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1.
Cesk Slov Oftalmol ; 76(2): 88-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33126803

RESUMO

PURPOSE: To assess the effect of intravitreal aflibercept on pigment epithelial detachment (PED) secondary to occult choroidal neovascularization (CNV) in treatment-naive patients. PATIENTS AND METHODS: Retrospective analysis of thirty-six patients (thirty-eight eyes) with mean age 77 (SD ± 7), who were treated with aflibercept 2.0 mg (Eylea, Bayer) at the Department of Ophthalmology of 1st Faculty of Medicine of the Charles University and the Military University Hospital Prague. All patients were treated in fixed regimen, which means 3 loading doases 1 month apart, followed by further 2-monthly doses over total 12-month period. Best corrected visual acuity (BCVA) was evaluated on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Diameters as PED height, width and central retinal thickness (CRT) were assesed using spectral-domain optical coherence tomography. All previously mentioned were analyzed et the baseline and than at every visit. Therapy complications were also evaluated. RESULTS: Borderline significant improvement in the mean of BCVA score of 3.2 letters (SD ± 11.6, p = 0.05) at the end of follow-up period was observed. Mean PED height at 12 months significantly decreased by 140 µm (SD ± 238, p < 0.01). Reductions in PED height were correlated with reductions in central macular thickness (R = 0.94, p < 0.001) simultaneously with PED width (R = 0.45, p < 0.01). There was no significant correlation between PED height decrease and visual acuity. PED rupture was observed in 3 eyes (8 %). CONCLUSION: Aflibercept intravitreal therapy in fixed regimen in patients with PED secondary to occult CNV shows great anatomical effect. However, correlation between PED diameters and visual acuity was not observed.


Assuntos
Descolamento Retiniano , Epitélio Pigmentado da Retina , Idoso , Inibidores da Angiogênese/uso terapêutico , Humanos , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Descolamento Retiniano/complicações , Descolamento Retiniano/tratamento farmacológico , Estudos Retrospectivos , Tomografia de Coerência Óptica
2.
Cesk Slov Oftalmol ; 1(Ahead of print): 1-3, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33086850

RESUMO

The issue of macular retinal degeneration is one of the key areas of ophthalmology. Recent advances in the targeted delivery of vascular endothelial growth factor (VEGF) suppressants have significantly impacted the patient's prognosis in the form of a significant deceleration in disease progression. Some of the drugs have gradually found their use in other indications (central retinal vein occlusion or diabetic macular edema). The following text gives a brief look at the physiology of VEGF, but not only in the eye, but throughout the human body, particularly in the context of adverse effects resulting from systemic inhibition of its effects.


Assuntos
Retinopatia Diabética , Degeneração Macular , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
3.
Medicine (Baltimore) ; 99(35): e21992, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871950

RESUMO

BACKGROUND: Diabetic macular edema (DME) can cause severe vision impairments for patients with diabetes. Recently, Conbercept has shown efficacy on DME with 3-monthly loading dose injection and pro re nata (PRN, 3+PRN) thereafter in retrospectivetrials. Furthermore, there are some other approaches have been recommended such as 2mg bimonthly (2q8) after 5 initial doses, or Conbercept 0.5mg treat-and-extend, however, some patients still have recurrence of the disease after treatment. Therefore, in order to identify more efficacy and safety approach on Conbercept inpatients with DME, a randomized controlled trial will be performed with 6-monthly loading dose injection and PRN (6+PRN) compared with 3+PRN treatments. METHODS: This study is a multicenter, randomized control trial of Conbecept treating DME in China. Patients with type 2 diabetes suffered from DEM who already planned to receive Conbercept treatment will be recruited. All subjects will be randomized divided into either a study agent treatment group (6+PRN) or a control group (3+PRN), and observes the subjects for 48 weeks after initiation of treatment. RESULTS: This study will provide a new powerful evidence of the efficacy and safety of Conbecept treating DME. DISCUSSION: This RTC study will determine whether multiple treatments of Conbercept provide better effectiveness in patients with DME. TRIAL REGISTRATION NUMBER: ChiCTR2000032728.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Angiografia , Estudos de Equivalência como Asunto , Humanos , Estudos Multicêntricos como Assunto , Tomografia de Coerência Óptica
4.
Life Sci ; 260: 118274, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827545

