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Of those patients diagnosed with generalized pustular psoriasis (GPP) in Japan, approximately 30% have a prior psoriasis vulgaris (PsV) diagnosis. Therefore, understanding factors associated with a GPP diagnosis is essential for early diagnosis of GPP in patients with PsV. This retrospective cohort study was conducted to identify associated factors for GPP diagnosis in patients with PsV. Eligible patients with two confirmed diagnoses of PsV with/without a confirmed GPP diagnosis (International Classification of Disease 10th revision codes L40.0 and L40.1, respectively) were identified from the Japanese Medical Data Center database (JMDC) (July 1, 2005–January 31, 2019). Weighted logistic regression was used to identify associated factors (based on recorded comorbidities) between the PsV only and PsV with GPP cohorts. Odds ratios (ORs) of ≥1.5, associated with a high probability of a GPP diagnosis, were reported for factors with ≥5 patients/cohort. The time from event to GPP diagnosis was evaluated. The highest associated factor for GPP diagnosis was psoriatic arthritis (OR 20.2, 95% confidence interval [CI] 17.06–23.92, P < 0.0001), which also had the shortest time from event to GPP diagnosis (median 119 days). Other comorbidities associated with GPP diagnosis were other psoriasis, tonsillitis, and sinusitis. Treatments associated with GPP diagnosis included systemic corticosteroids (OR 2.19, 95% CI 1.98–2.43, P < 0.0001; median time from treatment initiation to GPP diagnosis 180 days). Other associated treatments (other immunosuppressants, interleukin [IL]‐17 or IL‐23 inhibitors, and phototherapy) had a delay of ≥1 year from treatment initiation to GPP diagnosis. Back pain, headache, and fever were also identified as associated with a GPP diagnosis. Patients with PsV requiring systemic therapies are more likely to receive a GPP diagnosis than those not requiring systemic treatment. These data will help identify patients with PsV at high risk of developing GPP and potentially support early GPP diagnosis. [ABSTRACT FROM AUTHOR]

This is the English version of the Japanese guidance for biologics in treating atopic dermatitis (AD). The signaling pathway mediated by interleukin (IL)‐4 and IL‐13 contributes to type 2 inflammatory responses and plays an important role in the pathogenesis of AD. IL‐31 is a cytokine mainly produced by activated T cells and is known to be involved in the pruritus of AD. Biologics for AD have been approved, including dupilumab, an anti‐IL‐4 receptor α antibody that was approved for expanded use in AD in 2018. In 2022, nemolizumab, an anti‐IL‐31 receptor α antibody, was approved for pruritus of AD, and tralokinumab, an anti‐IL‐13 antibody, was approved for AD. Physicians who intend to use these drugs should sufficiently understand and comply with the contents of the guidelines prepared by the Japanese Ministry of Health, Labour, and Welfare to promote the optimal use of the drugs. In treatment with biologics, it is important to consider disease factors (activity and severity), treatment factors (dosage and administration as well as the efficacy and safety), and patients' background characteristics (age and comorbidities) and share this information with patients when choosing treatment options. This guidance was developed for board‐certified dermatologists who specialize in treating AD, and for promoting the proper use of biologics, taking into account the variety of factors in individual patients. [ABSTRACT FROM AUTHOR]

Alopecia area (AA) is a common autoimmune disorder, characterized by hair loss. Although its impact on quality of life is fairly well understood, studies on the economic impact of AA are limited. The aim of this study was to quantify the personal and nationwide economic burden of AA in Japan. Data were drawn from the Adelphi AA Disease Specific Programme (DSP)™, a real‐world, cross‐sectional survey with retrospective data collection, of Japanese physicians and patients with AA. The study was conducted in 2021, before the approval of Janus kinase inhibitors for AA. Physicians and their consulting AA patients completed questionnaires regarding disease severity, treatment, and AA‐related costs. The Work Productivity and Activity Impairment questionnaire was used to evaluate the impact of AA on patients' work and activity. Nationwide estimates of cost and productivity loss were extrapolated from collected patient data. A total of 50 physicians provided data on 235 patients; 58.7% were female, mean ± SD age was 41.1 ± 11.8 years, and mean physician‐estimated scalp hair loss was 40.4% ± 30.2%. Prescription medication use was high (92.3% of patients), but the use of over‐the‐counter medication was low, at 8.7%. Mean cost to patients for medication was ¥ 4263 (US$ 32.42) per month. Productivity while at work (presenteeism) was significantly impaired (23.9% ± 25.7%), but absenteeism was low (0.9% ± 2.8%). The total nationwide cost of AA was estimated at 112.7 billion yen (US$ 857 million), of which 88.1 billion yen (78.2%) was due to productivity loss. Over 2 million days per year of activity time were estimated to be lost due to AA. Thus, despite not being a physically limiting disease, AA has a significant impact in terms of cost and time, both on a personal and national level. These data highlight the need for more targeted interventions to reduce the effects of AA on the Japanese economy. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS), is a chronic inflammatory skin disorder that confers a substantial financial burden to patients. The aim of the current study was to assess the patient‐reported financial impact of HS. Patients presenting to a wound center between 2010 and 2021 were retrospectively reviewed. Demographics, comorbidities, and disease characteristics were collected. The financial impact of HS was assessed via the Comprehensive Score for Financial Toxicity ‐ Functional Assessment of Chronic Illness Therapy (COST‐FACIT) version 2 and investigator‐generated surveys. Of 199 patients contacted, 27.1% (n = 54) completed the survey. The majority were women (77.8%, n = 42) and had private health insurance (n = 30; 55.6%). Most patients (66.7%, n = 36) had Hurley stage III disease. Mean follow‐up was 2.3 + 2.8 years. The overall COST score was 19.7 + 12.4, indicating grade 1 financial toxicity (FT). Grade 0 FT was reported in 31.5% (n = 17) of patients, grade 1 in 37.0% (n = 20), grade 2 in 27.8% (n = 15), and grade 3 in 3.7% (n = 2). The mean self‐reported 12‐month out‐of‐pocket cost and credit scores were $2250 + 3269.24 and 674.6 + 95.3, respectively. Patients with private insurance had lower FT compared with Medicaid and Medicare (p = 0.003). Higher out‐of‐pocket costs were positively correlated with FT (p = 0.042), while higher credit scores were negatively correlated (p = 0.003). Patients with HS lesions in three or more anatomic regions reported the highest FT (p = 0.031). HS is a debilitating skin disorder that affects the livelihood of patients in a multifaceted manner. These patient‐reported outcomes highlight the impact that HS has on an individual's financial security, calling for further attention to this vulnerable population. [ABSTRACT FROM AUTHOR]

