ABSTRACT
Systemic Lupus Erythematosus (SLE) is an autoimmune sickness with unclear pathogenesis. The goal of this research was to reveal the heterogeneity of immune cells in SLE patients of Han and Zang nationality by single-cell RNA sequencing (scRNA-seq) and bioinformatics profiling. METHODS: A total of 94,102 peripheral blood mononuclear cells (PBMCs) from six volunteers with SLE (3 Zang, 3 Han) and six healthy controls were first conducted through scRNA-seq analysis. The immune cell subsets in the pathogenesis of SLE were analyzed as well. Real-time quantitative PCR (RT-qPCR) was applied to confirm the results of sc-RNA seq analysis. RESULTS: For the Tibetan samples, the ratios of Naïve CD4 RPS4Y1 cells, Naïve CD4 cells, Memory BC CD24 and Memory BC differed significantly between the SLE and control samples, while that of CD8 CTL MAL cells was significantly different between the two groups in Han nationality samples. Variable differentiation states of CD8 CTL MAL cells, CD8 CTL GZMK cells, and Naïve CD4 cells were detected through pseudotime analysis. Moreover, T-cell receptor (TCR) abundance was notably higher in Tibetan SLE specimens than that in controls, while B-cell receptor (BCR) abundance in Tibetan and Han samples was higher than in control groups. CONCLUSIONS: In summary, the immune cellular heterogeneity of SLE patients both Han and Zang nationality was explored based on various bioinformatics approaches, providing new perspectives for immunological characteristics of SLE among different ethnic groups.
Subject(s)
Leukocytes, Mononuclear , Lupus Erythematosus, Systemic , Humans , Cell Differentiation , Ethnicity , Lupus Erythematosus, Systemic/genetics , Sequence Analysis, RNAABSTRACT
BACKGROUND: Systemic lupus erythematosus is an immunologically dysregulated disease characterized by the presence of multiple autoantibodies. In SLE, B lymphocytes contribute to the dysregulated production of autoantibodies and cytokines. Recently, we discovered that miR-99a-3p binds to both EIF4EBP1 and NCAPG mRNA and that lowering miR-99a-3p can promote B cell autophagy in SLE by increasing EIF4EBP1 expression. However, the functions of miR-99a-3p and NCAPG in SLE have not been extensively investigated. OBJECTIVE: This work aims to evaluate the levels of miR-99a-3p and NCAPG expression in SLE B cells and to determine whether the aberrant expression of miR-99a-3p and NCAPG contributes to the pathological mechanisms in SLE. METHODS: B lymphocytes were obtained through immunomagnetic negative selection. Using RT-qPCR, miR-99a-3p and NCAPG mRNA expressions in B lymphocytes and in the BALL-1 cell line were measured. To determine the relative abundance of NCAPG, PI3K, p-PI3K, AKT, and p-AKT, we normalize them to the level of ß-actin using Western blotting. Evaluation of miR-99a-3p and NCAPG's impact on cell proliferation was done utilizing CCK-8 assay. Using flow cytometry, the cell cycle and apoptosis were both measured. RESULTS: Comparing SLE B cells to healthy controls, miR-99a-3p expression was significantly downregulated. Additionally, it was observed that SLE B cells had significantly higher NCAPG mRNA expression. Blocking miR-99a-3p expression in BALL-1 cells with an antagomir elevated NCAPG expression, facilitated PI3K/AKT pathway activation, improved cell proliferation, raised the fraction of S-phase cells, and prevented cell apoptosis. The opposite effects of upregulated miR-99a-3p levels on BALL-1 cells were observed by using an agomir. Furthermore, the effect of decreased miR-99a-3p expression on cell proliferation was partially mediated by elevating NCAPG levels and activating the PI3K/AKT pathway. CONCLUSION: Our research indicates that lower miR-99a-3p expression in SLE B cells appears to boost B cell number via the NCAPG and PI3K/AKT pathways.