RESUMO

AIMS: Triple-negative breast cancer (TNBC) is not sensitive to current endocrine treatments, so new treatment strategies need to be explored. Based on previous antitumour studies on anti-TNFα nanobody, we designed a novel fusion nanobody to enhance antitumour activity of the anti-TNFα nanobody in TNBC. MAIN METHODS: The RGD4C contains RGD sequence, which is the smallest recognition unit binding to the αvß3 receptor on tumour cell membranes and involved in tumour cell adhesion, proliferation, and metastasis. RGD4C was fused to anti-TNFα nanobody to investigate the antitumour activity in vitro and in vivo. KEY FINDINGS: The antitumour effects of fusion nanobody V-L-R-H could effectively bind to αvß3 and inhibit cell migration and proliferation of MDA-MB-231, which had satisfying purification efficiency and approving antigen or receptor binding activity. V-L-R-H could inhibit the TNFα-mediated PI3K/AKT/NF-κB signal pathway and integrin αvß3 correlative FAK focal adhesion signal pathway. Mouse xenograft tumour experiments showed that the V-L-R-H could inhibit tumour proliferation and metastasis; reduce the TNFα, HIFα, Ki67, and CD31 concentrations in tumour; and inhibit the process of epithelial-mesenchymal transition. SIGNIFICANCE: The fusion nanobody enhanced antitumour activity of the anti-TNFα nanobody on TNBC. It provided a reference for the design of dual functional fusion proteins and development of tumour treatment strategies of antagonistic TNFα and αvß3, and a new therapeutic strategy and research direction for the treatment of TNBC.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Oligopeptídeos/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Anticorpos de Domínio Único/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fator de Necrose Tumoral alfa/imunologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Expressão Gênica , Humanos , Integrina alfaVbeta3/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/prevenção & controle , Oligopeptídeos/química , Oligopeptídeos/genética , Pichia/metabolismo , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Anticorpos de Domínio Único/genética , Neoplasias de Mama Triplo Negativas/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Drugs Today (Barc) ; 56(7): 447-458, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32648855

RESUMO

Recently, after years of research often characterized by disappointments and frustrations, finally a new drug impacting on pathological human erythropoiesis has been developed and approved. This drug, luspatercept-aamt (Reblozyl), proved to be effective in both malignant and nonmalignant disease characterized by ineffective erythropoiesis with consequent life-threatening severe anemia. Moreover, for the first time, a medication demonstrated efficacy and effectiveness in ß-thalassemia where no other drug, including recombinant human erythropoietin, showed effectiveness in improving anemia. Despite recent impressive advances in understanding human normal and abnormal erythropoiesis, there are few new drugs and limited pharma research focusing on ineffective erythropoiesis. This review will discuss recent advances in understanding normal and pathological erythropoiesis that represent the background to discuss pharmacology, toxicology, efficacy, safety and effectiveness of this new drug for the treatment of human ß-thalassemia.


Assuntos
Receptores de Activinas Tipo II , Fragmentos Fc das Imunoglobulinas , Proteínas Recombinantes de Fusão , Talassemia beta , Receptores de Activinas Tipo II/uso terapêutico , Ativinas , Humanos , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Talassemia beta/tratamento farmacológico
6.
Medicine (Baltimore) ; 99(21): e20222, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481293

RESUMO

BACKGROUND: The objective of this review and meta-analysis is to investigate the efficacy of conbercept and ranibizumab, combined with or without laser photocoagulation, in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Several databases have been used to identify relevant publications. After screening, a meta-analysis was conducted to compare conbercept and ranibizumab with the support of RevMan 5.3 (Cochrane Library Software, Oxford, UK). RESULTS: In this study, 9 randomized controlled trials and 6 retrospective trials were included with a total of 1180 patients. No significant difference was found in best corrected visual acuity (BCVA) or central macular thickness (CMT) in the baseline parameters [BCVA (weighted mean difference (WMD): -0.01; 95% confidence interval CI: -0.03 to 0.01; P = .17), CMT (WMD: 20.14; 95% CI: -26.70 to 66.97; P = .40). No significant differences were found in the improvements of BCVA and adverse events (AEs) between the 2 groups after injection of loading dosage [the 1st month BCVA (WMD: -0.01; 95% CI: -0.04 to 0.02; P = .54),the 3rd month BCVA (WMD: -0.02; 95% CI: --0.05 to 0.01; P = .23), the 6th month BCVA (WMD: -0.02; 95% CI: -0.05 to 0.01; P = .27), AEs (odds ratio: 0.84; 95% CI: 0.38 to 1.84; P = .66)]. However, there were significant differences between conbercept and ranibizumab treatment in terms of CMT [1st month CMT (WMD: -11.70; 95% CI: -19.71 to -3.68; P < .01), 3rd month CMT (WMD: -10.08; 95% CI: -15.62 to -4.53; P < .01), 6th month CMT (WMD: -15.83; 95% CI: -22.88 to -8.78; P < .01)] and the number of injections (WMD, -0.36; 95% CI: -0.68 to -0.04; P = .03). CONCLUSION: The current pooled evidence suggested that both therapies of intravitreal conbercept and intravitreal ranibizumab with or without laser photocoagulation are effective in vision function in RVO-ME patients, and confirmed that conbercept has advantages over ranibizumab in terms of CMT and the number of injections for treating RVO-ME. In addition, conbercept has the statistically same visual gains and safety as ranibizumab in RVO-ME patients. Longer-term follow-up surveys on the safety and effectiveness of these 2 treatment regimens are required.


