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2.
Pediatr Blood Cancer ; 70(1): e30061, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36326084

RESUMO

Vedolizumab, an anti-α4ß7 integrin monoclonal antibody, impairs homing of T-cells to the gastrointestinal (GI) endothelium and acts as a gut-selective anti-inflammatory agent. Recent reports of the efficacy of vedolizumab in treating lower GI acute graft-versus-host disease (aGVHD) are promising, but experience in children is scarce. We present a cohort of 13 pediatric patients who were treated with vedolizumab for GI aGVHD. Ten of the patients were treated for steroid-refractory disease, out of which, six suffered from severe (stage 3 or 4) GI disease before the first dose of vedolizumab. In the other three patients, vedolizumab was introduced early in the disease course. Median time between GI GVHD onset to vedolizumab treatment was 23 days (range 7-59 days), with a median of 3 doses (range 1-5) per patient. GI GVHD staging was evaluated at various time points after the first vedolizumab dose, showing improvement in nine of the 13 patients. After a median follow-up time of 13 months (range 6-34 months), eight patients completely recovered, two had ongoing chronic colitis, and three patients died. During the vedolizumab treatment period, 38 infectious episodes were noted, most of them GI related. The unique activity profile of vedolizumab makes it an appealing treatment option for lower GI aGVHD, but caution for concurrent infections is warranted.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Esteroides , Doença Aguda
3.
Bone ; 166: 116598, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36341949

RESUMO

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is an ultra-rare mosaic disorder manifesting as skeletal dysplasia and FGF23-mediated hypophosphatemia, with some experiencing extra-osseous/extra-cutaneous manifestations, including both benign and malignant neoplasms. Like other disorders of FGF23-mediated hypophosphatemia including X-linked hypophosphatemia (XLH) and tumor-induced osteomalacia (TIO), patients with CSHS have low serum phosphorus and active 1,25-dihydroxyvitamin D levels. Current treatment options for patients with CSHS include multiple daily doses of oral phosphorus and one or more daily doses of active vitamin D analog to correct the deficits. Recently, the fully human monoclonal antibody against FGF23 burosumab received US approval for the treatment of XLH and TIO, two rare diseases characterized by FGF23-mediated hypophosphatemia leading to rickets and osteomalacia. Given the similarities between the pathobiologies of these disorders and CSHS, we investigated the impact of burosumab on two patients, one pediatric and one adult, with CSHS who participated in separate, but similarly designed trials. In both the pediatric and adult patients, burosumab therapy was well-tolerated and contributed to clinically meaningful improvements in disease outcomes including normalization of phosphorus metabolism and markers of bone health, and improvements in skeletal abnormalities, fractures, and physical function. Reported adverse events were minimal, with only mild injection site reactions attributed to burosumab therapy. Together, these findings suggest that burosumab therapy is a promising therapeutic option for patients with CSHS.


Assuntos
Anticorpos Monoclonais Humanizados , Hipofosfatemia , Adulto , Criança , Humanos , Raquitismo Hipofosfatêmico Familiar/complicações , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Hipofosfatemia/tratamento farmacológico , Osteomalacia/tratamento farmacológico , Fósforo , Anticorpos Monoclonais Humanizados/uso terapêutico
4.
J Pharm Biomed Anal ; 223: 115163, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36410129

RESUMO

Emicizumab is a new therapeutic monoclonal antibody indicated for prophylaxis in severe haemophilia A patients. Pharmacokinetic variability has been reported in clinical studies, thus dose optimisation based on quantification of plasma drug concentration could be considered to reduce this variability. Therefore, a reliable and accurate quantification of emicizumab is required. In this study, we developed a method for absolute quantification of emicizumab using liquid chromatography coupled to triple quadrupole mass spectrometry (LC-MS/MS). Sample preparation was based on organic solvent precipitation of proteins followed by trypsin digestion. A signature peptide of emicizumab was used for quantification by LC-MS/MS. A stable isotope-labelled peptide was used as an internal standard. Finally, 6 samples from patients treated with emicizumab were quantified by LC-MS/MS and compared with those obtained with the modified one-stage activated partial prothrombin time technique (aPTT) based FVIII activity. The LC-MS/MS method was validated according to FDA recommendations. Good linearity of the calibration curves was observed over the range 5-150 µg/mL. The cross-validation showed an acceptable correlation of the developed LC-MS/MS method with the modified aPTT-based FVIII activity assay, and the Bland-Altman analysis did not show any significant bias.


