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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. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00645-2.

Dupilumab demonstrated high efficacy and tolerable safety profiles in moderate‐to‐severe atopic dermatitis (AD) patients in clinical trials; however, certain patients suffer from facial redness, while obtaining good responses on the trunk and limbs to dupilumab in the real‐world setting. In our study, we investigated the effectiveness of tacrolimus ointment on facial lesions refractory to topical corticosteroid in patients with AD receiving dupilumab. This study included Japanese adult patients with moderate‐to‐severe AD who developed facial lesions during dupilumab treatment and whose facial lesions became refractory to topical corticosteroid treatment. Nine patients (one female, eight males) were included in this study. One patient newly developed facial erythema after initiating dupilumab. Facial lesions were refractory to dupilumab treatment in the other patients. Five of the nine patients showed improvement in EASI scores of head and neck by switching the facial treatment from topical corticosteroid to tacrolimus ointment. The patient who developed newly facial erythema showed improvement after applying tacrolimus ointment. Although we explored the predictors of effectiveness of tacrolimus ointment in patients with facial lesions during dupilumab treatment, no significant differences were observed in age, duration of dupilumab prior treatment, or prior head and neck EASI between patients who showed improvement after changing to tacrolimus and those who did not. Tacrolimus ointment is worth trying if facial lesions are refractory to topical corticosteroid.

Background Psoriasis is a chronic inflammatory skin disease. Interleukin (IL)-17A plays a key role in the pathogenesis of psoriasis. Fingolimod, which is available for the treatment of multiple sclerosis, exerts anti-inflammatory effects by sequestrating inflammatory lymphocytes in secondary lymphoid tissues and the thymus. The effect of fingolimod on psoriasis has not been reported yet. Objective Our objectives were to investigate the effect of fingolimod on psoriasis utilizing mice with imiquimod (IMQ)-induced psoriasiform dermatitis, and explore the possibility of fingolimod as a therapeutic agent for psoriasis. Methods Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Fingolimod prepared in phosphate-buffered saline (PBS), or PBS alone as a control, was administered intraperitoneally daily from days 0 to 5. Results Fingolimod ameliorated IMQ-induced psoriasis dermatitis clinically and histologically. On day 6, the mRNA expression level of IL-17A was lower in the skin of fingolimod-treated mice than in that of PBS-treated mice, whereas it was higher in the inguinal lymph nodes of fingolimod-treated mice than in those of PBS-treated mice. Flow cytometric analyses revealed that fingolimod reduced IL-17A-producing ?d T cells infiltrating into the skin, whereas it increased these cells in the inguinal lymph nodes. Fingolimod inhibited egress of Langerhans cells from the skin to lymph nodes. Conclusion Our results demonstrated that fingolimod showed effectiveness for IMQ-induced psoriasiform dermatitis by hindering the emigration of IL-17A-producing ?d T cells from the lymph nodes to the skin, and suggest that fingolimod is a promising candidate for the treatment of psoriasis.

Background A wide gender gap exists in many fields in Japan, including the academic society of dermatology. Women are substantially underrepresented in the highest academic ranks. Objective We aimed to clarify the possible factors contributing to the current gender gap in the field of academic dermatology and to recommend necessary measures to decrease the gender gap. Methods We performed a cross-sectional study of faculty members’ academic productivity at the dermatology departments of all the educational institutions in Japan in 2019. Results Women had significantly lower academic productivity than men. A significant gender difference in academic productivity was found in lecturers and assistant professors but not in associate professor and professor positions. This gender difference was still significant after normalizing the productivity for career length. Conclusion Our findings suggest the need to encourage women lecturers and assistant professors to improve their academic achievement to decrease the gender gap in academic dermatology.