Assuntos
Fotocoagulação/métodos , Edema Macular/tratamento farmacológico , Edema Macular/terapia , Oclusão da Veia Retiniana/complicações , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Terapia Combinada/métodos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Ranibizumab/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/efeitos dos fármacos
7.
Lancet Neurol ; 19(7): 582-590, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32562683

RESUMO

BACKGROUND: Diabetes is an independent risk factor for cognitive impairment. We aimed to investigate the association between the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide and cognitive impairment as an exploratory analysis within the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial. METHODS: REWIND is a randomised, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women (aged ≥50 years) with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors, glycated haemoglobin of up to 9·5% (80 mmol/mol) on a maximum of two oral glucose-lowering drugs with or without basal insulin, and a body-mass index of at least 23 kg/m2. Participants were randomly assigned (1:1) subcutaneous injections once a week of either dulaglutide (1·5 mg) or an equal volume of matching placebo. Randomisation was done using a computer-generated code with stratification by site. Participants and all study personnel were masked to treatment allocation until the database was locked. Participants were followed up at least every 6 months for the composite primary outcome of stroke, myocardial infarction, or death from cardiovascular or unknown causes. Cognitive function was assessed at baseline and during follow-up using the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST). We present here the exploratory primary cognitive outcome, which was the first occurrence of a follow-up score on MoCA or DSST that was 1·5 SDs or more below the baseline mean score in the participant's country. All analyses were done using an intention-to-treat approach. The REWIND trial is registered with ClinicalTrials.gov, NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide (n=4949) or placebo (n=4952). During median follow-up of 5·4 (IQR 5·1-5·9) years, 8828 participants provided a baseline and one or more follow-up MoCA or DSST scores, of whom 4456 were assigned dulaglutide and 4372 were assigned placebo. The cognitive outcome occurred in 4·05 per 100 patient-years in participants assigned dulaglutide and 4·35 per 100 patient-years in people assigned placebo (hazard ratio [HR] 0·93, 95% CI 0·85-1·02; p=0·11). After post-hoc adjustment for individual standardised baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those assigned dulaglutide (HR 0·86, 95% CI 0·79-0·95; p=0·0018). INTERPRETATION: Long-term treatment with dulaglutide might reduce cognitive impairment in people with type 2 diabetes. Further studies of this drug focused on brain health and cognitive function are clearly indicated. FUNDING: Eli Lilly and Company.


Assuntos
Disfunção Cognitiva/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Adulto , Idoso , Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Feminino , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
PLoS One ; 15(6): e0235213, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579608

RESUMO

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Doenças da Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Corioide/fisiologia , Doenças da Coroide/patologia , Terapia Combinada , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Lasers , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Verteporfina/uso terapêutico , Acuidade Visual
9.
MAbs ; 12(1): e1782600, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546047

RESUMO

While the potential therapeutic utility of angiotensin-converting enzyme 2 (ACE2) is well established, the clinical development of ACE2 drugs has been limited, likely due in part to the short half-life of the protein. In contrast, Ig-like ACE2 fusion proteins have exhibited greatly extended plasma half-life in vivo, and they have been shown to have a potent neutralization effect against SARS-CoV-2. Clinical investigation of Ig-like ACE2 fusion proteins as COVID-19 interventions is thus warranted.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Peptidil Dipeptidase A/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/efeitos adversos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Pandemias , Peptidil Dipeptidase A/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento
10.
Am J Ophthalmol ; 218: 225-241, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32565050

