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1.
Front Immunol ; 15: 1325356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835766

RESUMO

Introduction: Circulating T follicular helper (cTfh) cells and circulating T peripheral helper (cTph) cells (which share common characteristics with the cTfh population) are implicated in the pathogenesis of immune-mediated and autoimmune diseases such as psoriasis (Ps). Their close interplay with the interleukin 17 (IL-17) axis and the ex vivo effect of IL-17-targeting biologic agents used to treat Ps on them are elusive. This study aimed to investigate the effect of biologics targeting IL-17 on cTfh and cTph cell subpopulations isolated from the blood of patients with Ps. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with Ps at treatment initiation and three months later. Samples were also collected from controls. Cells were stained using monoclonal antibodies. Flow cytometry assessed the fraction of cTfh (CD3+CD4+CXCR5+) and cTph (CD3+CD4+CXCR5-PD-1hi) cells.. Results: Flow cytometric analysis showed increased fractions of activated cTfh subsets including ICOS+ and ICOS+PD-1+ expressing cells, in patients compared to controls. Biologic blocking of IL-17A diminished the cTfh population. Furthermore, ICOS+ and ICOS+PD-1+ sub-populations were also inhibited. Finally, the cTph cell fraction significantly decreased after three months of successful treatment with biologics. Conclusion: Early anti-IL-17-mediated clinical remission in Ps is associated with decreased cTfh and cTph cell subpopulations.


Assuntos
Produtos Biológicos , Interleucina-17 , Psoríase , Humanos , Psoríase/imunologia , Psoríase/tratamento farmacológico , Masculino , Feminino , Interleucina-17/metabolismo , Interleucina-17/antagonistas & inibidores , Adulto , Pessoa de Meia-Idade , Produtos Biológicos/uso terapêutico , Produtos Biológicos/farmacologia , Células T Auxiliares Foliculares/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos
3.
Folia Biol (Praha) ; 70(1): 53-61, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38830123

RESUMO

Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.


Assuntos
Apoptose , Proteínas de Ciclo Celular , Movimento Celular , Proliferação de Células , Ácido Gálico , Inflamação , Queratinócitos , Psoríase , Fatores de Transcrição , Humanos , Psoríase/metabolismo , Psoríase/patologia , Psoríase/tratamento farmacológico , Fatores de Transcrição/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Ácido Gálico/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Apoptose/efeitos dos fármacos , Inflamação/patologia , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Interleucina-17/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Adulto , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Masculino , Células HaCaT , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Linhagem Celular , Proteínas que Contêm Bromodomínio
4.
Arch Dermatol Res ; 316(7): 362, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850346

RESUMO

Secukinumab is a fully human IgG1 antibody that selectively binds to and neutralizes the proinflammatory cytokine interleukin-17A. Secukinumab is an effective and well-tolerated treatment for plaque psoriasis. There is a limited real-word evidence for dose optimisation of secukinumab based on clinical response. PURE is a multi-national, prospective, observational study in patients with moderate to severe chronic plaque psoriasis in Canada and Latin America, assessing the real-world safety and effectiveness of secukinumab and other indicated therapies. The aim of the current snapshot analysis was to evaluate the effectiveness and safety of on-label dose and updosed secukinumab in patients with plaque psoriasis enrolled in the PURE study. At the time of analysis, 676 patients received secukinumab, of which 84.6% (n = 572) remained on the on-label dose, while 15.4% (n = 104) were updosed. With on-label secukinumab, the absolute Psoriasis Area and Severity Index (PASI) score was reduced from 13.6 at baseline to 1.2 over 36 months, with treatment persistence of 73% at 40 months. At Month 36, 73.2% of the patients receiving on-label secukinumab achieved Investigator's Global Assessment (IGA) 0/1. With updosed secukinumab (300 mg every 2 weeks, 300 mg every 3 weeks, 450 mg every 4 weeks, or 450 mg every 3 weeks), 57.9% of the patients showed improvement in the absolute PASI score at the first visit after updosing, with treatment persistence of 50% at 12 months after updosing. At Month 15, 40% of patients receiving updosed secukinumab achieved IGA 0/1. Patients with previous biologic exposure (odds ratio [OR]: 3.25; 95% confidence interval [CI]: 2.03, 5.18, p < 0.0001) were more likely to be updosed while those with a body weight < 90 kg (OR: 0.49; 95% CI [0.31, 0.77], p = 0.0019) were less likely to be updosed. Previous biologic exposure (HR [hazard ratio]: 1.47; 95% CI [1.24, 1.75], p < 0.0001) and current biologic exposure (secukinumab vs. other indicated therapies: HR 0.57; 95% CI [0.43, 0.75], p = 0.0001) were significantly associated with time to secukinumab updosing. No new or unexpected safety signals were observed with updosed secukinumab. Secukinumab updosing was efficacious and well-tolerated in patients with psoriasis who failed to respond to the approved on-label regimen, suggesting that updosing may be a useful therapeutic option for approved dose non-responders.


