388 results on '"Hidemi NAKAGAWA"'
Search Results
2. Bimekizumab Efficacy and Safety in Japanese Patients with Plaque Psoriasis in BE VIVID: A Phase 3, Ustekinumab and Placebo-Controlled Study
- Author
-
Akihiko Asahina, Yukari Okubo, Akimichi Morita, Yayoi Tada, Atsuyuki Igarashi, Richard G. Langley, Delphine Deherder, Mizuho Matano, Veerle Vanvoorden, Maggie Wang, Mamitaro Ohtsuki, and Hidemi Nakagawa
- Subjects
Absolute PASI ,Active control ,Bimekizumab ,Japan subpopulation ,Plaque psoriasis ,Randomized controlled trial ,Dermatology ,RL1-803 - Abstract
Abstract Introduction Bimekizumab treatment resulted in improved clinical outcomes in patients with moderate-to-severe plaque psoriasis in BE VIVID, a 52-week, phase 3, randomized, ustekinumab and placebo-controlled study. We present data from the BE VIVID Japan patient subpopulation. Methods Globally, patients were randomized to receive bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16, then bimekizumab 320 mg Q4W). Efficacy endpoints included week 16 Psoriasis Area and Severity Index (PASI) 90 and Investigator’s Global Assessment (IGA) 0/1, and other outcomes [PASI 100, PASI 75, IGA 0, Dermatology Life Quality Index (DLQI) 0/1, absolute PASI, scalp IGA, Psoriasis Symptoms and Impacts Measure (P-SIM) responses]. Safety analyses were conducted. Results There were 108 Japanese randomized patients (bimekizumab: 62; ustekinumab: 29; placebo: 17). At week 16, bimekizumab-treated patients had a higher clinical response versus ustekinumab and placebo (PASI 90: 85.5% versus 51.7% and 5.9%; IGA 0/1: 82.3% versus 48.3% and 0.0%). Over 52 weeks, improved clinical response was maintained with bimekizumab, including patients switching from placebo at week 16. Overall, the safety profile in Japanese patients was consistent with that observed in the global population. Conclusion Bimekizumab resulted in improved clinical response versus ustekinumab and placebo, and was well-tolerated in Japanese patients. Trial registration NCT03370133. Graphical Abstract
- Published
- 2023
- Full Text
- View/download PDF
3. Interstitial Pneumonia in Psoriasis
- Author
-
Hironori Kawamoto, MD, Hiromichi Hara, MD, Shunsuke Minagawa, MD, Takanori Numata, MD, Jun Araya, MD, Yumi Kaneko, MD, Yoshinori Umezawa, MD, Akihiko Asahina, MD, Hidemi Nakagawa, MD, and Kazuyoshi Kuwano, MD
- Subjects
Medicine (General) ,R5-920 - Abstract
Objective: To investigate the relationship between psoriasis and interstitial pneumonia (IP). Patients and Methods: We analyzed the clinical data of patients with psoriasis treated with biologic agents from June 1, 2008, to June 30, 2017, retrospectively. Chest computed tomography was performed in 392 patients before treatment. The clinical characteristics and radiographic findings of these patients were evaluated. Results: Of the 392 patients with psoriasis, IP was detected in 8 patients (2%). Bilateral ground-glass and/or irregular linear (reticular) opacity in the lower lung zone was the most common chest computed tomography finding. Five of the 8 patients with IP were treated with anti–interleukin (IL) 12/IL-23 or IL-17 antibodies, leading to decreased or stable IP activity. Conclusion: Interstitial pneumonia was detected in 2% of patients with psoriasis who needed systemic treatments. Ground-glass and/or irregular linear (reticular) opacity in the bilateral lower lobes was characteristic of IP with psoriasis. The IL-23/IL-17 axis may play important roles in the pathogenesis of IP in psoriasis.
- Published
- 2018
- Full Text
- View/download PDF
4. Characteristics of anti-IL-17/23 biologics-induced interstitial pneumonia in patients with psoriasis.
- Author
-
Hanae Miyagawa, Hiromichi Hara, Jun Araya, Shunsuke Minagawa, Takanori Numata, Yoshinori Umezawa, Akihiko Asahina, Hidemi Nakagawa, and Kazuyoshi Kuwano
- Subjects
Medicine ,Science - Abstract
ObjectivesAnti-IL-17/23 biologics are increasingly used to treat psoriasis. We aimed to elucidate characteristics of drug-induced interstitial pneumonia (DIIP) caused by anti-IL-17/23 biologics.MethodsWe retrospectively analyzed the clinical data of psoriasis patients treated with anti-IL-17/23 biologics. Chest CT was performed to evaluate DIIP. Serum KL-6 levels were measured before treatment (baseline) and during treatment.ResultsA total of 603 psoriasis patients were treated with anti-IL-17/23 biologics with mean follow-up of 21.1 months. Six patients developed DIIP at mean 14 months after initiation of the therapy. Older age, higher baseline KL-6 value and more frequent pre-existing IPs were associated with development of DIIP by univariate analysis. At the onset of DIIP, elevated serum KL-6 levels with concomitantly increased ground glass opacity (GGO) in Chest CT were demonstrated. DIIP was improved by only cessation of causative agents in five patients but steroid therapy was needed in one patient.ConclusionsDIIP is a plausible complication of anti-IL-17/23 biologics. Age, baseline KL-6 level and underlying IP could be the risk factors for DIIP development. Serum KL-6 levels and chest CT are useful for not only predicting but also detecting DIIP caused by anti-IL-17/23 biologics.
- Published
- 2021
- Full Text
- View/download PDF
5. Crystal structures of 1-hydroxy-4-propyloxy-9,10-anthraquinone and its acetyl derivative
- Author
-
Hidemi Nakagawa and Chitoshi Kitamura
- Subjects
crystal structure ,anthraquinone ,hydrogen bonding ,π–π stacking ,C—H ...O interactions ,Crystallography ,QD901-999 - Abstract
1-Hydroxy-4-propyloxy-9,10-anthraquinone, C17H14O4, (I), and its acetyl derivative, 4-acetyloxy-4-propyloxy-9,10-anthraquinone, C19H16O5, (II), were synthesized from the commercially available dye quinizarin. In both compounds, the anthraquinone frameworks are close to planarity. There is a large difference in the conformation of the propyloxy group; the molecule of (I) adopts a gauche conformation [O—C—C—C = −64.4 (2)°], although the molecule of (II) takes a trans-planar conformation (zigzag) [O—C—C—C = 176.1 (3)°]. In the molecule of (I), there is an intramolecular O—H...O hydrogen bond. In both crystals, the molecules are linked by C—H ...O hydrogen bonds. A difference in the molecular arrangements of (I) and (II) is found along the stacking directions.
- Published
- 2017
- Full Text
- View/download PDF
6. Relationship between the Degrees of Itch and Serum Lipocalin-2 Levels in Patients with Psoriasis
- Author
-
Norie Aizawa, Yozo Ishiuji, Mitsutoshi Tominaga, Sanae Sakata, Nobuaki Takahashi, Koichi Yanaba, Yoshinori Umezawa, Akihiko Asahina, Utako Kimura, Yasushi Suga, Kenji Takamori, and Hidemi Nakagawa
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Background. Lipocalin-2 (LCN2), a protein secreted mainly by activated neutrophils, has been associated with neurodegeneration, obesity, and inflammatory responses. Serum LCN2 concentration has been reported elevated in patients with psoriasis, but lower in patients with atopic dermatitis (AD). Spinal astrocyte-derived LCN2 was found to be involved in enhancement of itch in a mouse model of AD. However, the relationship between LCN2 and itch in patients with psoriasis has not been determined. Objective. This study examined the correlation between serum LCN2 levels and the degrees of itch in patients with psoriasis. Methods. Serum LCN2 concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in patients with psoriasis and AD and in healthy controls. The degree of itch was assessed using a visual analog scale (VAS), and disease severity was determined by measuring psoriasis area and severity index (PASI) and scoring atopic dermatitis (SCORAD). Correlations among serum LCN2 level, VAS, PASI, and SCORAD were analyzed statistically. We further examined the serum LCN levels in psoriasis patients before and after biological treatment. Results. Serum LCN2 concentrations were significantly higher in patients with psoriasis and AD than those in healthy controls. In patients with psoriasis, serum LCN2 concentrations were significantly correlated with VAS, but not with PASI. In contrast, serum LCN2 concentrations did not correlate with VAS or SCORAD in patients with AD. Serum LCN2 levels in psoriasis patients significantly decreased after the biological treatment along with improvement of VAS. Conclusion. Serum LCN2 concentration is associated with the degree of itch in patients with psoriasis, suggesting that serum LCN2 may be a useful clinical marker for itch in psoriasis.
- Published
- 2019
- Full Text
- View/download PDF
7. Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a patient with recessive dystrophic epidermolysis bullosa (RDEB) carrying two compound heterozygous mutations in the COL7A1 gene
- Author
-
Munenari Itoh, Shiho Kawagoe, Katsuto Tamai, Hirotaka James Okano, and Hidemi Nakagawa
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Expanded human T cells from a Japanese female with recessive dystrophic epidermolysis bullosa (RDBE) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, RDEB-iPSC26, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. RDEB-iPSC26 may be a useful cell resource for the establishment of in vitro RDEB modeling and the study for developing gene and cell therapy.