RESUMO

PURPOSE: To perform 11- and 2-year health care sector (ophthalmic) and societal cost perspective reference case, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD). DESIGN: Cost-utility analysis. METHODS: The authors performed 11-year and 2-year ophthalmic and societal cost perspective, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD). We employed patient utilities, bilateral outcomes, 2018 U.S. dollars, vision-related mortality, a Medicare fee schedule, and CATT (Comparison of Age-Related Macular Degeneration Treatments) study and VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) trial. Cochrane data were also used. SETTING: Center for Value-Based Medicine. Patient/study population: patients with NVAMD. INTERVENTION: Cost-utility analyses using published data. Data-modeled 10-year vision outcomes were modeled forward to year 11. MAIN OUTCOME MEASUREMENT: These included cost-utility ratios (CURs), costs, and quality-adjusted life-years (QALYs) gained. $100,00/QALY was considered the US cost-effectiveness upper limit. RESULTS: Bevacizumab and ranibizumab each conferred an 11-year, 1.339 QALY gain versus observation. Aflibercept conferred a 1.380 QALY gain. Aflibercept conferred greater QALY gain for less cost than ranibizumab but was not cost-effective compared to bevacizumab ($1,151,451/QALY incremental CUR). The average ophthalmic cost perspective CUR for bevacizumab was $11,033/QALY, $79,600/QALY for ranibizumab, and $44,801/QALY for aflibercept. Eleven-year therapies saved a 1.0 year-of-life loss without treatment from the 11.0-year life expectancy. Early treatment was 138%-149% more cost-effective than late treatment. Two-year therapy prevented a 1-month-of-life loss, and revealed bevacizumab, ranibizumab, and aflibercept conferred 0.141, 0.141, and 0.164 QALY gains, respectively, with corresponding average CURs of $40,371/QALY, $335,726/QALY, and $168,006/QALY, respectively. CONCLUSIONS: From an ophthalmic (medical) cost perspective, bevacizumab, ranibizumab, and aflibercept NVAMD monotherapies were all cost-effective over 11 years, with bevacizumab 6.21× more cost-effective than ranibizumab and 3.06× more cost-effective than aflibercept. Two-year modeling revealed bevacizumab was cost-effective, whereas ranibizumab and aflibercept were not. Early treatment was critical for obtaining optimal vision and cost-effectiveness, as is long-term follow-up and adherence to treatment.


Assuntos
Inibidores da Angiogênese/economia , Neovascularização de Coroide/economia , Análise Custo-Benefício , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/economia , Degeneração Macular Exsudativa/economia , Idoso , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/economia , Bevacizumab/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Custos de Medicamentos , Feminino , Custos de Cuidados de Saúde , Humanos , Injeções Intravítreas , Masculino , Medicare , Anos de Vida Ajustados por Qualidade de Vida , Ranibizumab/economia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/economia , Proteínas Recombinantes de Fusão/uso terapêutico , Estados Unidos , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico
11.
J Biol Regul Homeost Agents ; 34(2): 525-533, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425017

RESUMO

To explore effects of the sDR5-Fc fusion protein on ulcerative colitis of infant mice via the TRAIL-DR5 pathway, 50 female mice were randomly divided into 5 groups, i.e., control group (group A), dextran sulfate sodium group (group B), hIgG group (group C), 10 mg/kg sDR5-Fc group (group D), and 20 mg/ kg sDR5-Fc group (group E). The acute ulcerative colitis models were established. The weights and disease activity index (DAI) of each group were monitored daily. In addition, the pathological changes of colon tissues were observed by Hematoxylin-Eosin staining. The number of macrophages in colon tissues was detected by immunohistochemistry assay. Changes in the expression of inflammatory factors in colon tissues were detected by quantitative real-time polymerase chain reaction (PCR). Lipopolysaccharide (LPS) of different concentrations was utilized alone or in combination with TRAIL to stimulate the NCM460 cells. The activation of NLRP3 inflammasomes was detected by Western blot. The apoptosis of NCM460 cells was detected by flow cytometry. The results showed that in groups B and C, the body weights decreased, the DAI increased, the colon epithelial cells were injured, the inflammatory cells were infiltrated, and the macrophages in colon tissues increased significantly. In groups D and E, the body weights increased, the DAI decreased, the inflammation was significantly improved, the macrophages decreased significantly, and the gene expression levels of NLRP3, Caspase-1, and IL-1ß decreased significantly. Thus, sDR5-Fc could inhibit the activation of NLRP3 inflammasomes induced by TRAIL, thereby decreasing the apoptosis of NCM460 cells. In conclusion, the sDR5-Fc fusion protein could block the TRAIL-DR5 pathway to reduce the expression of NLRP3 inflammasomes, thereby improving ulcerative colitis.


