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1.
Arerugi ; 68(7): 869-873, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31406083

RESUMO

The two biologic therapies, anti-IgE (omalizumab) and anti-IL-5 antibodies (mepolizumab), are used in the treatment of severe pediatric asthma. We present here a case study of a 13-year-old girl with severe asthma who switched from omalizumab to mepolizumab therapy and achieved good control over her asthma. The patient was diagnosed with asthma at one year of age and presented with poor disease control, even while taking high doses of inhaled corticosteroids (ICS). As such, she was considered to have severe persistent asthma. At 10 years old, she began omalizumab therapy which improved asthma control. However, after two years of this therapy, she manifested frequent acute exacerbations. At 12 years old, she switched to mepolizumab and has since maintained good control of asthma. Additionally, total serum IgE levels and peripheral eosinophil counts decreased. As the underlying mechanisms of omalizumab and mepolizumab therapy are distinct, it is recommended to use either one if the other proves ineffective.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Substituição de Medicamentos , Omalizumab/uso terapêutico , Adolescente , Corticosteroides , Criança , Feminino , Humanos
2.
Medicine (Baltimore) ; 98(33): e16834, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415404

RESUMO

RATIONALE: Pembrolizumab, an immune-checkpoint inhibitor (ICI), has been shown to be effective for treatment-naive patients with non-small cell lung cancer (NSCLC) and high expression of programmed death-ligand 1 (PD-L1). Therefore, treatment regimens containing pembrolizumab have become a standard therapy for these patients. However, the use of pembrolizumab is limited owing to the side effects of ICIs. PATIENT CONCERNS AND DIAGNOSES: The patient was a 65-year-old man with a left lung mass surrounded by interstitial shadow. The tumor was diagnosed as adenocarcinoma, cT4N3M0, stage IIIC, and the tumor cells showed high PD-L1 expression. It was unclear whether the interstitial shadow was interstitial lung disease (ILD) or lymphangitis carcinomatosa. INTERVENTIONS AND OUTCOMES: The patient received carboplatin and nab-paclitaxel, a less risky regimen for ILD, as the first-line therapy. Administration of 2 cycles of this regimen markedly improved both the tumor diameter and interstitial shadow. The interstitial shadow was clinically diagnosed as lymphangitis carcinomatosa and not ILD. Subsequently, the patient was treated with pembrolizumab, and the tumor showed much further shrinkage with no deterioration of the interstitial shadow. To date, the patient is alive with no complaints and no disease progression, and has continued pembrolizumab treatment for a total of 12 months. LESSONS: In patients at a high risk of ICI-related side effects, platinum-doublet chemotherapy may be permitted as the first-line therapy for NSCLC with high PD-L1 expression. However, if the risk associated with ICIs is resolved, early switching from chemotherapy to pembrolizumab might be desirable, even if the chemotherapy is effective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Neoplasias Pulmonares/diagnóstico , Linfangite/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfangite/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos de Platina/uso terapêutico
3.
Medicine (Baltimore) ; 98(26): e15947, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261500

RESUMO

To assess the hypothesis if tocilizumab (TCZ) is effective on disease activity, and also its effect in fatigue and other clinical and psychological disease-related factors in patients with rheumatoid arthritis (RA) treated with TCZ.A 24-week, multicenter, prospective, observational study in patients with moderate to severe RA receiving TCZ after failure or intolerance to disease-modifying antirheumatic drugs or tumor necrosis factor-alpha was conducted.Of the 122 patients included, 85 were evaluable for effectiveness (85% female, 51.9 ±â€Š12.5 years, disease duration 8.7 ±â€Š7.4 years). Mean change in C-reactive protein level from baseline to week 12 was -11.2 ±â€Š4.0 (P < .001). Mean Disease Activity Index score (DAS28) decreased from 5.5 ±â€Š1.0 at baseline to 2.7 ±â€Š1.3 (P < .001) at week 24. Mean change in Functional Assessment of Chronic Illness Therapy score was -5.4 ±â€Š11.2 points at week 24. Multiple regression analysis showed that the improvement in DAS28, sleep, and depression explained 56% and 47% of fatigue variance at week 12 and 24, respectively.Tocilizumab is effective in reducing disease activity and results in a clinically significant improvement in fatigue, pain, swollen joint count, morning stiffness, sleepiness, depression, and DAS28; the last 3 were specifically identified as factors explaining fatigue variance with the use of TCZ in RA patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/psicologia , Artrite Reumatoide/terapia , Fadiga/psicologia , Fadiga/terapia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/fisiopatologia , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Depressão/fisiopatologia , Depressão/terapia , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Retratamento , Sono , Resultado do Tratamento , Fator de Necrose Tumoral alfa/uso terapêutico
4.
Nursing ; 49(8): 24-32, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268951
5.
Medicine (Baltimore) ; 98(30): e16542, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348273