Subject(s)
Lupus Erythematosus, Systemic , MicroRNAs , Humans , Autoantibodies/pharmacology , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/pharmacology , Cell Proliferation/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , RNA, Messenger , Signal TransductionABSTRACT
BACKGROUND: There are no standards for evaluating skin photoaging. Dermoscopy is a non-invasive detection method that might be useful for evaluating photoaging. OBJECTIVE: To assess the correlation between the dermoscopic evaluation of photoaging and clinical and pathological evaluations. METHODS: The age, clinical evaluation (Fitzpatrick classification, Glogau Photoaging Classification, and Chung's standardized image ruler), histopathology (Masson staining and MMP-1 immunohistochemistry), and dermoscopy (Hu's and Isik's) of 40 donor skin samples were analyzed statistically, and Spearman rank correlation analysis was performed. RESULTS: There was a robust correlation between the total Hu scores and Isik dermoscopy. The correlation of dermoscopy with histopathology was higher than that of clinical evaluation methods. There is a strong correlation between telangiectases and lentigo. Xerosis, superficial wrinkle, diffuse erythema, telangiectases, and reticular pigmentation were significantly correlated with the three clinical evaluation methods. Superficial wrinkles were correlated with Masson, MMP-1, various clinical indicators, and other dermoscopic items. CONCLUSION: There is a good correlation between dermoscopy and clinical and histopathological examination. Dermoscopy might help evaluate skin photoaging.
Subject(s)
Lentigo , Skin Aging , Skin Neoplasms , Telangiectasis , Humans , Matrix Metalloproteinase 1 , Dermoscopy/methods , Telangiectasis/diagnostic imaging , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.
ABSTRACT
Photoaging is unique to the skin and is accompanied by an increased risk of tumors. To explore the transcriptomic regulatory mechanism of skin photoaging, the epidermis, and dermis of 16 healthy donors (eight exposed and eight non-exposed) were surgically excised and detected using total RNA-Seq. Weighted gene co-expression network analysis (WGCNA) identified the most relevant modules with exposure. The hub genes were identified using correlation, p-value, and enrichment analysis. The critical genes were identified using Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, then enriched using single-gene GSEA. A competitive endogenous RNA (ceRNA) network was constructed and validated using qRT-PCR. Compared with non-exposed sites, 430 mRNAs, 168 lncRNAs, and 136 miRNAs were differentially expressed in the exposed skin. WGCNA identified the module MEthistle and 12 intersecting genes from the 71 genes in this module. The enriched pathways were related to muscle. The critical genes were KLHL41, MYBPC2, and ERAP2. Single-gene GSEA identified the Hippo signaling pathway, basal cell carcinoma, cell adhesion molecules, and other pathways. Six miRNAs and 18 lncRNAs related to the critical genes constituted the ceRNA network and were verified using qPCR. The differential expression of KLHL41, MYBPC2, and ERAP2 at the protein level was verified using immunohistochemistry. KLHL41, MYBPC2, and ERAP2 genes are related to skin photoaging. The prediction model based on the three critical genes can indicate photoaging. These critical genes may have a role in skin photoaging by regulating cell growth, intercellular adhesion, and substance metabolism pathways.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Humans , Skin , MicroRNAs/genetics , Gene Expression Profiling , Transcriptome , Gene Regulatory Networks , AminopeptidasesABSTRACT