Assuntos
Colite Ulcerativa/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Animais , Apoptose , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana , Feminino , Inflamassomos , Macrófagos/citologia , Camundongos , Distribuição Aleatória
12.
Drugs Today (Barc) ; 56(5): 311-320, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32406878

RESUMO

Wet age-related macular degeneration (w-AMD) represents the main cause of vision loss in the elderly in the western countries. The important role displayed by vascular endothelial growth factor (VEGF) in the pathogenesis of this disease has been largely demonstrated. For this reason, anti-VEGF drugs have been developed and currently are considered as the first-line treatment options in the management of w-AMD. Among the novel anti-VEGF agents studied, conbercept is a fusion protein composed of the combination between VEGF receptor domains with the Fc fragment of human immunoglobulin. It was already approved in China in 2014 for treating w-AMD. In this regard, the phase III PHOENIX trial has reported a good clinical efficacy and safety profile of conbercept for w-AMD, also by adopting a quarterly regimen. In this review, we will discuss its pharmacokinetics, pharmacodynamics, clinical efficacy, without neglecting also its safety and tolerability profile.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Ensaios Clínicos Fase III como Assunto , Humanos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
13.
PLoS One ; 15(5): e0232353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369500

RESUMO

IMPORTANCE: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited. OBJECTIVE: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab. METHOD: Retrospective cohort study of patients with treatment-naïve neovascular AMD seen at an academic hospital between October 2006 and February 2019. Study eyes were treated with intravitreal injections of aflibercept, bevacizumab, and/or ranibizumab and followed for two years. MAIN OUTCOMES AND MEASURES: cRORA prevalence, location, size, and growth rate. Eyes were imaged with Cirrus spectral domain optical coherence tomography (SD-OCT). Presence and size of cRORA were calculated using the FDA-approved Advanced RPE Analysis software. Linear regression models were used to correlate cRORA progression with baseline demographic and ocular characteristics, anti-VEGF drug, and number of injections. Unpaired t-tests, ANOVA, and linear regression models were computed with SAS 9.4. RESULTS: 197 eyes from 158 patients (mean age 78.9, 62.9% women) received an average of 13 anti-VEGF injections over 24 months. 22% developed new cRORA. Mean cRORA area increased from 1.71 mm2 to 2.93 mm2. At 24 months, eyes with 11+ injections had significantly less cRORA area (11+ injections, 4.02 mm2; ≤ 10 injections, 2.46 mm2; p = 0.01) and growth rate (11+ injections, 0.41 mm2/year; ≤ 10 injections, 1.05 mm2/year; p = 0.02). Choice of anti-VEGF drug yielded no significant difference in cRORA progression. CONCLUSIONS AND RELEVANCE: Treating nAMD with aflibercept, bevacizumab or ranibizumab demonstrated comparable cRORA development at 24 months. Number of injections inversely correlated with cRORA area and growth. These results warrant further investigation in the pathophysiology of cRORA in anti-VEGF treated eyes.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Atrofia , Bevacizumab/uso terapêutico , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador , Injeções Intravítreas , Masculino , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Retiniana/diagnóstico por imagem , Epitélio Pigmentado da Retina/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
14.
PLoS One ; 15(4): e0232494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353052

RESUMO

BACKGROUND AND OBJECTIVE: To develop a semi-automated, machine-learning based workflow to evaluate the ellipsoid zone (EZ) assessed by spectral domain optical coherence tomography (SD-OCT) in eyes with macular edema secondary to central retinal or hemi-retinal vein occlusion in SCORE2 treated with anti-vascular endothelial growth factor agents. METHODS: SD-OCT macular volume scans of a randomly selected subset of 75 SCORE2 study eyes were converted to the Digital Imaging and Communications in Medicine (DICOM) format, and the EZ layer was segmented using nonproprietary software. Segmented layer coordinates were exported and used to generate en face EZ thickness maps. Within the central subfield, the area of EZ defect was measured using manual and semi-automated approaches via a customized workflow in the open-source data analytics platform, Konstanz Information Miner (KNIME). RESULTS: A total of 184 volume scans from 74 study eyes were analyzed. The mean±SD area of EZ defect was similar between manual (0.19±0.22 mm2) and semi-automated measurements (0.19±0.21 mm2, p = 0.93; intra-class correlation coefficient = 0.90; average bias = 0.01, 95% confidence interval of limits of agreement -0.18-0.20). CONCLUSIONS: A customized workflow generated via an open-source data analytics platform that applied machine-learning methods demonstrated reliable measurements of EZ area defect from en face thickness maps. The result of our semi-automated approach were comparable to manual measurements.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Monitoramento de Medicamentos/métodos , Aprendizado de Máquina , Edema Macular/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Adulto , Bevacizumab/uso terapêutico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Macula Lutea/diagnóstico por imagem , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Oclusão da Veia Retiniana/complicações , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fluxo de Trabalho
15.
Mol Immunol ; 123: 88-96, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32447084