This real‐world study at a single academic center retrospectively examined the drug survival of apremilast for patients with psoriasis. Retrospective information was extracted from the medical records of patients with psoriasis treated with apremilast at the Department of Dermatology, Jichi Medical University Hospital, between March 1, 2017, and June 31, 2021. In total, 281 patients were included in this study. Of these patients, 22% had psoriatic arthritis and 57% had a history of prior systemic treatment, including biologics, before the initiation of apremilast. The 1‐, 2‐, 3‐, and 4‐year drug survival rates were 54%, 41%, 32%, and 30%, respectively. Cox regression analysis revealed that sex, duration of plaque psoriasis (<10 years vs ≥10 years), presence of psoriatic arthritis, involvement of scalp lesions, involvement of palmoplantar lesion, involvement of nail lesions, having cardiometabolic comorbidities, and a history of prior systemic treatment did not have any significant impact on drug survival. The most common reason for apremilast discontinuation was inadequate efficacy (27%), followed by adverse events (12%). Approximately 49% of the patients experienced one or more adverse events. Diarrhea was the most common adverse event (24%), followed by nausea (19%) and headache (11%). [ABSTRACT FROM AUTHOR]

Dupilumab, a monoclonal antibody inhibiting interleukin (IL) 4 and IL‐13, is approved for the treatment of moderate to severe atopic dermatitis (AD) in children aged ≥6 years, adolescents, and adults. Both clinical trials and real‐life data demonstrate its efficacy and safety. However, some cutaneous adverse events (cAEs) have been observed during real‐world experiences. The authors' aim was to analyze the spectrum of cAEs in patients receiving dupilumab for the treatment of AD in a real‐world setting. A retrospective review of electronic medical records was conducted for 916 patients (475 males and 541 females; mean age, 50.23 ± 19.66 years [range, 18–91 years]) who had received dupilumab for a minimum of 1 month for the treatment of AD from December 2018 to November 2022 at the Department of Dermatology of University Federico II of Naples (Italy). The mean duration of dupilumab treatment was 27.31 ± 21.26 months. A total of 148 of 916 (16.15%) (90 males; mean age, 50.91 ± 15.34 years) patients reported other cAEs apart of AD flare; namely, facial redness (82 of 916; 8.95%), psoriasis (39 of 916; 4.25%), alopecia areata (11 of 916; 1.2%), skin peeling (11 of 916; 1.2%), parapsoriasis (three of 916; 0.32%), and vitiligo (two of 916; 0.21%). Thirty‐one of 916 (3.38%) patients discontinued dupilumab because of cAEs (18 of 916; 1.96%) for facial redness, 10 of 916 (1.09%) for psoriasis, and three of 916 (0.32%) for parapsoriasis. In our population, most of the cAEs were mild and did not require discontinuation of dupilumab. These findings would enable dermatologists understand the cutaneous side effects of dupilumab better, resulting in improved treatment plan decisions in clinical practice. [ABSTRACT FROM AUTHOR]

Psoriasis affects approximately 0.3% of the Japanese population. Recently, various effective systemic drugs have become available, and the continuation of a given treatment has become critical because of the chronic nature of psoriasis. Factors affecting drug survival (the time until treatment discontinuation) in psoriasis treatment include efficacy, safety, ease of use, and patient preference. In the present study, the authors retrospectively surveyed a multifacility patient registry to determine the real‐world evidence of the survival rate of systemic interventions for psoriasis treatment. Patients with psoriasis who visited 20 facilities in the Western Japan area between January 2019 and May 2020 and gave written consent were registered as study participants, and their medical history of systemic interventions for psoriasis (starting from 2010) was retrospectively collected and analyzed. The drugs investigated were adalimumab, infliximab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, cyclosporine, and apremilast. When drugs were discontinued, the reasons were also recorded. A total of 1003 patients with psoriasis including 268 with psoriatic arthritis (PsA) were enrolled. In biologics, more recently released drugs such as interleukin 17 inhibitors showed a numerically higher survival rate in the overall (post‐2010) analysis. However, in the subset of patients who began treatment after 2017, the difference in the survival rate among the drugs was smaller. The reasons for discontinuing drugs varied, but a loss of efficacy against dermatological or joint symptoms were relatively frequently seen with some biologics and cyclosporine. The stratification of drug survival rates based on patient characteristics such as bio‐naive or experienced, normal weight or obese, and with or without PsA, revealed that bio‐experienced, obese, and PsA groups had poorer survival rates for most drugs. No notable safety issues were identified in this study. Overall, the present study revealed that the biologics show differences in their tendency to develop a loss of efficacy, and the factors that negatively impact the survival rate of biologics include the previous use of biologics, obesity, and PsA. [ABSTRACT FROM AUTHOR]

This is the English version of Japanese guidance for the use of oral Janus kinase (JAK) inhibitors (JAK1 and tyrosine kinase 2 [TYK2] inhibitors) in the treatments of psoriasis. Several cytokines, such as interleukin (IL)‐6, IL‐7, IL‐12, IL‐21, IL‐22, IL‐23, interferon (IFN)‐α, and IFN‐γ, are involved in the pathogenesis of psoriasis (including psoriatic arthritis). As oral JAK inhibitors hinder the JAK‐signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of psoriasis. JAK has four types: JAK1, JAK2, JAK3, and TYK2. Regarding the use of oral JAK inhibitors for the treatment of psoriasis in Japan, indications of the JAK1 inhibitor upadacitinib were extended also to psoriatic arthritis in 2021, and the use of the TYK2 inhibitor deucravacitinib for plaque‐type psoriasis, pustular psoriasis, and erythrodermic psoriasis became covered by health insurance in 2022. This guidance was developed for board‐certified dermatologists who specialize in the treatment of psoriasis and to promote the proper use of oral JAK inhibitors. In the package inserts and guides for appropriate use, upadacitinib and deucravacitinib are classified as a "JAK inhibitor" and a "TYK2 inhibitor", respectively, and it is possible that there may be differences in safety between the two drugs. The safety of these drugs will be evaluated for the future by the postmarketing surveillance for molecularly targeted drugs for psoriasis of the Japanese Dermatological Association. [ABSTRACT FROM AUTHOR]

Deucravacitinib is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor that demonstrated superior efficacy versus placebo and apremilast in a global phase 3 trial (POETYK PSO‐1; NCT03624127) in patients with moderate to severe plaque psoriasis (N = 666). This report describes efficacy and safety in Japanese patients from this study (N = 66) who were randomly assigned to treatment with deucravacitinib 6 mg once daily (n = 32), placebo (n = 17), or apremilast 30 mg twice daily (n = 17). Patients randomized to placebo crossed over to deucravacitinib at Week 16. Patients randomized to apremilast who did not achieve ≥50% reduction from baseline in Psoriasis Area and Severity Index (PASI 50) score at Week 24 switched to deucravacitinib. The proportion of Japanese patients achieving ≥75% reduction from baseline in PASI (PASI 75) score was numerically higher with deucravacitinib versus placebo and apremilast at Week 16 (78.1% vs. 11.8% and 23.5%, respectively) and versus apremilast at Week 24 (78.1% vs. 29.4%). A numerically higher proportion of patients achieved a static Physician's Global Assessment score of 0 or 1 (clear or almost clear) with at least a two‐point improvement from baseline (sPGA 0/1) with deucravacitinib versus placebo or apremilast at Week 16 (75.0% vs. 11.8% and 35.3%) and versus apremilast at Week 24 (75.0% vs. 29.4%). Findings for other clinical and patient‐reported outcomes also favored deucravacitinib. Response rates were maintained through 52 weeks in the deucravacitinib group. Incidence rates for adverse events per 100 person‐years (PY) in the Japanese patients were comparable across treatment groups through Week 52 (deucravacitinib, 336.8/100 PY; placebo, 321.0/100 PY; apremilast, 358.6/100 PY). The most frequently reported adverse event with deucravacitinib was nasopharyngitis. The efficacy and safety of deucravacitinib in Japanese patients was consistent with those in the global population in POETYK PSO‐1. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