Assuntos
Anticorpos Monoclonais Humanizados , Psoríase , Sistema de Registros , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Resultado do Tratamento , Sistema de Registros/estatística & dados numéricos , Adulto , Canadá , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , América Latina , Interleucina-17/antagonistas & inibidores , Interleucina-17/imunologia
5.
Int Immunopharmacol ; 136: 112383, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38843642

RESUMO

The treatment of autoimmune and inflammatory diseases often requires targeting multiple pathogenic pathways. KYS202004A is a novel bispecific fusion protein designed to antagonize TNF-α and IL-17A, pivotal in the pathophysiology of autoimmune and inflammatory diseases. Our initial efforts focused on screening for optimal structure by analyzing expression levels, purity, and binding capabilities. The binding affinity of KYS202004A to TNF-α and IL-17A was evaluated using SPR. In vitro, we assessed the inhibitory capacity of KYS202004A on cytokine-induced CXCL1 expression in HT29 cells. In vivo, its efficacy was tested using a Collagen-Induced Arthritis (CIA) model in transgenic human-IL-17A mice and an imiquimod-induced psoriasis model in cynomolgus monkeys. KYS202004A demonstrated significant inhibition of IL-17A and TNF-α signaling pathways, outperforming the efficacy of monotherapeutic agents ixekizumab and etanercept in reducing CXCL1 expression in vitro and ameliorating disease markers in vivo. In the CIA model, KYS202004A significantly reduced clinical symptoms, joint destruction, and serum IL-6 concentrations. The psoriasis model revealed that KYS202004A, particularly at a 2  mg/kg dose, was as effective as the combination of ixekizumab and etanercept. This discovery represents a significant advancement in treating autoimmune and inflammatory diseases, offering a dual-targeted therapeutic approach with enhanced efficacy over current monotherapies.


Assuntos
Artrite Experimental , Interleucina-17 , Macaca fascicularis , Psoríase , Proteínas Recombinantes de Fusão , Fator de Necrose Tumoral alfa , Animais , Interleucina-17/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/induzido quimicamente , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Camundongos , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Células HT29 , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Camundongos Transgênicos , Modelos Animais de Doenças , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/farmacologia , Masculino , Avaliação Pré-Clínica de Medicamentos , Imiquimode , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos DBA
7.
J Dermatolog Treat ; 35(1): 2346282, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38880492

RESUMO

BACKGROUND: Biologics are essential in treating psoriasis. In recent years, the pathogenesis exploration and development of new target drugs have provided a more complete evidence-based foundation for the biological treatment of psoriasis. This study aims to use bibliometrics to analyze the research status and development trends of biologics in psoriasis. METHODS: The bibliometric analysis of publications related to biologics in psoriasis from 2004 to 2023 was conducted using the Web of Science Core Collection (WoSCC) database as the search data source. To perform the bibliometric analysis and create visual knowledge graphs, CiteSpace, the Bibliometrix R package, and VOSviewers were utilized. RESULTS: The study included a total of 3800 articles. The United States had the highest number of publications. The leading authors and institutions were Steven R. Feldman and the University of Manchester, respectively, in the global partnership. The cluster plot divided all keywords into 11 categories. Currently, Secukinumab and Guselkumab are representative biological agents being studied due to their considerable efficacy and long-term safety. CONCLUSIONS: Targeted therapy has emerged as a significant trend in the current treatment of psoriasis. Early and active use of biologics can effectively control disease progression, prevent or delay the occurrence of comorbidities, and may even alter the natural course of psoriasis. However, further investigation is required to fully understand the specific mechanisms of psoriasis and the use of biological agents.


