Publications by authors named "Yukari Okubo"

72 Publications

Patient characteristics and burden of disease in Japanese patients with generalized pustular psoriasis: Results from the Medical Data Vision claims database.

J Dermatol 2021 Jul 1. Epub 2021 Jul 1.

Department of Dermatology, Tokyo Medical University Hospital, Tokyo, Japan.

Generalized pustular psoriasis (GPP) is a rare and severe systemic, neutrophilic skin disease. To date, accurate clinical profiling of patients with GPP remains poorly understood. In this study, we present the characteristics and estimate the burden of disease in patients with GPP compared with those with plaque psoriasis, in Japan. This retrospective study was conducted using the Medical Data Vision database between January 1, 2015, and December 31, 2019. Patients with at least one confirmed inpatient or outpatient diagnostic code for GPP (L40.1) or psoriasis vulgaris (L40.0) were included for analysis. The main outcome measures included comparisons of the prevalence of comorbidities, medication use, and healthcare resource utilization between patients with GPP, patients with plaque psoriasis, and a general population-matched cohort. In total, 718 patients with GPP and 27,773 patients with plaque psoriasis were identified. Patients with GPP were more likely to be female than those with plaque psoriasis (51.6% vs. 38.7%). During the 12-month follow-up period, patients with GPP were more likely to experience comorbidities than those with plaque psoriasis, including psoriatic arthritis, other forms of psoriasis, osteoporosis, interstitial pneumonia, and peptic ulcer disease. Medication use also differed between those with GPP and those with plaque psoriasis: patients with GPP were more likely to be prescribed antibiotics and psychiatric medication. Patients with GPP were also more likely to require more healthcare resource utilization with longer hospitalizations than those with plaque psoriasis. Overall, in Japan, patients with GPP have a higher burden of illness than those with plaque psoriasis.
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http://dx.doi.org/10.1111/1346-8138.16022DOI Listing
July 2021

Evaluation of treatment satisfaction misalignment between Japanese psoriasis patients and their physicians - Japanese psoriasis patients and their physicians do not share the same treatment satisfaction levels.

Curr Med Res Opin 2021 Jul 19;37(7):1103-1109. Epub 2021 May 19.

Department of Dermatology, Jichi Medical University, Tochigi, Japan.

Objectives: High treatment satisfaction in both patients and physicians is an important factor in improving quality of life in psoriasis patients. This study aimed to evaluate treatment satisfaction alignment between psoriasis patients and physicians and to identify factors associated with satisfaction misalignment, especially "physician-predominant" misalignment.

Methods: This is a nationwide multicenter cross-sectional study. Subjects were paired moderate to severe psoriasis outpatients and their physicians. Treatment satisfaction was evaluated on a scale from 0 to 10. Subjects were defined as "misaligned" when the difference in treatment satisfaction was over ±1 between the patient-physician pair.

Results: A total of 425 pairs were collected from 54 facilities in Japan. The mean patient age and disease duration were 56.5 years and 18.7 years, respectively. The mean physician age was 50.6 years and 69.6% of physicians specialized in psoriasis. Treatment satisfaction misalignment was found in 49.9% of the patient-physician pairs. Among misaligned pairs, 43.6% were "physician-predominant" pairs. In the multivariate logistic regression analyses, "treatment is effective" was the most important reason for treatment satisfaction (odds ratio [OR]: 35.5; 95% confidence interval [CI]: 5.43, 231.78). Symptoms in the genital area (OR: 10.2; 95% CI: 2.55, 40.93) and lack of understanding of treatment options by patients (OR: 7.5; 95% CI: 2.19, 25.94) were key factors leading to "physician-predominant" status.

Conclusions: The results suggest that genital psoriasis plays an important role in treatment satisfaction from the patient perspective, and illustrate the importance of communication between patients and physicians which potentially resolves these factors and improves misalignment.
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http://dx.doi.org/10.1080/03007995.2021.1920898DOI Listing
July 2021

Efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 64-week phase 3 study (reSURFACE 1).

J Dermatol 2021 Jun 25;48(6):853-863. Epub 2021 Feb 25.

Jichi Medical University, Tochigi, Japan.

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.
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http://dx.doi.org/10.1111/1346-8138.15789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247960PMC
June 2021

Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial.