Excessive activation of immune cells plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). The regulation of immune cells by miRNAs is a research hotspot. In this study, second-generation high-throughput sequencing revealed a reduction in miR-99a-3p expression in patients with SLE; however, the specific mechanism underlying this phenomenon remains unclear. After transfection with an miR-99a-3p agomir, the proliferation of Ball-1 cells decreased and the levels of their apoptosis increased. The opposite effects were observed in cells transfected with the miR-99a-3p antagomir. Luciferase reporter assay indicated that miR-99a-3p directly targeted EIF4EBP1. Rescue experiments confirmed the proposed interaction between miR-99a-3p and EIF4EBP1. In vitro, in vivo and clinical investigations further confirmed that the miR-99a-3p agomir reduced the expression of EIF4EBP1, LC3B and LAMP-2A. In the in vivo experiments, serum levels of anti-nuclear antibodies, double-stranded DNA, IgE, IgM, IL-6, IL-10 and B lymphocyte stimulator were higher in mice from the antagomir group than those in mice from the MRL/lpr group. Furthermore, the protein and mRNA levels of EIF4EBP1, LC3B and LAMP-2A, the intensity of immunohistochemical staining of EIF4EBP1, LC3B and LAMP-2A, the urinary protein levels, and the C3 immunofluorescence deposition increased in mice from the antagomir group. The upregulation of miR-99a-3p expression protected B cells from EIF4EBP1-mediated autophagy, whilst the downregulation of miR-99a-3p expression induced autophagy via the EIF4EBP1-mediated regulation of the autophagy signalling pathway in B cells isolated from individuals with SLE. Based on these results, miR-99a-3p and EIF4EBP1 may be considered potential targets for SLE treatment.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Autophagy/genetics , B-Lymphocytes/metabolism , Cell Cycle Proteins/genetics , Gene Expression Regulation , Lupus Erythematosus, Systemic/etiology , Lupus Erythematosus, Systemic/metabolism , MicroRNAs/genetics , 3' Untranslated Regions , Animals , B-Lymphocytes/immunology , Biomarkers , Cell Line , Humans , Immunophenotyping , Lupus Erythematosus, Systemic/diagnosis , Mice , Mice, Inbred MRL lpr , RNA Interference , Signal TransductionABSTRACT
Cutaneous lupus erythematosus (CLE) is an inflammatory, autoimmune disease encompassing a broad spectrum of subtypes including acute, subacute, chronic and intermittent CLE. Among these, chronic CLE can be further classified into several subclasses of lupus erythematosus (LE) such as discoid LE, verrucous LE, LE profundus, chilblain LE and Blaschko linear LE. To provide all dermatologists and rheumatologists with a practical guideline for the diagnosis, treatment and long-term management of CLE, this evidence- and consensus-based guideline was developed following the checklist established by the international Reporting Items for Practice Guidelines in Healthcare (RIGHT) Working Group and was registered at the International Practice Guideline Registry Platform. With the joint efforts of the Asian Dermatological Association (ADA), the Asian Academy of Dermatology and Venereology (AADV) and the Lupus Erythematosus Research Center of Chinese Society of Dermatology (CSD), a total of 25 dermatologists, 7 rheumatologists, one research scientist on lupus and 2 methodologists, from 16 countries/regions in Asia, America and Europe, participated in the development of this guideline. All recommendations were agreed on by at least 80% of the 32 voting physicians. As a consensus, diagnosis of CLE is mainly based on the evaluation of clinical and histopathological manifestations, with an exclusion of SLE by assessment of systemic involvement. For localized CLE lesions, topical corticosteroids and topical calcineurin inhibitors are first-line treatment. For widespread or severe CLE lesions and (or) cases resistant to topical treatment, systemic treatment including antimalarials and (or) short-term corticosteroids can be added. Notably, antimalarials are the first-line systemic treatment for all types of CLE, and can also be used in pregnant patients and pediatric patients. Second-line choices include thalidomide, retinoids, dapsone and MTX, whereas MMF is third-line treatment. Finally, pulsed-dye laser or surgery can be added as fourth-line treatment for localized, refractory lesions of CCLE in cosmetically unacceptable areas, whereas belimumab may be used as fourth-line treatment for widespread CLE lesions in patients with active SLE, or recurrence of ACLE during tapering of corticosteroids. As for management of the disease, patient education and a long-term follow-up are necessary. Disease activity, damage of skin and other organs, quality of life, comorbidities and possible adverse events are suggested to be assessed in every follow-up visit, when appropriate.