RESUMO

The anaerobic pathogen Clostridium perfringens is the most potent cause of intestinal diseases, such as enterotoxemia, hemorrhagic enteritis, and lamb dysentery, in sheep. Three toxinotypes (B, C, and D) are usually the cause of these diseases and are mainly mediated via three important exotoxins: alpha toxin (CPA), beta toxin (CPB), and epsilon toxin (ETX). We have designed a chimeric protein, rCpa-b-x, that contains the C-terminal binding region of CPA, partial sequence of CPB, and ETX (Cpa247-370, Cpb108-305, and EtxH118P, respectively) according to the principle of structural vaccinology. The rCpa-b-x protein was then expressed by pHT43 plasmid in vivo using Bacillus subtilis as a delivery vector (Bs-pHT43-Cpa-b-x). The immunological activity of the rCpa-b-x protein was verified by western blot and its immunological efficacy was evaluated in a murine model. Oral administration with a recombinant agent caused local mucosal and systemic immune responses, and serum lgG and intestinal mucosal secretory IgA (sIgA) antibody titers were significantly increased. Levels of IL-2, IL-4, and IFN-γ were significantly higher in lymphocytes isolated from the Bs-pHT43-Cpa-b-x group compared with levels from the control groups. The percentages of CD4+ and CD8+ T lymphocytes in the Bs-pHT43-Cpa-b-x and inactivated vaccine (IV) groups were in the normal range. Mice of vaccine groups and control groups were challenged with 1x LD100 unit filtrate containing alpha, beta, and epsilon toxins. Mice in the Bs-pHT43-Cpa-b-x group were found to have lower rates of morbidity. The active immunization of mice with Bs-pHT43-Cpa-b-x still maintained 85% to 90% survival at the end of the 10-day observation period, whereas mice of control groups died within two to five days. The results of this study demonstrate the effectiveness of Bs-pHT43-Cpa-b-x in preventing C. perfringens infection in mice, and that Bs-pHT43-Cpa-b-x could be considered a potential vaccine against C. perfringens.


Assuntos
Bacillus subtilis/metabolismo , Toxinas Bacterianas/imunologia , Vacinas Bacterianas/metabolismo , Vacinas Bacterianas/uso terapêutico , Infecções por Clostridium/prevenção & controle , Clostridium perfringens/imunologia , Animais , Bacillus subtilis/genética , Toxinas Bacterianas/metabolismo , Vacinas Bacterianas/química , Vacinas Bacterianas/genética , Infecções por Clostridium/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Ligação Proteica , Estrutura Quaternária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/uso terapêutico , Vacinação/métodos , Vacinas Sintéticas/química , Vacinas Sintéticas/genética , Vacinas Sintéticas/metabolismo , Vacinas Sintéticas/uso terapêutico
16.
Lancet Diabetes Endocrinol ; 8(5): 392-406, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333876

