Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.777
Filtrar
1.
Medicina (Kaunas) ; 57(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34577837

RESUMO

Background and Objectives: Treatment for elderly (aged ≥75 years) patients with rheumatoid arthritis (RA) is important because they usually have several complications and organ dysfunction and are more susceptible to drug-related adverse events. Abatacept (ABT) treatment is relatively safe in elderly RA patients; however, the real-world data of efficacy and long-term retention of ABT is sparse in such patients. This study aimed to investigate the clinical efficacy and long-term retention rates of ABT in elderly Japanese RA patients. Materials and Methods: This 10-year retrospective observational cohort study was performed in two centers in Fukushima, Japan. We reviewed the clinical features of elderly RA patients who received ABT and investigated the differences in retention rates with concomitant administration of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Results: The clinical characteristics of younger (<75 years old, 39 cases) and elderly (≥75 years old, 20 cases) RA patients were generally similar. Although the efficacy was also similar, the concomitant administration of csDMARDs with ABT differed between the two groups. Younger patients significantly decreased methotrexate (MTX) administration than elderly patients (p < 0.01), and elderly patients significantly received tacrolimus (TAC) (p < 0.01) or salazosulfapyridine (SASP; p = 0.01) than younger patients. The overall retention and infection-free survival rates were similar between the two groups. Conclusion: Elderly RA patients showed sustained retention rates compared to younger RA patients. TAC and SASP can help to maintain sustained retention rates in elderly RA patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Abatacepte/uso terapêutico , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metotrexato/efeitos adversos , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Resultado do Tratamento
2.
Pan Afr Med J ; 38: 17, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567344

RESUMO

Methotrexate (MTX) is an effective, economical and safe drug used in the treatment of ectopic pregnancy. Complications are very rare. Herein, we reported a case of febrile neutropenia following single low-dose methotrexate for the treatment of ectopic pregnancy. Febrile neutropenia developed on day 4 of single-dose methotrexate administered intramuscularly. Although methotrexate single-dose regimen is quite effective and safe in ectopic pregnancy, febrile neutropenia can occur very rarely.


Assuntos
Abortivos não Esteroides/efeitos adversos , Neutropenia Febril/induzido quimicamente , Metotrexato/efeitos adversos , Abortivos não Esteroides/administração & dosagem , Adulto , Feminino , Humanos , Injeções Intramusculares , Metotrexato/administração & dosagem , Gravidez , Gravidez Ectópica/tratamento farmacológico
3.
S D Med ; 74(7): 304-305, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34449990

RESUMO

Methotrexate is often prescribed for the treatment of autoimmune conditions. There are many well-known side effects of methotrexate, a lesser known side effect is methotrexate-induced cutaneous ulceration. Only eight cases have been reported in the literature. Here we report a ninth case report of methotrexate-induced cutaneous ulceration in a 73-year-old female who had recently had her methotrexate dose increased for her seronegative rheumatoid arthritis. She presented to the emergency department with painful ulcerative nodules on her hands. In addition, laboratory evaluation found her to be pancytopenic. Methotrexate was discontinued and patient was given a dose of leucovorin. Within a couple weeks of methotrexate discontinuation, the ulcers resolved. Our case in addition to a review of the literature suggests that methotrexate-induced cutaneous ulceration may be an indication of life-threatening pancytopenia.


Assuntos
Antirreumáticos , Artrite Reumatoide , Úlcera Cutânea , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Metotrexato/efeitos adversos , Úlcera Cutânea/induzido quimicamente , Úlcera Cutânea/tratamento farmacológico , Úlcera
4.
Hematology ; 26(1): 620-627, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34411497