- Published
- 2016
- Full Text
- View/download PDF
8. A Case of Advanced Extramammary Paget's Disease Successfully Controlled by Monthly but Not Weekly Docetaxel Chemotherapy
- Author
-
Yuki Yoshihara, Munenari Itoh, Yoshimasa Nobeyama, and Hidemi Nakagawa
- Subjects
Docetaxel ,Extramammary Paget’s disease ,Chemotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Extramammary Paget's disease (EMPD) is an uncommon cutaneous adenocarcinoma arising from the apocrine glands within the epidermis or underlying skin appendages in the anogenital and axillary regions. Surgical excision is basically performed as a treatment for EMPD. However, therapeutic options for EMPD in an advanced stage are limited. Herein, we report the case of a Japanese woman with advanced EMPD successfully controlled by monthly but not weekly docetaxel therapy. We also demonstrate the possibility that a monthly regimen of docetaxel is a more effective and optimal schedule than a weekly one through this case report.
- Published
- 2016
- Full Text
- View/download PDF
9. Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a healthy individual: WT-iPSC2
- Author
-
Munenari Itoh, Shiho Kawagoe, Hirotaka James Okano, and Hidemi Nakagawa
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Expanded human T cells from a Japanese healthy male were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, WT-iPSC2, was confirmed by the expressions of stem cell markers and the differentiation capability into three germ layer. WT-iPSC2 may be a useful cell resource as a normal control for the comparative study using disease-specific iPSCs.
- Published
- 2016
- Full Text
- View/download PDF
10. Integration-free T cell-derived human induced pluripotent stem cells (iPSCs) from a patient with lymphedema-distichiasis syndrome (LDS) carrying an insertion–deletion complex mutation in the FOXC2 gene
- Author
-
Munenari Itoh, Shiho Kawagoe, Hirotaka James Okano, and Hidemi Nakagawa
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Expanded human T cells from a Japanese male with lymphedema-distichiasis syndrome (LDS) were used to generate integration-free induced pluripotent stem cells (iPSCs) by exogenous expression of four reprogramming factors, OCT3/4, SOX2, cMYC, KLF4, using Sendai virus vector (SeVdp). The authenticity of established iPSC line, LDS-iPSC8, was confirmed by the expression of stem cell markers and the differentiation capability into three germ layers. LDS-iPSC8 may be a useful cell resource for the establishment of in vitro LDS modeling and the study for vascular and lymph vessel development.
- Published
- 2016
- Full Text
- View/download PDF
11. Silencing of interferon regulatory factor gene 6 in melanoma.
- Author
-
Yoshimasa Nobeyama and Hidemi Nakagawa
- Subjects
Medicine ,Science - Abstract
Methylation of a CpG island (CGI; a dense cluster of CpGs) located in the 5' region of a gene suppresses transcription of that gene. Interferon regulatory factor 6 (IRF6) is associated with the expression of interferon, which is used as an effective adjuvant therapy for melanoma, and is regarded as a tumor suppressor. However, little is known about the methylation status of the IRF6 gene in melanoma.The purpose was to determine the methylation status of the CGI located in the 5' region of IRF6 (5' IRF6 CGI) in melanoma.Quantitative real-time methylation-specific PCR (RT-MSP) and bisulfite sequencing were performed to examine IRF6 gene methylation status. Quantitative real-time reverse transcription-PCR (RT-PCR) was performed to examine IRF6 expression.The methylation level of the 5' IRF6 CGI was completely inversely correlated with cell sensitivity to interferon-β in eight examined melanoma cell lines. These methylation levels were high in the melanoma cell lines with suppression of IRF6 expression and were low in the cell lines with IRF6 expression. The methylation levels of the 5' IRF6 CGI ranged widely from 0.0% to 65.4% in 21 clinical melanoma samples but showed a narrow range of low levels between 0.0% to 7.2% in 24 clinical melanocytic nevus samples. These methylation levels were not associated with clinical parameters except for melanoma subtypes.IRF6 is aberrantly silenced by DNA methylation of the 5' IRF6 CGI in melanoma. The methylation status of IRF6 is potentially associated with the sensitivity of melanoma to interferon.
- Published
- 2017
- Full Text
- View/download PDF
12. Silencing of G0/G1 switch gene 2 in cutaneous squamous cell carcinoma.
- Author
-
Yoshimasa Nobeyama, Yoshinori Watanabe, and Hidemi Nakagawa
- Subjects
Medicine ,Science - Abstract
Methylation of a CpG island (CGI; a dense cluster of CpGs) located in the 5' region of a gene suppresses that gene's transcription. The expression of G0/G1 switch gene 2 (G0S2) is potentially associated with tumorigenesis. The aim of this study is to elucidate the methylation status of the CGI located in the 5' region of G0S2 (hereinafter called 5' G0S2 CGI) in cutaneous squamous cell carcinoma (SCC).Quantitative real-time methylation-specific PCR (RT-MSP) and bisulfite sequencing were performed to evaluate the methylation statuses of cutaneous SCC and normal epithelial cell samples. Quantitative real-time reverse transcription-PCR was performed to evaluate RNA expression levels. Immunohistochemical analysis was performed to detect protein expression.G0S2 was suppressed in the five SCC cell lines with 5' G0S2 CGI methylation levels of nearly 100.0% and was expressed in the two normal cultured keratinocytes with methylation levels of almost 0.0%. G0S2 was re-expressed in SCC cell lines treated with a demethylating agent. The in vivo methylation levels of 5' G0S2 CGI as determined by RT-MSP varied widely (0.0% to 77.7%) in 17 cutaneous SCC samples and narrowly (0.1% to 7.3%) in 6 normal epidermis samples. Nine cutaneous SCC samples exhibited higher methylation levels than the highest methylation level (7.3%) of the 6 normal epidermis samples. Bisulfite sequencing showed dense methylated CpG sites within 5' G0S2 CGI in these highly methylated cutaneous SCC samples. The methylation levels of the cutaneous SCC samples did not correlate with any clinical parameters investigated or with histopathological grading.G0S2 is silenced by aberrant DNA methylation in a subset of cutaneous SCCs.
- Published
- 2017
- Full Text
- View/download PDF
13. Aberrant DNA Methylation in Keratoacanthoma.
- Author
-
Yoshimasa Nobeyama and Hidemi Nakagawa
- Subjects
Medicine ,Science - Abstract
Keratoacanthoma (KA) is a self-limiting epidermal tumor for which histopathological examination sometimes suggests malignancy. Based on inconsistent clinical views, KA can be regarded as both a benign tumor and a variant of squamous cell carcinoma (SCC). Aberrant DNA methylation frequently occurs in malignant tumors but it scarcely occurs in benign tumors. Whether aberrant methylation occurs in KA has not been previously examined.The aim is to elucidate whether aberrant methylation of CpG islands (CGI) containing a high density of cytosine-guanine dinucleotide (CpG) sites occurs in KA.Five SCC cell lines, two cultured samples of normal human epidermal keratinocytes (NHEKs), 18 clinical SCC samples, and 21 clinical KA samples were analyzed with Infinium HumanMethylation450 BeadChips, quantitative real-time methylation-specific PCR (RT-MSP) and/or bisulfite sequencing.Genome-wide analyses of NHEK, KA, and SCC indicated that there was a greater number of aberrantly hypermethylated CGIs in SCC than in KA and there were aberrantly hypermethylated CGIs which are common in both. Among the common hypermethylated CGIs, RT-MSP and bisulfite sequencing targeting CGIs located on CCDC17, PVR, and MAP3K11 gene bodies also showed that methylation levels were significantly higher in KA than in normal epidermis. Statistical analyses suggested that the methylation level of CGI located on PVR in SCC might be correlated to lymph node metastasis (P = 0.013, Mann-Whitney U test) and that the methylation level of CGI in MAP3K11 in KA might be correlated to age (P = 0.031, linear regression analysis).Aberrant DNA methylation occurs in KA.
- Published
- 2016
- Full Text
- View/download PDF
14. Effect of Epinastine Hydrochloride, a Second-generation Histamine H1-receptor Antagonist, on Sensory Neurons in vitro
- Author
-
Masahiko Toyoda, Motokazu Nakamura, Kaori Nakada, Maki Iida, Masaki Nakamura, Masahiro Otani, Takafumi Etoh, Hidemi Nakagawa, and Masaaki Morohashi
- Subjects
epinastine ,histamine H1 antagonists ,nerve growth factor ,substance P ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Epinastine hydrochloride (epinastine) is a second-generation histamine Hi-receptor antagonist widely used as an anti-allergic and anti-pruritic. To explore possible new aspects of the anti-pruritic mechanism of epinastine, in particular any effects on the peripheral nervous system, we examined epinastine's effects on sensory neurons using cultured murine dorsal root ganglion (DRG). Methods: We performed a quantitative assessment of neurite growth and substance P (SP) release from isolated DRG in the presence versus the absence of epinastine. Mechanism(s) of epinastine’s effects on sensory neurons were detected by examining its neurotoxicity, inhibitory action on nerve growth factor (NGF), and modulatory function on NGFreceptors. Results: The percentage of DRG with outgrowing neurites, total number of neurites, and average extension length of neurites were decreased by epinastine in a concentration-dependent manner. Epinastine did not exhibit any evidence of neurotoxicity on sensory neurons, degradation and inactivation ability on NGF, or effects on expression of NGF receptors. Also, no effects on neural progenitor cells of the central nervous system in culture were observed. Epinastine suppressed capsaicin-induced SP release from DRG neurons in a dosedependent fashion. Conclusions: The results demonstrate that epinastine has inhibitory effects on sensory neuronal growth, which may explain its clinical effects including potent anti-pruritic activity.