RESUMO

BACKGROUND: New glucose-lowering medications need to be investigated in east Asian populations, as the clinical characteristics of type 2 diabetes differ between western and east Asian patients. The PIONEER 10 study aimed to evaluate the safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes. METHODS: PIONEER 10 was an open-label, randomised, active-controlled, phase 3a trial done at 36 sites (clinics and university hospitals) in Japan. Patients aged 20 years and older with uncontrolled type 2 diabetes were randomly assigned (2:2:2:1) to receive once-daily oral semaglutide 3 mg, 7 mg, or 14 mg, or once-weekly subcutaneous dulaglutide 0·75 mg for 52 weeks, as an add-on to their background medication. The primary endpoint was the number of treatment-emergent adverse events over 57 weeks. Supportive secondary endpoints (not controlled for multiplicity) included mean change from baseline in HbA1c and bodyweight at 52 weeks. This trial is registered with ClinicalTrials.gov, NCT03015220. FINDINGS: Between Jan 10, and May 30, 2017, 492 patients were screened and 458 were randomly assigned to oral semaglutide 3 mg (n=131), 7 mg (n=132), or 14 mg (n=130), or dulaglutide 0·75 mg (n=65). 448 (98%) patients completed the trial. Adverse events occurred in 101 (77%) of 131 patients with oral semaglutide 3 mg, 106 (80%) of 132 with oral semaglutide 7 mg, 111 (85%) of 130 with oral semaglutide 14 mg, and 53 (82%) of 65 with dulaglutide. The most common adverse events were infections and gastrointestinal events. Gastrointestinal adverse events (mostly mild and transient constipation and nausea) occurred in a dose-dependent manner with oral semaglutide. Adverse events led to premature treatment discontinuation in four (3%) of 131 patients receiving oral semaglutide 3 mg, eight (6%) of 132 receiving oral semaglutide 7 mg, eight (6%) of 130 receiving oral semaglutide 14 mg, and two (3%) of 65 receiving dulaglutide. No deaths or severe hypoglycaemic events were reported. Based on the treatment policy estimand (ie, regardless of study drug discontinuation or rescue medication use), estimated mean reductions in HbA1c from baseline (8·3%) to week 52 were -0·9 percentage points (SE 0·1) with oral semaglutide 3 mg, -1·4 percentage points (0·1) with oral semaglutide 7 mg, -1·7 percentage points (0·1) with oral semaglutide 14 mg, and -1·4 percentage points (0·1) with dulaglutide (estimated treatment difference -0·3% [95% CI -0·6 to -0·1] for oral semaglutide 14 mg vs dulaglutide; p=0·0170). Estimated mean changes in bodyweight from baseline (72·1 kg) to week 52 were 0·0 kg (SE 0·3) with oral semaglutide 3 mg, -0·9 kg (0·3) with oral semaglutide 7 mg, -1·6 kg (0·3) with oral semaglutide 14 mg, and 1·0 kg (0·4) with dulaglutide (estimated treatment difference -2·6 kg [95% CI -3·5 to -1·6] for oral semaglutide 14 mg vs dulaglutide; p<0·0001). INTERPRETATION: Oral semaglutide was well tolerated in Japanese patients with type 2 diabetes. Once-daily oral semaglutide significantly reduced HbA1c (14 mg dose) and bodyweight (7 mg and 14 mg doses) versus weekly subcutaneous dulaglutide 0·75 mg by week 52. FUNDING: Novo Nordisk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Administração Oral , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Feminino , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hemoglobina A Glicada/análise , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/efeitos adversos
17.
PLoS One ; 15(4): e0231240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287299

RESUMO

OBJECTIVE: REG-O3 is a 24-aminoacid chimeric peptide combining a sequence derived from growth hormone (GH) and an analog of somatostatin (SST), molecules displaying cartilage repair and anti-inflammatory properties, respectively. This study aimed to investigate the disease-modifying osteoarthritis drug (DMOAD) potential of REG-O3 by analyzing its effect on pain, joint function and structure, upon injection into osteoarthritic rat knee joint. DESIGN: Osteoarthritis was induced in the right knee of mature male Lewis rats (n = 12/group) by surgical transection of the anterior cruciate ligament (ACLT) combined with partial medial meniscectomy (pMMx). Treatments were administered intra-articularly from fourteen days after surgery through three consecutive injections one week apart. The effect of REG-O3, solubilized in a liposomal solution and injected at either 5, 25 or 50 µg/50 µL, was compared to liposomal (LIP), dexamethasone and hyaluronic acid (HA) solutions. The study endpoints were the pain/function measured once a week throughout the entire study, and the joint structure evaluated eight weeks after surgery using OARSI score. RESULTS: ACLT/pMMx surgery induced a significant modification of weight bearing in all groups. When compared to liposomal solution, REG-O3 was able to significantly improve weight bearing as efficiently as dexamethasone and HA. REG-O3 (25 µg) was also able to significantly decrease OARSI histological global score as well as degeneration of both cartilage and matrix while the other treatments did not. CONCLUSION: This study provides evidence of a remarkable protecting effect of REG-O3 on pain/knee joint function and cartilage/matrix degradation in ACLT/pMMx model of rat osteoarthritis. REG-O3 thus displays an interesting profile as a DMOAD.