This is the English version of Japanese guidance for use of biologics for psoriasis (the 2022 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. Moreover, after 2015, three IL‐17 inhibitors, the IL‐17A antibody preparations secukinumab and ixekizumab, and an anti‐IL‐17 receptor antibody preparation brodalumab were marketed. Furthermore, after 2018, the anti‐IL23p19 antibody preparations guselkumab and risankizumab, the TNF inhibitor certolizumab pegol, the IL‐23 inhibitor tildrakizumab, and the anti‐IL‐17A/F antibody bimekizumab were marketed. 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 followings 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. [ABSTRACT FROM AUTHOR]

The systemic treatment of psoriasis has changed markedly with the introduction of many novel drugs. However, clinicians have had limited opportunities to evaluate these new therapies. One of the new drugs, apremilast (a phosphodiesterase‐4 inhibitor), was approved in 2017 in Japan. We previously reported oral treatment for psoriasis before the introduction of apremilast. In this study, we investigated the impact of apremilast on oral medication for psoriasis by comparing data obtained before and after apremilast became available. This retrospective study enrolled patients who visited the Department of Dermatology, Fukuoka University Hospital, who were diagnosed with psoriasis and treated with anti‐psoriatic oral medications. Patients were divided into two groups: Group 1, who first visited our clinic between January 2010 and March 2016; and Group 2, who first visited our clinic between April 2016 and March 2022. The information collected included patient demographics, drug use (apremilast, cyclosporine, methotrexate, and etretinate), and treatment duration. In Group 1 (n = 149 patients), cyclosporine, methotrexate, and etretinate were prescribed to 59.1%, 16.6%, and 24.3% of the patients, respectively. In Group 2 (n = 129 patients), apremilast was prescribed to 52.5% of patients, while the number of prescriptions for cyclosporine and etretinate had decreased to 17.1% and 8.3%, respectively. The number of methotrexate prescriptions did not change significantly. Apremilast, methotrexate, and etretinate had longer continuation rates than cyclosporine in Group 2. In conclusion, apremilast replaced cyclosporine and etretinate mainly because of its better safety profile, whereas methotrexate remained in constant demand in both eras. New oral treatments for psoriasis, such as tyrosine kinase‐2 inhibitors, are now in the pipeline, and our data will serve as a control for oral anti‐psoriatic medicine before the coming era. [ABSTRACT FROM AUTHOR]

This is the English version of guidance for the use of oral Janus kinase (JAK) inhibitors in the treatment of atopic dermatitis. Several cytokines, such as interleukin (IL)‐4, IL‐13, IL‐22, IL‐31, thymic stromal lymphopoietin, and interferon‐γ, are involved in the pathogenesis of atopic dermatitis. As oral JAK inhibitors hinder the JAK‐signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of atopic dermatitis. In Japan, as oral JAK inhibitors for atopic dermatitis, a JAK1/2 inhibitor, baricitinib, expanded its authorized indications for atopic dermatitis in 2020. Consequentially, a JAK1 inhibitor, upadacitinib, also expanded its indications to atopic dermatitis in 2021, followed by new approval of another JAK1 inhibitor, abrocitinib, for the use under the Japanese health insurance system. Physicians who intend to use them should sufficiently understand and comply with contents of guidelines prepared by the Japanese Ministry of Health, Labour and Welfare to promote optimal use of these drugs. In the treatment with oral JAK inhibitors, it is important to sufficiently consider disease factors, treatment factors and patient backgrounds, and share them with patients to choose treatment options. Points to be considered for drug selection include the efficacy and safety of drugs, age of patients, and dosage and administration of the drug. This guidance was developed for board certified dermatologists, who are specialized in the treatment of atopic dermatitis, and for promoting proper use of oral JAK inhibitors, taking into account a variety of factors in individual patients. [ABSTRACT FROM AUTHOR]

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence‐based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity‐related patient outcomes with respect to several important points requiring decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

Real‐world and long‐term data on biologic treatment changes – including switching, discontinuation, dose escalation, and interval change (both increasing and decreasing) – are required to understand treatment patterns for psoriasis (PsO) in Canada. The study objectives were to evaluate the time to first biologic treatment change and to document these changes in Canadian patients with moderate‐to‐severe chronic plaque PsO. Charts from 13 Canadian sites were queried retrospectively (2005–2019); a period covering all biologic classes commonly used for PsO in Canada. Included were patients diagnosed with, and currently using biologics for, moderate‐to‐severe chronic plaque PsO. Time to first treatment change, nature of treatment change, number of lines of treatment, proportion of patients on each drug, and drug survival were collected. Based on 1149 medical charts, adalimumab had the longest time to first treatment change (49.3 months; 95% confidence interval, 37.4–67.4). Approximately half of the patients had a treatment change, and nearly 75% of these changes were either an interval change or a biologic switch. Lack of efficacy was the most prevalent primary reason for biologic switch (67.3%), whereas 6.7% of patients switched due to adverse events. Drug survival for etanercept and infliximab was approximately twice as long for patients who had dose optimization (i.e., dose escalation or interval change) than patients without dose optimization. The survival curve of adalimumab was similar to the one of ustekinumab after 48 months of treatment, showing approximately 60% of patients remaining on treatment after 132 months, with or without dose optimization. Assessing treatment patterns of all commonly used biologics for moderate‐to‐severe chronic plaque PsO in Canada between 2005 and 2019 showed that approximately half of the patients required a treatment change (mainly interval change or biologic switch) while the other half remained on treatment. [ABSTRACT FROM AUTHOR]

Dermatomyositis, an idiopathic inflammatory myopathy, is characterized by cutaneous itchy manifestations, which are frequently refractory and recurrent even after intensive immunosuppressive treatments. To evaluate the effectiveness and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in treating skin‐dominant dermatomyositis in which myositis and interstitial lung disease are absent or in remission, we performed this prospective, single‐arm, interventional study. A total of five Japanese patients (one male and four females, median [range] age, 64 [37–71] years) with refractory dermatomyositis‐associated cutaneous manifestations were recruited and treated with a 12‐week course of oral apremilast. Among five enrolled patients, three experienced diarrhea with full‐dose apremilast (30 mg twice daily), two of whom withdrew from the study and recovered quickly afterwards. A total of three evaluable female patients (median [range] age, 65 [64–71] years) received apremilast treatment for 12 weeks. A 39.4% reduction from baseline Cutaneous Dermatomyositis Disease Area and Severity Index total activity score, but not the damage score, at week 12 was observed in all three patients. Visual analog scale of itching, and quality of life by Dermatology Life Quality Index were slightly improved in one and two apremilast‐treated patients, respectively. As apremilast was effective, with expected and recoverable digestive adverse events (diarrhea), in patients with refractory and recurrent dermatomyositis‐associated cutaneous manifestations in this first phase Ib study, it can be suggested as a possible treatment when aggressive immunosuppressive therapies with high‐dose systemic corticosteroid and/or immunosuppressive agents for other manifestations, myositis, and interstitial lung disease, are not required. [ABSTRACT FROM AUTHOR]