- Published
- 2005
- Full Text
- View/download PDF
15. A Case of Angioedema Associated with Decreased C1 Inhibitor Activity
- Author
-
Chizuko Yano, Arihito Ota, and Hidemi Nakagawa
- Subjects
Angioedema ,C1 inhibitor ,complement ,HAE ,triggering factor ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: We report a case of a 31-year-old woman who began to notice swelling of her arms at age 20. She was once given a diagnosis of cellulitis, but her symptoms spontaneously resolved. The patient had swelling of the left forearm and palm and was referred to our department for evaluation. She had slight pain but no obvious weight gain. Case Summary: Antinuclear antibody and other autoantibodies, including anti-ds-DNA antibody, anti-RNP antibody, anti-Sm antibody, and anti-SS-A antibody were not detected. C1 inhibitor activity was low, C3 was normal, C4 was low, CH50 was low, and C1q was normal. Discussion: Based on the presence of the typical clinical features and the positive results on the complement tests, we diagnosed hereditary angioedema. A decrease in C1 inhibitor activity and an increase in specific protein concentrations indicated type 1.
- Published
- 2007
- Full Text
- View/download PDF
16. Generation of induced pluripotent stem cell ( <scp>iPSC</scp> ) from <scp>NY‐ESO‐I</scp> ‐specific cytotoxic T cells isolated from the melanoma patient with minor <scp>HLAs</scp> : The practical pilot study for the adoptive immunotherapy for melanoma using <scp>iPSC</scp> technology
- Author
-
Munenari Itoh, Shiho Kawagoe, Hidemi Nakagawa, Akihiko Asahina, and Hirotaka James Okano
- Subjects
Dermatology ,Molecular Biology ,Biochemistry - Published
- 2022
17. Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study
- Author
-
Hidemi Nakagawa, Atsuyuki Igarashi, Hidehisa Saeki, Kenji Kabashima, Tomomi Tamaki, Hironobu Kaino, and Yasushi Miwa
- Subjects
Immunology and Allergy ,General Medicine - Published
- 2023
18. Safety and efficacy of delgocitinib ointment in adult patients with atopic dermatitis based on disease severity
- Author
-
Atsuyuki Igarashi and Hidemi Nakagawa
- Published
- 2022
19. Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: Effect of Demographics and Baseline Disease Characteristics on Efficacy
- Author
-
Shinichi Imafuku, Yayoi Tada, Shinya Sakurai, Yoshinori Umezawa, Naoki Hoshii, and Hidemi Nakagawa
- Subjects
Moderate to severe ,Plaque psoriasis ,medicine.medical_specialty ,Demographics ,business.industry ,Dermatology ,Anti-tumour necrosis factor ,Placebo ,BMI ,Japan ,Certolizumab pegol ,Psoriasis Area and Severity Index ,Internal medicine ,medicine ,Disease characteristics ,business ,Body mass index ,Original Research ,medicine.drug - Abstract
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.
- Published
- 2021
20. Generation of induced pluripotent stem cell (iPSC) from NY-ESO-I-specific cytotoxic T cells isolated from the melanoma patient with minor HLAs: The practical pilot study for the adoptive immunotherapy for melanoma using iPSC technology
- Author
-
Munenari, Itoh, Shiho, Kawagoe, Hidemi, Nakagawa, Akihiko, Asahina, and Hirotaka James, Okano
- Abstract
Melanoma is one of the most severe skin cancers, derived from melanocytes. Among various therapies for melanoma, adoptive immunotherapy using tumor-infiltrating lymphocytes/chimeric antigen receptor-T cells (TCs) is advanced in recent years; however, the efficacy is still limited, and major challenges remain in terms of safety and cell supply. To solve the issues of adoptive immunotherapy, we utilized induced pluripotent stem cells (iPSCs), which have an unlimited proliferative ability and various differentiation capability. First, we monoclonally isolated CD8+ TCs specifically reactive with NY-ESO-1, one of tumor antigens, from the melanoma patient's monocytes after stimulated with NY-ESO-1 peptide by manual procedure, and cultured NY-ESO-1-specific TCs until proliferated and formed colonies. iPSCs were consequently generated from colony-forming TCs by exogenous expression of reprogramming factors using Sendai virus vector. After the RAG2 gene in TC-derived iPSCs (T-iPSCs) was knocked out for preventing T-cell receptor (TCR) rearrangement, T-iPSCs were re-differentiated into rejuvenated cytotoxic TCs. We confirmed that TCR of T-iPSC-derived TC was maintained as the same of original TCs. In conclusion, T-iPSCs have a potential to be an unlimited cell source for providing cytotoxic TCs. Our study could be a "touchstone" to develop iPSC-based adoptive immunotherapy for the treatment of melanoma for the future clinical use.
- Published
- 2022
21. Certolizumab Pegol for the Treatment of Moderate to Severe Plaque Psoriasis: 16-Week Results from a Phase 2/3 Japanese Study
- Author
-
Yoshinori Umezawa, Naoki Hoshii, Hidemi Nakagawa, and Shinya Sakurai
- Subjects
Body surface area ,medicine.medical_specialty ,business.industry ,MedDRA ,Incidence (epidemiology) ,Dermatology ,Dermatology Life Quality Index ,Placebo ,humanities ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Certolizumab pegol ,Psoriasis Area and Severity Index ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Tumor necrosis factor-alpha ,Plaque psoriasis ,business ,Adverse effect ,Original Research ,medicine.drug - Abstract
Introduction Certolizumab pegol (CZP), the Fc-free, PEGylated anti-tumor necrosis factor, is approved for the treatment of moderate to severe plaque psoriasis (PSO) in Western countries and in Japan, among other indications. Methods We report results from the first 16 weeks of a 52-week phase 2/3 trial of CZP in Japanese patients with PSO. Patients ≥ 20 years with PSO ≥ 6 months (Psoriasis Area and Severity Index [PASI] ≥ 12, body surface area affected ≥ 10%, and Physician’s Global Assessment [PGA] ≥ 3 on a 5-point scale) were randomized 2:2:1 to CZP 400 mg every 2 weeks (Q2W), CZP 200 mg Q2W (400 mg weeks 0/2/4), or placebo Q2W. Outcomes assessed to week 16: PASI 75, PASI 90, PGA 0/1 (Markov chain Monte Carlo), Dermatology Life Quality Index (DLQI 0/1) and Itch Numeric Rating Scale (INRS 0) (non-responder imputation), and DLQI and INRS change from baseline (last observation carried forward). Safety data were reported for patients receiving ≥ 1 dose of study medication through weeks 0–16; adverse events were evaluated using Medical Dictionary for Regulatory Activities version 18.1. Results A total of 127 patients were randomized to CZP 400 mg Q2W (N = 53), CZP 200 mg Q2W (N = 48), placebo (N = 26). Week 16 responder rates for CZP 400 mg/200 mg Q2W versus placebo were 87.1%/73.0% versus 7.9% for PASI 75; 75.7%/53.8% versus 0.2% for PASI 90; 66.7%/52.7% versus 0.0% for PGA 0/1 (all p
- Published
- 2021
22. Efficacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Foam in Japanese Patients with Psoriasis Vulgaris : A Phase Ⅲ Study
- Author
-
Hidemi Nakagawa, Takafumi Etoh, Tadao Okamoto, and Kazuo Isomae
- Subjects
medicine.medical_specialty ,chemistry.chemical_compound ,chemistry ,business.industry ,Psoriasis ,medicine ,Betamethasone dipropionate ,Dermatology ,medicine.disease ,business ,Calcipotriol ,medicine.drug - Published
- 2021
23. Efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 64‐week phase 3 study (reSURFACE 1)
- Author
-
Yukari Okubo, Shigetoshi Sano, Masaru Honma, Alan M. Mendelsohn, Yayoi Tada, Atsuyuki Igarashi, Akimichi Morita, Hidemi Nakagawa, Shinichi Imafuku, Masaki Kawamura, and Mamitaro Ohtsuki
- Subjects
Adult ,medicine.medical_specialty ,interleukin‐23 subunit p19 ,Population ,Tildrakizumab ,monoclonal ,Dermatology ,Placebo ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,law.invention ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,Japan ,law ,Psoriasis Area and Severity Index ,Internal medicine ,Psoriasis ,tildrakizumab ,medicine ,antibodies ,Humans ,education ,Adverse effect ,Body surface area ,education.field_of_study ,humanized ,business.industry ,General Medicine ,Original Articles ,psoriasis ,medicine.disease ,Treatment Outcome ,030220 oncology & carcinogenesis ,randomized controlled trial ,Japanese ,Original Article ,business - Abstract
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.
- Published
- 2021
24. 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)
- Author
-
Yayoi Tada, Akimichi Morita, Atsuyuki Igarashi, Shinichi Imafuku, Hidemi Nakagawa, Shigetoshi Sano, Stephen J. Rozzo, Yukari Okubo, Osamu Nemoto, Masaki Kawamura, and Mamitaro Ohtsuki
- Subjects
Adult ,Moderate to severe ,medicine.medical_specialty ,Tildrakizumab ,Phases of clinical research ,Subgroup analysis ,Dermatology ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Psoriasis Area and Severity Index ,0302 clinical medicine ,Double-Blind Method ,Japan ,Psoriasis ,Internal medicine ,tildrakizumab ,medicine ,Humans ,biologic therapy ,Adverse effect ,business.industry ,IL‐23p19 ,Original Articles ,psoriasis ,General Medicine ,medicine.disease ,Discontinuation ,Treatment Outcome ,030220 oncology & carcinogenesis ,Original Article ,business - Abstract
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.