Lancet 2021 02;397(10273):487-498

Icahn School of Medicine, New York, NY, USA.

Background: There is an unmet need for a treatment for psoriasis that results in complete skin clearance with a reliably quick response. Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. We aimed to compare the efficacy and safety of bimekizumab with placebo and ustekinumab in patients with moderate to severe plaque psoriasis over 52 weeks.

Methods: BE VIVID was a multicentre, randomised, double-blind, active comparator and placebo controlled phase 3 trial done across 105 sites (clinics, hospitals, research units, and private practices) in 11 countries in Asia, Australia, Europe, and North America. Adults aged 18 years or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥12, ≥10% body surface area affected by psoriasis, and Investigator's Global Assessment [IGA] score ≥3 on a five point scale) were included. Randomisation was stratified by geographical region and previous exposure to biologics; patients, investigators, and sponsors were masked to treatment assignment. Patients were randomly assigned (4:2:1) using an interactive response technology to bimekizumab 320 mg every 4 weeks, ustekinumab 45 mg or 90 mg (baseline weight-dependent dosing) at weeks 0 and 4, then every 12 weeks, or placebo every 4 weeks. At week 16, patients receiving placebo switched to bimekizumab 320 mg every 4 weeks. All study treatments were administered as two subcutaneous injections. Coprimary endpoints were the proportion of patients with 90% improvement in the PASI (PASI90) and the proportion of patients with an IGA response of clear or almost clear (score 0 or 1) at week 16 (non-responder imputation). Efficacy analyses included the intention-to-treat population; safety analysis included patients who received at least one dose of study treatment. This trial was registered at ClinicalTrials.gov, NCT03370133 (completed).

Findings: Between Dec 6, 2017, and Dec 13, 2019, 735 patients were screened and 567 were enrolled and randomly assigned (bimekizumab 320 mg every 4 weeks n=321, ustekinumab 45 mg or 90 mg every 12 weeks n=163, placebo n=83). At week 16, 273 (85%) of 321 patients in the bimekizumab group had PASI90 versus 81 (50%) of 163 in the ustekinumab group (risk difference 35 [95% CI 27-43]; p<0·0001) and four (5%) of 83 in the placebo group (risk difference 80 [74-86]; p<0·0001). At week 16, 270 (84%) patients in the bimekizumab group had an IGA response versus 87 (53%) in the ustekinumab group (risk difference 30 [95% CI 22-39]; p<0·0001) and four (5%) in the placebo group (risk difference 79 [73-85]; p<0·0001). Over 52 weeks, serious treatment-emergent adverse events were reported in 24 (6%) of 395 patients in the bimekizumab group (including those who switched from placebo at week 16) and 13 (8%) of 163 in the ustekinumab group.

Interpretation: Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. The bimekizumab safety profile was consistent with that observed in previous studies.

Funding: UCB Pharma.
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http://dx.doi.org/10.1016/S0140-6736(21)00125-2DOI Listing
February 2021

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

J Dermatol 2021 Jun 1;48(6):844-852. Epub 2021 Feb 1.

Jichi Medical University, Tochigi, Japan.

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.
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http://dx.doi.org/10.1111/1346-8138.15763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248015PMC
June 2021

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

J Dermatol Sci 2021 Mar 7;101(3):185-193. Epub 2021 Jan 7.

Biostatistics Center, Kurume University, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1016/j.jdermsci.2021.01.002DOI Listing
March 2021

Dietary habits in Japanese patients with palmoplantar pustulosis.

J Dermatol 2021 Mar 6;48(3):366-375. Epub 2021 Jan 6.

Department of Dermatology, Nippon Medical School Chiba Hokusoh Hospital, Inzai, Chiba, Japan.