RESUMO

Methotrexate (MTX) is one of the main therapeutic agents currently used for the prophylaxis of graft-versus-host disease (GvHD) following hematopoietic stem cell transplantation. However, it is associated with significant toxicity and considerable side effects in many patients, which lead to either early withdrawal or dose reductions that may expose patients to the risk of GvHD and graft failure. Folinic acid (FA) can bypass the inhibitory effects of MTX on folate availability and control MTX toxicity. However, concerns that FA might inhibit the anti-GvHD effect of MTX and limited reports on its clinical usefulness have led to reluctance in its inclusion in standard GvHD prophylaxis regimens. Additionally, universal dosing and timing guidelines are lacking. I discuss the available literature and evaluate the evidence for the effect of FA on MTX toxicity and its safety regarding GvHD development and graft rejection in both adult and pediatric patients. Although FA administration appears to be safe, its efficacy for routine use in all types of transplants in adult patients is unproven and further research is required to confirm its MTX toxicity-lowering effect, identify the individual parameters that influence its usefulness in clinical practice, and evaluate its potential when developing a personalized prophylaxis regimen.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Leucovorina/uso terapêutico , Metotrexato/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/efeitos adversos , Metotrexato/efeitos adversos
5.
S D Med ; 74(8): 363-366, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34461001

RESUMO

Methotrexate therapy has evolved over the years to become a fundamental component in the management of rheumatoid arthritis and psoriasis. Liver toxicity remains an ever-present concern when prescribing methotrexate. As such, methotrexate liver toxicity monitoring guidelines have been developed independently by rheumatologists and dermatologists. The main differentiating factor between the dermatology and rheumatology guidelines is risk stratification. Dermatology guidelines are largely based off of the presence or absence of hepatoxicity risk factors (alcohol usage, obesity, type II diabetes, among other) while the rheumatology guidelines do not emphasize this distinction. Thus, the aim of this review is to identify why these screening guidelines differences exist and discuss if the differences in stratification and screening are valid. We will also briefly examine alternatives to the current gold standard hepatoxicity screening test: the liver biopsy.


Assuntos
Artrite Reumatoide , Doença Hepática Induzida por Substâncias e Drogas , Diabetes Mellitus Tipo 2 , Psoríase , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Consenso , Humanos , Metotrexato/efeitos adversos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico
6.
Life Sci ; 284: 119911, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34450167

RESUMO

AIM: Male reproductive toxicity is becoming of growing significance due to clinical chemotherapy usage. Methotrexate (MTX) is an anti-folate used on a large scale for different tumors and autoimmune conditions. Despite its wide clinical use, MTX is associated with severe testicular intoxication. The exact underlying mechanism is unclear. METHODS: Our study was conducted to explore the pathogenesis mechanism of MTX-induced testicular damage and the potential testicular protective effects of apocynin (APO) on testicular injury induced by single i.p. MTX (20 mg/kg). APO was administered orally (100 mg/kg) for ten days. RESULTS: As compared to rats given MTX alone, co-administration of MTX with APO demonstrated multiple beneficial effects evidenced by a marked increase in testosterone, FSH, and LH and significantly restored testes histopathological alterations. Mechanistically, APO restored antioxidant status through up-regulation of Nrf2, cytoglobin, PPAR-γ, SIRT1, AKT, and p-AKT, while effectively lowering Keap-1. Moreover, APO significantly attenuated inflammation by down-regulating NF-κB-p65, iNOS, and TLR4 expressions confirmed by in-silico evidence. Additionally, network pharmacology analysis, a bioinformatics approach, was used to decipher various cellular processes' molecular mechanisms. SIGNIFICANCE: The current investigation proves the beneficial effects of APO in MTX-associated testicular damage through activation of cytoglobin, Keap-1/Nrf2/AKT, PPAR-γ, SIRT1, and suppressing of TLR4/NF-κB-p65 signal. Our data collectively encourage extending the investigation to the clinical setting to explore APO effects in MTX-treated patients.


Assuntos
Acetofenonas/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Metotrexato/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Testículo/patologia , Receptor 4 Toll-Like/metabolismo , Acetofenonas/química , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Inflamação/patologia , Interleucina-6/metabolismo , Masculino , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Peroxidase/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
RMD Open ; 7(2)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34385364