Assuntos
Bibliometria , Psoríase , Psoríase/tratamento farmacológico , Humanos , Produtos Biológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Pesquisa Biomédica
8.
J Dermatolog Treat ; 35(1): 2333016, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38839072

RESUMO

Dupilumab is a novel treatment agent for moderate to severe atopic dermatitis (AD) with few adverse effects. Drug-induced psoriasiform lesions are rare.We report a 4-year-old boy with AD who developed pustular psoriasis during treatment with dupilumab.Pustular psoriasis appeared within 1 week of treatment and worsened in the second week. After stopping dupilumab administration, topical corticosteroids (desonide and mometasone furoate creams) and oral desloratadine without relief. Pustular psoriasis was confirmed by pathological examination, and thiamphenicol was administered. After 2 weeks of treatment, the lesions nearly resolved without recurrence in 1-year follow-up.Dupilumab-induced pustular psoriasis is rare in children.


Assuntos
Anticorpos Monoclonais Humanizados , Dermatite Atópica , Psoríase , Humanos , Masculino , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/patologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Pré-Escolar , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Furoato de Mometasona , Fármacos Dermatológicos/efeitos adversos
9.
J Dermatolog Treat ; 35(1): 2347440, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38857894

RESUMO

Purpose: The incidence of cutaneous paradoxical reactions associated with IL-17 inhibitors has gained attention in recent literature. Our report aims to investigate the characteristics of one rare paradoxical reaction, presenting as Behcet's disease.Methods: We reported one case of Behcet's-like disease induced by secukinumab in a patient with psoriasis. This patient, a young woman with a long history of psoriasis, showed significant improvement in her psoriatic condition after receiving four doses of secukinumab. Unexpectedly, she developed symptoms such as high fever, painful oral and genital ulcers, facial maculopapules, and erythema nodosum-like lesions on her lower limbs. Despite neutrophilia, there was no evidence of infection found in her laboratory tests. Histological analysis of a skin biopsy highlighted subcutaneous panniculitis and a mixed inflammatory cell infiltrate in the dermis. The patient was consequently diagnosed with secukinumab-induced Behcet's-like disease. Additionally, we have reviewed nine other documented cases of Behcet's-like disease triggered by IL-17 inhibitors.Results: This group showed no significant gender preference, suffering from conditions such as psoriasis, ankylosing spondylitis, and hidradenitis suppurativa. Oral and genital ulcers were prevalent among the paradoxical reactions noted. Marked improvement was observed in all patients upon discontinuation of the IL-17 inhibitors.Conclusions: Our report serves to alert physicians to this uncommon but significant paradoxical effect that may arise with anti-IL-17 treatment.


Assuntos
Anticorpos Monoclonais Humanizados , Síndrome de Behçet , Psoríase , Humanos , Feminino , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/complicações , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Psoríase/patologia , Adulto , Interleucina-17/antagonistas & inibidores , Pele/patologia , Pele/efeitos dos fármacos
10.
Einstein (Sao Paulo) ; 22: eGS0413, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865570

RESUMO

Palhano et al. demonstrate the feasibility of incorporating secukinumab and ustekinumab into the Clinical Protocol and Therapeutic Guidelines for moderate to severe psoriasis in pediatric patients. OBJECTIVE: Therefore, this study aimed to evaluate the impact of secukinumab and ustekinumab against moderate-to-severe plaque psoriasis in a Brazilian pediatric population with access to public healthcare. METHODS: A survey of immunobiological treatments registered for use against pediatric psoriasis at the National Health Surveillance Agency was conducted. These treatments were compared to the list available in the same treatment category in the public health system through the Clinical Protocol and Therapeutic Guidelines for psoriasis. A quantitative analysis of the data of patients treated with immunobiological drugs the previous year in accordance with the Clinical Protocol and Therapeutic Guidelines was performed using data available in the DATASUS portal. RESULTS: The public budget impact scenarios analyzed were comparable to the investment already planned for acquiring the only available drug option. CONCLUSION: The incorporation of two therapeutic options in the Clinical Protocol and Therapeutic Guidelines list for moderate-to-severe pediatric psoriasis was feasible in a horizon of 5 years compared to the investment into the single option available to pediatric patients. These findings can facilitate the local analysis of budgetary impact and discussions on the feasibility of this therapeutic incorporation at the state level. Incorporation of secukinumab and ustekinumab was economically feasible. These drugs are options for those who do not respond to or have contraindications to etanercept.


