRODUCTION: We report an exploratory analysis of the efficacy and safety of certolizumab pegol (CZP) in Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) (NCT03051217). METHODS: Patients ≥ 20 years with GPP or EP were randomized 1:1 to open-label CZP 400 mg every 2 weeks (Q2W) or 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks; patients who achieved "much improved" or "very much improved" on the Global Improvement Score (GIS; for GPP) or a PASI 50 response (≥ 50% reduction from baseline Psoriasis Area and Severity Index; for EP) continued to week 52. Efficacy outcomes assessed included Clinical Global Impression of Improvement (CGI-I), Dermatology Life Quality Index (DLQI 0/1), and Itch Numeric Rating Scale (INRS 0). GIS and Japanese Dermatological Association (JDA) severity index were assessed in patients with GPP, and PASI and Physician's Global Assessment (PGA) in patients with EP. Treatment-emergent adverse events (TEAEs) were evaluated through weeks 0-52. RESULTS: Of 22 patients randomized, 19 completed week 52. At week 16, all reported outcomes improved with both CZP doses and were generally maintained through week 52. At week 52, 6/7 GPP and 12/12 EP patients achieved CGI-I response ("improved" or "remission"). Also, 4/7 GPP and 7/12 EP patients achieved DLQI 0/1; 2/7 GPP and 2/12 EP patients achieved INRS 0. Meanwhile, 6/7 patients with GPP achieved GIS response, and JDA severity index was reduced from baseline. We found that 9/12 and 5/12 patients with EP achieved PASI 90 and PGA 0/1, respectively. Overall, three serious TEAEs were reported in three CZP 400 mg Q2W-treated patients. CONCLUSION: CZP treatment over 16 weeks improved the signs and symptoms of GPP and EP, and improvements were maintained through week 52. No new safety signals were identified. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03051217.

Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: Effect of Demographics and Baseline Disease Characteristics on Efficacy.

INTRODUCTION: We present certolizumab pegol (CZP) efficacy data across patient demographic and baseline disease characteristic subgroups from a phase 2/3 trial investigating CZP treatment in Japanese patients with moderate to severe plaque psoriasis (PSO; ClinicalTrials.gov identifier: NCT03051217). METHODS: Patients were randomised 1:2:2 to placebo once every 2 weeks (Q2W), CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0, 2 and 4) for 16 weeks. Patients who achieved ≥ 50% reduction in their baseline Psoriasis Area and Severity Index (PASI 50) score at week 16 continued therapy to week 52. PASI 75/90 (75% and 90% reduction, respectively) and Physician's Global Assessment (PGA) 0/1 responder rates at weeks 16 and 52 were reported for patient demographic and baseline disease characteristic subgroups, including body mass index (BMI), PASI, disease duration and prior biologic use. Non-responder imputation was used. RESULTS: Of the randomised patients, 2/26 patients in the placebo group, 47/53 patients in the CZP 400 mg Q2W group and and 39/48 patients in the CZP 200 mg Q2W group completed week 52. In the subgroups evaluated, week 16 efficacy was generally maintained through week 52. At week 52, PASI 75 was achieved by 84.2, 85.7 and 80.0% of patients receiving CZP 400 mg Q2W in the low (15.0-23.7 kg/m2)/intermediate (> 23.7-27.4 kg/m2)/high (> 27.4-47.0 kg/m2) BMI subgroups, respectively, and by 77.8, 70.6 and 69.2%, respectively of patients treated with CZP 200 mg Q2W. PASI 75 at week 52 was achieved by 92.9, 75.0 and 84.2% of patients receiving CZP 400 mg Q2W in the low (12.0-18.0)/intermediate (> 18.0-27.0)/high (> 27.0-67.2) baseline PASI subgroups, respectively, and by 85.0, 58.3 and 68.8% of patients receiving CZP 200 mg Q2W, respectively. Similar responses were observed across other subgroups evaluated for both CZP doses in PASI 75/90 and PGA 0/1. CONCLUSION: Clinically meaningful improvements in signs and symptoms of PSO were maintained through week 52 for CZP dosed at 400 mg Q2W or 200 mg Q2W, across patient subgroups. In general, a numerically greater response was observed for patients receiving CZP 400 mg Q2W versus those receiving CZP 200 mg Q2W across patient subgroups. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03051217.

Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results.

INTRODUCTION: Certolizumab pegol (CZP), an Fc-free, PEGylated anti-tumour necrosis factor biologic, dosed at 400 mg every 2 weeks (Q2W) and 200 mg Q2W over 16 weeks, resulted in improvements in Japanese patients with moderate to severe plaque psoriasis (PSO); no new safety signals were identified. We present 52-week efficacy and safety results. METHODS: Patients ≥ 20 years with PSO ≥ 6 months [Psoriasis Area and Severity Index (PASI) ≥ 12, body surface area ≥ 10%, Physician's Global Assessment (PGA) ≥ 3] were randomised 1:2:2 to placebo Q2W, CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks. Week 16 PASI 50 responders continued through week 52; CZP 200 mg Q2W-randomised patients were re-randomised 1:1 to CZP 200 mg Q2W or CZP 400 mg Q4W; patients initially randomised to other treatment groups continued in the same group. Outcomes included PASI 75/90/100, PGA 0/1, Dermatology Life Quality Index (DLQI) 0/1, Itch Numeric Rating Scale (INRS) 0, modified Nail Psoriasis Severity Index (mNAPSI), durability of response for week 16 PASI 75/90 responders, and safety. RESULTS: Of 26/53/48 patients randomised to placebo, CZP 400 mg Q2W and CZP 200 mg Q2W, 2/47/39 completed week 52, respectively. PASI 75/90 responses were generally maintained from weeks 16 to 52 for all CZP doses. Most week 16 PASI 75/90 achievers maintained their response through week 52. PASI 75/90/100 responses at week 52 in the CZP 400 mg Q2W and CZP 200 mg Q2W groups were 83.0/81.1/41.5% and 72.9/60.4/18.8%, respectively; DLQI/INRS remission rates were 64.2/50.9% in CZP 400 mg Q2W and 58.3/27.1% in CZP 200 mg Q2W-treated patients. Reductions in mNAPSI observed for CZP-treated groups were maintained through week 52. No new safety signals were identified. CONCLUSION: CZP treatment resulted in improvements in signs and symptoms of PSO, which were maintained through week 52. The 400 mg Q2W dose could provide additional clinical benefit. TRIAL REGISTRATION: NCT03051217.

Certolizumab Pegol for the Treatment of Moderate to Severe Plaque Psoriasis: 16-Week Results from a Phase 2/3 Japanese Study.

INTRODUCTION: Certolizumab pegol (CZP), the Fc-free, PEGylated anti-tumor necrosis factor, is approved for the treatment of moderate to severe plaque psoriasis (PSO) in Western countries and in Japan, among other indications. METHODS: We report results from the first 16 weeks of a 52-week phase 2/3 trial of CZP in Japanese patients with PSO. Patients ≥ 20 years with PSO ≥ 6 months (Psoriasis Area and Severity Index [PASI] ≥ 12, body surface area affected ≥ 10%, and Physician's Global Assessment [PGA] ≥ 3 on a 5-point scale) were randomized 2:2:1 to CZP 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (400 mg weeks 0/2/4), or placebo Q2W. Outcomes assessed to week 16: PASI 75, PASI 90, PGA 0/1 (Markov chain Monte Carlo), Dermatology Life Quality Index (DLQI 0/1) and Itch Numeric Rating Scale (INRS 0) (non-responder imputation), and DLQI and INRS change from baseline (last observation carried forward). Safety data were reported for patients receiving ≥ 1 dose of study medication through weeks 0-16; adverse events were evaluated using Medical Dictionary for Regulatory Activities version 18.1. RESULTS: A total of 127 patients were randomized to CZP 400 mg Q2W (N = 53), CZP 200 mg Q2W (N = 48), placebo (N = 26). Week 16 responder rates for CZP 400 mg/200 mg Q2W versus placebo were 87.1%/73.0% versus 7.9% for PASI 75; 75.7%/53.8% versus 0.2% for PASI 90; 66.7%/52.7% versus 0.0% for PGA 0/1 (all p < 0.0001 for both CZP doses versus placebo). Significant improvements in DLQI and INRS were reported at week 16 by patients receiving both CZP doses compared with placebo (p < 0.0001). Incidence of treatment-emergent adverse events within the CZP 400 mg Q2W, CZP 200 mg Q2W, and placebo groups were 326.1, 404.9, and 682.4 per 100 patient-years. No new safety signals were identified compared to previously reported data. CONCLUSION: CZP dosed at 400 mg or 200 mg Q2W was associated with improved PSO signs and symptoms. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03051217.