Topical Janus kinase (JAK) and phosphodiesterase‐4 (PDE4) inhibitors are novel treatment approaches for atopic dermatitis (AD). This study aimed to compare the efficacy and safety of JAK and PDE4 inhibitors for AD treatment. The databases of PubMed, EMBASE, Web of Science, and Cochrane Library were searched until June 2021 for eligible studies of AD patients treated with topical JAK and PDE4 inhibitors. Baseline and follow‐up data were extracted. Efficacy of JAK inhibitors was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear", with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA response"). A Bayesian multiple treatment network meta‐analysis with fixed effects was performed. Odds ratio (OR) with 95% credibility interval (CrI) were used for comparing the efficacy of JAK and PDE4 inhibitors with placebo for AD. A total of 10 randomized controlled trials of topical JAK and PDE4 inhibitors with 4689 patients were included for analysis. A total of three topical JAK inhibitors and two topical PDE4 inhibitors were included. Compared with placebo, all JAK and PDE4 inhibitors had higher IGA response at 4 weeks of treatment. Notably, with similar safety profile, tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d., and delgocitinib 3% b.i.d. showed favorable IGA response compared with topical tacrolimus and corticosteroids. Ranking analysis suggested that among all included JAK and PDE4 inhibitors, tofacitinib 2% b.i.d. had the highest probability of achieving IGA response (SUCRA = 0.880). Besides, JAK and PDE4 inhibitors showed non‐inferior safety profile with placebo. This study confirmed that topical JAK and PDE4 inhibitors had promising treatment efficacy and safety for AD patients. Tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d. and delgocitinib 3% b.i.d. showed superior efficacy over other JAK and PDE4 inhibitors. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) inhibitors are emerging treatments for atopic dermatitis (AD). Due to this novel role as a therapeutic option for patients with AD, we aimed to review current evidence on the pathophysiology and the safety and adverse effects (AEs) of oral JAK inhibitors for the treatment of AD utilizing the key terms atopic dermatitis, JAK inhibitors, and adverse effect or event. Our study indicated that oral JAK inhibitors have a moderate safety profile for use in AD in several reviews and phase II or III clinical trials. Headaches, nausea, and nasopharyngitis are the most commonly reported systemic AEs. Furthermore, acne, herpes simplex, herpes zoster, and eczema herpeticum are the most commonly recorded dermatological AEs. Current evidence indicates JAK inhibitors may also have less association with some of the serious AEs, although there is potential for increased risk of asthma, acute pancreatitis, neutropenia, and thrombocytopenia. Whereas data remain limited for the long‐term safety of JAK inhibitor use in patients with AD, many ongoing clinical trials have promising preliminary results. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic disease centered on tumor necrosis factor (TNF), interleukin (IL)‐23, and IL‐17 axis. While psoriasis patients benefit from biologics targeting TNF, IL‐17s, and IL‐23 nowadays, suppression of these molecules could modulate the balances of immune systems. However, the incidence of autoimmune disease and T‐helper 2 reaction during biologic treatments for psoriasis patients is not well documented. We retrospectively examined antinuclear antibody (ANA), eosinophil counts, and immunoglobulin E (IgE) levels for psoriasis patients who underwent biologic treatments in our dermatology clinic from June 10, 2010 to January 29, 2020. A cumulative total of 199 biologic treatments were performed for a total of 128 psoriasis patients. Compared to the non‐biologic group of 109 psoriasis patients who received non‐biologic treatment, patients treated with infliximab showed more incidents of high ANA (14%, p = 0.039) and high eosinophils (14%, p = 0.021). The use of brodalumab increased incidents of high eosinophils (21%, p = 0.005) but did not affect increase in ANA and IgE. The increase in high IgE level was observed significantly more during the use of risankizumab (15%, p = 0.011). Methotrexate was the most frequently used concomitant systemic treatment, but methotrexate did not affect ANA, eosinophil counts, and IgE levels. Since the biologics for psoriasis treatment modulate the balance of T‐helper cells, careful observation is required to detect unexpected changes of systemic immune conditions under biologic treatments. [ABSTRACT FROM AUTHOR]

Apremilast is an orally available phosphodiesterase 4 inhibitor used for the treatment of moderate to severe psoriasis. The aims of this analysis were to develop a population pharmacokinetic (PPK) model of apremilast based on observed data from phase 1 studies combined with clinical trial data from subjects with moderate to severe psoriasis, and to develop exposure–response (E‐R) models to determine whether Japanese subjects with moderate to severe psoriasis achieve response to apremilast treatment similar to that observed in non‐Japanese, predominantly Caucasian subjects with moderate to severe psoriasis. The PPK model demonstrated that apremilast plasma concentrations and overall apparent clearance rate were comparable between the Japanese and Caucasian subgroups. The E‐R analyses of ≥75% or ≥50% improvement from baseline in Psoriasis Area and Severity Index score and achievement of static Physician Global Assessment score of 0 (clear) or 1 (almost clear) at week 16 indicated that apremilast treatment in Japanese subjects approached the maximal effect with response rates comparable to those in predominantly Caucasian subjects. Overall, the analyses confirm that the approved apremilast 30 mg b.i.d. dose is appropriate for Japanese subjects with moderate to severe psoriasis, with an efficacy profile similar to that previously observed in Caucasian subjects. [ABSTRACT FROM AUTHOR]