Palmoplantar pustulosis (PPP) is a chronic dermatitis characterized by sterile intra-epidermal pustules associated with erythema and scales on the palms and soles. Tumor necrosis factor (TNF)-α/interleukin (IL)-23/IL-17 inflammatory pathway may be involved in the pathogenesis of PPP, and the skin lesions manifest the enhanced expression of IL-8 in keratinocytes and increased levels of antimicrobial peptide cathelicidin, leucine leucine-37 in vesicles/pustules. Some PPP patients are associated with arthro-osteitis, called pustulotic arthro-osteitis (PAO). Dietary habits may modulate the pathogenesis of PPP, however, have not been investigated in PPP patients. We evaluated dietary habits in adult Japanese PPP patients, using a validated, brief-type self-administered diet history questionnaire, and compared their results to those of age- and sex-matched healthy controls. The results in PPP patients with PAO were compared to those in the patients without. Japanese PPP patients showed higher body mass indices (BMIs), higher intakes of pulses and sugar/sweeteners, and lower intake of vitamin A, compared to those of healthy controls. The bivariate and multivariable logistic regression analysis showed that PPP was associated with high BMI, high intake of pulses, and low intake of vitamin A. The sodium intake and BMI were positively correlated with palmoplantar pustulosis area and severity index (PPPASI). The linear multivariate regression analysis revealed that sodium intake and BMI were predictors of PPPASI. The age and sodium intake in the patients with PAO were lower than those in the patients without. The bivariate and multivariable logistic regression analysis showed that PAO was negatively associated with age and sodium intake. This is the first study showing the dietary habits in patients with PPP. Further studies should clarify if the dietary intervention to correct the BMI and sodium intake will alter the progress of PPP.
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http://dx.doi.org/10.1111/1346-8138.15719DOI Listing
March 2021

Long-term analysis of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa: Open-label phase 3 results.

J Dermatol 2021 Jan 7;48(1):3-13. Epub 2020 Oct 7.

Nihon University School of Medicine, Tokyo, Japan.

This phase 3, multicenter, open-label single-arm study evaluated adalimumab (ADA) in Japanese patients with moderate to severe hidradenitis suppurativa (HS). Fifteen patients received ADA 160 mg s.c. at week 0, 80 mg at week 2 and 40 mg at week 4 and every week thereafter. At any time after week 52, patients were given the option to receive 80 mg ADA every other week or remain on 40 mg every week. The primary end-point (achievement of HS Clinical Response [HiSCR] at week 24) and results up to week 24 were published previously. Secondary end-points included total abscess and inflammatory nodule (AN) count, 30% or more and 1 unit or more reduction in Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS30), modified Sartorius score and quality of life (QoL). After 12 weeks of ADA treatment, the achievement rate in HiSCR was 86.7%; HiSCR achievement rate was sustained through week 52 at 66.7%. Improvements at week 12 were also seen in the proportion of patients achieving an AN count of 0-2; NRS30 response rate among the nine patients with a baseline NRS of 3 or more; mean decrease in modified Sartorius score (61.4); and QoL as assessed by Dermatology Life Quality Index and Treatment Satisfaction Questionnaire; these improvements were maintained through 52 weeks. Similar efficacy was observed when patients switched dosing from ADA 40 mg every week to ADA 80 mg every other week. There were no new safety findings with ADA 40 mg weekly dosing during the study, and no differences in safety were found between patients who switched to 80 mg ADA every other week and patients who remained on 40 mg every week. The results of this study indicate that long-term ADA treatment is effective and well tolerated in Japanese patients with moderate to severe HS.
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http://dx.doi.org/10.1111/1346-8138.15605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821142PMC
January 2021

Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial.

J Dermatol 2021 Jan 10;48(1):80-84. Epub 2020 Sep 10.

Jichi Medical University, Shimotsuke, Japan.

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.
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http://dx.doi.org/10.1111/1346-8138.15596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821327PMC
January 2021

Characteristics of Japanese patients with pustulotic arthro-osteitis associated with palmoplantar pustulosis: a multicenter study.

Int J Dermatol 2020 Apr 26;59(4):441-444. Epub 2020 Jan 26.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

Background: Pustulotic arthro-osteitis (PAO) is a major comorbidity of palmoplantar pustulosis (PPP), which is frequently seen in Japanese patients. To determine the characteristics of Japanese patients with PAO, we conducted a multicenter, retrospective epidemiologic survey at four university hospitals.

Methods: Clinical features including age, gender, duration of disease, extrapalmoplantar lesion, smoking habit, focal infection, site of joint pain, bone scintigraphy with Technetium , and therapies were retrospectively evaluated.