Long-term efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 5-year extension of a phase 3 study (reSURFACE 1).

The three part, double-blind, randomized, controlled reSURFACE 1 trial and extension study (NCT01722331) evaluated efficacy and safety of tildrakizumab in adults with moderate to severe plaque psoriasis. Patients with ≥50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50) following treatment with tildrakizumab 100 mg (TIL100) or 200 mg (TIL200) could enter the optional long-term extension study and continue treatment at the same dose for an additional 192 weeks. This subgroup analysis assessed the long-term efficacy and safety of tildrakizumab treatment for Japanese patients enrolled in reSURFACE 1 for up to 5 years of treatment. The primary efficacy outcomes were the proportions of patients who maintained PASI 75 and Physician Global Assessment (PGA) clear or minimal with ≥2-grade reduction from baseline (PGA 0/1) from base study week 64 to extension week 192. Secondary outcomes were the proportion of patients who maintained PASI 90/100 from base study week 64 to extension week 192. Adverse events (AEs) were monitored throughout the study and for up to 20 weeks after the last study visit. Of the 120 Japanese patients who entered the reSURFACE 1 extension study, 43 (79.6%) patients receiving tildrakizumab 100 mg and 58 (87.9%) patients receiving tildrakizumab 200 mg completed the extension study. Of all Japanese patients with PASI 75/90/100 and PGA 0/1 at week 64, 85%/88% receiving TIL100/TIL200 maintained PASI 75, 70%/96% maintained PASI 90, 63%/67% maintained PASI 100, and 68%/72% maintained PGA 0/1 at extension week 192. AEs led to discontinuation in 1.7 patients per 100 patient-years (P100PY) receiving tildrakizumab 100 mg and 0.8 P100PY receiving tildrakizumab 200 mg. Incidences of severe infections, malignancies, confirmed major adverse cardiac events, and hypersensitivity reactions were low in both treatment groups. Through 5 years of treatment, tildrakizumab maintained efficacy and was well tolerated with low rates of AEs of special interest.

Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis.

BACKGROUND: KHK4083, a fully human anti-OX40 monoclonal antibody, is a potential novel therapeutic option for moderate to severe atopic dermatitis (AD), targeting the immunopathogenic pathways. OBJECTIVE: Assess the safety and tolerability of repeated doses of KHK4083 in patients with moderate to severe AD, and investigate the pharmacokinetics and immunogenicity of KHK4083. Additionally, assess the clinical efficacy and pharmacodynamics as exploratory objectives. METHODS: In this phase 1, single-center, open-label, repeated-dose study, a total of 22 patients received KHK4083 10 mg/kg IV on Day 1, Day 15 and Day 29, and were followed until Day 155. RESULTS: There were no deaths, serious adverse events (SAEs), or discontinuations due to adverse events (AEs). Common treatment-emergent AEs were mild or moderate pyrexia (11 patients, 50.0 %), and chills (8 patients, 36.4 %). No clinically meaningful changes in the laboratory values, vital signs, and electrocardiogram recordings were observed. The Cmax was 267 ± 53 µg/mL and the t1/2 was 303 ± 88 h at Day 29. The overall assessment of antibodies against KHK4083 (immunogenicity) showed low positive responses. Continued improvement in the Eczema Area and Severity Index (EASI) and Investigator's Global Assessment (IGA) scores were observed throughout the study. The mean and median percent changes in thymus and activation-regulated chemokine (TARC) continued to decrease over time to -70.4 and -78.8 % until Day 155. CONCLUSION: Repeated intravenous infusion of KHK4083 had an acceptable safety profile in patients with moderate to severe AD. Sustained improvement in the symptoms of AD was observed after completion of KHK4083 treatment.

Long-term safety of brodalumab in Japanese patients with plaque psoriasis: An open-label extension study.

