Generalized pustular psoriasis (GPP) is a severe inflammatory skin disease characterized by the presence of sterile pustules covering almost the entire body and systemic symptoms such as fever. Secukinumab, a fully human-recombinant anti-interleukin-17A monoclonal antibody was indicated for psoriasis vulgaris and psoriatic arthritis in Japan but is not yet investigated for GPP. In this phase III, open-label multicenter single arm study, the efficacy and safety of secukinumab as monotherapy or with co-medication was evaluated in 12 Japanese patients with GPP. All the patients received secukinumab 150 mg s.c. at baseline, week 1, 2, 3 and 4, and then every 4 weeks. Two non-responders were up-titrated to 300 mg. Change in GPP severity from baseline was evaluated by clinical global impression (CGI) categorized as "worsened", "no change", "minimally improved", "much improved" or "very much improved". Treatment success was achieved by 83.3% (n = 10) of patients at week 16 (primary end-point) with CGI evaluated as "very much improved" (n = 9) and "much improved" (n = 1). Moreover, the area of erythema with pustules improved as early as week 1 and resolved by week 16 in most of the patients. The improvements were sustained throughout 52 weeks. Over the 52-week treatment period, secukinumab was well tolerated with no unexpected safety signals. Nasopharyngitis, urticaria, diabetes mellitus and arthralgia were the frequent adverse events reported. The data from this study shows that secukinumab can become one of the potent treatment options for GPP.

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Background: Psoriasis severity categories have been important tools for clinicians to use in treatment decisions as well as to determine eligibility criteria for clinical studies. However, owing to the heterogeneity of severity classifications and their lack of consideration for the impact of psoriasis involvement of special areas or past treatment history, patients may be miscategorized, which can lead to undertreatment of psoriasis.Objective: To develop a consensus statement on the classification of psoriasis severity.Methods: A modified Delphi approach was developed by the International Psoriasis Council to define psoriasis severity.Results: After completion of the exercise, 7 severity definitions were preferentially ranked. This most preferred statement rejects the mild, moderate, and severe categories in favor of a dichotomous definition: Psoriasis patients should be classified as either candidates for topical therapy or candidates for systemic

IMPORTANCE Palmoplantar pustulosis (PPP) is a recalcitrant skin disease with no biologics currently approved for treatment. The involvement of interleukin 23 (IL-23) and cytokines of the type 17 helper T cell lineage in the pathogenesis of PPP has been recently postulated. OBJECTIVE To evaluate the efficacy and safety of guselkumab, an anti-IL-23 monoclonal antibody, in Japanese patients with PPP. DESIGN, SETTING, AND PARTICIPANTS This double-blind, randomized, placebo-controlled, parallel-group, 24-week trial was conducted between May 14, 2013, and September 27, 2014, at 11 centers in Japan. Participants were patients with moderate to severe PPP that did not respond adequately to conventional treatments. INTERVENTIONS Patients were randomized 1:1 to receive guselkumab, 200 mg, by subcutaneous injection or matching placebo at weeks 0 and 4. MAIN OUTCOMES AND MEASURES Changes in total scores of skin-related outcomes from baseline at the end of week 16 (primary clinical cutoff) and through week 24 were measured. Serum biomarker analyses were performed at baseline, week 4, and week 16, and safety was monitored through week 24. RESULTS Of 49 randomized patients (35 [71%] women; median [range] age, 52 [28-77] years), 41 completed the study at week 24. Mean (SD) PPP severity index total scores (primary end point) improved significantly from baseline in guselkumab-treated patients (−3.3 [2.43]) vs placebo (−1.8 [2.09]) (least squares mean difference, −1.5; 95% CI,-2.9 to-0.2; P = .03). At week 16, PPP area and severity index scores (least squares mean difference, −5.65; 95% CI, −9.80 to −1.50; P = .009) and proportion of patients achieving 50% reduction in these scores (difference in proportion, 39.2; 95% CI, 14.0-64.3; P = .009) improved significantly. A numerically higher proportion of patients had a physician's global assessment score of 1 or less in the guselkumab group vs placebo. Improvement in efficacy scores was maintained through week 24 in the guselkumab group. Significant reductions from baseline in serum IL-17A and IL-17F cytokine levels were observed at weeks 4 and 16. Frequency of treatment-emergent adverse events was comparable between the guselkumab group (19 of 25 patients [76%]) and the placebo group (18 of 24 patients [75%]). Frequent adverse effects included nasopharyngitis (14 patients [29%]), headache (3 patients [6%]), contact dermatitis (3 patients [6%]), and injection site erythema (3 patients [6%]). No major safety concerns emerged during the study. CONCLUSIONS AND RELEVANCE Targeting IL-23 and its associated immune cascade with guselkumab may be a safe and useful therapeutic option for treatment of PPP.