- Published
- 2021
25. Subanalysis of Efficacy by Body Region and Sign and Safety by Body Region of Delgocitinib Ointment
- Author
-
Atsuyuki Igarashi and Hidemi Nakagawa
- Published
- 2021
26. Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Generalized Pustular Psoriasis and Erythrodermic Psoriasis: 52-Week Results
- Author
-
Yukari Okubo, Yoshinori Umezawa, Shinya Sakurai, Naoki Hoshii, and Hidemi Nakagawa
- Subjects
Dermatology - Abstract
We report an exploratory analysis of the efficacy and safety of certolizumab pegol (CZP) in Japanese patients with generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) (NCT03051217).Patients ≥ 20 years with GPP or EP were randomized 1:1 to open-label CZP 400 mg every 2 weeks (Q2W) or 200 mg Q2W (400 mg weeks 0/2/4) for 16 weeks; patients who achieved "much improved" or "very much improved" on the Global Improvement Score (GIS; for GPP) or a PASI 50 response (≥ 50% reduction from baseline Psoriasis Area and Severity Index; for EP) continued to week 52. Efficacy outcomes assessed included Clinical Global Impression of Improvement (CGI-I), Dermatology Life Quality Index (DLQI 0/1), and Itch Numeric Rating Scale (INRS 0). GIS and Japanese Dermatological Association (JDA) severity index were assessed in patients with GPP, and PASI and Physician's Global Assessment (PGA) in patients with EP. Treatment-emergent adverse events (TEAEs) were evaluated through weeks 0-52.Of 22 patients randomized, 19 completed week 52. At week 16, all reported outcomes improved with both CZP doses and were generally maintained through week 52. At week 52, 6/7 GPP and 12/12 EP patients achieved CGI-I response ("improved" or "remission"). Also, 4/7 GPP and 7/12 EP patients achieved DLQI 0/1; 2/7 GPP and 2/12 EP patients achieved INRS 0. Meanwhile, 6/7 patients with GPP achieved GIS response, and JDA severity index was reduced from baseline. We found that 9/12 and 5/12 patients with EP achieved PASI 90 and PGA 0/1, respectively. Overall, three serious TEAEs were reported in three CZP 400 mg Q2W-treated patients.CZP treatment over 16 weeks improved the signs and symptoms of GPP and EP, and improvements were maintained through week 52. No new safety signals were identified.ClinicalTrials.gov identifier, NCT03051217.
- Published
- 2022
27. Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis
- Author
-
Hajime Iizuka, Hidemi Nakagawa, Yasunobu Furukawa, Natsuko Kikuta, Kenji Ootaki, Munetake Shimabe, and Osamu Nemoto
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Fever ,Cmax ,OX40 Ligand ,Dermatology ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,Biochemistry ,Eczema Area and Severity Index ,Gastroenterology ,Drug Administration Schedule ,Dermatitis, Atopic ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,Infusions, Intravenous ,Adverse effect ,Molecular Biology ,business.industry ,Atopic dermatitis ,Middle Aged ,medicine.disease ,Chills ,Treatment Outcome ,030104 developmental biology ,Tolerability ,Pharmacodynamics ,Female ,medicine.symptom ,business - Abstract
Background KHK4083, a fully human anti-OX40 monoclonal antibody, is a potential novel therapeutic option for moderate to severe atopic dermatitis (AD), targeting the immunopathogenic pathways. Objective Assess the safety and tolerability of repeated doses of KHK4083 in patients with moderate to severe AD, and investigate the pharmacokinetics and immunogenicity of KHK4083. Additionally, assess the clinical efficacy and pharmacodynamics as exploratory objectives. Methods In this phase 1, single-center, open-label, repeated-dose study, a total of 22 patients received KHK4083 10 mg/kg IV on Day 1, Day 15 and Day 29, and were followed until Day 155. Results There were no deaths, serious adverse events (SAEs), or discontinuations due to adverse events (AEs). Common treatment-emergent AEs were mild or moderate pyrexia (11 patients, 50.0 %), and chills (8 patients, 36.4 %). No clinically meaningful changes in the laboratory values, vital signs, and electrocardiogram recordings were observed. The Cmax was 267 ± 53 μg/mL and the t1/2 was 303 ± 88 h at Day 29. The overall assessment of antibodies against KHK4083 (immunogenicity) showed low positive responses. Continued improvement in the Eczema Area and Severity Index (EASI) and Investigator’s Global Assessment (IGA) scores were observed throughout the study. The mean and median percent changes in thymus and activation-regulated chemokine (TARC) continued to decrease over time to −70.4 and −78.8 % until Day 155. Conclusion Repeated intravenous infusion of KHK4083 had an acceptable safety profile in patients with moderate to severe AD. Sustained improvement in the symptoms of AD was observed after completion of KHK4083 treatment.
- Published
- 2020
28. Footprint-free gene mutation correction in induced pluripotent stem cell (iPSC) derived from recessive dystrophic epidermolysis bullosa (RDEB) using the CRISPR/Cas9 and piggyBac transposon system
- Author
-
Katsuto Tamai, Hirotaka James Okano, Hidemi Nakagawa, Shiho Kawagoe, Munenari Itoh, and Akihiko Asahina
- Subjects
Keratinocytes ,0301 basic medicine ,Transposable element ,Collagen Type VII ,Induced Pluripotent Stem Cells ,Dermatology ,Biology ,Gene mutation ,Biochemistry ,Cell Line ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Genome editing ,Humans ,CRISPR ,Homologous Recombination ,Induced pluripotent stem cell ,Molecular Biology ,Transposase ,Gene Editing ,Genetics ,Cas9 ,Cell Differentiation ,Genetic Therapy ,Epidermolysis Bullosa Dystrophica ,030104 developmental biology ,PiggyBac Transposon System ,Mutation ,DNA Transposable Elements ,CRISPR-Cas Systems - Abstract
Background Recessive dystrophic epidermolysis bullosa (RDEB) is a monogenic skin blistering disorder caused by mutations in the type VII collagen gene. A combination of biological technologies, including induced pluripotent stem cells (iPSCs) and several gene-editing tools, allows us to develop gene and cell therapies for such inherited diseases. However, the methodologies for gene and cell therapies must be continuously innovated for safe clinical use. Objective In this study, we used the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology to correct the pathogenic mutation in RDEB-specific iPSCs, and the piggyBac transposon system so that no residual gene fragments remained in the genome of iPSCs after correcting the mutation. Methods For homologous recombination (HR)-based gene editing using CRISPR/Cas9, we designed guide RNA and template DNA including homologous sequences with drug-mediated selection cassette flanked by inverted repeat sequences of the transposon. HR reaction using CRISPR/Cas9 was induced in RDEB-specific iPSCs, and mutation-corrected iPSCs (MC-iPSCs) was obtained. Consequently, the selection cassette in the genome of MC-iPSCs was removed by transposase expression. Results After CRISPR/Cas9-induced gene editing, we confirmed that the pathogenic mutation in RDEB-specific iPSCs was properly corrected. In addition, MC-iPSCs had no genetic footprint after removing the selection cassette by transposon system, and maintained their “stemness”. When differentiating MC-iPSCs into keratinocytes, the expression of type VII collagen was restored. Conclusions Our study demonstrated one of the safer approaches to establish gene and cell therapies for skin hereditary disorders for future clinical use.
- Published
- 2020
29. Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study
- Author
-
Kenji Ootaki, Yukie Yamaguchi, Hidemi Nakagawa, and Nobumichi Takatsu
- Subjects
Adult ,Male ,brodalumab ,safety ,medicine.medical_specialty ,Brodalumab ,Postmarketing surveillance ,Dermatology ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,Drug Administration Schedule ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Psoriatic arthritis ,0302 clinical medicine ,Japan ,Candidiasis, Oral ,Psoriasis Area and Severity Index ,Internal medicine ,Psoriasis ,Influenza, Human ,medicine ,Humans ,Adverse effect ,Receptors, Interleukin-17 ,Dose-Response Relationship, Drug ,business.industry ,Original Articles ,psoriasis ,General Medicine ,Dermatology Life Quality Index ,Middle Aged ,medicine.disease ,long‐term care ,Rheumatology ,Treatment Outcome ,Nasopharyngitis ,030220 oncology & carcinogenesis ,Female ,Original Article ,business - Abstract
Brodalumab, an interleukin‐17 receptor A inhibitor, demonstrated rapid and robust efficacy with a favorable safety profile in patients with moderate to severe plaque psoriasis. Here, we present data from a multicenter, open‐label extension study in patients with plaque psoriasis with/without psoriatic arthritis who completed 64 weeks of treatment with brodalumab (140 or 210 mg, every 2 weeks [Q2W]). Patients were enrolled to evaluate the long‐term safety and efficacy of a modified dose of brodalumab. Eligible patients were switched to a reduced dose of brodalumab (140 mg every 4 weeks on day 1) in the extension study; the dose and dosing interval were modified sequentially at the physician’s discretion (minimum 140 mg every 8 weeks and maximum 210 mg Q2W) until drug approval, after which all patients were switched to 210 mg Q2W for postmarketing surveillance. Of the 129 patients enrolled, 107 (82.9%) completed the 108‐week or more extension study. All patients had psoriasis that was well controlled with brodalumab treatment on day 1. Improvement in psoriasis‐related symptoms, evaluated with the Psoriasis Area and Severity Index, Psoriasis Scalp Severity Index, Dermatology Life Quality Index, Nail Psoriasis Severity Index, and American College of Rheumatology 20, 50 and 70, was maintained during the 108‐week extension study. Brodalumab treatment was well tolerated throughout, and no new safety signals were identified. The most commonly reported treatment‐related adverse event was nasopharyngitis, followed by influenza and oral candidiasis. No cases of serious candida infection or Crohn’s disease were observed in this study. Serious treatment‐related adverse events, such as appendicitis, brain abscess, bacterial meningitis, colon cancer, immunoglobulin A nephropathy and tubulointerstitial nephritis, were reported in one patient each. No anti‐brodalumab‐binding antibodies or brodalumab‐neutralizing antibodies were detected in any patient throughout the extension study. Overall, the long‐term efficacy and safety of brodalumab were demonstrated over 108 weeks.