Brodalumab, an interleukin-17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open-label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long-term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician's discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108-week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis-related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108-week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment-related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn's disease were observed in this study. Serious treatment-related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti-brodalumab-binding antibodies or brodalumab-neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long-term efficacy and safety of brodalumab were demonstrated over 108 weeks.

Japanese guidance for use of biologics for psoriasis (the 2019 version).

As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Since 2015, three IL-17 inhibitors of secukinumab and ixekizumab, anti-IL-17A antibodies, and brodalumab, an anti-IL-17 receptor antibody, and two anti-IL-23p19 antibodies of guselkumab and risankizumab, have also been launched. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors and patient background factors, sharing such information with patients. The following can be listed as points to be considered for the selection of biologics: drug effects (e.g. strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g. infections, administration-related reactions and relationships with other comorbidities), convenience for patients (e.g. hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration) and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors.

Role of interleukin-24 in the tumor-suppressive effects of interferon-ß on melanoma.

BACKGROUND: Type 1 interferons (IFNs), including IFN-ß, are widely used in adjuvant therapy for patients who undergo surgery for malignant melanoma to inhibit recurrence and in-transit metastasis. The precise mechanisms underlying the tumor-suppressive effects of IFN-ß on melanoma are not yet completely understood. OBJECTIVE: The purpose was to reveal the mechanisms underlying the tumor-suppressive effects of IFN-ß via interleukin (IL)-24. METHODS: Genome-wide oligonucleotide microarray, quantitative real-time reverse transcription-polymerase chain reaction (PCR), enzyme-linked immunosorbent assay and western blotting assay were performed using four melanoma cell lines (A375, RPMI-7951, SK-MEL-5 and SK-MEL-1) treated with natural-type IFN-ß to assess the expression of IL-24. Proliferation assay was performed using these melanoma cells and IL-24 knock-down melanoma cells. RESULTS: Genome-wide microarray analysis detected candidate genes upregulated in IFN-ß-sensitive cells after treatment with IFN-ß. We focused on IL-24 among the candidate genes encoding secretory proteins. Peak IL-24 mRNA expression completely correlated with the order of sensitivity of melanoma cells to IFN-ß. IFN-ß treatment induced extracellular IL-24 protein in IFN-ß-sensitive cells, but did not induce intracellular IL-24 protein. Knock-down of IL-24 changed melanoma cells into IFN-ß-resistant cells. The expression ratio of IL-22R1, one of the IL-24 receptors, correlated with the order of sensitivity of melanoma cells to IFN-ß. Treatment with recombinant human IL-24 did not have any effects on all the melanoma cell lines. CONCLUSION: Our data suggest that IFN-ß suppresses the proliferation of melanoma cells through extracellular IL-24 protein derived from melanoma cells.

Relationship between the Degrees of Itch and Serum Lipocalin-2 Levels in Patients with Psoriasis.

BACKGROUND: Lipocalin-2 (LCN2), a protein secreted mainly by activated neutrophils, has been associated with neurodegeneration, obesity, and inflammatory responses. Serum LCN2 concentration has been reported elevated in patients with psoriasis, but lower in patients with atopic dermatitis (AD). Spinal astrocyte-derived LCN2 was found to be involved in enhancement of itch in a mouse model of AD. However, the relationship between LCN2 and itch in patients with psoriasis has not been determined. Objective. This study examined the correlation between serum LCN2 levels and the degrees of itch in patients with psoriasis. METHODS: Serum LCN2 concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in patients with psoriasis and AD and in healthy controls. The degree of itch was assessed using a visual analog scale (VAS), and disease severity was determined by measuring psoriasis area and severity index (PASI) and scoring atopic dermatitis (SCORAD). Correlations among serum LCN2 level, VAS, PASI, and SCORAD were analyzed statistically. We further examined the serum LCN levels in psoriasis patients before and after biological treatment. RESULTS: Serum LCN2 concentrations were significantly higher in patients with psoriasis and AD than those in healthy controls. In patients with psoriasis, serum LCN2 concentrations were significantly correlated with VAS, but not with PASI. In contrast, serum LCN2 concentrations did not correlate with VAS or SCORAD in patients with AD. Serum LCN2 levels in psoriasis patients significantly decreased after the biological treatment along with improvement of VAS. CONCLUSION: Serum LCN2 concentration is associated with the degree of itch in patients with psoriasis, suggesting that serum LCN2 may be a useful clinical marker for itch in psoriasis.