RESUMO

Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017. Patients in any clinical trial during the study period were excluded. Overall survival (OS) and time on treatment from pembrolizumab initiation were analyzed using the Kaplan-Meier (KM) method. Subgroup analyses were conducted to examine OS for several patient characteristics including Eastern Cooperative Oncology Group (ECOG) performance status >1, brain metastases, and corticosteroids before pembrolizumab initiation.Pembrolizumab was administered to 315 (59%), 152 (29%), and 65 (12%) patients as first-, second-, and third-line/later therapy. Median age at pembrolizumab initiation was 68 years (range, 18-84); most patients were male (66%) and white (94%). Of those with available data, 38% had BRAF-mutant melanoma, 21% had elevated lactate dehydrogenase (LDH) level, and 23% had ECOG >1. Overall, 18% had brain metastases, and 23% were prescribed corticosteroids <3 months before initiating pembrolizumab. Median study follow-up was 12.9 months (range, 0.03-39.6). Median OS was 21.8 months (95% confidence interval [CI] 16.8-29.1); KM 1-year and 2-year survival rates were 61% and 48%, respectively; and median time on pembrolizumab treatment was 4.9 months (95% CI 3.7-5.5). Median OS for first-line pembrolizumab was not reached, and for second-line and third-line/later was 13.9 and 12.5 months, respectively (log-rank P = .0095). Significantly better OS (all P ≤.0014, log-rank test) was evident for patients with ECOG performance status (PS) of 0 to 1 (vs >1), normal (vs elevated) LDH level, and no (vs yes) corticosteroid prescription <3 months before. No difference was recorded in OS by brain metastases (log-rank P = .22) or BRAF mutation status (log-rank P = .90).These findings support effectiveness of pembrolizumab in the real-world clinical setting and provide important insights into patient characteristics and outcomes associated with pembrolizumab therapy for a heterogeneous patient population with advanced melanoma, including patients who would not be eligible for clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
6.
Drugs Today (Barc) ; 55(7): 439-448, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31347612

RESUMO

Lanadelumab is a human monoclonal antibody against plasma kallikrein indicated for prevention of attacks of hereditary angioedema (HAE). HAE is caused by SERPING1 gene mutations resulting in decreased or dysfunctional plasma protease C1 inhibitor (C1-INH) leading to a loss of inhibition of plasma kallikrein activity with subsequent cleavage of high-molecular weight kininogen and release of bradykinin. There is a clear need for a non-plasma-derived, safe, effective and convenient prophylaxis of HAE attacks to reduce patients' daily burden of disease and disability. The percentage of patients who were attack-free for the last 16 weeks of a controlled study was 77% in the group receiving 300 mg lanadelumab every 2 weeks, compared with 3% with placebo. The most common side effects were mild injection-site reactions. Lanadelumab has the potential to change the approach from on-demand treatment to prophylaxis in HAE. Future studies will have to confirm long-term safety and efficacy of prophylactic long-term inhibition of plasma kallikrein.