Assuntos
Anticorpos Monoclonais Humanizados , Psoríase , Ustekinumab , Humanos , Psoríase/tratamento farmacológico , Criança , Ustekinumab/uso terapêutico , Brasil , Anticorpos Monoclonais Humanizados/uso terapêutico , Índice de Gravidade de Doença , Fármacos Dermatológicos/uso terapêutico , Adolescente , Guias de Prática Clínica como Assunto , Masculino , Feminino
12.
Front Immunol ; 15: 1410540, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846952

RESUMO

Psoriasis is a common, life-long skin disease with a significant negative health and societal impact. Data on rates of disease control and treatment strategies are lacking in Central and Eastern European countries. We aimed to describe the real-world disease severity, control, and treatment strategies for psoriasis in patients from Central and Eastern European countries. CRYSTAL (EUPAS36459) was a cross-sectional, retrospective study in adults (18-75 years) from Bulgaria, Estonia, Hungary, Latvia, Lithuania, Romania, and Russia. We enrolled patients with moderate-to-severe psoriasis receiving continuous systemic treatment for ≥24 weeks. We used the Psoriasis Area and Severity Index (PASI) to describe disease severity and the Dermatology Life Quality Index (DLQI) to assess quality of life (QoL) and collected other outcomes [psoriasis work productivity and activity impairment (WPAI-PSO), patient satisfaction] at enrollment. Analyses were descriptive. A total of 690 patients were included in the analyses. Median disease duration was 11.8 years. Current treatment was monotherapy for most patients (95.8%) with either biological (BIO group; 88.4%) or conventional (NON-BIO group; 7.4%) agents. Mean (± standard deviation) absolute PASI scores were 3.5 ± 5.7, 3.1 ± 5.3, and 6.6 ± 7.4 in the overall population, the BIO group, and the NON-BIO group, respectively. Among patients treated with monotherapy, absolute PASI scores ≤1, ≤3, and ≤5 were observed for 44.1%, 72.0%, and 82.6% of BIO patients and 21.6%, 33.3%, and 49.0% of NON-BIO patients. Mean DLQI total score was 3.3 ± 5.1; higher scores were noted for higher absolute PASI. The most impacted WPAI-PSO domain was presenteeism; for all domains, impact increased with increased absolute PASI. A total of 91.8% of BIO patients and 74.5% of NON-BIO patients were satisfied with the current treatment. We observed a better disease control in BIO than NON-BIO patients. However, around half of BIO patients did not reach clear skin status and reported an impact on QoL. An improvement in treatment strategies is still needed in Central and Eastern European countries to optimize outcomes of moderate-to-severe psoriasis.


Assuntos
Psoríase , Qualidade de Vida , Índice de Gravidade de Doença , Humanos , Psoríase/tratamento farmacológico , Psoríase/psicologia , Psoríase/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Estudos Transversais , Idoso , Estudos Retrospectivos , Europa Oriental/epidemiologia , Adulto Jovem , Adolescente , Resultado do Tratamento , Europa (Continente) , Fármacos Dermatológicos/uso terapêutico , Satisfação do Paciente
13.
Arch Dermatol Res ; 316(7): 363, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850287