- Published
- 2020
30. Japanese guidance for use of biologics for psoriasis (the 2019 version)
- Author
-
Tadashi Terui, Hidemi Nakagawa, Akira Watanabe, Akimichi Morita, Mayumi Komine, Akihiko Asahina, Shinichi Imafuku, Hiroshi Yotsuyanagi, Mamitaro Ohtsuki, Shigetoshi Sano, Hideshi Torii, Takafumi Etoh, Atsuyuki Igarashi, Hidehisa Saeki, and Masatoshi Abe
- Subjects
medicine.medical_specialty ,Brodalumab ,Dermatology ,Antibodies, Monoclonal, Humanized ,Patient Care Planning ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Ustekinumab ,medicine ,Adalimumab ,Humans ,Psoriasis ,Intensive care medicine ,Biological Products ,Risankizumab ,Drug Substitution ,business.industry ,Patient Selection ,Contraindications, Drug ,Antibodies, Monoclonal ,General Medicine ,Infliximab ,Ixekizumab ,Guselkumab ,030220 oncology & carcinogenesis ,Drug Therapy, Combination ,Secukinumab ,Dermatologic Agents ,business ,medicine.drug - Abstract
As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Since 2015, three IL-17 inhibitors of secukinumab and ixekizumab, anti-IL-17A antibodies, and brodalumab, an anti-IL-17 receptor antibody, and two anti-IL-23p19 antibodies of guselkumab and risankizumab, have also been launched. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors and patient background factors, sharing such information with patients. The following can be listed as points to be considered for the selection of biologics: drug effects (e.g. strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g. infections, administration-related reactions and relationships with other comorbidities), convenience for patients (e.g. hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration) and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors.
- Published
- 2020
31. Long‐term safety and efficacy of delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with atopic dermatitis
- Author
-
Takeshi Nagata, Osamu Nemoto, Hidehisa Saeki, Hidemi Nakagawa, Atsuyuki Igarashi, Ryusei Murata, and Hironobu Kaino
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Population ,Dermatology ,Dermatitis, Contact ,Eczema Area and Severity Index ,Severity of Illness Index ,Drug Administration Schedule ,Dermatitis, Atopic ,Ointments ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Japan ,Acne Vulgaris ,medicine ,Humans ,Janus Kinase Inhibitors ,Pyrroles ,topical ,Adverse effect ,education ,Janus kinase inhibitor ,Acne ,delgocitinib ,Folliculitis ,education.field_of_study ,atopic dermatitis ,business.industry ,Incidence (epidemiology) ,Incidence ,General Medicine ,Atopic dermatitis ,Original Articles ,medicine.disease ,Treatment Outcome ,Nasopharyngitis ,030220 oncology & carcinogenesis ,long‐term safety ,Original Article ,Female ,business ,Contact dermatitis - Abstract
Previous studies demonstrated that delgocitinib ointment, a novel topical Janus kinase inhibitor, rapidly improved clinical signs and symptoms of atopic dermatitis (AD) in Japanese adult patients. We sought to evaluate the long‐term safety and efficacy of delgocitinib 0.5% ointment in a 52‐week study (QBA4‐2). Japanese patients aged 16 years or older with AD received delgocitinib 0.5% ointment b.i.d. for up to 52 weeks. Topical corticosteroids for the treatment of worsening of AD could be used at the investigators’ discretion during the treatment period. Safety end‐points included the incidence and severity of adverse events (AEs). Pooled safety analyses included the data from the other long‐term study (QBA4‐1). Efficacy end‐points included the percentage change from baseline in the modified Eczema Area and Severity Index (mEASI). A total of 506 patients were included in the pooled safety population. Overall, AEs were reported in 69.0% of patients; most AEs were mild and unrelated to delgocitinib ointment. The most common AE was nasopharyngitis, followed by contact dermatitis, acne, and application site folliculitis. No skin atrophy or telangiectasia was found at the application sites of delgocitinib ointment. Application site irritation symptoms were infrequent (
- Published
- 2019
32. IL-10–Producing Regulatory B Cells Are Decreased in Patients with Atopic Dermatitis
- Author
-
Akihiko Asahina, Hidemi Nakagawa, Miki Kurita, Takaoki Ishiji, Koichi Yanaba, Mitsuha Hayashi, Ayumi Yoshizaki, Yuki Yoshihara, and Yozo Ishiuji
- Subjects
Adult ,Male ,Adolescent ,Regulatory B cells ,Dermatology ,Severity of Illness Index ,Biochemistry ,Dermatitis, Atopic ,Young Adult ,medicine ,Humans ,In patient ,Lymphocyte Count ,SCORAD ,Molecular Biology ,B-Lymphocytes, Regulatory ,medicine.diagnostic_test ,business.industry ,Cell Biology ,Atopic dermatitis ,Middle Aged ,medicine.disease ,Healthy Volunteers ,Interleukin-10 ,Interleukin 10 ,Case-Control Studies ,Immunology ,Female ,business - Published
- 2019
33. Interstitial Pneumonia in Psoriasis
- Author
-
Shunsuke Minagawa, Hidemi Nakagawa, Hironori Kawamoto, Yoshinori Umezawa, Jun Araya, Hiromichi Hara, Kazuyoshi Kuwano, Akihiko Asahina, Yumi Kaneko, and Takanori Numata
- Subjects
medicine.medical_specialty ,SEC, secukinumab ,Radiography ,IP, interstitial pneumonia ,UST, ustekinumab ,Gastroenterology ,Pathogenesis ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Psoriasis ,Ustekinumab ,medicine ,030212 general & internal medicine ,lcsh:R5-920 ,Lung ,business.industry ,Interleukin ,PASI, psoriasis area severity index ,medicine.disease ,CT, computed tomography ,IL, interleukin ,KL-6, Krebs von den Lungen-6 ,medicine.anatomical_structure ,Reticular connective tissue ,Secukinumab ,Original Article ,business ,lcsh:Medicine (General) ,medicine.drug - Abstract
Objective To investigate the relationship between psoriasis and interstitial pneumonia (IP). Patients and Methods We analyzed the clinical data of patients with psoriasis treated with biologic agents from June 1, 2008, to June 30, 2017, retrospectively. Chest computed tomography was performed in 392 patients before treatment. The clinical characteristics and radiographic findings of these patients were evaluated. Results Of the 392 patients with psoriasis, IP was detected in 8 patients (2%). Bilateral ground-glass and/or irregular linear (reticular) opacity in the lower lung zone was the most common chest computed tomography finding. Five of the 8 patients with IP were treated with anti–interleukin (IL) 12/IL-23 or IL-17 antibodies, leading to decreased or stable IP activity. Conclusion Interstitial pneumonia was detected in 2% of patients with psoriasis who needed systemic treatments. Ground-glass and/or irregular linear (reticular) opacity in the bilateral lower lobes was characteristic of IP with psoriasis. The IL-23/IL-17 axis may play important roles in the pathogenesis of IP in psoriasis.
- Published
- 2018
34. Effect of anti-interleukin-17 biologics on Krebs von den Lungen-6 level in patients with psoriasis
- Author
-
Hidemi Nakagawa, Shunsuke Minagawa, Yoshinori Umezawa, Kazuyoshi Kuwano, Hiromichi Hara, Takanori Numata, Hanae Miyagawa, Akihiko Asahina, and Jun Araya
- Subjects
medicine.medical_specialty ,Future studies ,Dermatology ,Gastroenterology ,Pathogenesis ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Psoriasis ,medicine ,Humans ,In patient ,Interstitial pneumonia ,Retrospective Studies ,Biological Products ,business.industry ,Mucin-1 ,Interleukin ,General Medicine ,medicine.disease ,030220 oncology & carcinogenesis ,Population study ,Interleukin 17 ,business ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,Biomarkers - Abstract
Interleukin (IL)-17 plays critical roles in the pathogenesis of both psoriasis and interstitial pneumonia (IP). We hypothesized that anti-IL-17 biologics might suppress both clinically relevant and latent IP activity and decrease Krebs von den Lungen-6 (KL-6) level in psoriasis patients. We aimed to elucidate the effects of anti-IL-17 biologics on KL-6 levels. We retrospectively analyzed the clinical data of psoriasis patients treated with anti-IL-17 biologics. KL-6 levels were measured before treatment (baseline) and at 3 and 6 months after the initiation of the treatment, and ratios of KL-6 levels at each time point to the baseline levels were calculated. Chest computed tomography (CT) was performed on patients with coexisting IP. The clinical characteristics and radiographic findings were evaluated. A total of 294 psoriasis patients were treated with anti-IL-17 biologics. Baseline KL-6 levels were higher than 401 U/mL in 34 patients (high baseline KL-6 group). While anti-IL-17 biologics did not affect KL-6 levels and ratios of KL-6 to the baseline levels at any time point in the overall study population, they decreased both KL-6 levels and ratios at 6 months after the initiation of the treatment in the high baseline KL-6 group. A total of 10 patients with coexisting IP showed decreasing ratios of KL-6 to the baseline levels at 6 months without affecting coexisting IP in CT performed at 3-12 months. Anti-IL-17 biologics decreased KL-6 levels in the high baseline KL-6 group regardless of recognizable IP. A decrease in KL-6 levels was not associated with a radiographic improvement of IP, which should be examined in large numbers with long-term observations in future studies.