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais , Ensaios Clínicos Controlados como Assunto , Humanos , Mutação
7.
Anticancer Res ; 39(7): 3727-3737, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262899

RESUMO

BACKGROUND/AIM: This study aims to investigate whether the combination of oncolytic viruses with chemoradiotherapy or other therapies is a promising strategy for cancer treatment. MATERIALS AND METHODS: The anticancer effects of measles virus (MeV) in combination with nimotuzumab in the treatment of laryngeal cancer were evaluated in vitro and in nude mice inoculated with Hep2 tumors. MTT assay and flow cytometry were used to examine cell death. RESULTS: Laryngeal cancer cells treated with MeV+nimotuzumab combination had a significantly lower survival rate compared to those treated with MeV or nimotuzumab alone (p<0.0001). In an animal model bearing human laryngeal tumor, the treated group had a higher survival rate (60%) compared to a untreated group (20%) (p<0.05), and the survival rate of the group treated with MeV+nimotuzumab combination was higher compared to the groups received single treatment. CONCLUSION: The MeV+nimotuzumab combination has greater anticancer activities in both laryngeal cancer cells and an animal model.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Laríngeas/terapia , Vírus do Sarampo , Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Linhagem Celular Tumoral , Cercopithecus aethiops , Terapia Combinada , Humanos , Vacina contra Sarampo , Camundongos Nus , Células Vero
8.
Anticancer Res ; 39(7): 3887-3892, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262917

RESUMO

BACKGROUND/AIM: Pembrolizumab was approved as second-line treatment for patients with metastatic urothelial cancer (UC) in Japan. We performed a retrospective pilot study to assess the potency of pembrolizumab treatment in Japan. PATIENTS AND METHODS: The medical records of 40 consecutive Japanese patients with metastatic UC who started pembrolizumab between January and October 2018 were reviewed and statistically analyzed to clarify the efficacy and safety of the drug. RESULTS: The objective response rate, median progression-free survival period, and median overall survival period were 20.6%, 4.1 months and 10.0 months, respectively. Multivariate analysis indicated the presence of liver metastasis, worse performance status (≥2), and higher C-reactive protein as factors predictive of shorter OS. CONCLUSION: We demonstrated for the first time, a comparable efficacy and safety profile of pembrolizumab for Japanese patients with metastatic UC, as in the KEYNOTE-045 study. The results indicate the features of pembrolizumab therapy in the current Japanese clinical practice.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Urológicas/patologia
9.
Anticancer Res ; 39(7): 3917-3921, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262921

RESUMO

AIM: To evaluate the efficacy and safety of re-treatment with anti-programmed death (PD)-L1 antibody (atezolizumab) after anti-PD-1 antibody (nivolumab/pembrolizumab) treatment in advanced non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: We retrospectively reviewed 18 NSCLC patients who received atezolizumab after anti-PD-1 antibody treatment. Data on patient characteristics, number of cycles of anti-PD-1 antibody and atezolizumab, regimens between anti-PD-1 antibody and atezolizumab, best response, and immune-related adverse events (irAEs) were collected and analyzed. RESULTS: Nine patients a had high (≥50%) PD-L1 expression. The median number of cycles of atezolizumab was 3 (range=2-7). The median progression-free survival was 2.9±1.8 months. Seven (38.9%) and 11 (61.1%) patients had stable and progressive disease, respectively. No patient achieved partial or complete response. There were no significant differences in the occurrence of irAEs between anti-PD-1 antibodies and atezolizumab. CONCLUSION: Preliminary results showed that patients previously treated with anti PD-1 antibodies received only limited benefit from subsequent atezolizumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
10.
Anticancer Res ; 39(7): 3945-3947, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262925

RESUMO

BACKGROUND/AIM: Malignant melanoma is a rare disease in the pediatric population and there are no recommendations regarding its management in children, while the current standard of care in metastatic or unresectable melanoma in adult patients includes immunotherapy (anti-CTLA-4 and anti-PD-1 antibodies). Advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. CASE REPORT: We describe a case of a 7-year-old patient with recurrent metastatic melanoma, for whom pembrolizumab was used as an adjuvant therapy on compassionate use basis. CONCLUSION: Due to adverse events, the treatment was discontinued after 5 months of pembrolizumab, but with 12-months of follow-up, patient remains in complete remission.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Antirreumáticos/uso terapêutico , Artrite Juvenil/induzido quimicamente , Artrite Juvenil/tratamento farmacológico , Criança , Feminino , Humanos , Metotrexato/uso terapêutico , Esteroides/uso terapêutico , Resultado do Tratamento , Uveíte/induzido quimicamente
11.
Anticancer Res ; 39(7): 3961-3965, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262928