IMPORTANCE Palmoplantar pustulosis (PPP) causes erythematous, scaly plaques with recurrent sterile pustules refractory to treatment and with few randomized clinical trials conducted. Evidence points to involvement of interleukin 23 in the pathogenesis of PPP.OBJECTIVE To determine the efficacy and safety of guselkumab, an anti-IL-23 monoclonal antibody, in Japanese patients with PPP. DESIGN, SETTING, AND PARTICIPANTSA phase 3 randomized clinical trial was conducted from December 15, 2015, to December 12, 2017. A total of 159 enrolled patients (aged Ն20 years) had an inadequate response to conventional therapies, with a diagnosis of PPP for 24 or more weeks before screening. Intention-to-treat analysis was performed.INTERVENTIONS Subcutaneous injections of guselkumab, 100 or 200 mg, at weeks 0, 4, and 12, and every 8 weeks thereafter were administered; placebo was given at weeks 0, 4, and 12. MAIN OUTCOMES AND MEASURESChanges from baseline in PPP Area and Severity Index (PPPASI) score (possible score range, 0-72, with higher scores indicating greater area and severity), PPP severity index (PPSI) score (possible score range, 0-12, with higher scores indicating greater severity), and proportion of PPPASI-50 (Ն50% reduction) responders at weeks 16 and 52 were assessed. Safety was monitored through week 52.RESULTS A total of 159 patients (mean [SD] age at diagnosis, 46.8 [11.9] years; 126 women [79.2%]) were enrolled. Treatment groups comprised guselkumab, 100 mg (n = 54), guselkumab, 200 mg (n = 52), or placebo (n = 53). Both guselkumab groups demonstrated significant improvement in least-squares mean changes in PPPASI score compared with placebo: −15.3 and −11.7 in the guselkumab 100-mg and 200-mg groups, respectively, and −7.6 in the placebo group (difference [SE] vs placebo: −7.7 [1.7] in the 100-mg group, P < .001; 95% CI, in the 200-mg group, P < .017; 95% CI, −7.47 to −0.75]). Least-squares mean changes in PPSI score showed significant improvement in both guselkumab groups (100 mg: −2.0 [0.5]; P < .001; 95% CI, −2.96 to −0.95; 200 mg: −1.0 [0.5; P = .04; 95% CI, −2.06 to −0.03). A significantly higher proportion of patients in the guselkumab 100-mg group (31 [57.4%]) achieved a PPPASI-50 response at week 16 vs placebo (18 [34.0%]; P = .02); however, the result was not significant for the guselkumab 200-mg group (19 [36.5%]) vs placebo; P = .78). Each efficacy end point improved consistently through week 52. Health-related quality of life improved significantly as indicated by a reduction in the Dermatology Life Quality Index score (100 mg: −2.6; 95% CI, −4.0 to −1.2; P < .001; 200 mg: −1.6; 95% CI, −3.1 to −0.2; P = .03). Serious treatmentemergent adverse events were observed in 8 patients (placebo group, 2 of 53 [3.8%]; combined guselkumab group, 6/157≠10.5%). No serious infections were reported. CONCLUSIONS AND RELEVANCETargeting interleukin 23 with guselkumab may be an effective and safe treatment option for a recalcitrant disease such as PPP.

Background/Aims: To investigate the effect of singing training on the cognitive function in Alzheimer's disease (AD) patients. Methods: Ten AD patients (mean age 78.1 years) participated in music therapy using singing training once a week for 6 months (music therapy group). Each session was performed with professional musicians using karaoke and a unique voice training method (the YUBA Method). Before and after the intervention period, each patient was assessed by neuropsychological batteries, and functional magnetic resonance imaging (fMRI) was performed while the patients sang familiar songs with a karaoke device. As the control group, another 10 AD patients were recruited (mean age 77.0 years), and neuropsychological assessments were performed twice with an interval of 6 months. Results: In the music therapy group, the time for completion of the Japanese Raven's Colored Progressive Matrices was significantly reduced (p = 0.026), and the results obtained from interviewing the patients' caregivers revealed a significant decrease in the Neuropsychiatric Inventory score (p = 0.042) and a prolongation of the patients' sleep time (p = 0.039). The fMRI study revealed increased activity in the right angular gyrus and the left lingual gyrus in the before-minus-after subtraction analysis of the music therapy intervention. Conclusion: Music therapy intervention using singing training may be useful for dementia patients by improving the neural efficacy of cognitive processing.

Generalized pustular psoriasis (GPP) is a rare, severe, neutrophilic skin disease characterized by episodes of widespread eruption of sterile, visible pustules, which can occur with or without systemic inflammation and with or without plaque psoriasis. 1,2 GPP is associated with potentially life-threatening systemic complications including sepsis and cardiac failure, and is described by the Japan Ministry of Health as an intractable disease. [1][2][3][4] Mutations in IL36RN, CARD14, or AP1S3 have been found in patients with GPP. 5,6 Small Japanese studies have identified a number of different IL36RN mutations in patients with GPP. [7][8][9] Patients with these mutations may be at risk of earlier onset of disease and more severe disease. 10 Indeed, one small study (n = 31 patients with GPP)

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.