Results: In total, 165 patients with PAO were identified among 576 patients with PPP (28.6%). The male to female ratio was 1 : 3.7, and the mean age was 50.2 years. The mean disease duration of PAO was 6.0 years. Smoking habit was observed in 104 patients. Focal infection was detected in 74 patients, who developed tonsillar infection (n = 41), sinusitis (8), odontogenic infection (40), and others (2). Fifteen patients had multifocal infection. Technetium bone scintigraphy was performed in 97 cases. Increased uptake was most frequently observed in the sternocostoclavicular regions, followed by wrist and ankle, sacroiliac joint, knee and elbow, finger and toe, lumbar spine, thoracic spine, scapula, and thigh. Patients were mainly treated with nonsteroidal anti-inflammatory drugs, methotrexate, cyclosporine, antibiotics, and biologics, as well as tonsillectomy and dental treatment.

Conclusion: PAO frequently involves the anterior chest wall of middle-aged women with smoking habit and is closely associated with focal infection.
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http://dx.doi.org/10.1111/ijd.14788DOI Listing
April 2020

A case of food allergy due to three different mushroom species.

Allergol Int 2020 Jan 29;69(1):152-153. Epub 2019 Aug 29.

Department of Asthma and Allergy, Toda Central General Hospital, Saitama, Japan.

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http://dx.doi.org/10.1016/j.alit.2019.08.003DOI Listing
January 2020

Twenty-four-week interim analysis from a phase 3 open-label trial of adalimumab in Japanese patients with moderate to severe hidradenitis suppurativa.

J Dermatol 2019 Sep 8;46(9):745-751. Epub 2019 Jul 8.

Nihon University School of Medicine, Tokyo, Japan.

Hidradenitis suppurativa (HS) is a chronic skin disease characterized by recurrent painful inflamed nodules/abscesses and draining fistulas that negatively impact quality of life. Adalimumab, a monoclonal antibody against tumor necrosis factor-α, has been approved in the EU, USA and Japan for the treatment of moderate to severe HS. This is an interim analysis of an ongoing phase 3, multicenter, open-label, single-arm study of the safety and efficacy of adalimumab weekly dosing in Japanese patients with moderate to severe HS. Fifteen patients received adalimumab 160 mg at week 0, 80 mg at week 2 and 40 mg every week thereafter starting at week 4. The fulfillment of Hidradenitis Suppurativa Clinical Response was assessed under adalimumab treatment; clinical response was assessed by skin pain, total abscess and inflammatory nodule count and modified Sartorius score; and quality of life and safety were assessed. At week 12, 86.7% of patients achieved clinical response, with improvements at week 12 across the primary and secondary end points generally sustained through week 24. Adalimumab weekly dosing was generally safe and well tolerated with no new safety findings through week 24. These results suggest that adalimumab is effective and well tolerated in Japanese patients with moderate to severe HS.
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http://dx.doi.org/10.1111/1346-8138.14997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771639PMC
September 2019

Efficacy and Safety of Guselkumab in Japanese Patients With Palmoplantar Pustulosis: A Phase 3 Randomized Clinical Trial.

JAMA Dermatol 2019 Oct;155(10):1153-1161

Janssen Pharmaceutical K.K., Tokyo, Japan.

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 Participants: A phase 3 randomized clinical trial was conducted from December 15, 2015, to December 12, 2017. A total of 159 enrolled patients (aged ≥20 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 Measures: Changes 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 (≥50% 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, -11.00 to -4.38; and -4.1 [1.7] 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 treatment-emergent 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 Relevance: Targeting interleukin 23 with guselkumab may be an effective and safe treatment option for a recalcitrant disease such as PPP.

Trial Registration: ClinicalTrials.gov identifier: NCT02641730.
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http://dx.doi.org/10.1001/jamadermatol.2019.1394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613288PMC
October 2019

A case of anaphylaxis due to fish collagen in a gummy candy.

Allergol Int 2020 Jan 28;69(1):146-147. Epub 2019 Jun 28.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.alit.2019.05.011DOI Listing
January 2020

Patient and physician preferences for atopic dermatitis injection treatments in Japan.

J Dermatolog Treat 2020 Dec 28;31(8):821-830. Epub 2019 Jun 28.