RESUMO

OBJECTIVE: This analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs). METHODS: This was a post hoc analysis of the phase III, randomised, double-blind, active-controlled, FINCH 3 study (clinicaltrials.gov NCT02886728). Patients received once-daily oral filgotinib 200 or 100 mg plus once-weekly oral MTX ≤20 mg (FIL200 + MTX and FIL100 + MTX), filgotinib 200 mg monotherapy (FIL200), or oral MTX monotherapy (MTX-mono) for up to 52 weeks. PPFs investigated were seropositivity for rheumatoid factor or anticyclic citrullinated peptide antibodies, high-sensitivity C reactive protein (CRP) ≥4 mg/L, Disease Activity Score in 28 joints with CRP (DAS28(CRP)) >5.1, and presence of erosions. Filgotinib efficacy and safety in patients with all four PPFs at baseline were explored versus MTX-mono within this subgroup and compared informally with the overall population. RESULTS: Of 1249 patients in FINCH 3, 510 (40.8%) had all PPFs. Efficacy of FIL200 + MTX among these patients was comparable to the overall population, with higher rates of 20%/50%/70% improvement from baseline by American College of Rheumatology criteria, DAS28(CRP) <2.6, and remission; greater improvement in physical function and pain; and better inhibition of structural damage relative to MTX-mono. FIL100 + MTX and FIL200 were not consistently more efficacious versus MTX-mono. Safety of filgotinib in patients with PPFs was comparable to the overall population; no new safety signals were observed. CONCLUSION: FIL200 + MTX efficacy and safety in patients with multiple PPFs were similar to the overall population.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metotrexato/efeitos adversos , Prognóstico , Piridinas , Resultado do Tratamento , Triazóis
8.
Transfus Apher Sci ; 60(5): 103200, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34215520

RESUMO

Psoriasis is a chronic inflammatory skin disease that is characterized by well-demarcated erythematous plaques with a silver scale. Although many new and emerging therapeutic agents are often sufficient to control the disease, there is still a need for alternative treatment options in challenging cases. Extracorporeal photopheresis (ECP) has been applied to many T-cell-mediated diseases to restore immune homeostasis and treat psoriasis effectively. In this paper, we present a psoriasis patient who did not respond to methotrexate, narrowband ultraviolet B, or acitretin. Because of a diagnosis of non-Hodgkin lymphoma, the patient had contraindications for cyclosporine, fumaric acid esters, and biologics but achieved remission with a total of 12 sessions of ECP in two and a half months. Although exacerbation was recorded after polymerase chain reaction (PCR) confirmed coronavirus 2019 (COVID-19) disease infection at the end of the first month, scores from the psoriasis area severity index (PASI) and dermatological life quality index (DLQI) were regressed significantly within two and a half months. ECP seems to provide an effective and rapid response for psoriasis and should be considered for psoriasis patients who fail to respond or have contraindications to existing treatments.


Assuntos
COVID-19/complicações , Linfoma não Hodgkin/complicações , Pandemias , Fotoferese , Psoríase/tratamento farmacológico , SARS-CoV-2 , Acitretina/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Terapia Combinada , Contraindicações de Medicamentos , Ciclosporina/efeitos adversos , Humanos , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Unhas/patologia , Psoríase/complicações , Psoríase/patologia , Psoríase/radioterapia , Qualidade de Vida , Índice de Gravidade de Doença , Terapia Ultravioleta
9.
Int J Clin Pharmacol Ther ; 59(9): 618-626, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34281633

RESUMO

OBJECTIVE: The relative efficacy and tolerability of tocilizumab, sarilumab, and sirukumab as monotherapy were assessed and compared with those of adalimumab in patients with rheumatoid arthritis (RA) who were intolerant to or responded inadequately to methotrexate (MTX). MATERIALS AND METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tocilizumab, sarilumab, and sirukumab, and adalimumab in RA patients who are intolerant to or show an inadequate response to MTX. RESULTS: Three RCTs comprising 1,066 patients met the inclusion criteria. Tocilizumab 8 mg monotherapy was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ACR20 response rate. Compared with adalimumab, tocilizumab, and sarilumab as monotherapy showed significantly higher ACR20 response rates. Ranking probability based on SUCRA indicated that tocilizumab 8 mg had the highest probability of being the best choice for achieving ACR20 response rate, followed by sarilumab 200 mg, adalimumab 40 mg, and sirukumab 50 mg. Moreover, the ACR50 response rate showed a similar distribution pattern to that of ACR20. Regarding adverse events, the ranking probability based on SUCRA indicated that sarilumab 200 mg was possibly the safest, followed by adalimumab 40 mg, tocilizumab 8 mg, and sirukumab 50 mg. However, the number of patients who experienced serious adverse events did not differ significantly between these biologics. CONCLUSION: Based on ACR20 and ACR50 response rates, monotherapy with tocilizumab 8 mg, followed by sarilumab and sirukumab monotherapy, was optimal for patients with RA responding inadequately to MTX or showing intolerance.