RESUMO

BACKGROUND/AIM: Immune check point inhibitors (ICIs) are changing cancer treatment in several malignancies, including non-small cell lung cancer (NSCLC). The introduction of these active new agents is associated with a relevant increase of costs and it is, therefore, important to create a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as overall survival (OS). This analysis was conducted to assess the pharmacological costs of first- and second-line treatments with ICIs (pembrolizumab, nivolumab and atezolizumab) for metastatic NSCLC. MATERIALS AND METHODS: The present evaluation was restricted to phase III randomized controlled trials (RCTs). We calculated the pharmacological costs necessary to get the benefit in OS. RESULTS: Six phase III RCTs were evaluated. Concerning first-line, the lowest cost per month of OS-gain was associated with the use of pembrolizumab at 2,734 €. Concerning second-line, the lowest cost per month of OS-gain was associated with the use of atezolizumab at 3,724 €. CONCLUSION: Pembrolizumab and atezolizumab are cost-effective in both first and second-line treatment for metastatic NSCLC, respectively.


Assuntos
Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais/economia , Antineoplásicos Imunológicos/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/economia , Nivolumabe/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Cancer Immunol Immunother ; 68(7): 1179-1185, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31175402

RESUMO

BACKGROUND: No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease. PATIENTS AND METHODS: In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed. RESULTS: Seventeen patients were enrolled. A median of 8 cycles were administered (range 2-28). Two patients achieved partial response (11.7%), 6 a disease stabilization (35.3%), whereas 9 (53%) had a progression. No complete response was observed. PFS of the overall population was 3.8 months. PFS was 9.7 months for patients with an interval higher than 5 years from diagnosis of primary tumor to metastatic disease and 2.6 months for patients with an interval lower than 5 years [p = 0.039, HR 0.2865 (95% CI 0.0869-0.9443)]. Median OS was not reached. The two responding patients were still on treatment with Pembrolizumab at the time of data analysis. Survival was 12.8 months for patients with clinical benefit, while OS for progressive patients was 3.1 months. PD-L1 expression and genomic abnormalities predictive of relapse after diagnosis of primary tumor were not associated with PFS. Toxicity was mild, without grade 3-4 side effects. CONCLUSIONS: The efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Uveais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/imunologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Estudos Prospectivos , Neoplasias Uveais/imunologia , Neoplasias Uveais/mortalidade
13.
Zhonghua Nei Ke Za Zhi ; 58(6): 444-448, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31159524

RESUMO

Objective: To assess the efficacy and safety of tocilizumab and cyclophosphamide in patients with Takayasu arteritis (TA). Methods: Twenty-seven TA patients treated with tocilizumab (TCZ group) and 22 treated with cyclophosphamide (CTX group) were enrolled and retrospectively analyzed. The duration of treatment was 6 months. Disease activity and side effects were compared between the two groups. Results: After treatment, the median C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and disease activity scores in TCZ group were significantly lower than those in CTX group respectively [ESR 3 mm/1h vs. 8 mm/1h; CRP 0.13 mg/L vs. 1.09 mg/L; National Institutes of Health (NIH) score 0(0,1) vs. 0(1,1); the Indian Takayasu clinical activity score (ITAS 2010) 0(0,2) vs. 2(0,3.5), and the Indian Takayasu activity score with the acute phase response (ITAS-A) 0(0,2) vs. 2.5(0,3.5); all P<0.05]. The daily prednisone doses before treatment and after treatment in TCZ group were significantly lower than those in CTX group [(20.1±15.9) mg/d vs. (39.3±16.7) mg/d;(5.1±4.2)mg/d vs. (12.1±4.6) mg/d,both P<0.05)].The incidence of drug-related side effects in TCZ group was significantly lower than that in CTX group, which was 22.2% vs. 54.5% (P<0.05). Conclusion: Compared with CTX treatment, TCZ treatment for TA with less prednisone has better efficacy and safety.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclofosfamida/uso terapêutico , Arterite de Takayasu/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Ciclofosfamida/administração & dosagem , Humanos , Estudos Retrospectivos , Arterite de Takayasu/patologia , Resultado do Tratamento
14.
J Headache Pain ; 20(1): 66, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159727