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

Herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus (VZV) in the cranial nerve or dorsal root ganglia, with spread of the virus along the sensory nerve to the dermatome. Postherpetic neuralgia is a feared complication of HZ and impairs patients' quality of life enormously. However, there is no predictor of the duration of neuralgia. Our objective was to investigate whether there are correlations between the duration of neuralgia and serum levels of potential biomarkers in order to find practical predictors of the duration of neuralgia. Patients who were diagnosed with HZ at our hospital from April 2013 to January 2014 were included in this study. Serum levels of cytokines and other biomarkers were measured using commercial enzyme-linked immunosorbent assay kits. Thirty patients (15 men and 15 women) with HZ were enrolled in this study. The mean age was 66.1 ± 9.2 (standard deviation) years (range, 51-84 years). Four patients were evaluated as having mild, 19 as having moderate, and seven as having severe HZ. Patients with severe HZ suffered from neuralgia for a significantly longer period of time than patients with mild-to-moderate HZ (9.86 ± 8.25 months vs. 2.01 ± 2.68 months, severe vs. mild-to-moderate, p = 0.0021). The serum interleukin (IL)-10 level was significantly higher in patients with severe HZ than in those with mild-to-moderate HZ (12.93 ± 3.27 pg/mL vs. 6.74 ± 3.72 pg/mL; severe vs. mild-to-moderate; p = 0.0487). Furthermore, the serum IL-10 level was significantly correlated with the duration of neuralgia (r = 0.5193, p = 0.0111). Lastly, the serum IL-10 level significantly decreased after treatment in comparison with that before treatment (from 8.15 ± 4.46 pg/mL to 4.32 ± 11.83 pg/mL, p < 0.0001). In conclusion, these results suggest that the serum IL-10 level is an objective biomarker of the severity of HZ, and that the serum IL-10 level can be a practical predictor of the duration of neuralgia.

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 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.

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.

Thymus and activation-regulated chemokine (TARC) is designated as a T-helper 2-type chemokine and its expression is upregulated in patients with atopic dermatitis. Previous studies reported that serum TARC levels in patients with psoriasis vulgaris (PsV) were comparable with those in healthy controls. However, the association of clinical severity of psoriasis with serum TARC levels and serum TARC levels in patients with psoriatic arthritis (PsA) or generalized pustular psoriasis (GPP) have never been reported. We investigated the association of serum TARC level with psoriasis by the type of psoriasis, and examine correlations of serum TARC levels with clinical severity scores and other results of blood tests. Data on 75 patients (51 men and 24 women; PsV, 30 patients; PsA, 29 patients; GPP, 16 patients) were analyzed. The serum TARC level was significantly higher in patients with GPP than in patients with PsV and patients with PsA. There was a positive correlation between serum TARC level and Psoriasis Area and Severity Index score (r = 0.3499, P = 0.0030). The serum TARC levels decreased after treatment in GPP patients. Our study revealed that the serum TARC level can potentially be one of the biomarkers reflecting the severity or systemic inflammation caused by psoriasis in patients with psoriasis, although not as much as in patients with atopic dermatitis. Furthermore, serum TARC levels were high in patients with GPP. Those were decreased by treatment, suggesting that serum TARC levels could be utilized as an objective biomarker to evaluate a therapeutic effect in individual GPP patients. Further accumulation of cases and further research are needed to elucidate the role of TARC in psoriasis.

Background The metastatic involvement of regional lymph nodes is the most important prognostic factor for overall survival of skin cancer patients. The sonographic technique of freehand real-time tissue elastography (RTE), which displays tissue rigidity as a colour overlay of the tissue image, was developed. Objective Our purpose was to evaluate the benefit of RTE for detecting lymph node metastases of skin cancer non-invasively before operation. Methods We first selected lymph nodes of skin cancer patients which had already been diagnosed by biopsy as being reactive or metastatic, and then retrospectively collected images of RTE and B-mode and colour Doppler ultrasound on those lymph nodes performed preoperatively. Twenty-one lymph nodes from 12 patients with squamous cell carcinoma (SCC), 23 lymph nodes from 14 patients with malignant melanoma (MM) and 14 lymph nodes from six patients with extramammary Paget disease (Paget) were investigated. Elastographic images were assessed on a scale of one to four according to the percentage of high elasticity (hard) area (HEA) in the lymph node. Results In all three skin cancers, lymph nodes evaluated as grade 3 or 4 by RTE were metastatic. All lymph nodes evaluated as grade 1 or 2 by RTE were reactive in SCC, whereas some lymph nodes evaluated as grade 1 or 2 were metastatic in MM and Paget. Conclusion Real-time tissue elastography may aid in distinguishing reactive lymph nodes from metastatic ones especially in SCC.