Specific studies on apremilast for nail psoriasis are lacking. Our objective was to evaluate the nail‐specific patient‐reported outcomes, clinical efficacy, ultrasound (US) parameters, and safety of apremilast for nail psoriasis. We conducted a prospective cohort study including adult patients with plaque and nail psoriasis with a fingernail Nail Psoriasis Severity Index (NAPSI) score of 12 or more. Patients were treated with apremilast 30 mg b.i.d. for 52 weeks. Forty‐five patients were included. At week 52, the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) Patient Benefit Index global weighted score was 2 or more in 52% of patients and NAPPA Quality of Life and fingernail NAPSI improved by 57% and 53%, respectively. US parameters improved from week 16 onwards. Target nail NAPSI improvements were higher for nail matrix scores (60%) than for nail bed scores (38%, p < 0.001). Baseline target nail bed NAPSI was associated with not achieving a target nail 50% reduction in NAPSI score at week 52 in the bivariate analysis (p = 0.024). Safety was consistent with the known apremilast profile. Results from apremilast therapy for 52 weeks in patients with psoriasis and predominant nail disease show significant improvements in nail‐specific quality of life, clinical signs, and structural restoration on US, suggesting that apremilast may be considered in the treatment of nail psoriasis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is the most common inflammatory skin disease affecting people of all age groups worldwide. To our knowledge, there are currently no studies estimating the effectiveness of tacrolimus ointment and dupilumab as a combination therapy for AD. Thus, here we describe the effectiveness and safety of tacrolimus ointment in combination with dupilumab for facial rashes in patients with AD. Overall, we included 109 patients who newly received dupilumab from April 2018 to July 2020 in the Dermatology Department of Hyogo College of Medicine Hospital. Of them, 60 patients were treated with tacrolimus ointment. Specifically, of the 60 patients, 40 were treated with dupilumab in combination with tacrolimus ointment and topical steroids, whereas the remaining 20 were prescribed tacrolimus ointment alone and were further analyzed. The analysis showed that the combination does not cause serious side‐effects at high frequency. The patients showed rapid improvement of facial dermatitis along with systemic dermatitis, and the rate of improvement of head/neck Eczema Area and Severity Index (EASI) score significantly correlated with the rate of improvement of overall EASI score. In addition, there was no complication of herpes simplex observed in these 20 patients. Thus, tacrolimus ointment combined with dupilumab is an effective and safe treatment option for facial AD. [ABSTRACT FROM AUTHOR]

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol‐induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism‐based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol‐induced leukoderma helps not only elucidate the mechanisms of non‐segmental vitiligo onset and progression, but also suggests prevention and treatment. [ABSTRACT FROM AUTHOR]

Tildrakizumab is a high‐affinity, humanized immunoglobulin G1κ, anti‐interleukin‐23p19 monoclonal antibody recently approved in Japan for treatment of plaque psoriasis. We report results from Japanese patients treated with tildrakizumab in the multinational, randomized, double‐blind, placebo‐controlled reSURFACE 1 study (clinicaltrials.gov NCT01722331). Adults with moderate to severe plaque psoriasis were randomized (2:2:1) to receive subcutaneous tildrakizumab 100 or 200 mg or placebo every 12 weeks. Placebo recipients were rerandomized to tildrakizumab 100 or 200 mg at week 12. The global study coprimary endpoints were the proportions of patients achieving 75% improvement from baseline Psoriasis Area and Severity Index (PASI 75) and Physician Global Assessment (PGA) response (0/1 with ≥2 grade reduction from baseline) at week 12. Analyses included 158 Japanese patients randomized to tildrakizumab 100 (n = 64) or 200 mg (n = 62) or placebo (n = 32). Japanese patients had higher mean baseline body surface area involvement and PASI versus all reSURFACE 1 patients. At week 12, significantly more Japanese patients receiving tildrakizumab 100 and 200 mg versus placebo achieved PASI 75 (54.7% and 54.8% vs 6.3%, respectively, both nominal p < 0.001) and PGA 0/1 response (54.7% and 56.5% vs 9.4%, respectively, both nominal P < 0.001). Response rates increased over time with maximal efficacy after 22‐28 weeks; >80% of patients achieving PASI 75 or PASI 90 at week 28 and continuing tildrakizumab treatment at the same dose maintained response at week 64. From baseline to week 28, absolute PASI decreased from >12 in all patients to ≤2 in >40% and ≤3 in >50% of patients receiving tildrakizumab. Tildrakizumab was generally well tolerated with an adverse event profile similar to that of placebo. Tildrakizumab treatment was associated with durable efficacy in Japanese patients with moderate to severe plaque psoriasis despite greater baseline disease severity versus the global reSURFACE 1 population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Psoriasis, a chronic inflammatory skin disease, negatively impacts patients' quality of life (QoL). This randomized, phase III, double‐blind, placebo‐controlled, multicenter study evaluated the efficacy and safety of brodalumab, a human anti‐interleukin‐17 receptor A monoclonal antibody, in Korean patients with moderate to severe plaque psoriasis. Coprimary end‐points were the percentage of patients with 75% or more improvement in Psoriasis Area and Severity Index (PASI 75) and static Physician's Global Assessment (sPGA) success (score 0/1) at week 12. Secondary end‐points included the percentage improvement from baseline in PASI score and proportion of patients with PASI 50/75/90/100 responses. QoL was assessed with the Dermatology Life Quality Index (DLQI). Eligible patients were randomized to receive brodalumab 210 mg (N = 40) or placebo (N = 22) every 2 weeks (Q2W) at a 2:1 ratio for 12 weeks. Subsequently, all patients entered an open‐label extension phase and received brodalumab 210 mg Q2W until week 62. At week 12, the proportion of patients who achieved the coprimary end‐points, PASI 75 and sPGA success, was significantly higher in the brodalumab 210 mg Q2W group compared with the placebo group (92.5% vs 0%). At week 12, the mean ± SD percentage improvement in the PASI score was 96.87 ± 6.01% in the brodalumab 210 mg Q2W group, which was maintained until study end (week 64). PASI 50/75/90 responses were achieved by 100% of patients receiving brodalumab 210 mg Q2W at weeks 6, 13, and 24, respectively; PASI 100 was achieved by 82.8% of patients at week 64. Brodalumab treatment rapidly improved DLQI scores. The most common treatment‐emergent adverse events were nasopharyngitis, upper respiratory tract infections, tinea pedis, and urticaria. Overall, treatment with brodalumab 210 mg Q2W resulted in a rapid and significant clinical benefit and was well tolerated in patients with moderate to severe plaque psoriasis in Korea. [ABSTRACT FROM AUTHOR]

Psoriasis is a multifactorial recalcitrant inflammatory skin disease characterized by bothersome scaly reddish plaques especially on frequently chafed body parts, such as the extensor sites of the extremities and scalp. Nonetheless, through recent advance in molecular‐targeted therapies including biologics and small‐molecule inhibitors, even the severest symptoms of psoriasis and its comorbidities, such as psoriatic arthritis, can be excellently treated. The superb clinical effects lead to not only remarkable alleviation of symptoms but also a deep understanding of patients' impaired "quality of life" caused by this disease. Along with the development of novel treatment options targeting various specific molecules, such as proinflammatory cytokines and signal transduction‐associated molecules, clinicians have thoroughly understood the molecular mechanism of psoriasis, and discovered that the IL‐23/IL‐17 axis mainly depending on Th17 cell function is a crucial pathogenesis of this disease. Accumulation of knowledge about the working mechanism and clinical effect of molecular‐targeted therapies is indispensable for clinicians to establish a more refined therapeutic strategy for treating psoriasis. [ABSTRACT FROM AUTHOR]