Assuntos
Anticorpos Biespecíficos , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida , Anticorpos Monoclonais Humanizados
5.
BMC Cancer ; 22(1): 335, 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35346114

RESUMO

OBJECTIVE: The purpose of this study was to explore the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib and camrelizumab (TACE + AC) for unresectable hepatocellular carcinoma (HCC), and the impact of the timing of the combination on it. METHODS: In this single-arm retrospective study, consecutive data of patients with unresectable HCC treated to our hospital from March 2017 to September 2021 were collected. These patients were treated with TACE and started on camrelizumab and apatinib within one week of TACE. Camrelizumab 200 mg intravenously once every three weeks and apatinib 250 mg orally once daily. Repeat TACE treatment was available on an on-demand basis. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. The univariate and multivariate Cox regression analyses were used to assess the effect of early and late combination on OS and PFS. RESULTS: A total of 80 patients were enrolled in this study. The median OS was 22.1 months (95% confidence interval [CI]: 13.8-30.5 months) and the median PFS was 15.7 months (95% CI: 14.7-16.6 months). The ORR was 58.8% (95% CI: 47.2-69.6) and DCR reached 81.2% (95% CI: 71.0-89.1). Multivariable Cox proportional hazard regression analyses showed that TACE late combined with apatinib and camrelizumab provided better OS than early combination (HR = 0.175, 95% CI:0.060-0.509, P = 0.001), as did PFS (HR = 0.422, 95% CI:0.184-0.967, P = 0.041). All treatment-related adverse events were tolerable, and no serious adverse events were observed. CONCLUSION: TACE combined with apatinib plus camrelizumab for patients with unresectable HCC has promising antitumor activity and a manageable safety profile. For unresectable HCC with large tumor burden, late combination provides better OS and PFS compared to early combination.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Piridinas , Estudos Retrospectivos
6.
Anticancer Res ; 42(4): 1905-1910, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35347009

RESUMO

AIM: The present study evaluated the efficacy and safety of ramucirumab (RAM) in clinical practice as post-treatment, following atezolizumab plus bevacizumab (Atz/Bev) for advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein (AFP) levels of ≥400 ng/ml. PATIENTS AND METHODS: Of the 77 patients treated with Atz/Bev at our institution, 13 patients for whom RAM was introduced as post-treatment following Atz/Bev were enrolled in this retrospective study. There were 9 patients (69.2%) with Child-Pugh A and 11 patients (84.6%) for whom RAM was initiated as 3rd- or later-line therapy. The median AFP level was 2259 ng/ml. RESULTS: The objective response rate by Response Evaluation Criteria in Solid Tumours at 6 weeks was 15.4%, and the disease control rate was 69.2%. The median time to progression was 3.0 months; AFP level decreased at 2 weeks in 11 patients (84.6%) and at 6 weeks in seven patients (53.8%). The most common adverse events (AEs) within 6 weeks were ascites, peripheral oedema, and proteinuria, while grade 3 AEs occurred in six patients (46.2%). Albumin-bilirubin scores at both 4 and 6 weeks were significantly worse than those at baseline. CONCLUSION: In HCC patients with AFP levels of ≥400 ng/mL, RAM after Atz/Bev is expected to be an effective treatment option. Careful attention should be paid to the development of AEs and deterioration of liver function, especially when RAM is used as 3rd- or later-line therapy. Additional studies are needed to confirm the efficacy and safety of RAM as 2nd-line treatment after Atz/Bev in Child-Pugh A patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estudos Retrospectivos
7.
Anticancer Res ; 42(4): 2045-2051, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35347027

RESUMO

BACKGROUND: In order to search for predictive biomarkers of efficacy of pembrolizumab therapy for metastatic urothelial cancer (UC), we investigated the relationship between treatment outcomes and early neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP) responses. PATIENTS AND METHODS: Medical records of 101 patients with metastatic UC who started pembrolizumab as a second-line or later treatment were reviewed. NLR, LDH, and CRP were recorded after 3 weeks of therapy. In addition, we investigated whether these factors had an association with prolonged progression-free (PFS) or overall (OS) survival. RESULTS: The objective response rate, median PFS, and median OS were 25.7%, 6.3 months, and 15.2 months, respectively. PFS and OS were significantly shorter in patients with NLR>3, LDH>upper limit of normal (ULN), and CRP>0.5 mg/dl after 3 weeks of pembrolizumab treatment (p<0.05). A predictive model comprising these factors (favorable risk group: 0 risk factors; intermediate-risk group: 1-2 risk factors; poor-risk group: 3 risk factors) revealed distinct PFS and OS curves (p<0.001). In the favorable risk group, 12-month OS was 79.6%; in the poor-risk group, it was 12.8%. Harrell's C-indices for NLR >3, LDH >ULN, CRP >0.5 mg/dl, and all three combined for predicting OS were 0.656, 0.625, 0.633 and 0.678, respectively. Early responses were also non-significantly associated with ORR (p=0.37). CONCLUSION: Pembrolizumab treatment outcomes are associated with early NLR, LDH, and CRP responses in metastatic urothelial cancer.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células de Transição , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Humanos , Linfócitos , Neutrófilos
8.
Dermatol Ther ; 35(2): e15231, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34820971