RESUMO

BACKGROUND: Monoclonal antibodies (mAbs) targeting the CGRP pathway are safe and efficacious therapies for the prevention of migraine. In this study we assessed the effects of discontinuation of preventive erenumab and galcanezumab treatment in patients with chronic migraine. METHODS: This retrospective pooled analysis included completers of the open-label extension study phase for the preventive treatment of chronic migraine with galcanezumab (NCT02614261; 9 months) and erenumab (NCT02174861; 12 months) in a single headache center. We compare migraine data until week 12 after open-label treatment completion, when patients did not have any pharmacological preventive medication, to study baseline values of the double-blind trial period, and to the last 4 weeks of the open-label extension. The assessment included changes in monthly migraine days, headache hours, days with severe headache and acute headache medication use. RESULTS: Data from 16 patients after galcanezumab (n = 9) and erenumab (n = 7) open-label treatment completion were analyzed. The mean number of monthly migraine days was 18.38 ± 3.74 at baseline, and 12.19 ± 4.53 in the last 4 weeks of the open-label extension (p < 0.001). Monthly migraine days remained significantly reduced compared to baseline during the entire 12-week observation period after open-label termination (p = 0.002), with a reduction of 5.38 ± 4.92 in weeks 1-4 (p = 0.001), 4.75 ± 4.15 in weeks 5-8 (p = 0.001), and 3.93 ± 5.45 in weeks 9-12 (p = 0.014). There was no significant difference in monthly migraine days between the 12 weeks after open-label termination and the last 4 weeks of the open-label phase (p = 0.228). All other analyses revealed numerical improvement through week 12 in comparison to baseline. CONCLUSIONS: In this small, self-selected cohort, the results indicate a therapeutic effect of monoclonal antibodies targeting the CRGP pathway in chronic migraine prevention after treatment termination up to 12 weeks.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Suspensão de Tratamento/tendências , Adulto , Doença Crônica , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
N Engl J Med ; 381(7): 603-613, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31180194

RESUMO

BACKGROUND: Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed. METHODS: We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals. RESULTS: A total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed. CONCLUSIONS: Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Complexo CD3/antagonistas & inibidores , Diabetes Mellitus Tipo 1/prevenção & controle , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Progressão da Doença , Método Duplo-Cego , Exantema/induzido quimicamente , Feminino , Teste de Tolerância a Glucose , Antígeno HLA-DR3 , Antígeno HLA-DR4 , Humanos , Contagem de Linfócitos , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Linfócitos T/imunologia , Adulto Jovem
16.
Vnitr Lek ; 65(5): 377-378, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163972

RESUMO

Budd-Chiari syndrome is a serious condition which in chronic course leads to the development of liver cirrhosis. Anti-coagulant treatment of this syndrome is fully indicated and in the treatment can be used dabigatran. Advanced cirrhosis of the liver due to this disease can be an indication for a liver transplant. In this case, it is a great advantage the existence of an antidote to dabigatran (idarucizumab) in order to adjust the coagulation ratios and prevent bleeding disorders. Referred to a case report describes the first experience with idarucizumab in context with liver transplant in a patient with Budd-Chiari syndrome.