RESUMO

Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains uncertain due to limited systematic evidence. Our objective was to analyze antistreptococcal therapies' effectiveness in improving psoriasis. We conducted a systematic review following PRISMA guidelines, evaluating antistreptococcal treatment efficacy in psoriasis patients from PubMed, Scopus, and Embase databases until August 14, 2022. Eligible studies included psoriasis patients undergoing antistreptococcal therapy, regardless of demographics or psoriasis type. 50 studies (1778 patients) were analyzed, with penicillins/aminopenicillins as the most studied antibiotics (21 studies), showing mixed outcomes, some reporting significant improvement in guttate psoriasis, while others showed no significant difference. Rifampin demonstrated positive results in most of ten studies, and macrolides showed varying effectiveness in two studies. Tonsillectomy in 14 studies (409 patients) mainly focusing on guttate and chronic plaque psoriasis showed positive outcomes, indicating improved symptoms and quality of life. Limitations include heterogeneous studies, sampling bias, and quality of evidence. This systematic review reveals limited and varied evidence for systemic antibiotic therapy efficacy in psoriasis treatment, while tonsillectomy emerges as a potentially beneficial antistreptococcal option, urging further well-designed, controlled studies with larger sample sizes and standardized protocols for better comparisons.


Assuntos
Antibacterianos , Psoríase , Infecções Estreptocócicas , Humanos , Psoríase/tratamento farmacológico , Antibacterianos/uso terapêutico , Infecções Estreptocócicas/tratamento farmacológico , Resultado do Tratamento , Qualidade de Vida , Penicilinas/uso terapêutico , Rifampina/uso terapêutico
14.
Int J Immunopathol Pharmacol ; 38: 3946320241260262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38876119

RESUMO

INTRODUCTION: TYK2 inhibitors and traditional natural drugs as promising drugs for psoriasis therapy are receiving increasing attention. They both affect different molecules of JAK/STAT pathway, but it is currently unclear whether their combination will enhance the effect on psoriasis. In this study, we used imiquimod (IMQ)-induced psoriasis mouse model to investigate the therapeutic effects of the combined administration of deucravacitinib (TYK2 inhibitor) and shikonin. METHODS: Aldara cream containing 5% IMQ was used to topically treat the dorsal skin of each mouse for a total of six consecutive days to induce psoriasis. The psoriasis area and severity index (PASI) scores were recorded every day. On the 7th day, skin tissues were taken for histopathological examination and the content of cytokines in skin were evaluated. The frequency of immune cells in peripheral blood, spleen and skin were detected through flow cytometry. RESULTS: Compared to the vehicle control group, the psoriasis symptoms and immune disorder improved significantly in the combination therapy group and deucravacitinib treatment group on the 7th day, and the expressions of p-STAT3 and Ki67 in skin were reduced as well. Moreover, the combined treatment of deucravacitinib and shikonin for psoriasis was superior to the monotherapy group, especially in inhibiting abnormal capillaries proliferation, reducing immune cells infiltration and decreasing the concentration of IL-12p70 in skin. CONCLUSION: The combination of deucravacitinib and shikonin is a promising clinical application.


Assuntos
Quimioterapia Combinada , Imiquimode , Naftoquinonas , Psoríase , Pele , Animais , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Camundongos , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Modelos Animais de Doenças , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Masculino , Feminino , Benzimidazóis , Quinolonas
15.
Narra J ; 4(1): e207, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38798877

RESUMO

Psoriasis vulgaris is a significant health problem and up to 30% of the patients are most likely to develop psoriatic arthritis. Secukinumab, an interleukin-17A (IL-17A) inhibitor, is used to treat patients with moderate-to-severe plaques associated with psoriatic arthritis. The aim of this case report was to highlight the efficacy of secukinumab treatment in a patient with both psoriasis vulgaris and psoriatic arthritis focusing the how to balance the benefits and adverse effects. A 36-year-old female came to Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia with chief complaint of itchy and scaly red plaques almost all over the body. The patient also experienced pain in both knees, both ankle joints and index finger as well as thumb in the right hand in the last year. The patient was diagnosed with psoriasis vulgaris and psoriatic arthritis, then treated with phototherapy and 15 mg of oral methotrexate each week for four weeks. Due to no improvement of the initial treatment, the patient received emollient and secukinumab at a dose of 300 mg/week subcutaneously for five weeks. The lesions began to disappear and the joint pain began to relieve. Secukinumab therapy was continued with a dose of 300 mg/month for six months. However, after six months, the patient complained of acnes appeared on the face. Therefore, the maintenance dose of secukinumab was decreased to 150 mg/month. After the reduced maintenance therapy was given, the patient came back with no complained of acnes. The erythematous plaques on trunk, back, arms and legs have subsided, as well as the joint pain. This case highlights that in a moderate-to-severe psoriasis associated with psoriatic arthritis, secukinumab is highly effective. However, since the potential adverse effects, education and regular follow-up are needed to analyze the success of the treatment and to be able to manage the adverse effects.