RESUMO

Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.


Assuntos
Psoríase , Adulto , Anticorpos Monoclonais Humanizados , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Arch. Soc. Esp. Oftalmol ; 97(11): 626-638, nov. 2022. ilus
Artigo em Espanhol | IBECS | ID: ibc-ADZ-895

RESUMO

Objetivo: Brolucizumab, un anti-VEGF de nueva generación, ha demostrado su eficacia y seguridad en la degeneración macular asociada a la edad neovascular exudativa (DMAEn) en los ensayos pivotales HAWK y HARRIER. Tras su comercialización, se han reportado eventos adversos relacionados con la inflamación intraocular no detectados previamente. Una revisión post hoc independiente de los ensayos pivotales cifra la tasa de inflamación intraocular (IIO) en el 4,6%. El objetivo de este trabajo es proponer una serie de recomendaciones para implementar el manejo de brolucizumab en la práctica clínica. Método: Las recomendaciones realizadas por los autores se han basado en su experiencia clínica y en la revisión crítica de: 1)los ensayos pivotales; 2)el análisis post hoc del Comité de Revisión de Seguridad, y 3)la literatura publicada. Resultados: En los ensayos pivotales, brolucizumab mostró ganancias funcionales sostenidas, resultados anatómicos superiores con intervalos entre inyecciones potencialmente más prolongados y un perfil de seguridad global bien tolerado. Los eventos adversos reportados tras la comercialización incluyen vasculitis retiniana y la oclusión vascular retiniana. De acuerdo con la información disponible, los expertos recomiendan: 1)descartar los perfiles de pacientes no recomendados (historial previo de IIO); 2)explorar al paciente antes de cada inyección para descartar la presencia de IIO activa; 3)monitorizar al paciente para detectar precozmente los signos de alerta, y 4)tratar de inmediato en el caso de que se desarrolle algún evento adverso. ConclusionesLos : eventos adversos reportados son poco frecuentes, pero pueden estar asociados con una pérdida severa e irreversible de agudeza visual. Las recomendaciones realizadas pretenden facilitar el manejo de brolucizumab en la práctica habitual de los retinólogos, garantizar la seguridad del paciente y, en caso de que se produzca alguno de los eventos adversos, minimizar su impacto sobre la visión. (AU)


Purpose: Brolucizumab, a new generation anti-VEGF, has demonstrated efficacy and safety in AMD in the pivotal HAWK and HARRIER trials. Post-marketing, previously undetected adverse events related to intraocular inflammation have been reported. An independent post hoc review of the pivotal trials puts the rate of intraocular inflammation (IOI) at 4.6%. The aim of this paper is to propose a set of recommendations for implementing the management of brolucizumab in clinical practice. Method: The recommendations made by the authors are based on their clinical experience and critical review of (i)the pivotal trials; (ii)the post-hoc analysis of the Safety Review Committee, and (iii)the published literature. Results: In the pivotal trials, brolucizumab showed sustained functional gains, superior anatomical outcomes with potentially longer intervals between injections and a well-tolerated overall safety profile. Adverse events reported post-marketing include retinal vasculitis and retinal vascular occlusion. Based on the available information, experts recommend (i)ruling out non-recommended patient profiles (prior history of ORI); (ii)screening the patient prior to each injection to rule out active IOI; (iii)monitoring the patient for early warning signs, and (iv)treating immediately should any adverse events develop. Conclusions: The adverse events reported are rare, but may be associated with severe and irreversible loss of visual acuity. The recommendations made are intended to facilitate the management of brolucizumab in the routine practice of retinologists, to ensure patient safety and, should any adverse events occur, to minimise their impact on vision. (AU)