Subject(s)
Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Cutaneous/therapy , Practice Guidelines as Topic , Humans , Lupus Erythematosus, Cutaneous/classificationABSTRACT
A novel nocardioform strain, CICC 11023T, was isolated from a tissue biopsy of neck lesions of a patient with primary cutaneous nocardiosis and characterized to establish its taxonomic position. The morphological, biochemical, physiological and chemotaxonomic properties of strain CICC 11023T were consistent with classification in the genus Nocardia. Whole-cell hydrolysates were rich in meso-diaminopimelic acid, galactose, arabinose and fructose. Mycolic acids were present. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and two unidentified lipids, and the predominant menaquinone was cyclo MK-8 (H4, ω-cyclo). The main fatty acids (>5â%) were C18â:â0 10-methyl (TBSA), C16â:â0, summed feature 4 (C16â:â1 trans 9/C15â:â0 iso 2OH), C15â:â0 and C17â:â0 10-methyl. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the isolate is most closely related (>98â% similarity) to the type strains Nocardia ninae OFN 02.72T, Nocardia iowensis UI 122540T and Nocardia alba YIM 30243T, and phylogenetic analysis of gyrB gene sequences showed similarity (89.1-92.2â%) to Nocardia vulneris NBRC 108936T, Nocardia brasiliensis IFM 0236T and Nocardia exalbida IFM 0803T. DNA-DNA hybridization results for strain CICC 11023T compared to Nocardia type strains ranged from 20.4 to 35.4â%. The genome of strain CICC 11023T was 8.78 Mbp with a G+C content of 67.4 mol% overall. The average nucleotide identity (ANI) values between strain CICC 11023T and N. alba YIM 30243T were low (OrthoANIu=77.47â%), and the ANI values between strain CICC 11023T and N. vulneris NBRC 108936 T were low (OrthoANIu=83.75 %). Consequently, strain CICC 11023T represents a novel Nocardia species on the basis of this polyphasic study, for which the name Nocardia colli sp. nov. is proposed. The type strain is CICC 11023T (=KCTC 39837T).
Subject(s)
Nocardia Infections/microbiology , Nocardia/classification , Phylogeny , Adult , Bacterial Typing Techniques , Base Composition , China , DNA, Bacterial/genetics , Diaminopimelic Acid/chemistry , Fatty Acids/chemistry , Female , Humans , Mycolic Acids/chemistry , Neck , Nocardia/isolation & purification , Nucleic Acid Hybridization , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Vitamin K 2/analogs & derivatives , Vitamin K 2/chemistryABSTRACT
OBJECTIVE: To determine clinical curative effects of ozone therapy for pemphigus vulgaris.â© Methods: Ozone hydrotherapy was used as an aid treatment for 32 patients with pemphigus vulgaris. The hydropathic compression of potassium permanganate solution for 34 patients with pemphigus vulgaris served as a control. The main treatment for both groups were glucocorticoids and immune inhibitors. The lesions of patients, bacterial infection, usage of antibiotics, patient's satisfaction, and clinical curative effect were evaluated in the 2 groups.â© Results: There was no significant difference in the curative effect and the average length of staying at hospital between the 2 groups (P>0.05). But rate for the usage of antibiotics was significantly reduced in the group of ozone hydrotherapy (P=0.039). The patients were more satisfied in using ozone hydrotherapy than the potassium permanganate solution after 7-day therapy (P>0.05).â© Conclusion: Ozone hydrotherapy is a safe and effective aid method for pemphigus vulgaris. It can reduce the usage of antibiotics.
Subject(s)
Dermatologic Agents/therapeutic use , Hydrotherapy/methods , Ozone/therapeutic use , Pemphigus/therapy , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Glucocorticoids , Humans , Length of Stay , Potassium Permanganate/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: We evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect. METHODS: Eighteen patients with WHO class III or IV LN were randomly assigned to hUC-MSC (dose 2×108 cells) or placebo. All patients received standard immunosuppressive treatment, which consisted of intravenous methylprednisolone and cyclophosphamide, followed by maintenance oral prednisolone and mycophenolate mofetil. RESULTS: Remission occurred in 9 of 12 patients (75%) in the hUC-MSC group and 5 of 6 patients (83%) in the placebo group. Remission was defined as stabilisation or improvement in renal function, reduction in urinary red cells and protein. A similar proportion of patients on hUC-MSC and placebo achieved complete remission. Improvements in serum albumin, complement, renal function, Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group scores were similar in both groups. One patient on placebo had a stroke and another had ascites. One patient on hUC-MSC had leucopenia, pneumonia and subcutaneous abscess and another died of severe pneumonia. The trial was abandoned after 18 patients were enrolled when it had become obvious it would not demonstrate a positive treatment effect. CONCLUSION: hUC-MSC has no apparent additional effect over and above standard immunosuppression. TRIAL REGISTRATION NUMBER: NCT01539902; Results.