This case report describes a 44‐year‐old male patient with atopic dermatitis who developed malignant lymphoma (diffuse large B‐cell lymphoma) during the dupilumab treatment.

is missing (Short communication)

The combination of BRAF inhibitor and MEK inhibitor is one of the first-line treatments for unresectable BRAF-mutant melanoma or as an adjuvant therapy. However, some patients who received the combination of dabrafenib and trametinib (CombiDT) or the combination of encorafenib and binimetinib (CombiEB) had adverse events (AEs) including pyrexia. We herein report a patient with BRAF-mutated melanoma who repeatedly developed elevated levels of D-dimer and pyrexia after CombiDT and CombiEB treatments. Moreover, concomitant edoxaban prevented these AEs, enabling the patient to continue receiving CombiEB.

Studies on the psychosocial and emotional burden of psoriasis have been extensive; however, there is limited knowledge and awareness of patients' attitude and behavior towards psoriasis treatment. To understand psoriasis patients' attitude and behavior towards treatment of psoriasis, especially those treated with biologics, a multi-stage study qualitative and quantitative methodology was conducted among psoriasis patients. An online survey was conducted with 45 moderate-to-severe psoriasis patients each in Australia, Japan, South Korea, and Taiwan for 20 min. This was followed by qualitative in-depth interviews conducted among psoriasis patients in Australia (n = 3) and Japan (n = 2) for 60 min. All of the findings were workshopped with key opinion leaders and patient advisory groups to identify potential solutions addressing patients' unmet needs. Five common insights were identified across the region, highlighting patients' attitude and behavior towards psoriasis treatment, especially for those treated with biologics. These insights comprised the following: (i) one of the key factors driving patients' treatment choice included their ability to enjoy clear skin for longer period (68%); (ii) bio-maintenance patients had a higher expectation (4.9 months) of how long their skin could stay clear, compared to their pre-biologics initiation days (2.9 months); (iii) once a good response is achieved, bio-maintenance patients were more concerned about symptoms returning (44%) than development of side-effects (19%); (iv) bio-maintenance patients felt psychologically and physically affected during flare-ups despite being on more efficacious treatment; and (v) bio-maintenance patients still felt they were at risk of flare-ups (4.5/7), almost similar risk perception as non-biologics patients (4.9/7). Findings from this study showed that psoriasis patients look for treatment with the least risk of flare-ups so that they were able to enjoy clear skin for a long time.

Background Psoriasis is a chronic inflammatory skin disease. Anti-TNFα, IL-17A and IL-23p19 antibodies are effective for psoriasis. However, the contribution of regulatory T cells (Treg) in their effectiveness remains to be elucidated. Objective We investigated the effects of TNFα, IL-17A and IL-23p19 inhibition on Tregs in imiquimod-induced psoriasiform dermatitis. Methods Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Mice were treated with anti-TNFα, IL-17A or IL-23p19 monoclonal antibodies every other day from one day before imiquimod application. Results Administration of anti-TNFα, IL-17A or IL-23p19 antibodies improved the clinical score and downregulated Th17-related cytokines and chemokines, while IL-23p19 antibodies upregulated IL-10 mRNA expression. Anti-IL-17A or IL-23p19 antibody-treated imiquimod-applied mice showed a significant increase in the number of Foxp3+ IL-10+ Tregs. Recipient mice adoptively transferred with Tregs derived from donor mice treated with antibodies demonstrated clinical and pathological improvement in imiquimod-induced psoriasiform dermatitis. Anti-IL-17A or IL-23p19 antibody-induced Tregs significantly increased the number of Foxp3+ cells and IL-10 expression in imiquimod-induced psoriasiform dermatitis in recipient mice but anti-TNFα antibody-induced Tregs did not. Conclusion Anti-IL-17A or IL-23p19 antibody inhibits the IL-17/IL-23 signaling pathway, and induces expansion of Tregs and their suppressive capacity in imiquimod-induced psoriasiform dermatitis.