Assuntos
Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Degeneração Macular/tratamento farmacológico , Degeneração Macular Exsudativa/tratamento farmacológico , Medição de Risco
10.
Rom J Ophthalmol ; 66(3): 209-213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36349171

RESUMO

Aim: The aim of this study was to show the efficacy of intravitreal treatment with Bevacizumab (Avastin) in patients with secondary neovascular glaucoma, in different stages of the disease. Method: A retrospective study was performed on 67 patients with neovascular glaucoma. The main parameters evaluated were the patients' history, slit lamp examination, visual acuity, ocular tonometry, fundus examination, gonioscopy, and visual field. Results: It was observed that the pathology had a preponderance in males of the 6th decade, with frequently unilateral damage. Patients were referred to an ophthalmologist when the diseases reached an advanced stage, usually when the visual acuity had no light perception and the intraocular pressure was over 45 mmHg. However, the treatment with Avastin intravitreal showed a good evolution, with regression of neovessels in the first 4-7 days and maintenance of intraocular pressure within normal limits in about 60% of cases, 3 months after injection. Conclusion: The most effective treatment in secondary neovascular glaucoma is the correct therapy of the main disease. The association of Avastin and laser photocoagulation leads to regression in iris and retinal neovessels. Abbreviations: anti-VEGF = anti-Vascular Endothelial Growth Factor, PDGF = Platelet Derived Growth Factor, bFGF = basic Fibroblast Growth Factor.


Assuntos
Glaucoma Neovascular , Masculino , Humanos , Glaucoma Neovascular/tratamento farmacológico , Bevacizumab/uso terapêutico , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Pressão Intraocular , Injeções Intravítreas
12.
J Cancer Res Ther ; 18(6): 1809-1810, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36412450

RESUMO

Bevacizumab is an angiogenesis inhibitor with Food and Drug Administration approval for multiple tumor types (including colon, nonsquamous nonsmall-cell lung cancer, kidney and glioblastoma multiforme, cervix, and ovarian cancer). Here, we present a patient with actinomycosis who was on treatment with bevacizumab maintenance therapy following chemotherapy combined with bevacizumab. A 60-year-old male patient with lung adenocarcinoma was treated four cycles of carboplatin, paclitaxel with bevacizumab. And then, bevacizumab maintenance therapy was continued. After 38 months of bevacizumab maintenance, computed tomography showed a newly developed cavitary lesion in the upper lobe of the right lung. Bronchoscopy was performed and the pathology report of the biopsy was reported as actinomycosis. Bevacizumab treatment was discontinued and the patient was treated with amoxicillin-clavulanate. To our knowledge, our case is the first case of actinomycosis infection due to the possible bevacizumab treatment.


Assuntos
Actinomicose , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Bevacizumab/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Actinomicose/diagnóstico , Actinomicose/tratamento farmacológico
13.
Target Oncol ; 17(6): 655-663, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36342619

RESUMO

BACKGROUND: DESTINY-Breast01 (NCT03248492) is a phase II single-arm trial evaluating trastuzumab deruxtecan (T-DXd) in adults with human epidermal growth factor receptor 2-positive (HER2+) unresectable or metastatic breast cancer (u/mBC) who have received two or more prior anti-HER2 therapies. OBJECTIVES: Objectives were to explore approaches for estimating long-term overall survival (OS) with T-DXd from immature data (June 2020 data-cut; median follow-up 20.5 months), and compare predicted long-term outcomes with UK-recommended non-targeted therapies eribulin, capecitabine, and vinorelbine. METHODS: Two methods were used to model T-DXd long-term OS: (1) applying a hazard ratio (HR) to the OS curve for another HER2 targeted therapy (third-line trastuzumab emtansine [T-DM1]) with longer trial follow-up; and (2) extrapolating T-DXd OS data directly. Comparator OS was based on direct extrapolation of published data (comparison with vinorelbine OS was not possible). Quality-adjusted life years (QALYs) were calculated using a previously published model of utility. RESULTS: Both extrapolation methods demonstrated longer mean/median OS with T-DXd versus eribulin, and capecitabine (44.7/32.9 months [applying an HR to the T-DM1 OS curve]; 47.7/29.9 months [using direct extrapolation]; vs 11.3/9.2, and 17.8/13.6 months, respectively), translating to 2.3, 2.3, 0.6, and 0.9 discounted QALYs. CONCLUSION: Alternative methods produced consistent results, showing T-DXd is associated with substantial gains in OS and QALYs versus eribulin, and capecitabine. Modelled median OS results were similar to a later data-cut (median of 29.1 months, March 2021 data-cut). The modelling approach in which an HR was applied to the T-DM1 OS curve informed a submission to the National Institute for Health and Care Excellence.