- Published
- 2021
35. Efficacy and Safety of Certolizumab Pegol in Japanese Patients with Moderate to Severe Plaque Psoriasis: 52-Week Results
- Author
-
Yoshinori Umezawa, Shigetoshi Sano, Nicola Tilt, Akimichi Morita, Hidemi Nakagawa, Naoki Hoshii, Shinichi Imafuku, Shinya Sakurai, Akihiko Asahina, and Yayoi Tada
- Subjects
Moderate to severe ,medicine.medical_specialty ,Dermatology ,Nail psoriasis ,Placebo ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Psoriasis Area and Severity Index ,Certolizumab pegol ,Internal medicine ,medicine ,Original Research ,Plaque psoriasis ,business.industry ,Dermatology Life Quality Index ,Anti-tumour necrosis factor ,humanities ,Japanese patients ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
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.
- Published
- 2021
36. Delgocitinib ointment in pediatric patients with atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and a subsequent open-label, long-term study
- Author
-
Atsuyuki Igarashi, Manabu Oda, Hidemi Nakagawa, Takeshi Nagata, Osamu Nemoto, Kenji Kabashima, and Hidehisa Saeki
- Subjects
Adult ,medicine.medical_specialty ,Eczema ,Dermatology ,Eczema Area and Severity Index ,Dermatitis, Atopic ,Double blind ,Ointments ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Rescue therapy ,Internal medicine ,medicine ,Humans ,Pyrroles ,Adverse effect ,Child ,Janus kinase inhibitor ,Emollients ,business.industry ,Atopic dermatitis ,medicine.disease ,Long term learning ,Treatment Outcome ,030220 oncology & carcinogenesis ,Open label ,business - Abstract
BACKGROUND Delgocitinib 0.5% ointment, a topical Janus kinase inhibitor, has been approved in Japan for adult patients with atopic dermatitis (AD). OBJECTIVE To evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD. METHODS Part 1 of this study was a 4-week double-blind period in which Japanese patients aged 2 through 15 years were randomized in a 1:1 ratio to delgocitinib 0.25% ointment or vehicle ointment. Part 2 was a 52-week extension period. Eligible patients entered part 2 to receive 0.25% or 0.5% delgocitinib ointment. RESULTS At the initiation of the study, approximately half of the patients had moderate AD. At the end of treatment in part 1, the least-squares mean percent change from baseline in modified Eczema Area and Severity Index score, the primary efficacy endpoint, was significantly greater for delgocitinib ointment than for vehicle (-39.3% vs +10.9%, P
- Published
- 2020
37. Relationship between serum trough levels and efficacy of brodalumab from a post hoc exploratory analysis of a Japanese study in patients with plaque psoriasis
- Author
-
Hidemi Nakagawa, Yukie Yamaguchi, Hiroki Kitabayashi, Hiroki Okada, and Yasumasa Kanai
- Subjects
brodalumab ,medicine.medical_specialty ,Post hoc ,Brodalumab ,Dermatology ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Psoriasis Area and Severity Index ,Internal medicine ,Psoriasis ,medicine ,pharmacodynamics ,Humans ,In patient ,biologics ,plaque psoriasis ,Plaque psoriasis ,business.industry ,Antibodies, Monoclonal ,General Medicine ,Exploratory analysis ,Original Articles ,medicine.disease ,Treatment Outcome ,030220 oncology & carcinogenesis ,Pharmacodynamics ,interleukin‐17 receptor A ,Original Article ,business - Abstract
Previous clinical studies have shown that efficacy and serum brodalumab levels are dose dependent in patients with psoriasis receiving the same dose of brodalumab during the study. This study aimed to investigate the association between dosage, serum levels, and efficacy of brodalumab in Japanese patients with plaque psoriasis with dosage variations during the study. This was a post hoc exploratory analysis of a 108‐week, multicenter, open‐label extension study, which changed into a post‐marketing surveillance study following brodalumab approval in Japan. Eligible patients with plaque psoriasis (n = 129) received brodalumab 140 mg every 4 weeks on Day 1; dosage change at physician’s discretion from 140 mg every 8 weeks to 210 mg every 2 weeks was permitted; patients switched to 210 mg every 2 weeks during the post‐marketing surveillance study. Exploratory endpoints included serum brodalumab levels at Weeks 28 and 108, its association with Psoriasis Area and Severity Index score, and Psoriasis Area and Severity Index score in patients receiving brodalumab 210 mg every 2 weeks at end of study. Median brodalumab trough levels were significantly higher (P 2 at Week 28 (P = 0.0153). Of 100 patients receiving 210 mg every 2 weeks at end of study, 89% had a Psoriasis Area and Severity Index score ≤2. In patients with plaque psoriasis, brodalumab efficacy may depend upon sustained serum trough levels and can be restored by using the approved dose.
- Published
- 2020
38. Patient satisfaction and efficacy of calcipotriol plus betamethasone dipropionate gel in plaque psoriasis patients with poor adherence
- Author
-
Masanori Hagiwara, Yuta Uwajima, Koma Matsuo, Hajime Sasaki, Hiroyasu Katayama, Hidemi Nakagawa, Hidetoshi Takahashi, Katsumi Tanito, and Masato Koda
- Subjects
Male ,medicine.medical_specialty ,patient satisfaction ,Betamethasone dipropionate ,Dermatology ,patient treatment preference ,Betamethasone ,030207 dermatology & venereal diseases ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Patient satisfaction ,Calcitriol ,Psoriasis Area and Severity Index ,Internal medicine ,Psoriasis ,medicine ,Humans ,adherence ,Calcipotriol ,plaque psoriasis ,Body surface area ,Plaque psoriasis ,business.industry ,Therapeutic effect ,General Medicine ,Original Articles ,Middle Aged ,medicine.disease ,Drug Combinations ,Treatment Outcome ,topical treatment ,chemistry ,030220 oncology & carcinogenesis ,Female ,Original Article ,Dermatologic Agents ,business ,medicine.drug - Abstract
Poor adherence to treatment makes achievement of expected therapeutic outcomes more difficult, especially in chronic disorders like psoriasis. There are several critical factors that affect adherence, including therapeutic efficacy, patient satisfaction, patient treatment preferences and ease of application, especially in topical therapy. The fixed combination of calcipotriol plus betamethasone dipropionate in a gel formulation (Cal/BDP gel) has been recommended as a first‐line topical treatment for mild to moderate plaque. To examine whether Cal/BDP gel can effectively improve treatment adherence, we investigated the effects of once‐daily Cal/BDP gel on factors affecting adherence at weeks 4, 8 and 12 in patients with plaque psoriasis who had poor adherence. A total of 46 subjects were enrolled and 41 subjects (26 men, 15 women; mean age, 50.5 years) were included in the analysis. The following items were evaluated: Patient Preference Questionnaire, nine‐item Treatment Satisfaction Questionnaire for Medication, Physician’s Global Assessment (PGA), modified Psoriasis Area and Severity Index (m‐PASI), body surface area (BSA), pruritus, medication adherence and application time. In patients with poor adherence, many preferred treatment with Cal/BDP gel and evaluated its convenience as “excellent” at weeks 4 and 12. At week 12, the proportion of “clear”/”very mild” ratings using PGA reached 20.5%, the change from baseline on m‐PASI was −61.3% and the change from baseline on BSA was −39.8%, suggesting that the skin symptoms of psoriasis had improved greatly. In most patients, the longer they used Cal/BDP gel, the greater their preference and satisfaction and the higher the therapeutic effect, which increased markedly over 12 weeks. These results suggest that Cal/BDP gel can effectively improve treatment adherence. Conversely, high adherence to Cal/BDP gel must enhance the therapeutic effect. Therefore, we expect that Cal/BDP gel could become the mainstay of topical psoriasis treatment in patients with poor adherence.
- Published
- 2020
39. Lack of association of TNFA , TNFRSF1B and TNFAIP3 gene polymorphisms with response to anti‐tumor necrosis factor therapy in Japanese patients with psoriasis
- Author
-
Mayumi Tamari, Hidemi Nakagawa, Osamu Fukuchi, Toshihiro Ito, Yoshinori Umezawa, Michiko Ito, Hidehisa Saeki, Akihiko Asahina, Tomomitsu Hirota, and Mami Momose
- Subjects
Adult ,Male ,Genotyping Techniques ,Drug Resistance ,Dermatology ,Polymorphism, Single Nucleotide ,Asian People ,Japan ,Psoriasis ,medicine ,Humans ,Receptors, Tumor Necrosis Factor, Type II ,Tumor Necrosis Factor alpha-Induced Protein 3 ,Aged ,Tumor Necrosis Factor-alpha ,business.industry ,Adalimumab ,General Medicine ,Middle Aged ,medicine.disease ,Infliximab ,Anti-Tumor Necrosis Factor Therapy ,Immunology ,Female ,Tumor necrosis factor alpha ,TNFAIP3 Gene ,Dermatologic Agents ,business - Published
- 2020
40. Tacrolimus ointment for the treatment of adult and pediatric atopic dermatitis: Review on safety and benefits
- Author
-
Hiroshi Morimoto, Hidemi Nakagawa, and Mamitaro Ohtsuki
- Subjects
Adult ,medicine.medical_specialty ,Skin Neoplasms ,Calcineurin Inhibitors ,Boxed warning ,Postmarketing surveillance ,Review Article ,Dermatology ,Administration, Cutaneous ,Tacrolimus ,Dermatitis, Atopic ,Ointments ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Medicine ,Adverse effect ,Review Articles ,Glucocorticoids ,Skin ,child ,atopic dermatitis ,drug labeling ,business.industry ,General Medicine ,Atopic dermatitis ,medicine.disease ,Calcineurin ,stomatognathic diseases ,Treatment Outcome ,030220 oncology & carcinogenesis ,Observational study ,Dermatologic Agents ,Atrophy ,Skin cancer ,business - Abstract
Atopic dermatitis (AD) requires long‐term management, mainly with topical anti‐inflammatory agents. Topical corticosteroids (TCS) and tacrolimus ointment (TAC‐O) are recommended as first‐line treatments for AD. However, the long‐term use of TCS is limited by cutaneous adverse events such as skin atrophy. For TAC‐O, Japanese and US labelings were updated in 2003 and 2006, respectively, to include a boxed warning about a theoretical risk of skin cancer and lymphoma in patients treated with topical calcineurin inhibitors. However, TAC‐O has been used worldwide for longer than 15 years to treat adult and pediatric patients with AD. Available data suggest that TAC‐O is effective and well tolerated, and can improve quality of life. TAC‐O has successfully been used in the proactive management of AD consisting of long‐term intermittent use to prevent, delay or reduce the occurrence of AD flares. Systemic drug absorption after TAC‐O application is negligible and unlikely to result in systemic immunosuppression. There is currently no strong evidence of an increased rate of malignancy in treated patients, and observational data from postmarketing surveillance studies have shown no safety concerns. In the absence of robust evidence, the warning about the carcinogenic potential in the Japanese labeling for TAC‐O does not appear justified and should be reconsidered. This mitigation of description would allow adult and pediatric patients with AD to receive the effective treatment more appropriately.