Subject(s)
Glucocorticoids/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/therapy , Mesenchymal Stem Cell Transplantation/methods , Adult , Cyclophosphamide/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Early Termination of Clinical Trials , Female , Humans , Induction Chemotherapy , Maintenance Chemotherapy , Male , Methylprednisolone/therapeutic use , Mycophenolic Acid/therapeutic use , Remission Induction , Transplantation, Homologous , Treatment Outcome , Umbilical Cord/cytology , Young AdultABSTRACT
Diabetes mellitus II (DM II) is a newly defined independent factor contributing to the morbidity and mortality of cryptococcosis. This retrospective case analysis aims to explore the epidemiology, clinical profile and strain characteristics of cryptococcosis in Chinese DM II patients. This study included 30 cases of cryptococcosis with DM II occurring from 1993 to 2015 in mainland China. The hospital-based prevalence of cryptococcosis in DM II was 0.21%. The mean age of the patients was 56.1 years (95% confidence interval: 51.5, 60.6), and 93% of the patients were older than 40 years. Sixty-two per cent of the patients experienced untreated or poorly controlled blood glucose before infection. Multilocus sequence typing analysis categorised all cultured strains as Cryptococcus neoformans and sequence type 5. Sixty-nine per cent of pulmonary cryptococcosis patients experienced misdiagnoses and treatment delays. Sixty per cent of cryptococcal meningitis patients received substandard antifungal therapy. The overall death rate was 33%. Considering the large population size of DM II patients in China, improved attention should be paid to the high prevalence of cryptococcosis as revealed by us. We also emphasised the importance of blood glucose control for infection prevention, especially among the elderly.
Subject(s)
Cryptococcosis/epidemiology , Cryptococcus neoformans/isolation & purification , Diabetes Mellitus, Type 2/epidemiology , Meningitis, Cryptococcal/epidemiology , Aged , China/epidemiology , Cryptococcosis/complications , Cryptococcosis/diagnosis , Cryptococcosis/microbiology , Cryptococcus neoformans/genetics , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Female , Genotype , Humans , Male , Meningitis, Cryptococcal/complications , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/microbiology , Middle Aged , Multilocus Sequence Typing , Retrospective StudiesABSTRACT
One hundred eleven clinical Trichophyton rubrum isolates were tested against 7 antifungal agents. The geometric mean MICs of all isolates were, in increasing order: terbinafine, 0.03 mg/liter; voriconazole, 0.05 mg/liter; posaconazole, 0.11 mg/liter; isavuconazole, 0.13 mg/liter; itraconazole, 0.26 mg/liter; griseofulvin, 1.65 mg/liter; and fluconazole, 2.12 mg/liter.
Subject(s)
Antifungal Agents/pharmacology , Triazoles/pharmacology , Trichophyton/drug effects , Humans , Microbial Sensitivity Tests , Tinea/drug therapy , Tinea/microbiologyABSTRACT
Facial flat wart, caused by human papilloma virus type 3 and less often, type 10, 27, and 41, often brings many cosmetic problems to children and young adults. Considering the disturbing cosmetic problem, the treatment of facial flat wart is always frustrating and often unsuccessful, although there are many treatment modalities. Considering the possible serious side effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), we designed step-up therapy of ALA-PDT on different clinical phases of facial flat wart. As a new protocol of ALA-PDT, we found the step-up therapy of ALA-PDT could also receive excellent effects with the lower side effects. Meanwhile, the tolerance of patients to ALA-PDT could improve with subsequent treatment sessions and escalating doses of ALA-PDT.