Assuntos
Neoplasias da Mama , Adulto , Humanos , Feminino , Neoplasias da Mama/metabolismo , Capecitabina/farmacologia , Capecitabina/uso terapêutico , Receptor ErbB-2/metabolismo , Vinorelbina/farmacologia , Vinorelbina/uso terapêutico , Anticorpos Monoclonais Humanizados , Ado-Trastuzumab Emtansina
14.
J Clin Endocrinol Metab ; 107(Suppl_1): S36-S46, 2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-36346685

RESUMO

CONTEXT: Thyroid eye disease (TED) is a sight-threatening and debilitating autoimmune condition, with limited therapies available, that often poses diagnostic and therapeutic challenges. In recent years, the treatment landscape has shifted to early intervention with targeted therapy. METHODS: A PubMed review of the literature was conducted for the period between 1979 and 2021. Search terms included thyroid eye disease, teprotumumab, targeted therapy, Graves disease, Graves ophthalmopathy, dysthyroid optic neuropathy, and related terms in different combinations. Novel biologic therapies for TED have emerged as alternatives to traditional steroid regimens in recent years. New insights into TED pathophysiology have uncovered the role of the insulin-like growth factor 1 receptor (IGF-1R) and led to the development of teprotumumab, an IGF-1R-inhibiting monoclonal antibody. RESULTS: Randomized clinical trials demonstrating the efficacy of teprotumumab for TED led to Food and Drug Administration approval. Teprotumumab is gradually replacing immunosuppressive agents as first-line therapy in the United States for active moderate-to-severe TED, while emerging reports also show its use in other stages of the disease. Recent data highlight risk factors for adverse events and screening protocols to maximize patient safety. Personalized therapeutic plans developed through effective partnership between endocrinologists and ophthalmologists aim to enhance the safety and outcomes of TED treatments and improve care for this complex disease. CONCLUSION: TED management is shifting to an era of targeted therapy with multidisciplinary care. Teprotumumab has demonstrated superior efficacy to conventional treatments and has transformed our therapeutic and surgical algorithms. Clinical guidelines and additional studies are needed to further guide and refine therapy.


Assuntos
Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico
15.
Curr Oncol ; 29(11): 7987-7993, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36354692

RESUMO

Penile squamous cell carcinoma (PSCC) is a rare disease. The treatment options for advanced penile cancer are often limited, and the prognosis remains poor. We reported a 52-year-old male recurrent and metastatic PSCC patient with high PD-L1 expression (90%) and TMB (14.4 muts/Mb). He had undergone penectomy, bilateral inguinal lymph node dissection, and excision of the abdominal wall mass. Despite cisplatin-based concurrent chemoradiotherapy and sequential chemotherapy with docetaxel plus cisplatin then being carried out, the carcinoma still progressed. The patient then obtained progression-free survival with continuous sintilimab, although he experienced the new onset of ICI-induced diabetes after 24 cycles of sintilimab and required sustained insulin treatment. He had negative type 1 diabetes-associated autoantibodies and the susceptible HLA genotype DR3-DQ2 haplotype. This is the first patient with radiation and multichemorefractory PSCC who has obtained the remarkable anti-tumor effect of partial regression exceeding 32 months during continuous sintilimab and anlotinib treatment.


Assuntos
Carcinoma de Células Escamosas , Diabetes Mellitus , Cetoacidose Diabética , Neoplasias Penianas , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/patologia , Cisplatino/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma de Células Escamosas/patologia
16.
Genes (Basel) ; 13(11)2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36360302