- Published
- 2018
41. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study
- Author
-
Ryosuke Goto, Hidemi Nakagawa, Mamitaro Ohtsuki, Richuan Zheng, Hitomi Morishima, and Hiroshi Kubo
- Subjects
Adult ,Male ,medicine.medical_specialty ,Placebo-controlled study ,Phases of clinical research ,Dermatology ,Antibodies, Monoclonal, Humanized ,Placebo ,Severity of Illness Index ,Gastroenterology ,Placebos ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Japan ,Psoriasis Area and Severity Index ,Psoriasis ,Internal medicine ,Interleukin 23 ,Humans ,Medicine ,Adverse effect ,plaque psoriasis ,business.industry ,Incidence ,Antibodies, Monoclonal ,Original Articles ,General Medicine ,Middle Aged ,medicine.disease ,guselkumab ,interleukin‐23 ,Treatment Outcome ,Guselkumab ,Nasopharyngitis ,030220 oncology & carcinogenesis ,Interleukin-23 Subunit p19 ,Female ,Original Article ,long term ,business - Abstract
Previous global studies of guselkumab have demonstrated clinical benefits in patients with psoriasis. The aim of this 52‐week, phase 3 study was to evaluate efficacy and safety of guselkumab in Japanese patients with moderate to severe plaque‐type psoriasis. Patients randomly received guselkumab 50 mg or 100 mg at weeks 0, 4 and every 8 weeks, or placebo with cross‐over to guselkumab 50 mg or 100 mg at week 16. Co‐primary end‐points were the proportion of patients achieving Investigator's Global Assessment (IGA) cleared/minimal (0/1) and 90% or more improvement in Psoriasis Area and Severity Index (PASI‐90) at week 16. Overall, 192 patients were randomized to placebo, guselkumab 50 mg or 100 mg. At week 16, patients in the placebo group were crossed over to guselkumab 50 mg or 100 mg. At week 16, a significantly (P < 0.001) higher proportion of patients receiving guselkumab 50 mg and 100 mg versus placebo achieved IGA 0/1 (92.3% and 88.9% vs 7.8%) and PASI‐90 (70.8% and 69.8% vs 0%). Patients in guselkumab 50 mg and 100 mg groups achieved significant improvement versus placebo in PASI‐75 (89.2% and 84.1% vs 6.3%, P < 0.001) at week 16; improvement was maintained through week 52. Incidences of treatment‐emergent adverse events were comparable among the groups through week 16; the most commonly reported was nasopharyngitis. No new safety concerns were observed until week 52. In conclusion, guselkumab treatment demonstrated superior efficacy over placebo and was well tolerated in Japanese patients with moderate to severe plaque‐type psoriasis.
- Published
- 2018
42. Introduction of the TERT and BMI1 genes into murine dermal papilla cells ameliorates hair inductive activity
- Author
-
Hidemi Nakagawa, Munenari Itoh, Hitoshi Okochi, Shigeharu G. Yabe, and Masahiro Kiso
- Subjects
Time Factors ,Dermatology ,Biology ,Transfection ,Biochemistry ,Mice ,Downregulation and upregulation ,medicine ,Animals ,Humans ,Telomerase ,Molecular Biology ,Gene ,Cells, Cultured ,Polycomb Repressive Complex 1 ,Phenotype ,Up-Regulation ,Cell biology ,Dermal papillae ,medicine.anatomical_structure ,BMI1 ,Vibrissae ,Signal transduction ,Hair Follicle ,Signal Transduction - Published
- 2018
43. Phase 1 studies to assess the safety, tolerability and pharmacokinetics of JTE-052 (a novel Janus kinase inhibitor) ointment in Japanese healthy volunteers and patients with atopic dermatitis
- Author
-
Hidemi Nakagawa, Osamu Nemoto, Takeshi Nagata, Hiroyuki Yamada, and Noriko Ninomiya
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Dermatology ,Administration, Cutaneous ,Placebo ,Severity of Illness Index ,Eczema Area and Severity Index ,Dermatitis, Atopic ,Ointments ,Placebos ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Pharmacokinetics ,Humans ,Janus Kinase Inhibitors ,Medicine ,Pyrroles ,White petrolatum ,Skin ,Janus kinase inhibitor ,business.industry ,Pruritus ,Patch test ,General Medicine ,Atopic dermatitis ,Middle Aged ,Patch Tests ,medicine.disease ,Healthy Volunteers ,medicine.drug_formulation_ingredient ,Treatment Outcome ,030104 developmental biology ,Tolerability ,Female ,business ,Dermatitis, Phototoxic - Abstract
The purpose of the present two phase 1 studies was to assess the safety, tolerability and pharmacokinetics for topical application of a novel Janus kinase (JAK) inhibitor, JTE-052, in Japanese healthy adult male volunteers and Japanese adult patients with atopic dermatitis (AD). Additionally, exploratory investigation was performed on the efficacy for disease severity and pruritus score in AD patients. In the QBX1-1 study, the cutaneous safety of JTE-052 ointment by a patch test and a photo patch test was assessed in an intra-individual comparative study using placebo ointment, white petrolatum and non-application as comparators. The study demonstrated that JTE-052 ointment would be associated with a low potential for phototoxicity but had no potential for skin irritation or photoallergy. In the QBX1-2 study, it was revealed that the systemic exposure to JTE-052 in both healthy volunteers with normal skin and AD patients with inflamed skin was low in application of not only 1% but also 3% JTE-052 ointment. JTE-052 ointments of 1% and 3% were generally safe and well tolerated in both populations. In a repeated twice-daily application for 7 days, the efficacy of JTE-052 ointment to AD patients was observed with both 1% and 3% ointments in the exploratory investigations evaluated by Eczema Area and Severity Index, Investigator's Global Assessment and Numeric Rating Scale assessments. The mean scores for each assessment declined from the baseline throughout the study. These results suggest that the treatment of JTE-052 ointment is generally safe and effective in AD patients, although further large confirmatory studies are needed.
- Published
- 2018
44. Guselkumab, a human interleukin-23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety analyses of a 52-week, phase 3, multicenter, open-label study
- Author
-
Hiroshi Kubo, Ryosuke Goto, Hitomi Morishima, Shigetoshi Sano, Richuan Zheng, and Hidemi Nakagawa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Dermatology ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,Drug Administration Schedule ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Psoriasis Area and Severity Index ,Psoriasis ,Internal medicine ,medicine ,Humans ,Adverse effect ,Aged ,Body surface area ,business.industry ,Antibodies, Monoclonal ,Original Articles ,General Medicine ,Dermatology Life Quality Index ,Middle Aged ,medicine.disease ,erythrodermic psoriasis ,guselkumab ,Treatment Outcome ,Guselkumab ,Nasopharyngitis ,030220 oncology & carcinogenesis ,Interleukin-23 Subunit p19 ,Quality of Life ,Japanese ,Generalized pustular psoriasis ,Clinical Global Impression ,Female ,Original Article ,long term ,generalized pustular psoriasis ,business ,Immunosuppressive Agents - Abstract
Generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP) are the rare and severe subtypes of psoriasis, which are often difficult to treat. The aim of this phase 3, open‐label study was to evaluate efficacy and safety of guselkumab, a human interleukin‐23 monoclonal antibody, in Japanese patients with GPP and EP. Guselkumab 50 mg was administrated to GPP (n = 10) and EP (n = 11) patients at weeks 0, 4 and thereafter every 8 weeks (q8w). Beginning at week 20, patients were escalated to 100 mg q8w if they met the dose escalation criteria. The primary end‐point was the proportion of patients achieving treatment success (Clinical Global Impression score of “very much improved”, “much improved” or “minimally improved”) at week 16. Safety evaluations included assessment of treatment‐emergent adverse events (TEAE) through week 52. At week 16, the proportions of GPP and EP patients achieving treatment success were 77.8% (7/9) and 90.9% (10/11), respectively. Furthermore, guselkumab treatment consistently showed improvement in responses of secondary end‐points such as Psoriasis Area and Severity Index, Investigator's Global Assessment, Japanese Dermatological Association severity index and improvement in body surface area involvement. Improvements in quality of life, as assessed by the Dermatology Life Quality Index, were also observed through week 52. The most commonly reported TEAE was nasopharyngitis (28.6%, 6/21). Safety findings were consistent with those observed previously in other studies. In conclusion, guselkumab treatment demonstrated efficacy and showed no safety concerns in Japanese patients with GPP and EP through week 52.