Sanofi K.K, Tokyo, Japan.

Recently, biologic agents administered as a subcutaneous injection have been introduced as treatment options for atopic dermatitis (AD). Biologic treatments differ considerably from traditional topical and systemic anti-inflammatory treatments, and it is unclear how this may impact patient and physician preferences for treatments. To examine the treatment preferences for new injection treatments of patients and physicians. Discrete choice experiment methodology was used to quantify preferences for treatments via an online survey. Participants were presented with a series of choice scenarios; treatment options were described using the following attributes: add-on or replacement treatment, efficacy of improving rashes and itching, time until response, place of administration, injection site reaction, risk of mild-to-moderate and severe side effects, frequency of administration and cost. 76.67% of physicians and 46.24% of patients opted-in to the new treatment in the scenarios presented. Of those who opted-in to treatment, physicians were more likely to value the efficacy of treating rashes and were more concerned about cost than patients. Patients preferred add-on treatments and were against self-administering the treatment at home. Overall patients and physicians differ in their preferences for AD treatments. These findings have implications for shared decision making and clinical practice.
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http://dx.doi.org/10.1080/09546634.2019.1623860DOI Listing
December 2020

Recent trends of ocular complications in patients with atopic dermatitis.

Jpn J Ophthalmol 2019 Sep 26;63(5):410-416. Epub 2019 Jun 26.

Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Purpose: To elucidate the recent trends in prevalence and characteristics of ocular complications of atopic dermatitis (AD).

Study Design: Cross-sectional observational study.

Methods: Among AD patients who visited our department between 2012 and 2015, 70 patients (140 eyes; recent AD group) who gave informed consent to participate in the study were analyzed. Following a medical interview, ophthalmological examinations were conducted for ocular complications related to AD. The data were compared to those of 280 AD patients (560 eyes) analyzed in a similar study conducted at our department in 1991-1993 (previous AD group).

Results: Blepharitis was found in 58 eyes (41%) in the recent AD group, and the frequency was significantly lower compared to the previous AD group (294 eyes, 53%) (p < 0.05). Tears in retina or pars plana ciliaris occurred in 22 eyes (4%) in the previous AD group, compared with none in the recent AD group (p < 0.01). Retinal detachment was observed in 12 eyes (2%) in the previous AD group, and none in the recent AD group (p < 0.01). Atopic keratoconjunctivitis (AKC) increased significantly in the recent AD group compared to the previous AD group (74.3% vs. 39.5%) (p < 0.001). Patients with a habit of slapping around the eye decreased significantly from 32.5% in the previous AD group to 12.1% in the recent AD group (p < 0.001).

Conclusions: Ocular complications in AD patients show a trend of decrease in recent years, which presumably is attributed to educational activities to increase patient awareness and advances in therapeutic strategy.
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http://dx.doi.org/10.1007/s10384-019-00678-3DOI Listing
September 2019

A case of anaphylaxis due to alpha-mannosidase from Auricularia.

Allergol Int 2019 Jul 26;68(3):394-395. Epub 2019 Mar 26.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.alit.2019.02.008DOI Listing
July 2019

Diagnostic histopathological features distinguishing palmoplantar pustulosis from pompholyx.

J Dermatol 2019 May 28;46(5):399-408. Epub 2019 Mar 28.

Department of Dermatology, Ehime University Graduate School of Medicine, Toon, Japan.

Palmoplantar pustulosis (PPP) and pompholyx are both chronic and relapsing diseases occurring on the palms and soles. Although these two diseases have been considered completely different from each other, it is sometimes very difficult even for dermatologists to differentiate them from each other because of their similarities in clinical presentation. In this study, we aimed to analyze the histopathological features of PPP and pompholyx and find out "clues" to differentiate between PPP and pompholyx by their histopathological features. The histopathology of 11 PPP and six pompholyx patients, who were diagnosed with typical clinical history and histopathology, were carefully observed. PPP cases were divided into three phases (vesicle, pustulovesicule and pustule) and pompholyx cases were divided into two phases (vesicle and pustule), and histopathological findings and a 4-point checklist to distinguish between PPP and pompholyx were preliminarily established. To confirm whether the checklist establishes the clues for diagnosis, biopsy samples from 43 patients (32 PPP and 11 pompholyx) who had been already diagnosed at five hospitals were examined according to our checklist without any additional clinical information. According to our 4-point checklist, 31 of 32 PPP patients and all 11 pompholyx patients were diagnosed histopathologically consistent with their clinical diagnosis. In conclusion, histopathological findings of "vesicles without spongiosis" and "microabscess on the edges of vesicles" would be impact points for the differential diagnosis between PPP and pompholyx. The 4-point checklist was trustworthy to distinguish between PPP and pompholyx.
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http://dx.doi.org/10.1111/1346-8138.14850DOI Listing
May 2019