Assuntos
Antirreumáticos , Artrite Reumatoide , Adalimumab/efeitos adversos , Anticorpos Monoclonais Humanizados , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metotrexato/efeitos adversos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
BMC Gastroenterol ; 21(1): 280, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238226

RESUMO

BACKGROUND: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a rare but critical complication that develops in patients treated with MTX. Although MTX-LPD has been recently reported, the incidence of follicular lymphoma in the intestine is very low. CASE PRESENTATION: A 73-year-old woman who had been receiving MTX for over 10 years visited our hospital complaining of postprandial abdominal pain and nausea. Upper and lower digestive tract endoscopies did not show any abnormal findings. A patency capsule was stagnated at the proximal part of the ileum with a mild dilation on the oral side. An oral balloon endoscopy revealed shallow ulcerative lesions in the jejunum. She was diagnosed with MTX-LPD based on histopathological findings. The symptoms did not improve with the discontinuation of MTX, and the patient required partial resection of the small intestine. The test result for Epstein-Barr virus-encoded small RNA was negative. She was diagnosed with follicular lymphoma based on the histology findings of a surgical specimen. Postoperative positron emission tomography-computed tomography and bone marrow aspiration did not show any findings of lymphoma. On follow-up, no recurrence was noted four years after the surgery. CONCLUSIONS: Herein, we report the first case of follicular lymphoma that occurred in the small intestine, negative for Epstein-Barr virus-encoded small RNA. If intestinal symptoms occur during MTX administration, it is important to directly observe by endoscopy and perform histological examination.


Assuntos
Artrite Reumatoide , Infecções por Vírus Epstein-Barr , Linfoma Folicular , Transtornos Linfoproliferativos , Idoso , Feminino , Herpesvirus Humano 4 , Humanos , Jejuno , Linfoma Folicular/induzido quimicamente , Linfoma Folicular/tratamento farmacológico , Metotrexato/efeitos adversos , Recidiva Local de Neoplasia
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 488-493, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238428

RESUMO

A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.


Assuntos
Artrite Reumatoide , Linfoma Difuso de Grandes Células B , Transtornos Linfoproliferativos , Artrite Reumatoide/tratamento farmacológico , Humanos , Linfoma Difuso de Grandes Células B/induzido quimicamente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Metotrexato/efeitos adversos
12.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201550

RESUMO

With the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while serving as an essential component in ALL treatment, has been reported to be related to various neurologic sequelae. Using combined intrathecal (IT) and intraperitoneal (IP) MTX model, we had demonstrated impaired spatial memory function in developing rats, which can be rescued by melatonin treatment. To elucidate the impact of MTX treatment on the epigenetic modifications of the myelination process, we examined the change of neurotrophin and myelination-related transcriptomes in the present study and found combined IT and IP MTX treatment resulted in altered epigenetic modification on the myelination process, mainly in the hippocampus. Further, melatonin can restore the MTX effect through alterations of the epigenetic pathways.


Assuntos
Encéfalo/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Metotrexato/toxicidade , Bainha de Mielina/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/toxicidade , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Ilhas de CpG , Metilação de DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , Injeções Espinhais , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Bainha de Mielina/patologia , Síndromes Neurotóxicas/patologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteína-Arginina N-Metiltransferases/genética , Ratos Sprague-Dawley , Fatores de Transcrição SOXE/genética
13.
BMJ Case Rep ; 14(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34244200

RESUMO

Methotrexate is a versatile antineoplastic and immunosuppressive agent. We report a case of a young adult on the Cancer and Leukaemia Group B 10403 treatment protocol for B-cell acute lymphoblastic leukaemia. She has previously completed the induction and consolidation phases with good tolerance then started on Capizzi methotrexate during the interim maintenance phase. Few days after receiving one intermediate dose of methotrexate, she developed severe multiorgan toxicities including pancytopaenia and several dermatologic toxicities. The patient underwent extensive diagnostic workup, with all results negative, pointing eventually towards severe methotrexate toxicity. This case highlights the broad spectrum of toxicities that can occur even with low doses of methotrexate. Capizzi methotrexate therapy implies no leucovorin therapy, hence putting patients at risk for multiorgan toxicity. Our experience reinforces the importance of close monitoring for patients receiving methotrexate, regardless of dose, and the prompt administration of high-dose leucovorin once toxicity suspected.