Subject(s)
Aminolevulinic Acid/administration & dosage , Facial Dermatoses/drug therapy , Photochemotherapy , Radiation-Sensitizing Agents/administration & dosage , Warts/drug therapy , Administration, Topical , Adolescent , Adult , Aminolevulinic Acid/adverse effects , Facial Dermatoses/diagnosis , Facial Dermatoses/virology , Female , Humans , Male , Photochemotherapy/adverse effects , Radiation-Sensitizing Agents/adverse effects , Severity of Illness Index , Treatment Outcome , Warts/diagnosis , Warts/virology , Young AdultABSTRACT
Background: Pyoderma gangrenosum (PG) is a rare cause of skin ulcers in children, posing challenges in diagnosis and treatment. As the disease is often associated with conditions such as inflammatory bowel disease (IBD), rheumatoid arthritis, haematological disorders and other diseases, diagnosis and treatment often require cooperation with other medical departments. Accordingly, dissemination of information about the disease to doctors in departments other than dermatologists, especially paediatricians, can help in its early detection. Case Presentation: The 11-year-old pediatric patient in the case initially diagnosed with acute febrile neutrophilic dermatosis was eventually confirmed as pustular PG through histopathological examinations of skin and other relevant examinations. The medical condition is lessened after treatment with a combination of glucocorticoids and adalimumab. Conclusion: PG is relatively rare in clinical settings, particularly among pediatric patients exhibiting persistent high fever and signs of pustular pyoderma gangrenosum. This case underscores the importance of considering the potential diagnosis of pediatric pustular PG when confronted with a child presenting persistent high fever and pustules after trauma. Additionally, the proactive initiation of adalimumab emerges as a promising treatment option for pediatric IBD -associated pustular PG.
ABSTRACT
We report a case of a patient initially diagnosed with keloid and eventually diagnosed by skin histopathology and immunohistochemistry with primary cutaneous ALK-negative anaplastic large cell lymphoma.
ABSTRACT
INTRODUCTION: Adalimumab has been used successfully in the treatment of psoriasis. The objective of the study is to compare the efficacy, safety, and immunogenicity between HLX03, an adalimumab biosimilar, and adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In this double-blind, active-controlled, parallel-group study, 262 patients with moderate-to-severe plaque psoriasis were randomized (1:1) to receive HLX03 or adalimumab (80 mg at week 1, 40 mg at week 2, and then 40 mg every 2 weeks) for 48 weeks. The primary endpoint was improvement in Psoriasis Area and Severity Index (PASI) score at week 16 comparing to baseline. Equivalence was demonstrated if 95% confidence interval (CI) of the between group difference fell within the equivalence margins of ± 15%. Other efficacy endpoints, safety and immunogenicity were also evaluated. RESULTS: In the full analysis set, PASI improvements at week 16 was 83.5% (n = 131) in the HLX03 group and 82.0% (n = 130) in the adalimumab group, with a least-square-mean difference of 1.5% (95% CI - 3.9% to 6.8%). There were no significant between-group differences in all secondary efficacy analyses including proportion of patients achieving ≥ 75% improvement from baseline PASI (PASI 75), physician global assessment (PGA) 0/1 (clear or almost clear) and change in dermatology life quality index (DLQI) score. The incidences of adverse events and the proportion of patients with antidrug antibodies were also comparable between the two treatment groups. CONCLUSION: HLX03 demonstrated equivalent efficacy, similar safety and immunogenicity to reference adalimumab, supporting its development as an alternative treatment for patients with plaque psoriasis in China. CLINICAL TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20171123 (November 27, 2017); ClinicalTrials.gov, NCT03316781 (October 20, 2017).
Plaque psoriasis is a chronic, autoimmune, inflammatory skin disease associated with significant morbidity and reduced quality of life. In China, the prevalence of plaque psoriasis increased four-fold between 1987 and 2012. Adalimumab is a biologic antibody used to treat plaque psoriasis globally. However, high treatment costs remain as a significant barrier to adalimumab therapy. Therefore, HLX03 has been developed as an adalimumab (Humira®) biosimilar, which is almost identical to the licensed reference adalimumab, but less expensive and more accessible to patients. In this randomized clinical trial, the efficacy (ability of a drug to produce the desired treatment effects), safety, and immunogenicity (ability of a drug to induce immune response which would affect its efficacy and safety) of HLX03 were compared with the reference adalimumab in Chinese patients with moderate-to-severe plaque psoriasis. Efficacy was evaluated by comparing the changes in severity and extent of disease using Psoriasis Area and Severity Index score between treatment initiation and week 16. Safety was monitored by adverse events, laboratory tests and vital signs. Immunogenicity was assessed by the incidence of antidrug antibodies. Among the 262 randomized patients, 131 received HLX03 and 130 received adalimumab. Both groups reported similar improvements in Psoriasis Area and Severity Index scores (between-group difference fell within the prespecified equivalence margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety and immunogenicity profiles. In summary, HLX03 demonstrated equivalent efficacy to adalimumab, validating it as an alternative treatment for patients with plaque psoriasis in China.