Background: The impact of treatment with interleukin 17 (IL-17) inhibitors on the efficacy of subsequent IL-17 inhibitor therapy is unknown. Objective: To evaluate the impact of previous treatment with IL-17 inhibitors on the 52-week efficacy of ixekizumab in patients with moderate-to-severe psoriasis. Methods: In a phase 3, randomized, double-blinded trial (IXORA-P; NCT02513550), patients with moderate-to-severe plaque psoriasis were randomized (2:1:1) to ixekizumab 80 mg every 2 weeks (IXE Q2W, n = 611), every 4 weeks (IXE Q4W, n = 310), or IXE Q4W/IXE Q2W dose adjustment (per predefined criteria; n = 306). Psoriasis Area and Severity Index 75%, 90%, and 100% response rates (PASI 75, PASI 90, and PASI 100) were assessed. Results: Overall, 288 (23.5%) of 1227 patients were IL-17 inhibitor experienced (brodalumab, 22.6%; secukinumab, 1.1%). The PASI 75, 90, and 100 at week 52 were similar between IL-17 inhibitor-naive and IL-17 inhibitor-experienced patients. The PASI 75 at week 52 for IL-17 inhibitor-naive and -experienced patients was 85% and 89% (IXE Q2W), 79% and 81% (IXE Q4W), and 83% and 85% (IXE Q4W/IXE Q2W), respectively. The PASI 90 at week 52 for IL-17 inhibitor-naive and -experienced patients was 79% and 82% (IXE Q2W), 65% and 67% (IXE Q4W), and 73% and 75% (IXE Q4W/IXE Q2W), respectively. The PASI 100 at week 52 for IL-17 inhibitor-naive and -experienced patients was 60% and 59% (IXE Q2W), 44% and 42% (IXE Q4W), and 49% and 52% (IXE Q4W/IXE Q2W), respectively. Safety findings were generally similar between IL-17 inhibitor-naive and -experienced patients. Conclusion: Ixekizumab was demonstrated to be an effective and safe therapeutic option for patients previously treated with other IL-17 inhibitors.

Psoriasis is a chronic autoimmune disease affecting skin which may also manifest in nails and joints. Several biologic treatments have been approved in Japan for psoriasis. Each biologic has a different profile for efficacy and safety, including different dosing regimens and co‐payment considerations which may complicate treatment decisions made by patients and physicians during short consultations. Elucidating patient preference is expected to contribute to shared decision‐making between patients and physicians to optimize treatment satisfaction and outcomes. However, the number of studies investigating this in Japan is very limited. The study used a discrete choice experiment methodology to elicit patient preferences for hypothetical options in an experimental framework. Participants were asked to choose their preferred treatment option from two hypothetical choices, defined by different levels of six attributes (i.e. early onset of efficacy, long‐term efficacy, sustained efficacy after drug withdrawal, dosing convenience, co‐payment and risk of serious infection). The survey included 16 treatment choice scenarios and was completed by 395 participants. Across all participants, the attribute regarded as most important was sustained efficacy after drug withdrawal, followed by dosing convenience, co‐payment, long‐term efficacy, early onset of efficacy and risk of serious infection. The study found that patients prefer treatments which have durable efficacy and lower treatment burden characterized as fewer injection frequency and lower co‐payment. These results may be helpful to understand patient preference for biologic treatments used for psoriasis in Japan and contribute to shared decision‐making between patients and physicians to improve patient satisfaction and treatment outcomes.