Assuntos
Metotrexato , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Leucovorina/efeitos adversos , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto Jovem
14.
Int J Clin Oncol ; 26(10): 1805-1811, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34236556

RESUMO

BACKGROUND: Addition of cytarabine to high-dose methotrexate (HD-MTX) chemotherapy improves outcome of primary CNS lymphoma (PCNSL); however, the combination therapy increases toxicity. Sequential chemotherapy and cranial radiation may decrease toxicity without altering efficacy. METHODS: This was a single-center, retrospective cohort study of consecutive newly diagnosed immunocompetent PCNSL patients treated with HD-MTX (5 cycles of 3 g/m2 every 2 weeks) followed by consolidation whole-brain radiotherapy (WBRT) and cytarabine (2 cycles of 3 g/m2/d for 2 days every 3 weeks) from January 2013 to December 2020. Initial WBRT before HD-MTX was allowed in patients with significant disability or brain edema at presentation. Primary outcome was progression-free survival (PFS). Key secondary outcomes were response rate, treatment-related toxicity, and overall survival (OS). RESULTS: Of 41 patients, 25 patients had a complete response (CR) and ten patients had a partial response, inferring an overall response rate (ORR) of 85.4% and a CR rate of 60.9%. More than 90% of patients were able to tolerate and complete the HD-MTX. The incidence of ≥ grade 3 hematologic and non-hematologic toxicities were 4.8% and 17.1%, respectively. Treatment-related mortality rate was 2.4%. There was no difference in toxicity between patients with age < 60 and ≥ 60 years. At the median follow-up duration of 39.8 months, the median PFS was 35.2 months (95% CI 12.4-69.3) and median OS was 46.5 months (95% CI 21.8-NR). CONCLUSION: High-dose methotrexate followed by consolidation whole-brain radiotherapy and cytarabine has acceptable efficacy, great tolerability, and low toxicity in newly diagnosed PCNSL patients.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encéfalo , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Estudos de Coortes , Citarabina/efeitos adversos , Humanos , Linfoma/tratamento farmacológico , Linfoma/radioterapia , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
J Obstet Gynaecol Res ; 47(10): 3737-3741, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34278664

RESUMO

We report a 34-year-old woman with recurrent gestational trophoblastic neoplasia (GTN) who showed hypersensitivity to etoposide. Computed tomography (CT) revealed a 32-mm solid mass in the right lung and a 101-mm cystic mass with solid components in the left side of the liver. The patient's serum human chorionic gonadotropin (HCG) level was 689 439 mIU/mL. After eight cycles of combined paclitaxel 175 mg/m2 on day 1, ifosfamide 1 g/m2 on days 2-5, and cisplatin 20 mg/m2 on days 2-5 (TIP) every 3 weeks, the serum HCG level decreased to 2.4 mIU/mL. CT scan revealed disappearance of the lung tumor and significant reduction in the solid components of the liver tumor. Then, left hemihepatectomy was performed. After 3 months, there was no evidence of the disease, and the serum HCG level normalized. Thus, TIP chemotherapy, followed by residual mass resection, might be effective for methotrexate-resistant GTN.


Assuntos
Doença Trofoblástica Gestacional , Metotrexato , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Dactinomicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/uso terapêutico , Feminino , Doença Trofoblástica Gestacional/tratamento farmacológico , Humanos , Ifosfamida/efeitos adversos , Metotrexato/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/uso terapêutico , Gravidez , Terapia de Salvação
16.
RMD Open ; 7(2)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34103405