- Published
- 2018
45. Efficacy and safety of calcipotriol plus betamethasone dipropionate gel in Japanese patients with psoriasis vulgaris: A phase III study
- Author
-
Hidemi Nakagawa, Takafumi Etoh, and Kazuo Isomae
- Subjects
030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,business.industry ,Medicine ,030212 general & internal medicine ,business - Published
- 2018
46. Crystal structures of 1-hydroxy-4-propyloxy-9,10-anthraquinone and its acetyl derivative
- Author
-
Chitoshi Kitamura and Hidemi Nakagawa
- Subjects
crystal structure ,Stereochemistry ,Stacking ,Crystal structure ,010402 general chemistry ,010403 inorganic & nuclear chemistry ,01 natural sciences ,Medicinal chemistry ,Anthraquinone ,Research Communications ,chemistry.chemical_compound ,Acetyl derivative ,C—H ⋯O interactions ,General Materials Science ,C—H ...O interactions ,Crystallography ,Hydrogen bond ,anthraquinone ,General Chemistry ,Condensed Matter Physics ,hydrogen bonding ,Planarity testing ,0104 chemical sciences ,3. Good health ,Quinone ,chemistry ,QD901-999 ,anthraquinone ,π–π stacking - Abstract
The title compounds were synthesized from the commercially available dye quinizarin. In both compounds, the anthraquinone frameworks are close to planarity but there is a large difference in the conformation of the propyloxy group., 1-Hydroxy-4-propyloxy-9,10-anthraquinone, C17H14O4, (I), and its acetyl derivative, 4-acetyloxy-4-propyloxy-9,10-anthraquinone, C19H16O5, (II), were synthesized from the commercially available dye quinizarin. In both compounds, the anthraquinone frameworks are close to planarity. There is a large difference in the conformation of the propyloxy group; the molecule of (I) adopts a gauche conformation [O—C—C—C = −64.4 (2)°], although the molecule of (II) takes a trans-planar conformation (zigzag) [O—C—C—C = 176.1 (3)°]. In the molecule of (I), there is an intramolecular O—H⋯O hydrogen bond. In both crystals, the molecules are linked by C—H ⋯O hydrogen bonds. A difference in the molecular arrangements of (I) and (II) is found along the stacking directions.
- Published
- 2017
47. Epidemiological survey from 2009 to 2012 of psoriatic patients in Japanese Society for Psoriasis Research
- Author
-
Hidetoshi Takahashi, Akira Kawada, Toshihiro Ito, Hajime Iizuka, and Hidemi Nakagawa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Erythroderma ,Etretinate ,Comorbidity ,Dermatology ,Severity of Illness Index ,Ultraviolet therapy ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Japan ,Psoriasis ,Ustekinumab ,Diabetes Mellitus ,medicine ,Adalimumab ,Humans ,Age of Onset ,Child ,Aged ,Aged, 80 and over ,030203 arthritis & rheumatology ,business.industry ,Arthritis ,Age Factors ,Infant, Newborn ,Infant ,General Medicine ,Middle Aged ,medicine.disease ,Health Surveys ,Infliximab ,Child, Preschool ,Generalized pustular psoriasis ,Female ,Ultraviolet Therapy ,Dermatologic Agents ,business ,medicine.drug - Abstract
Since 1982, the Japanese Society for Psoriasis Research has conducted annual epidemiological surveys of patients with psoriasis. Kawada et al. have reported data for 1982-2001 and Takahashi et al. have reported data for 2002-2008. The present study evaluated 9290 psoriatic cases according to age and sex (2009-2012). The male : female ratio was 2.08:1 (6281 male patients [67.6%] to 3009 female patients [32.4%]). The most prevalent type was psoriasis vulgaris (85.6% of all cases), which was followed by psoriasis arthropathica (6.0%), psoriasis guttate acuta (3.2%), Zumbusch-type generalized pustular psoriasis (1.8%) and psoriasis erythroderma (1.5%). Psoriasis vulgaris was the most prevalent type for all ages, while psoriasis arthropathica and psoriasis guttate acuta were most prevalent among patients aged less than 65 years. The present survey detected an increased number of cases with comorbid diabetes and/or arthritis symptoms compared with the previous surveys. We found that treatments frequently involved topical corticosteroids (89.7% of cases) and vitamin D3 ointments (78.0% of cases), with a notable increase in the use of vitamin D3 ointments. Systemic treatments were used in 33.3% of cases, including cyclosporin (33.6%), etretinate (19.5%), methotrexate (8.6%), infliximab (11.4%), adalimumab (10.9%) and ustekinumab (6.2%). Phototherapy was used in 30.9% of cases. Although psoralen plus ultraviolet A therapy was the predominant phototherapy during previous studies, the present survey revealed that narrowband ultraviolet B therapy was used in 84.5% of phototherapy-treated cases. Thus, the present survey revealed major changes in treatment trends.
- Published
- 2017
48. 25094 Delgocitinib ointment in pediatric patients with atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study
- Author
-
Osamu Nemoto, Atsuyuki Igarashi, Manabu Oda, Takeshi Nagata, Hidemi Nakagawa, Hidehisa Saeki, and Kenji Kabashima
- Subjects
Double blind ,medicine.medical_specialty ,business.industry ,Extension study ,medicine ,Dermatology ,Atopic dermatitis ,Open label ,medicine.disease ,business ,Term (time) - Published
- 2021
49. Epidemiological survey of patients with psoriasis in Matsumoto city, Nagano Prefecture, Japan
- Author
-
Naoki Oiso, Masahiko Muto, Tomoko Seki, Akira Kawada, Ryuhei Okuyama, Eisaku Ogawa, Aya Kobayashi, and Hidemi Nakagawa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Etretinate ,Dermatology ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Psoriatic arthritis ,chemistry.chemical_compound ,0302 clinical medicine ,Japan ,Psoriasis ,Ustekinumab ,Prevalence ,medicine ,Humans ,Child ,Calcipotriol ,Aged ,Aged, 80 and over ,030203 arthritis & rheumatology ,Psoriatic erythroderma ,Biological Products ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Health Surveys ,chemistry ,Child, Preschool ,Female ,Ultraviolet Therapy ,Secukinumab ,business ,Guttate psoriasis ,medicine.drug - Abstract
A local epidemiological survey of psoriasis was conducted from 19 February to 30 June 2016 in Matsumoto city, Nagano Prefecture, Japan. Patients were predominantly male (268 cases, 71.5% males vs 107 cases, 28.5% females). We estimated that the prevalence of psoriasis was 0.097% in the Matsumoto area. The clinical types of psoriasis identified were psoriasis vulgaris (90.7%), psoriatic arthritis (5.9%), pustular psoriasis (2.1%), guttate psoriasis (1.0%) and psoriatic erythroderma (0.3%). The topical therapeutic agents included corticosteroids (84.0%), vitamin D3 analogs (61.5%), and a combination of calcipotriol and betamethasone dipropionate (31.0%). Current systemic treatments included cyclosporin (9.0%), etretinate (7.4%) and methotrexate (1.3%). Biologic treatments included adalimumab (4.0%), ustekinumab (2.7%), infliximab (1.3%) and secukinumab (0.8%). Ultraviolet B therapy (11.3%) was the predominant phototherapy in which narrow band ultraviolet B therapy accounted for the majority, followed by psoralen and ultraviolet A therapy (1.0%). According to the recent evolution of psoriasis treatment, the use of biologics has been increasing. This study demonstrates the changes of treatment trends of psoriasis in a non-metropolitan regional area.
- Published
- 2017
50. New onset or transition of disease state of psoriatic arthritis during treatment with ustekinumab: A single-center retrospective study
- Author
-
Hidemi Nakagawa, Yoshinori Umezawa, Hiromi Honda, Koichi Yanaba, Mami Momose, and Akihiko Asahina
- Subjects
Adult ,Male ,medicine.medical_specialty ,Arthritis ,Dermatology ,urologic and male genital diseases ,Single Center ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Psoriatic arthritis ,0302 clinical medicine ,Psoriasis ,Internal medicine ,Ustekinumab ,medicine ,Humans ,Adverse effect ,Aged ,Retrospective Studies ,Subclinical infection ,Aged, 80 and over ,030203 arthritis & rheumatology ,business.industry ,Arthritis, Psoriatic ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Female ,Dermatologic Agents ,business ,medicine.drug - Abstract
Ustekinumab (UST) is a treatment option for psoriatic arthritis (PsA), but recent observations indicate that some psoriatic patients may experience new onset of PsA or worsening of pre-existent PsA. We retrospectively analyzed all cases of psoriasis vulgaris (PsV) and PsA treated with UST in our facility between 2011 and 2015. PsA developed in eight out of 179 PsV patients, mostly later than 8 months after initiation of UST. It was generally not severe, and none had received tumor necrosis factor (TNF)-α inhibitors previously, indicating that the possibility of unmasking pre-existing subclinical arthritis is minimal. The eruptions were well controlled at the time of the onset of arthritis in most cases. Interestingly, those who developed arthritis showed a significantly lower body mass index. Regarding pre-existing PsA, nine PsA patients received UST, and at least partial improvement of PsA could be achieved in two out of three bio-naive and three out of six bio-switched patients from TNF-α inhibitors. PsA was largely more refractory to UST than the eruptions. Altogether, our present study is in agreement with the notion that UST may be less efficient than TNF-α inhibitors for PsA. While UST cannot fully prevent new development of PsA, it is unlikely that UST increases the risk of new onset of PsA as a paradoxical adverse reaction.
- Published
- 2017
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.