Background Apremilast, a selective inhibitor of the enzyme phosphodiesterase 4, is efficacious for psoriasis. However, detailed in vivo effects of apremilast on psoriasis remain to be elucidated. Objective To examine the in vivo effects of apremilast on psoriasis. Methods Psoriasiform dermatitis was induced by applying imiquimod (IMQ) on the murine shaved back skin for six days. Mice were treated with apremilast or vehicle intraperitoneally daily. Results Apremilast alleviated IMQ-induced psoriasiform dermatitis clinically and pathologically on days 3–6 by reducing infiltration of antigen-presenting cells and interleukin (IL)-17A-positive cells and increasing infiltration of Foxp3-postive cells into the skin on day 6, although a significant increase in IL-10 mRNA level was not observed on day 2. In addition, mRNA expression of IL-17A, IL-17F, and IL-22 was lower in the skin of IMQ-applied mice treated with apremilast than in those without apremilast on day 2, and apremilast inhibited infiltration of IL-17A-producing γδ T cells into the dermis on day 6. Furthermore, apremilast induced regulatory T cells and regulatory B cells in the spleen but not in the draining lymph nodes. Conclusion Apremilast downregulated IL-17 production and induced splenic regulatory B cells and regulatory T cells in an IMQ-induced psoriasiform dermatitis mouse model.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00520-0.

Topical therapy is the mainstay of treatment for the majority of patients with psoriasis vulgaris (chronic plaque psoriasis), with combinations of vitamin D analogues and glucocorticoids having been shown to negate many of the negative effects associated with either monocomponent individually. Following the established efficacy of fixed‐dose combination calcipotriol (Cal; 50 µg/g) plus betamethasone dipropionate (BD; 0.5 mg/g) ointment and gel formulations, a novel Cal/BD foam formulation was developed. When applied, Cal/BD foam forms a supersaturated solution on the skin, increasing the penetration and bioavailability of Cal and BD. Early data indicate that this results in improved efficacy outcomes versus Cal/BD ointment, without negatively affecting safety outcomes (such as the incidence/severity of side effects or impacted calcium homeostasis or hypothalamic‐pituitary‐adrenal axis). This article discusses the potency and absorption of fixed‐dose combination Cal/BD foam, as well as the positive early efficacy and safety data associated with its utilisation in the treatment of psoriasis vulgaris., Video abstract

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.

Psoriasis is a chronic inflammatory skin disease characterized by scaly indurated erythema. It impairs patients’ quality of life enormously. It has been recognized not only as a skin disease but as a systemic disease, since it also causes arthritis (psoriatic arthritis) and mental disorders. Furthermore, an association with cardiovascular events is indicated. With the advent of biologics, treatment of psoriasis dramatically changed due to its high efficacy and tolerable safety. A variety of biologic agents are available for the treatment of psoriasis nowadays. However, characteristics such as rapidity of onset, long-term efficacy, safety profile, and effects on comorbidities are different. Better understanding of those characteristic leads to the right choice for individual patients, resulting in higher persistence, longer drug survival, higher patient satisfaction, and minimizing the disease impact of psoriasis. In this paper, we focus on the efficacy and safety profile of biologics in psoriasis patients, including plaque psoriasis and psoriatic arthritis. In addition, we discuss the impact of biologics on comorbidities caused by psoriasis.

Background Psoriasis is a Th1/Th17-mediated inflammatory dermatosis treated with topical corticosteroids and vitamin D3 analogs (VD3 As). Objective To compare the effects of a VD3 A maxacalcitol and betamethasone valerate (BV) steroid lotion on topical imiquimod (IMQ)-induced psoriasiform skin inflammation. Methods Female BALB/c mice were treated with vehicle, maxacalcitol or BV lotion on the skin for 3 days, and IMQ cream for 6 days. q-PCR, H&E, immunohistochemistry and immunofluorescence studies were performed on skin samples. Additionally, mice were treated with vehicle, maxacalcitol or BV lotion for 3 days and CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− cells from each group were isolated from lymph nodes. Adoptive transfer of the cells was performed on recipient mice which were treated with IMQ cream for 6 days, and skin samples were obtained for q-PCR and H&E staining. Results Maxacalcitol and BV were comparable in regards clinical improvement, although maxacalcitol reduced the MHC Class II+ inflammatory cell infiltration more than BV in IMQ skin. While both treatments downregulated IL-17 A, IL-17 F, IL-22, IL-12p40, TNF-α and IL-6 mRNA expression levels, only maxacalcitol downregulated IL-23p19 expression. Significantly increased Foxp3+ cell infiltrations and IL-10 expression were noted in maxacalcitol-treated IMQ skin. Adoptive transfer of Treg cells from maxacalcitol-treated donor mice improved IMQ-induced inflammation clinically and histopathologically more than the recipients of Treg cells from BV-treated donor groups, showing reduced levels of inflammatory cytokines and increased IL-10 expression. Conclusion These results indicate that maxacalcitol reduces psoriasiform skin inflammation by inducing Treg cells as well as downregulating IL-23 and IL-17 production.