Real-World Postmarketing Study of the Impact of Adalimumab Treatment on Work Productivity and Activity Impairment in Patients with Psoriatic Arthritis.

INTRODUCTION: This study investigated the effectiveness of adalimumab treatment in improving Work Productivity and Activity Impairment (WPAI) in patients with psoriatic arthritis (PsA) in real-world settings in Japan. METHODS: This 24-week, single-arm, postmarketing surveillance study (2014-2017), conducted at 75 centers in Japan, enrolled adalimumab-naïve patients (paid workers, including part-time) meeting ClASsification criteria for Psoriatic ARthritis (CASPAR). The primary endpoint was improvement in overall work impairment (OWI) scores from baseline to week 24. Secondary endpoints included changes in WPAI-PsA (OWI, absenteeism, presenteeism, and activity impairment), Psoriasis Area and Severity Index (PASI), psoriatic arthritis screening and evaluation (PASE) scores, Disease Activity Scores in 28 joints using C-reactive protein (DAS28[CRP]), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and PASI75/90 and American College of Rheumatology (ACR) 20/50/70 rates. RESULTS: In the effectiveness population (n = 106; 72.6% men; mean ± standard deviation [SD] age, 49.3 ± 10.7 years), OWI scores significantly improved (mean ± SD change, - 25.2 ± 35.3; p < 0.0001) from baseline to week 24. Other WPAI domain scores also improved significantly. Changes in OWI were significantly correlated (p < 0.0001) with PASE (r = 0.6284), DAS28(CRP) (r = 0.6059), BASDAI (r = 0.7281), and HAQ-DI (r = 0.6161) scores and were significantly influenced by previous nonsteroidal anti-inflammatory drug use (p = 0.0142), and baseline PASE (p = 0.0098), DAS28(CRP) (p = 0.0026), HAQ-DI (p = 0.0004), and BASDAI (p < 0.0001) scores. At the last evaluation, rate (95% confidence interval) of PASI 75 and 90 (n = 100) was 58.0% (47.7-67.8) and 39.0% (29.4-49.3), respectively, and that of ACR 20, 50, and 70 (n = 58) was 86.2% (74.6-93.9), 70.7% (57.3-81.9), and 53.4% (39.9-66.7), respectively. No new safety signals were observed in the safety population (n = 148). CONCLUSION: Adalimumab treatment improved WPAI in patients with PsA. Improvements in OWI and joint symptoms were significantly associated. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02414633. FUNDING: AbbVie GK and Eisai Co., Ltd.

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.

Tacrolimus ointment for the treatment of adult and pediatric atopic dermatitis: Review on safety and benefits.

Atopic dermatitis (AD) requires long-term management, mainly with topical anti-inflammatory agents. Topical corticosteroids (TCS) and tacrolimus ointment (TAC-O) are recommended as first-line treatments for AD. However, the long-term use of TCS is limited by cutaneous adverse events such as skin atrophy. For TAC-O, Japanese and US labelings were updated in 2003 and 2006, respectively, to include a boxed warning about a theoretical risk of skin cancer and lymphoma in patients treated with topical calcineurin inhibitors. However, TAC-O has been used worldwide for longer than 15 years to treat adult and pediatric patients with AD. Available data suggest that TAC-O is effective and well tolerated, and can improve quality of life. TAC-O has successfully been used in the proactive management of AD consisting of long-term intermittent use to prevent, delay or reduce the occurrence of AD flares. Systemic drug absorption after TAC-O application is negligible and unlikely to result in systemic immunosuppression. There is currently no strong evidence of an increased rate of malignancy in treated patients, and observational data from postmarketing surveillance studies have shown no safety concerns. In the absence of robust evidence, the warning about the carcinogenic potential in the Japanese labeling for TAC-O does not appear justified and should be reconsidered. This mitigation of description would allow adult and pediatric patients with AD to receive the effective treatment more appropriately.