The goal of a treatment regimen for atopic dermatitis is to reach and maintain a state where the patient exhibits mild symptoms or an absence of symptoms, and the patient should not experience disturbance during daily activities. The basis of a treatment regimen for atopic dermatitis is topical therapy, and currently there exist topical corticosteroids, tacrolimus and delgocitinib. Using these, proactive therapy is performed as maintenance therapy after remission induction therapy. However, in cases of moderate to severe atopic dermatitis, topical drugs alone cannot induce remission and systemic therapies such as cyclosporin, ultraviolet therapy, and dupilumab should be used in combination. In particular, dupilumab has many advantages such as high efficacy, relatively few adverse reactions, and ease of use in elderly patients with severe atopic dermatitis. In this review, we present a treatment algorithm for atopic dermatitis that emphasizes the importance of maintaining remission after induction of remission, and summarizes the characteristics of current medication therapy for atopic dermatitis in Japan. [ABSTRACT FROM AUTHOR]

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman's rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis. [ABSTRACT FROM AUTHOR]

Dupilumab shows high efficacy and tolerable safety for the treatment of atopic dermatitis (AD). However, the extent of its effectiveness varies in individual patients. To date, practical predictors of later effectiveness of dupilumab in AD patients have not been reported. To explore practical predictors of later effectiveness of dupilumab in AD, we retrospectively investigated the correlation of baseline demographics and baseline laboratory results with the percentage reduction in Eczema Area and Severity Index (EASI) scores at 1, 3, 6 and 12 months after initiating dupilumab. Furthermore, multiple regression analyses were conducted. Data were collected from patients' charts. Data on 54 Japanese adult patients (43 men and 11 women) with moderate to severe AD were analyzed. Baseline serum lactate dehydrogenase (LDH) level was negatively correlated with the percentage reduction in EASI score at 3, 6 and 12 months after initiating dupilumab but not at 1 month. Multiple regression analyses also revealed that effectiveness of dupilumab at 3 and 6 months was associated with lower baseline serum LDH level. AD patients with allergic diseases tended to have lower percentage reduction in EASI at 1 month, but had higher percentage reduction in EASI in the long term than patients without allergic diseases. In conclusion, higher baseline serum LDH level was associated with poor effectiveness of dupilumab in the long term in patients with AD. Furthermore, it tended to take a longer time for AD patients with allergic diseases to respond to dupilumab, and these patients responded better to dupilumab in the long term than patients without allergic diseases. [ABSTRACT FROM AUTHOR]

Psoriasis is a common inflammatory skin condition, affecting 2–4% of the worldwide population. Psoriasis remains an important public health challenge because there are many clinical forms of psoriasis in particular sites, probably related to the dysregulation of different cytokines. Therefore, there is a continuous need to improve treatment options with mechanisms of action different from those of the currently known therapies. Advances in knowledge of the molecular bases of pathogenesis lead to a better understanding of the disease, thus influencing the development and management of effective treatments. Moreover, data from recent published work indicate that psoriasis coexists with cardiovascular diseases, metabolic syndrome, diabetes mellitus and psychiatric disorders. We present results from our 52‐week open‐label trial in a cohort of psoriatic and psoriatic arthritis patients treated with daily p.o. doses of apremilast 60 mg. We confirmed the efficacy and safety of the drug in favoring the improvement of skin and joint disease as well as the modulation of metabolic biomarkers in diabetic and non‐diabetic psoriatic patients. Apremilast could be used successfully in psoriatic patients affected by cardiometabolic comorbidities, ensuring an improvement in both diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Biologics have been shown to constitute a highly effective treatment for patients with psoriasis. However, a significant number of patients treated with biologics will discontinue them due to loss of efficacy over time, a phenomenon known as biologic fatigue or secondary failure. Combination therapy of biologics with other agents can be considered as a treatment option in such cases. Information regarding the efficacy and safety of adding apremilast to biologic therapy in patients with psoriasis is limited. In the present study, we retrospectively evaluated the efficacy and safety of apremilast combined with biologics in 14 patients with psoriasis showing biologic fatigue at a single hospital. Before the addition of apremilast, the mean Psoriasis Area and Severity Index (PASI) score was 3.2 ± 0.4. At week 24 following the addition of apremilast, the mean PASI score decreased to 1.6 ± 0.3, and four (29%) and seven (50%) patients had achieved 75% and 50% reduction in PASI score, respectively. During the 24 weeks of treatment, diarrhea was observed in four patients, and diarrhea and nausea were observed in one patient. Weight loss of more than 5% bodyweight was observed in two patients. None of the patients discontinued therapy because of these side‐effects. These results suggest that the combination therapy of apremilast and biologics could be a safe, effective option for the management of patients with psoriasis showing biologic fatigue. [ABSTRACT FROM AUTHOR]

This is a Japanese retrospective single‐center study carried out between 1 January 2010 and 21 November 2018 at the Department of Dermatology in Jichi Medical University Hospital. The drug survival rate for six biologic agents used for the treatment of psoriasis was investigated. We reviewed the clinical records of 315 treatment series of 205 patients with moderate to severe psoriasis treated with adalimumab (103 cases), infliximab (70 cases), ustekinumab (66 cases), secukinumab (38 cases), brodalumab (12 cases) and ixekizumab (26 cases). In our study, ustekinumab revealed a trend towards higher drug survival among the six biologic agents. Ustekinumab had a higher drug survival rate than infliximab and secukinumab with significant differences by log–rank test among all patients and among biologic‐naive (bio‐naive) patients. There was no significant difference in drug survival between bio‐naive and biologic‐experienced (non‐naive) patients in the treatment courses with adalimumab, infliximab, ustekinumab, secukinumab and ixekizumab. The dose augmentation therapy in infliximab‐treated patients was associated with longer drug survival. Of all patients, 25 cases with generalized pustular psoriasis (GPP) were included, who functioned as the negative predictor for drug persistence with a hazard ratio of 1.87 (95% confidence interval, 1.12–3.11; P = 0.016). Our results reveal that ustekinumab had a superior drug survival, which is supported by the previous studies. Further studies are needed to clarify the efficacy of biologic agents on patients with GPP. [ABSTRACT FROM AUTHOR]

Psoriasis, though not an immediately life‐threatening disorder, still lowers quality of life and disrupts daily functions. While many treatments for psoriasis exist, few are convenient and safe long term; even if sufficiently effective, treatments themselves often decrease quality of life and make long‐term treatment adherence difficult. Approved in Japan in December 2016, apremilast was expected to function as a simple, long‐term, systemic therapeutic agent for psoriasis. We report on the clinical outcomes of administrating apremilast for 2 years as observed in 46 psoriatic patients at the Saruwatari Dermatology Clinic between March 2017 and February 2019. We believe the ease of clinic consultation (as compared with large general hospital consultation) draws patients who are busy or have mild symptoms, and consequently poor adherence to regular visits and treatment, reflecting realistic conditions. Major adverse events with apremilast treatment were diarrhea (37.0%) and nausea (15.3%), with most cases of diarrhea being mild. Drug survival analysis by the Kaplan–Meier method revealed a 1‐year continuation rate of 46.8% and a 2‐year continuation rate of 37.4%. Dermatology Life Quality Index (DLQI) scores during the observation period declined from 9.3 to 2.8 (P < 0.0001) on average, with the DLQI‐0/1 achievement rate being 28.6%. Based on our findings, we conclude that apremilast is suitable as a long‐lasting basic treatment that is easy to prescribe in small clinics and easy to use in everyday life. [ABSTRACT FROM AUTHOR]