Subject(s)
Biosimilar Pharmaceuticals , Psoriasis , Adalimumab/adverse effects , Biosimilar Pharmaceuticals/adverse effects , Double-Blind Method , Humans , Psoriasis/drug therapy , Severity of Illness Index , Treatment OutcomeABSTRACT
INTRODUCTION: This phase III study aimed to compare the efficacy, safety, and immunogenicity of SCT630 with the reference adalimumab. METHODS: A total of 367 Chinese patients with moderate-to-severe plaque psoriasis were randomly assigned to receive 80 mg of SCT630 or adalimumab subcutaneously at week 1, 40 mg at week 2, then 40 mg biweekly. At week 16, those with 50 % or more improvement in psoriasis area and severity index (PASI) were eligible to enter an extension period up to week 52. Patients on SCT630 continued the same treatment, whereas patients receiving adalimumab were re-randomized at a ratio of 1:1 to adalimumab or SCT630 group. The primary endpoint was percentage improvement in PASI at week 16. Other endpoints included PASI 50/75/90/100, Physician's Global Assessment, Dermatology Life Quality Index, safety, and immunogenicity. RESULTS: PASI improvement at week 16 was 85.07 % for SCT630 and 84.82 % for adalimumab. The mean difference (3.10 %, 95 % CI: -1.875 %, 8.066 %) was within the equivalence interval. Other efficacy endpoints, safety and immunogenicity profiles were similar across the two groups. There were no safety or immunogenicity difference between switched/continued groups. CONCLUSION: This phase III study demonstrated the equivalences in efficacy, safety and immunogenicity of SCT630 to adalimumab in patients with moderate to severe psoriasis.
Subject(s)
Biosimilar Pharmaceuticals , Psoriasis , Humans , Adalimumab/therapeutic use , Biosimilar Pharmaceuticals/therapeutic use , Psoriasis/drug therapy , Psoriasis/chemically induced , Double-Blind Method , Hyperplasia/drug therapy , China , Treatment Outcome , Severity of Illness IndexABSTRACT
ABSTRACT: Acne is associated with depression and anxiety; however, the relationship between acne and suicide is still unclear. This study is aimed to evaluate the association between acne and suicide by conducting a meta-analysis. Studies were identified by electronic searches of the PubMed and EMBASE databases from their inception through Jan 10, 2020. Two authors separately assessed the quality and extracted data from the selected studies. When the heterogeneity was significant, we used a random-effects model to calculate overall pooled risk estimates.Five studies involving a total of 2,276,798 participants were finally included in the meta-analysis; 52,075 participants had acne. Suicide was positively associated with acne in the overall analysis (odds ratio (OR) 1.50, 95% confidence interval (95% CI): 1.09-2.06, Pâ=â.004, I2â=â74.1%). Subgroup analyses were performed for suicidal behavior groups (Pâ=â.002, I2â=â80.4%), suicidal ideation or thoughts groups (Pâ=â.849, I2â=â0.0%), International Classification of Diseases version 9 (ICD-9) groups (Pâ=â.137, I2â=â49.6%), non-ICD-9 groups (Pâ=â.950, I2â=â0.0%), American groups (Pâ=â.311, I2â=â2.4%), and non-American groups (Pâ=â.943, I2â=â0.0%). Sensitivity analyses indicated flawed results. No publication bias was detected.Acne may significantly increase suicide risk. Clinicians should actively treat acne and consider suicide screening. Further international studies with high-quality analyses are needed as more data are published.Ethical approval and patient consent are not required because this study is a literature-based study.