RESUMO

OBJECTIVES: To report the efficacy, safety and patient-reported outcome measures (PROs) of tofacitinib modified-release 11 mg once daily plus methotrexate in patients with rheumatoid arthritis (RA) from the open-label phase of Oral Rheumatoid Arthritis Trial (ORAL) Shift. METHODS: ORAL Shift was a global, 48-week, phase 3b/4 withdrawal study in patients with moderate to severe RA and an inadequate response to methotrexate. Patients received open-label tofacitinib modified-release 11 mg once daily plus methotrexate; those who achieved low disease activity (LDA; Clinical Disease Activity Index (CDAI)≤10) at week 24 were randomised to receive blinded tofacitinib 11 mg once daily plus placebo (ie, blinded methotrexate withdrawal) or continue with blinded tofacitinib 11 mg once daily plus methotrexate for another 24 weeks. Efficacy, PROs and safety from the open-label phase are reported descriptively. RESULTS: Following screening, 694 patients were enrolled and received tofacitinib plus methotrexate in the open-label phase. At week 24, 527 (84.5%) patients achieved CDAI-defined LDA. Improvements from baseline to weeks 12 and 24 were generally observed for all efficacy outcomes (including measures of disease activity, and response, LDA and remission rates) and PROs. Adverse events (AEs), serious AEs and discontinuations due to AEs were reported by 362 (52.2%), 20 (2.9%) and 41 (5.9%) patients, respectively. No deaths were reported. CONCLUSIONS: Tofacitinib modified-release 11 mg once daily plus methotrexate conferred improvements in disease activity measures, functional outcomes and PROs, with most (84.5%) patients achieving CDAI-defined LDA after 24 weeks of open-label treatment; the safety profile was generally consistent with the historic safety profile of tofacitinib.Funded by Pfizer Inc; NCT02831855.


Assuntos
Antirreumáticos , Artrite Reumatoide , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Humanos , Metotrexato/efeitos adversos , Piperidinas , Pirimidinas , Resultado do Tratamento
17.
Toxicology ; 458: 152840, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34175381

RESUMO

Methotrexate (MTX) is one of the most effective and widely used drugs in the management of autoimmune and dermatological diseases. Rheumatoid arthritis and psoriasis patients who are under long term MTX-therapy are at high risk of developing a liver injury. Accumulation of intracellular MTX-polyglutamate (MTX-PG), a metabolite of MTX triggers oxidative stress, inflammation, steatosis, fibrosis, and apoptosis in hepatocytes. MTX-PG causes oxidative stress in the liver by inducing lipid peroxidation thereby releasing reactive oxygen species and suppressing antioxidant response elements. MTX-PG induces several pro-inflammatory signaling pathways and cytokines such as tumor necrosis factor-α, nuclear factor kappa B and interleukin 6 (IL-6), IL- ß1, IL-12. MTX-PG depletes hepatic folate level and decreases RNA and DNA synthesis leading to hepatocyte death. MTX-PG inhibits 5-aminoimidazole-4-carboxamide ribonucleotide transformylase enzyme and thereby causes accumulation of intracellular adenosine, which causes activation of hepatic stellate cells, extracellular matrix accumulation and hepatic fibrosis. MTX-PG induces hepatocytes apoptosis by activation of caspase 3 via the intrinsic pathway. Clinically, aggravation of underlying fatty liver to non-alcoholic steatohepatitis with fibrosis seems to be an important mechanism of liver injury in MTX-treated RA patients. Therefore, there is a need for monitoring liver injury in RA, psoriatic and cancer patients with NAFLD and fibrosis risk factors during MTX treatment. This review summarizes the possible molecular mechanism of MTX-induced hepatotoxicity. It may pave the way for early detection of liver injury and develop novel strategies for treating MTX mediated hepatotoxicity.


Assuntos
Antirreumáticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/terapia , Fármacos Dermatológicos/toxicidade , Metotrexato/toxicidade , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Humanos , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Psoríase/complicações , Psoríase/tratamento farmacológico
18.
Z Rheumatol ; 80(6): 552-554, 2021 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34132881

RESUMO

The question whether an ongoing treatment with methotrexate (MTX) actually impairs the protective immune response after SARS-CoV­2 vaccination cannot be answered with certainty on the basis of the available data. However, in view of the fact that a short discontinuation (once or twice) of the weekly MTX treatment in patients with a stable disease situation is probably associated with a comparatively low risk of inducing a flare of the underlying inflammatory rheumatic disease, such a short discontinuation of treatment can be considered according to the individual decision involving the patient and the treating rheumatologist. Nevertheless, discontinuation of MTX treatment does not appear to be absolutely necessary-especially since discontinuation would have to occur twice within a short period of time for most COVID-19 vaccines. Under no circumstances should longer periods of discontinuation of treatment be considered as this could result in a flare of the underlying disease. A more detailed assessment of the data situation and the resulting consequences (also with respect to DMARD) will follow soon in the updated recommendations for action of the German Society for Rheumatology (DGRh) on the management of patients with inflammatory rheumatic diseases in the context of the SARS-CoV­2 pandemic, especially COVID-19.