[THE ANALYSIS OF ANAPHYLAXIS DIAGNOSED AT DERMATOLOGY OF TOKYO MEDICAL UNIVERSITY HOSPITAL].

Arerugi 2019;68(1):43-47

Department of Dermatology, Tokyo Medical University.

Objective: There are few epidemiological reports of anaphylaxis since childhood. We herein examined cases of anaphylaxis diagnosed in our department.

Methods: One hundred-thirty-two patients who were examined at the Dermatology Department of Tokyo Medical University Hospital between January 2011 and March 2017 and were prescribed epinephrine autoinjector (EpiPen) for treatment were enrolled. The referral institution if any, severity of anaphylaxis, diagnostic method, causative antigen, and recurrence rate was examined.

Results: The referral rate was 54% while 46% of patients requested examination of their own accord. Anaphylaxis severity was mild to moderate in 75% of cases. Food allergy accounted for 71% of the symptoms, with wheat as the most common causative antigen, followed by Anisakis allergy. After diagnosis only 37% of patients continued periodic consultations, and 16 patients recurred anaphylaxis of the diagnosis.

Conclusion: Wheat and WDEIA were the most frequent causes of anaphylaxis diagnosed in our department. We also found that as many as 15% of patients had Anisakis allergy, suggesting that it may be an important item in antigen testing.
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http://dx.doi.org/10.15036/arerugi.68.43DOI Listing
May 2019

Long-term efficacy and safety of secukinumab in Japanese patients with moderate to severe plaque psoriasis: 3-year results of a double-blind extension study.

J Dermatol 2019 Mar 23;46(3):186-192. Epub 2019 Jan 23.

The Jikei University School of Medicine, Tokyo, Japan.

Secukinumab, a fully human monoclonal antibody neutralizing interleukin-17A, has been shown to have significant efficacy in the treatment of moderate to severe psoriasis. Long-term (3-year) efficacy and safety of secukinumab in Japanese patients with moderate to severe psoriasis were evaluated in an extension study of a large phase 3 global study (SCULPTURE). In the core study, 52 Japanese patients with 75% improvement of Psoriasis Area and Severity Index (PASI-75) response at week 12 were re-randomized to a fixed interval (FI; every 4 weeks) schedule and retreatment as needed (RAN), in which patients received placebo until start of relapse, at which time secukinumab was reinitiated. Fifty Japanese patients completed the 52-week core study, and 47 patients entered the extension study with the same double-blind regimens up to week 152. All patients in the secukinumab 300 mg FI and seven patients in 150 mg FI groups completed 3 years of treatment. PASI-90 and -100 at the end of year 3 were achieved in 69.2% and 53.8%, respectively, in 300 mg FI and 42.9% and 42.9%, respectively, in 150 mg FI, indicating high sustained response in 300 mg FI. Mean absolute PASI was continually low in 300 mg FI and numerically higher in 150 mg FI. Dermatology Life Quality Index of 0/1 was maintained by approximately two-thirds of 300 mg FI patients, and all EuroQoL 5-Dimension Health Questionnaire domain measures were also improved. FI dosing was consistently more efficacious than RAN. The safety profile of secukinumab remained favorable, with no new safety concerns identified.
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http://dx.doi.org/10.1111/1346-8138.14761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590222PMC
March 2019

Evaluation of the efficacy of granulocyte and monocyte adsorption apheresis on skin manifestation and joint symptoms of patients with pustulotic arthro-osteitis.