Although biologics for plaque psoriasis brought epoch‐making efficacy, not all patients achieve treatment success with all reagents. The aim of this study was to clarify the correlation between clinical plaque psoriasis subtypes, age at onset, and the efficacy of biologics. Clinical records for patients with plaque psoriasis at Fukuoka University Hospital were reviewed retrospectively. The efficacy of biologics was compared using the survival of the first biologics administered in treatment‐naïve patients. The survival of infliximab, adalimumab, and ustekinumab were followed until December 2016. The patients were clinically classified into three subtypes: small, large, or gigantic plaques using the size of the plaques on the back; early onset psoriasis (EOP, onset <40 years); or late‐onset psoriasis (LOP, ≥40 years). Eighty‐seven patients were enrolled. The survival of biologics was significantly better in large plaques compared with small or gigantic plaques (P = 0.0007). In patients treated with tumor necrosis factor (TNF) inhibitors, large plaques had significantly better survival than did the other types (P = 0.0122), while ustekinumab showed good survival in all three subtypes. The survival of biologics was numerically better in EOP than in LOP, but this was not significant. The efficacy of TNF inhibitors was different among clinical subtypes. Psoriatic patients with small plaques may be less responsive to TNF inhibitors. Further studies are needed. [ABSTRACT FROM AUTHOR]

Systemic treatment options for chronic hand eczema are limited. Dupilumab is used in atopic dermatitis (AD) but is not licensed for (isolated) hand eczema. In this observational prospective study we aimed to determine the response of hand eczema to dupilumab in patients with AD. Adult patients with hand eczema and AD received dupilumab s.c. at a 600 mg loading dose, followed by 300 mg every 2 weeks. Primary outcome was a minimum improvement of 75% on the Hand Eczema Severity Index after 16 weeks (HECSI‐75). Secondary outcomes were severity, measured using the Photographic guide; quality of life improvement as patient‐reported outcome, measured using the Dermatology Life Quality Index (DLQI); and AD severity, measured using the Eczema Area and Severity Index (EASI). Forty‐seven patients were included (32 males; mean age, 45 years). HECSI‐75 was achieved by 28 (60%). Mean HECSI score reduction was 49.2 points (range, 0–164; 95% within‐subject confidence interval, 46.4–52.0), which was already significantly decreased after 4 weeks (P < 0.001). DLQI score mean improvement was 8.8 points (standard deviation [SD], 6.0) or 70.0% decrease (SD, 26.4) (P < 0.001). Eighteen patients (38%) were classified as responders on the Photographic guide. There was no difference in response between chronic fissured and recurrent vesicular clinical subtypes. Similar percentages of patients achieving EASI‐75 and HECSI‐75 were seen after 16 weeks. In conclusion, this study shows a favorable response of hand eczema to dupilumab in patients with AD. This raises the question whether a response will also be seen in isolated hand eczema. [ABSTRACT FROM AUTHOR]

Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, selectively inhibits interleukin‐23, a key cytokine in the pathogenesis of psoriasis, by binding to its p19 subunit. In SustaIMM (ClinicalTrials.gov/NCT03000075), a phase 2/3, double‐blinded, placebo‐controlled study, Japanese patients with moderate to severe plaque psoriasis (n = 171) were stratified by bodyweight and concomitant psoriatic arthritis and randomized 2:2:1:1 to 75 mg risankizumab, 150 mg risankizumab, placebo with cross‐over to 75 mg risankizumab and placebo with cross‐over to 150 mg risankizumab. Dosing was at weeks 0, 4, 16, 28 and 40, with placebo cross‐over to risankizumab at week 16. The primary end‐point was 90% or more improvement from baseline in Psoriasis Area and Severity Index (PASI‐90) at week 16 for risankizumab versus placebo. Missing data were imputed as non‐response. All primary and psoriasis‐related secondary end‐points were met for both risankizumab doses (P < 0.001). At week 16, PASI‐90 responses were significantly higher in patients receiving 75 mg (76%) or 150 mg (75%) risankizumab versus placebo (2%). Corresponding response rates were 86%, 93% and 10% for static Physician Global Assessment (sPGA) score of clear/almost clear; 90%, 95% and 9% for PASI‐75; and 22%, 33% and 0% for PASI‐100, with significantly higher responses for both risankizumab doses versus placebo. Through week 52, PASI and sPGA responses increased or were maintained and treatment‐emergent adverse events were comparable across treatment groups. Both doses of risankizumab were superior to placebo in treating patients with moderate to severe plaque psoriasis. The safety profile was consistent with previous risankizumab trials, with no new or unexpected safety findings. [ABSTRACT FROM AUTHOR]

Biologics are efficacious for treating psoriasis vulgaris (PsV) and psoriatic arthritis (PsA), but sometimes must be terminated or changed for various reasons including ineffectiveness or adverse events. To find the optimal choice of biologics for treating psoriasis, we analyzed the real‐world data on drug survival and the reason for terminating or switching biologics. Medical records from patients with PsV or PsA, who visited the Department of Dermatology, Fukuoka University Hospital from 2010 to 2017, were analyzed. Two hundred and eleven patients received biologics, and 147 patients (69.7%) were treated with only one biologic, while 64 patients (30.3%) were switched to different products. Frequently used biologics in PsV were ustekinumab (UST), infliximab and adalimumab when calculated by patient‐year. Tumor necrosis factor inhibitor (TNFi) use decreased while UST and interleukin (IL)‐17 inhibitors increased in newly introduced patients. UST showed the highest survival rate as a first‐line drug, but the advantage was lost in the second reagent's group. The major reasons for terminating/switching biologics were as follows: primary ineffectiveness (26.4%), secondary loss of efficacy (36.5%), patient's preference, including referral to nearby hospital, or stopped visiting (22.6%), side‐effects (7.7%), comorbidities (3.4%) and economic burden (2.4%). In PsA patients, TNFi are more frequently employed than in PsV patients, although switching to UST or IL‐17 inhibitors showed an increasing trend. Biologic reagents were changed mostly because of primary or secondary loss of efficacy, which affected drug survival. Further research is needed to find the optimal choice of biologics with larger samples at multiple facilities. [ABSTRACT FROM AUTHOR]