Rhododendrol (RD), 4‐(4‐hydroxyphenyl)‐2‐butanol, inhibits melanin synthesis and had been used in skin‐whitening cosmetic products until 2013. However, some individuals developed leukoderma on the skin where RD had been applied and have suffered from refractory depigmentation even after discontinuing RD application. Bimatoprost is a prostaglandin F2α analog and is often used for eyelash growth for cosmetic reasons as well as in the treatment of glaucoma. It was reported that bimatoprost induced skin pigmentation in addition to iris pigmentation as adverse effects. Therefore, we conducted an open‐label single‐center pilot study to evaluate the effectiveness of bimatoprost on refractory RD‐induced leukoderma. Eleven Japanese female patients with skin type III who developed leukoderma on the exact or slightly extended area of skin where RD had been applied and gained a halt of enlargement of leukoderma or repigmentation on a part of the affected skin after discontinuation of RD were enrolled. Bimatoprost 0.03% solution was applied on the leukoderma once daily for 3 months, and then the frequency of application was increased to twice daily for the subsequent 3 months. Ten patients completed the 6‐month course of bimatoprost application. In four patients, bimatoprost application brought slight improvement in RD‐induced refractory leukoderma by dermatologists’ evaluation. Because the number of enrolled patients was limited, further larger studies are necessary to better assess the effectiveness of bimatoprost in inducing repigmentation in patients with RD‐induced refractory leukoderma.

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.

Bullous pemphigoid (BP) is an acquired autoimmune blistering disease in which autoantibodies against epitopes in the basement membrane zone of the skin such as BP180 or BP230 are produced. Dipeptidyl peptidase (DPP)-4 inhibitors have become commonly used to treat diabetes. As DPP-4 inhibitors are more commonly prescribed for diabetes, BP related to DPP-4 inhibitors has been reported and has attracted attention. Therefore, we retrospectively investigated patients who were diagnosed with BP in order to examine characteristics of DPP-4 inhibitor-related BP (nine patients; median age, 85 years) in comparison with non-DPP-4 inhibitor-related BP (21; median age, 85 years). There was no significant difference in Bullous Pemphigoid Disease Area Index between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients, except for erosions/blisters score in mucosa. Laboratory tests revealed no significant differences between DPP-4 inhibitor-related BP patients and non-DPP-4 inhibitor-related BP patients in total white blood cell count, eosinophil count, neutrophil count and the titer of anti-BP180 antibody. The number of eosinophils infiltrating into the skin was significantly lower in patients with DPP4 inhibitor-related BP than in patients with non-DPP4 inhibitor-related BP. Our results showed that DPP-4 inhibitor-related BP has some distinct pathological characteristics from BP not associated with DPP-4 inhibitor.

Systemic plasmacytosis is a rare skin disorder characterized by marked infiltration of plasma cells in the dermis. IgG4-related disease is pathologically characterized by lymphoplasmacytic infiltration rich in IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis, accompanied by elevated levels of serum IgG4. Reports of cases of systemic plasmacytosis with abundant infiltration of IgG4+ plasma cells has led to discussion about the relationship between systemic plasmacytosis and IgG4-related disease. This study examined IgG4+/IgG+ plasma cell ratios in 4 patients with systemic plasmacytosis and 12 patients with other skin diseases that show marked infiltration of plasma cells. Furthermore, we examined whether these cases met one of the pathological diagnostic criteria for IgG4-related disease (i.e. IgG4+/IgG plasma cells ratio of over 40%). Only one out of 4 patients with systemic plasmacytosis met the criterion. These results suggest that systemic plasmacytosis and IgG4-related disease are distinct diseases.