J Dermatol 2019 Feb 14;46(2):144-148. Epub 2018 Dec 14.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

Pustulotic arthro-osteitis, occasionally complicated with palmoplantar pustulosis, affects patients' activities of daily living. Granulocyte and monocyte adsorption apheresis selectively removes activated granulocytes and monocytes by means of extracorporeal circulation. Although the efficacy of granulocyte and monocyte adsorption apheresis in the treatment of generalized pustular psoriasis has been proved, very few reports have assessed its efficacy in the treatment of palmoplantar pustulosis and pustulotic arthro-osteitis. Ten pustulotic arthro-osteitis patients with five palmoplantar skin manifestations were treated with weekly granulocyte and monocyte adsorption apheresis over 5 weeks. Skin manifestations were assessed using palmoplantar pustulosis area and severity index, and joint symptoms were assessed using a visual analog scale of joint pain, tender joint count, swollen joint count and C-reactive protein immediately before, after and at the 3-month follow up of the five granulocyte and monocyte adsorption apheresis sessions. Two out of five patients with skin manifestations achieved more than 50% improvement in their score (remarkably improved). However, in two patients, deterioration was noted, in one of whom the skin manifestations remained unchanged at the 3-month follow up. In five out of the 10 patients, the joint symptoms were assessed as better than improved at the 3-month follow up. No deterioration was noted at the 3-month follow up. In three patients, reduction or cessation of medication for arthralgia was possible. We concluded that granulocyte and monocyte adsorption apheresis is a therapeutic option to consider when pustulotic arthro-osteitis is recalcitrant to conventional therapy.
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http://dx.doi.org/10.1111/1346-8138.14717DOI Listing
February 2019

Allergic contact dermatitis caused by isopropyl lauroyl sarcosinate.

Contact Dermatitis 2019 Jan 20;80(1):58-59. Epub 2018 Sep 20.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

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http://dx.doi.org/10.1111/cod.13117DOI Listing
January 2019

Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients.

J Dermatol 2018 Aug 24;45(8):971-977. Epub 2018 May 24.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

Inflammasomes are multimolecular complexes that control the inflammatory response. The function of inflammasomes in the pathogenesis of psoriasis is still unclear. To clarify the relationship between inflammasomes and the pathophysiology of psoriasis, and in particular, to identify molecules interacting with caspase-1, a crucial component of inflammasomes, scale extracts obtained from patients with psoriasis were immunoprecipitated with anti-caspase-1 antibody and analyzed by liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). The expression of the inflammasome component was assessed by immunohistochemical analysis and an in vitro assay. We identified several candidates for caspase-1-interacting proteins from the psoriatic scale extracts by immunoprecipitation and LC-MS/MS. Nucleotide-binding oligomerization domain-containing protein-like receptor family CARD domain-containing protein 4 (NLRC4) was the only inflammasome component among the candidates; thus, the protein is considered to be a key factor of inflammasomes in psoriasis. No inflammasome component was found in the extracts of atopic dermatitis or normal skin by LC-MS/MS. Immunohistochemical analysis demonstrated upregulation of NLRC4 in the lesional epidermis of some psoriatic patients whereas weak expression of NLRC4 was detected in the normal and non-lesional epidermis. The mRNA expression of the NLRC4 gene increased in keratinocytes at confluency, 48 h after air exposure and after the addition of 1.5 mmol/L calcium chloride. Our findings suggest that NLRC4 may be involved in the exacerbation or modification of psoriatic lesions.
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http://dx.doi.org/10.1111/1346-8138.14478DOI Listing
August 2018

Efficacy and Safety of Guselkumab, an Anti-interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis: A Randomized Clinical Trial.

JAMA Dermatol 2018 03;154(3):309-316

Janssen Pharmaceutical K.K., Tokyo, Japan.

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.

Trial Registration: clinicaltrials.gov Identifier: NCT01845987.
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http://dx.doi.org/10.1001/jamadermatol.2017.5937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885837PMC
March 2018

Granulocyte/Monocyte Adsorption Apheresis as a Novel Therapeutic Approach in the Treatment of an Impetigo Herpetiformis Case.

Ther Apher Dial 2018 08 9;22(4):414-416. Epub 2018 Jan 9.

Department of Dermatology, Tokyo Medical University, Tokyo, Japan.

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http://dx.doi.org/10.1111/1744-9987.12653DOI Listing
August 2018
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