Assuntos
Antirreumáticos , COVID-19 , Doenças Reumáticas , Antirreumáticos/efeitos adversos , Vacinas contra COVID-19 , Humanos , Metotrexato/efeitos adversos , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2 , Vacinação
19.
In Vivo ; 35(4): 2163-2169, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182493

RESUMO

BACKGROUND/AIM: High-dose methotrexate is a therapy for acute leukemia, malignant lymphoma, and osteosarcoma. Glycyrrhizin has been used to treat hepatic dysfunction caused by high-dose methotrexate. However, few studies have investigated the interaction between glycyrrhizin and high-dose methotrexate. MATERIALS AND METHODS: Male Wistar rats were treated with high-dose methotrexate (500 or 1,000 mg/kg) alone, or with co-administration of 100 mg/kg glycyrrhizin. Plasma concentrations of methotrexate, alanine aminotransferase, aspartate aminotransferase, and total bilirubin were measured. RESULTS: At both methotrexate doses, the blood concentration of methotrexate was significantly increased and total clearance was significantly reduced using co-administration of glycyrrhizin compared with methotrexate alone, which led to increased levels of hepatic enzymes. These results suggest that glycyrrhizin significantly increases the plasma level and delays the clearance of methotrexate, resulting in hepatic toxicity. CONCLUSION: The concomitant use of methotrexate and glycyrrhizin should be considered with caution.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Animais , Ácido Glicirrízico , Masculino , Metotrexato/efeitos adversos , Ratos , Ratos Wistar
20.
Rheumatology (Oxford) ; 60(6): 2963-2968, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34144603

RESUMO

OBJECTIVES: Methotrexate is widely used at low dosages (LD-MTX) for non-oncologic indications and is associated with a variety of adverse effects (AEs). We sought to determine whether concentrations of the active metabolite, MTX polyglutamates (MTX-PGs) 1-5, correlate with AEs. METHOD: We examined data from the LD-MTX arm of the randomized double-blind Cardiovascular Inflammation Reduction Trial (CIRT). All AEs were blindly adjudicated and monitoring laboratories were tested centrally. The MTX-PGs 1-5 were assessed in one reference laboratory using liquid chromatography-tandem mass spectrometry. Based on prior literature, MTX-PGs 3-5 were chosen as the exposure of interest and quartiles of MTX-PGs 3-5 were assessed for their relationship with all AEs and each pre-specified category of AE using adjusted Cox proportional hazards regression. RESULTS: Of the 2391 subjects randomized to LD-MTX, MTX-PG levels were available for 1319 subjects (median dosage 16.1 mg/week) from the 8 month visit. We followed these subjects for a median of 2.2 years [interquartile range (IQR) 1.5-2.9]. Higher MTX-PG3-5 levels were related to an increased risk of anaemia [compared with quartile 1 (Q1); hazard ratio (HR) for Q4 1.27 (95% CI 0.98, 1.65), P for trend = 0.05] and a decreased risk of thrombocytopenia [HR for Q4 0.52 (95% CI 0.32, 0.84), P for trend = 0.05]. MTX-PG3-5 levels >134 nmol/l were associated with an increased risk of liver abnormalities [HR 1.36 (95% CI 1.08, 1.72)]. CONCLUSIONS: Higher MTX- PG3-5 levels were modestly associated with LD-MTX AEs, including anaemia and liver function abnormalities, but a reduced risk of thrombocytopenia and haemorrhage. CLINICAL TRIAL REGISTRATION: NCT01594333.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Metotrexato/análogos & derivados , Ácido Poliglutâmico/análogos & derivados , Idoso , Antirreumáticos/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Poliglutâmico/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...