RESUMO

Human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase is overexpressed in 20-30% of breast cancers and is associated with poor prognosis and worse overall patient survival. Most women with HER2-positive breast cancer receive neoadjuvant chemotherapy plus HER2-targeted therapies. The development of HER2-directed therapeutics is an important advancement in targeting invasive breast cancer. Despite the efficacy of anti-HER2 monoclonal antibodies, they are still being combined with adjuvant chemotherapy to improve overall patient outcomes. Recently, significant progress has been made towards the development of a class of therapeutics known as antibody-drug conjugates (ADCs), which leverage the high specificity of HER2-targeted monoclonal antibodies with the potent cytotoxic effects of various small molecules, such as tubulin inhibitors and topoisomerase inhibitors. To date, two HER2-targeting ADCs have been approved by the FDA for the treatment of HER2-positive breast cancer: Ado-trastuzumab emtansine (T-DM1; Kadcyla®) and fam-trastuzumab deruxtecan-nxki (T-Dxd; Enhertu®). Kadcyla and Enhertu are approved for use as a second-line treatment after trastuzumab-taxane-based therapy in patients with HER2-positive breast cancer. The success of ADCs in the treatment of HER2-positive breast cancer provides novel therapeutic advancements in the management of the disease. In this review, we discuss the basic biology of HER2, its downstream signaling pathways, currently available anti-HER2 therapeutic modalities and their mechanisms of action, and the latest clinical and safety characteristics of ADCs used for the treatment of HER2-positive breast cancer.


Assuntos
Antineoplásicos , Neoplasias da Mama , Imunoconjugados , Maitansina , Humanos , Feminino , Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Maitansina/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais
17.
J Headache Pain ; 23(1): 146, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36404301

RESUMO

ABSTACT: BACKGROUND: DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. METHODS: DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18-65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. RESULTS: At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was - 8.2 days for erenumab and - 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: - 1.57 [95%CI: - 2.83, - 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (- 5.34 vs - 4.66) and mMIDAS scores (- 14.67 vs - 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). CONCLUSION: DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. TRIAL REGISTRATION: NCT03867201.


Assuntos
Dor Aguda , Transtornos de Enxaqueca , Humanos , Feminino , Masculino , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Transtornos de Enxaqueca/epidemiologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Ásia/epidemiologia , Cânfora/uso terapêutico , Cefaleia/tratamento farmacológico , Mentol/uso terapêutico , Dor Aguda/tratamento farmacológico
18.
Rinsho Ketsueki ; 63(10): 1392-1396, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36351645

RESUMO

From a young age, a 63-year-old Japanese man had experienced difficulties with hemostasis during tooth extraction and epistaxis and swelling of bruised areas. He had previously been diagnosed with mild hemophilia (FVIII:C 8.5%) at age of 60 due to swelling of a right hip bruise and was administered FVIII concentrate for the first time. He had frequent bleeding around his shoulder joints and was given FVIII concentrates every time, but his hemostasis was poor. He was referred to our hospital because his FVIII activity decreased to<1% and a low-titer inhibitor (2.0 BU/ml) was detected. Because of a shoulder hematoma and new subcutaneous bleeding on both forearms, recombinant FVIIa was used to perform the hemostatic treatment. Following hemostasis, emicizumab was administered subcutaneously every 2 weeks at a dose of 3.0 mg/kg. Approximately 2 months after starting emicizumab, inhibitors were no longer detected, and FVIII activity increased to 8% after 9 months. We encountered a case of mild hemophilia A with an inhibitor that was first diagnosed in old age. The incidence of inhibitors in non-severe hemophilia A is about 10%, and about 70% of those resolves spontaneously. In this case, suppression of bleeding by emicizumab may have contributed to the spontaneous disappearance of the inhibitor.


Assuntos
Anticorpos Biespecíficos , Hemofilia A , Masculino , Humanos , Pessoa de Meia-Idade , Hemofilia A/tratamento farmacológico , Hemofilia A/diagnóstico , Fator VIII/uso terapêutico , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia
19.
Eur Rev Med Pharmacol Sci ; 26(21): 7980-7985, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394748

RESUMO

INTRODUCTION: Bullous systemic lupus erythematosus (BSLE) is a rare form of subcutaneous blistering lupus erythematosus (SLE). There is currently no effective treatment for BSLE. However, here, we present the first report of the successful treatment of refractory BSLE with belimumab in a 16-year-old girl. CASE PRESENTATION: A 16-year-old girl with BSLE had undergone different treatment options, with no significant improvement. Since B-lymphocyte stimulator plays an important role in the pathophysiology of SLE, belimumab was administered and showed remarkable effects for the first time in this patient with both SLE and BSLE. The patient's skin lesions improved steadily over the course of three weeks and completely disappeared in 30 days. In addition, no sign of recurrence of BSLE was observed over the 9-month follow-up period. CONCLUSIONS: To our knowledge, this is the first report of the successful short-term therapy of refractory BSLE/SLE overlap syndrome with belimumab in a pediatric patient. Although the use of belimumab resulted in excellent.


Assuntos
Lúpus Eritematoso Sistêmico , Feminino , Criança , Humanos , Adolescente , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento
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