Apremilast is a novel oral phosphodiesterase 4 inhibitor effective for psoriasis. It regulates the production of pro‐inflammatory mediators. Apremilast was approved in December 2016 in Japan; however, its efficacy and safety in a real‐world setting among Japanese patients have not been reported. We report on 44 patients treated with apremilast between March and October 2017. The median treatment duration was 25 weeks (range, 2–33). Thirty‐five patients (79.5%) continued the drug for at least 23 weeks, and five (11.4%) achieved a Psoriasis Area and Severity Index 100 response within 12 weeks. Nine patients discontinued the drug within 24 weeks mainly due to insufficient efficacy (n = 3) and adverse events (n = 4). Seven patients continued their previous systemic therapies such as cyclosporin (n = 1), methotrexate (n = 1), etretinate + methotrexate (n = 1) and biologics (n = 4) combined with apremilast. Of these patients, 55.9% had at least one adverse event although no severe adverse events. The most common adverse event was diarrhea (31.8%), followed by nausea (25.0%), headache (13.6%), abdominal discomfort (6.8%) and vomiting (6.8%). The proportion of diarrhea in our patients was higher than those of previous clinical trials. Among 10 patients with psoriatic arthritis, apremilast did not improve joint pain in nine (90%). To investigate the relationship between treatment efficacy and plaque size, we defined a small plaque as an individual rash diameter of 1 inch or less. The efficacy of apremilast was greater in patients with small plaques than in patients with large plaques. [ABSTRACT FROM AUTHOR]

Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leukocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leukocytes. Reports on the clinical efficacy of GMA in patients with skin lesions have appeared in the published work. Dermatological diseases, which are known to respond to GMA, include pyoderma gangrenosum, skin lesions of Behcçet's disease, rheumatoid arthritis, pustular psoriasis, psoriatic arthritis, adult-onset Still's disease, Sweet's syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus rashes. In association with clinical studies, efforts to understand the mechanisms of GMA have made significant progress. GMA selectively depletes elevated myeloid lineage leukocytes through binding between blood immunoglobulin G or complement iC3b, which form on the surface of CA beads and the Fcγ receptors or complement receptors expressed on the myeloid lineage cells. However, GMA has immunomodulatory effects including down-modulation of inflammatory cytokine profile, changes in leukocyte surface receptors and induction of regulatory T cells. These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations. [ABSTRACT FROM AUTHOR]

Abstract: A working group of dermatologists in Asian countries assessed the current status of psoriatic management in the region to prepare a consensus report on topical treatment in mild to moderate plaque psoriasis. Even though the association of psoriasis with systemic comorbidities is increasingly acknowledged, psoriasis is still lower in health‐care priority lists in the region. The psychosocial impact of psoriasis may be greater in Asian countries due to cultural norms and social discrimination. Non‐adherence to treatment is also common among Asians. The current care given to patients with mild to moderate psoriasis needs to be streamlined, enhanced and organized with a patient‐centered care approach to achieve better outcomes. A comprehensive assessment of the disease severity and its impact on a patient's life is required before initiating treatment. Education and active involvement of the patient in the treatment plan is an important part of psoriatic management. It is recommended to personalize topical treatment to meet the needs of the patient, depending on disease severity, psychosocial impact, the patient's expectations and, more importantly, the patient's willingness and ability to actively follow the treatment procedure. Fixed‐dose combination of corticosteroid and vitamin D analogs is the preferred topical medication for both initial and maintenance phases of treatment. The fast containment of the disease is the goal of the initial phase of 4–8 weeks and it demands a potent fast‐acting topical therapy. Satisfactory control of the disease and prevention of relapses should be achieved during the maintenance phase with twice a week or weekend applications. [ABSTRACT FROM AUTHOR]

Abstract: Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side‐effects of biologics, dose‐reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation‐regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI‐clear with biologics than in the group which did not achieve PASI‐clear. Among biologics, the group treated with secukinumab, an anti‐interleukin (IL)‐17A agent, showed significantly higher TARC level compared with the group treated with anti‐tumor necrosis factor agents. In certain populations achieving PASI‐clear, serum TARC level may be a potent marker reflecting better response to IL‐17A inhibitors, and in this case step down of treatment for psoriasis is possible. [ABSTRACT FROM AUTHOR]

Abstract: The advent of biologics brought a paradigm shift in ways to treat psoriatic patients because they have dramatic efficacy. At the same time, safety concerns about biologics have been raised. In this paper, we focus on the safety profile of biologics for psoriasis. As of 2017, six biologics are available in Japan. Two tumor necrosis factor‐α inhibitors; infliximab and adalimumab, one anti‐interleukin (IL)‐12/23p40 antibody; ustekinumab, and IL‐17 inhibitors; secukinumab, ixekizumab and brodalumab. Secukinumab and ixekizumab are anti‐IL‐17A antibodies. Brodalumab is an anti‐IL17RA antibody. In this review, we pick up topics which have drawn attention regarding the safety of biologics and discuss them with recent published work. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA), a chronic inflammatory arthropathy associated with psoriasis, is an intractable immune disorder and refractory to pharmacological intervention. We assessed efficacy of selective depletion of myeloid lineage leukocytes in patients with PsA in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were included. Eligible patients had 3 points or more in the classification criteria for PsA. Each patient received five sessions, once a week, of adsorptive granulocyte and monocyte apheresis ( GMA) with the Adacolumn®. The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 ( ACR20). Partial responders could receive an additional five GMA sessions. Of 20 patients, two did not complete the study, nine responded to five GMA sessions and nine received 10 sessions. At the first evaluation 2 weeks after the last GMA session, 13 of the 20 (65.0%) patients achieved ACR20. ACR20 was maintained in seven of 10 (70%) and five of 10 (50%) patients at the follow-up evaluation points 8 and 20 weeks after the last GMA session, respectively. GMA was well tolerated without any safety concern. This study demonstrates that GMA with the Adacolumn was effective with good safety profile in patients with PsA refractory to pharmacologicals. The results indicate a major role for myeloid leukocytes in the immunopathogenesis of PsA. A large controlled study is warranted to fully evaluate the efficacy of Adacolumn GMA in patients with PsA. [ABSTRACT FROM AUTHOR]

Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score ( PASI-75; primary) and achievement of static Physician Global Assessment ( sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events ( AEs) with placebo, apremilast 20 and apremilast 30 (0-16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies. [ABSTRACT FROM AUTHOR]

Apremilast is a novel oral phosphodiesterase‐4 inhibitor approved for treatment of plaque psoriasis and psoriatic arthritis in Japan in December 2016. We have treated a substantial number of patients with psoriasis with apremilast and investigated the length of the treatment period with apremilast (drug survival of apremilast) in 138 patients with psoriasis who were treated at the Department of Dermatology in Jichi Medical University Hospital from 1 March 2017 to 31 August 2018 using the Kaplan–Meier survival curve. The drug survival rate of apremilast at 1 year was 53.4%. The median length of the drug survival period was 453 days. There were no statistical differences in the drug survival rate in terms of the type of psoriasis, previous systemic treatment or presence of one or more adverse events. Drug efficacy was investigated in 115 patients who were followed for more than 16 weeks. There was no correlation between drug efficacy and sex, previous systemic treatment or presence of one or more adverse events; however, there was a correlation between drug efficacy and plaque size (P < 0.01, rs = −0.29). The result of our study indicates that apremilast is effective regardless of the history of prior systemic treatment, and it supports our previous finding that small plaque‐type psoriasis is more sensitive to treatment with apremilast. [ABSTRACT FROM AUTHOR]