Assuntos
Lesões do Ligamento Cruzado Anterior/complicações , Anti-Inflamatórios não Esteroides/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Hormônio do Crescimento/uso terapêutico , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Somatostatina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Cartilagem Articular/patologia , Modelos Animais de Doenças , Hormônio do Crescimento/farmacologia , Articulação do Joelho/patologia , Masculino , Osteoartrite do Joelho/etiologia , Ratos , Ratos Endogâmicos Lew , Proteínas Recombinantes de Fusão/farmacologia , Somatostatina/análogos & derivados , Somatostatina/farmacologia
18.
Eur J Ophthalmol ; 30(3): 586-594, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32347762

RESUMO

PURPOSE: To report 12-month outcomes of a Polish National Treatment Program using aflibercept and ranibizumab in eyes with wet, age-related macular degeneration in routine clinical practice. MATERIAL AND METHODS: This was a non-randomized, retrospective, observational multicenter study. Anonymous data contained in the electronic Therapeutic Program Monitoring System were utilized in this study. RESULTS: The study population consisted of 2828 eyes from 2718 patients. The median age was 76.0 [70.0, 81.0] years; 61.7% were female. Best corrected visual acuity increased from 58.86 [50.05, 69.95] letters to 65.1 [50.1, 73.9] letters (p < 0.001). The median change in best corrected visual acuity was 0.0 [-4.0, 12.2] letters: 2.9 [-2.9, 15.1] letters for treatment-naïve eyes and 0.0 [-4.0, 8.8] letters for those continuing treatment (p < 0.001). The median central retinal thickness was significantly reduced from 341.0 [281.0, 422.0] to 275.0 [221.0, 344.0] µm (p < 0.001). The median number of visits was 9.0 [8.0, 9.0]. The median number of injections was 7.0 [6.0, 8.0]: 8.0 [7.0, 8.0] for treatment-naïve eyes and 6.0 [5.0, 7.0] for those continuing treatment (p < 0.001). CONCLUSION: Eyes treated as part of the Polish therapeutic program gained functional stability and morphological improvement. Treatment-naïve eyes showed the greatest functional benefit.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/fisiopatologia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Polônia , Retina/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia
19.
Medicine (Baltimore) ; 99(17): e19955, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32332680

RESUMO

The aim of this study was to identify any changes that occur in the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) in patients with exudative age-related macular degeneration (AMD) during treatment with anti-vascular endothelial growth factor (VEGF) injections.Patients were enrolled in this retrospective study if they had exudative AMD, had received at least 3 injections of ranibizumab or aflibercept, and had a minimum of 12 months of follow-up. We analyzed the changes in the RNFL and GC-IPL using spectral-domain optical coherence tomography in rescan mode.Fifty-two eyes of 52 patients who had been treated with repeated anti-VEGF injections for exudative AMD were included. At the final visit, there was no significant between-group difference in best-corrected visual acuity or intraocular pressure. There was a significant decrease in central macular thickness in all groups (P < .05). There was a decrease in RNFL thickness that was only statistically significant in the ranibizumab group and when the ranibizumab or aflibercept groups were combined (P = .036 and .044, respectively). The thickness of the GC-IPL layer was significantly decreased in the aflibercept and total group (P = .035 and P = .048, respectively).The thicknesses of the RNFL and GC-IPL decreased in patients with exudative AMD who underwent repeated anti-VEGF injections.


Assuntos
Degeneração Macular/tratamento farmacológico , Retina/patologia , Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Pesos e Medidas , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ranibizumab/farmacologia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Retina/fisiopatologia , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Crescimento do Endotélio Vascular/farmacologia
20.
N Engl J Med ; 382(13): 1219-1231, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-32212518

RESUMO

BACKGROUND: Patients with transfusion-dependent ß-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor ß superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent ß-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 µg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS: The percentage of patients with transfusion-dependent ß-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.).


Assuntos
Receptores de Activinas Tipo II/uso terapêutico , Transfusão de Eritrócitos/estatística & dados numéricos , Hematínicos/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Talassemia beta/tratamento farmacológico , Receptores de Activinas Tipo II/efeitos adversos , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Ferritinas/sangue , Hematínicos/efeitos adversos , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Análise de Intenção de Tratamento , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Razão de Chances , Proteínas Recombinantes de Fusão/efeitos adversos , Esplenectomia , Adulto Jovem , Talassemia beta/genética , Talassemia beta/cirurgia , Talassemia beta/terapia
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