Assuntos
Anticorpos Monoclonais Humanizados , Antitrombinas , Síndrome de Budd-Chiari , Hemorragia , Transplante de Fígado , Anticorpos Monoclonais Humanizados/uso terapêutico , Dabigatrana , Humanos
17.
Brain Nerve ; 71(6): 555-564, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31171752

RESUMO

The complement was named after "a complement", a protein molecule that supports an antibody. It was considered previously that the complement mainly participates in protecting against microbial infections. But later, as research on biological functions in complement activation advanced drastically, it was elucidated that the complement could be involved in the onset of various diseases. In 2007, eculizumab (ECZ), an anti-C5 (complement factor 5) monoclonal antibody, was approved as a drug for paroxysmal nocturnal hemoglobinuria (PNH) in the United States. In Japan, ECZ was approved for PNH and atypical hemolytic uremic syndrome (aHUS) in 2010 and 2013, respectively. The success of ECZ created an opportunity for drug companies to develop new therapeutics targeting the complement system; development of complement therapeutics is now a major venture of pharmaceutical companies worldwide. Here, I will provide an outline of the approved complement therapeutics and those that are in development and clinical trial phase currently.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Inativadores do Complemento/uso terapêutico , Proteínas do Sistema Complemento , Hemoglobinúria Paroxística/tratamento farmacológico , Ensaios Clínicos como Assunto , Complemento C5/antagonistas & inibidores , Humanos , Japão
18.
Brain Nerve ; 71(6): 565-570, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31171753

RESUMO

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction mainly caused by anti-nicotinic acetylcholine receptor (AChR) antibodies. Complements are known to play a prominent role in the pathogenesis of MG. Long-term remission may not necessarily be achieved in MG patients with conventional therapies. Recently, complement inhibitor, the humanized monoclonal anti-C5 antibody eculizumab, complement inhibitor, was approved for patients with anti-AChR antibody-positive generalized refractory MG in Japan. In this review, we focus on the role of complements in the pathogenesis of MG and the action mechanism, efficacy, and future prospects of eculizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Proteínas do Sistema Complemento , Miastenia Gravis/tratamento farmacológico , Receptores Nicotínicos/imunologia , Autoanticorpos , Humanos , Japão
19.
Brain Nerve ; 71(6): 573-580, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31171754

RESUMO

Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and long myelitis; and is associated with aquaporin-4 immunoglobulin-G (AQP4-IgG), an autoantibody directed against aquaporin-4 (AQP4), which is an astrocytic water channel protein. Until recent years, the treatment of NMO has mainly focused on the suppression of lymphocytes and depletion of autoantibodies. However, several studies on the pathogehesis of the disease in human pathology, cultured cells, and animal models have revealed that astrocyte injury in NMO is mainly caused by the complement-dependent cytotoxicity following AQP4-IgG binding to AQP4. Moreover, complement-targeting therapy has recently been translated into practical applications in several hematological disorders. and similary, also in the cases of NMO. In this article, we review the relevance of the complement system in the pathogenesis of NMO. Additionally, we review the current status and prospects of the complement-targeting therapy for NMO, including the clinical trials of eculizumab and C1 inhibitor for NMO, and the experimental studies on C1 inhibition by monoclonal antibodies.


Assuntos
Aquaporina 4/imunologia , Inativadores do Complemento/uso terapêutico , Proteínas do Sistema Complemento , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/patologia , Animais , Anticorpos Monoclonais Humanizados/uso terapêutico , Autoanticorpos , Ensaios Clínicos como Assunto , Complemento C1/antagonistas & inibidores , Humanos , Imunoglobulina G
20.
Brain Nerve ; 71(6): 581-587, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31171755

RESUMO

Complement activation is involved in the pathogenetic mechanism of Guillain-Barré syndrome (GBS). To date, the effectiveness of complement inhibitors for GBS has been shown by in vitro and in vivo studies. A recent Japanese randomized controlled trial with eculizumab, a monoclonal antibody against the complement C5, indicated that eculizumab might improve the outcomes of GBS patients at six months from onset. In future, the prognosis of severe GBS cases may possibly be improved by a novel therapy targeting the complement.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Inativadores do Complemento/uso terapêutico , Proteínas do Sistema Complemento , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/patologia , Anticorpos Monoclonais , Complemento C5/antagonistas & inibidores , Humanos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto
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