There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate‐to‐severe psoriasis. In this multicenter, open‐label, phase IV study, 34 patients with moderate‐to‐severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end‐point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end‐point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy.

Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that presents with erythema and sterile pustules, pathologically characterized by Kogoj's spongiform pustules. GPP is sometimes accompanied by mucosal involvement, and the most common lesion is on the tongue. IL36RN mutation was found to contribute to the pathogenesis of GPP especially in patients who develop GPP without a past medical history of psoriasis vulgaris. The association of IL36RN mutation with mucosal involvement in GPP is controversial. We herein report a 60-year-old male GPP patient with no past history of plaque psoriasis presenting with not only severe skin lesions and arthritis but also severe mucosal involvements of pharyngeal and gastrointestinal lesions, which led to gastrointestinal bleeding. Our case did not have any mutation in the IL36RN gene. We should be aware that severe GPP can cause gastrointestinal bleeding. The relevancy of IL36RN mutation with mucosal involvement in GPP remains to be elucidated.

summary Conjunctivitis in patients with atopic dermatitis treated with dupilumab is associated with baseline serum levels of IgE and TARC but not subjective severity scores in a real-world setting. These objective parameters are useful as practical predictors of later development of conjunctivitis.

Background Complete lesion clearance is important to patients with psoriasis. Objective To conduct a network meta-analysis of randomized controlled trials of biologic agents available for psoriasis in Japan, using mixed-treatment comparisons. Methods MEDLINE and EMBASE were searched to identify randomized clinical trials (placebo-controlled or head-to-head) of infliximab, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, risankizumab or guselkumab in adult patients with moderate-to-severe plaque psoriasis published in English between 01 January 2000 and 31 August 2019. We assessed the proportion of patients who achieved a 100 %, 90 % and 75 % reduction in their Psoriasis Area and Severity Index (PASI) score (PASI100, PASI90 and PASI75) at 10, 12 or 16 weeks after starting biologic treatment, using contrast-based network meta-analysis methods and risk difference (RD). Probabilities of rank and surface under the cumulative ranking (SUCRA) were also estimated. Results Data were pooled from 41 trials in 19,248 patients. All biologics were significantly more effective than placebo for PASI100, PASI90 and PASI75. The RD for PASI100 for brodalumab vs ixekizumab was 0.05 (95 % Confidence intervals [CI] –0.02, 0.11), brodalumab vs risankizumab was 0.04 (95 %CI –0.03, 0.11), and risankizumab vs ixekizumab was –0.01 (95 %CI –0.08, 0.06). The SUCRA for PASI100 and PASI90 achievement was 96.8 % and 86.8 %, respectively, for brodalumab, 82.6 % and 90.3 %, respectively for risankizumab, and 78.3 %, 80.9 %, respectively, for ixekizumab. Conclusion Of the biologics assessed, brodalumab, ixekizumab and risankizumab were the greatest rates of PASI90 and PASI100 achievement, and a higher probability of being most effective in the induction phase, compared with the other biologics.

The association of psoriasis with thyroid dysfunction has been investigated; however, it remains controversial. Some papers indicate it, and others do not. Thereby, we investigated the prevalence of thyroid dysfunction in patients with psoriasis vulgaris (PsV), psoriatic arthritis (PsA) and generalized pustular psoriasis (GPP), and the relationship between the severity of psoriasis with serum free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone levels. Data on 85 psoriatic patients visiting our hospital from January 2015 to November 2017 (54 men and 31 women; 51 PsV, 23 PsA 23 and 11 GPP) were retrospectively analyzed. Fourteen percent of psoriatic patients had thyroid dysfunction. The percentage of patients with thyroid dysfunction was the highest in those with GPP (45% GPP, 13% PsA, 8% PsV). Patients with thyroid dysfunction demonstrated significantly higher Psoriasis Area and Severity Index scores and elevated serum C-reactive protein (CRP) levels than those without thyroid dysfunction. A significant negative correlation was observed between the serum levels of CRP and fT3 (P = 0.0032, r = -0.4635). Our data indicate that thyroid dysfunction in patients with psoriasis is associated with inflammation caused by psoriasis.