Assuntos
Anticorpos Monoclonais Humanizados , Artrite Psoriásica , Interleucina-17 , Psoríase , Humanos , Feminino , Adulto , Artrite Psoriásica/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Psoríase/tratamento farmacológico , Interleucina-17/antagonistas & inibidores
16.
Int Immunopharmacol ; 134: 112225, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759368

RESUMO

Itolizumab is a humanized monoclonal antibody that selectively targets the CD6-ALCAM pathway. This article reports on the safety and efficacy of itolizumab in the treatment of moderate-to-severe plaque psoriasis in a clinical study conducted in Cuba in the setting of an expanded-access program (EAP). The study included 84 patients who had previously received conventional anti-psoriatic systemic therapies but were either intolerant, had an inadequate response, or had contraindications to these therapies. It consisted of multiple phases, including a 12-week induction phase, a 40-week maintenance phase, and a 24-week off-treatment follow-up phase, using either a 0.4 or 1.6 mg/Kg dose. The results showed that itolizumab monotherapy was safe and effective during 52 weeks of continuous treatment and the subsequent 24 follow-up weeks. Itolizumab treatment resulted in a significant improvement (PASI 75) in 80 % of patients at the end of the induction phase, and this effect was sustained till week 52 during the maintenance phase. Moreover, 24 weeks after treatment stopped nearly two-thirds of patients still showed a PASI ≥ 75. The observed effects were dose-dependent, with 1.6 mg/kg being the most convenient dose. This study further supports the strategy of targeting the CD6-ALCAM signaling pathway for the treatment of psoriasis and the use of itolizumab as a valuable asset in the armamentarium of anti-psoriasis drugs.


Assuntos
Anticorpos Monoclonais Humanizados , Psoríase , Humanos , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Índice de Gravidade de Doença , Idoso , Cuba
18.
Expert Opin Biol Ther ; 24(5): 399-409, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38767132

RESUMO

BACKGROUND: Switch patterns among different biologics and from originators to biosimilars (and vice versa) can be complex in patients with psoriasis (PsO) and psoriatic arthritis (PsA). OBJECTIVE: The aim of this study was to describe switching patterns of biological drugs in PsO/PsA patients and to explore predictors of multiple switches and switch-back. RESEARCH DESIGN AND METHODS: A large-scale retrospective cohort study was conducted using the Italian VALORE database. Bio-naïve users treated for PsO/PsA during 2010-2022 were included. Time to switch/swap and predictors of multiple switches and switch-back were analyzed. RESULTS: Thirty-thousand seven hundred bio-naïve users were included. At 3 and 5 years of follow-up, patients with at least one switch/swap were 37.1% and 47.8%, respectively. The median time to first switch/swap was significantly shorter (p< 0.001) for TNF-α inhibitors (2,068 days) than anti-IL (2,780 days). At 1 year of follow-up patients starting with IL-23 switched/swapped biological therapy less frequently than those with anti-IL-12/23 and anti-IL-17 (4.9% vs. 8.7% and 9.4%, respectively). Patients starting with anti-IL-12/23 reported a significantly lower risk of multiple switches and switch-back (0.74, 95% CI, 0.67-0.83; 0.58, 95% CI, 0.44-0.77, respectively) than those with TNF-α inhibitors. CONCLUSIONS: Patients with PsO/PsA starting with TNF-α inhibitors switch/swap more rapidly and frequently than those with anti-IL, which are also associated with a reduced risk of multiple switches during follow-up.


Assuntos
Artrite Psoriásica , Produtos Biológicos , Bases de Dados Factuais , Substituição de Medicamentos , Psoríase , Humanos , Artrite Psoriásica/tratamento farmacológico , Masculino , Feminino , Psoríase/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Itália/epidemiologia , Medicamentos Biossimilares/uso terapêutico , Medicamentos Biossimilares/efeitos adversos
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