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1.
Rinsho Ketsueki ; 62(10): 1505-1509, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34732624

RESUMO

A 66-year-old woman was being treated with methotrexate and etanercept for rheumatoid arthritis (RA). Because her RA symptoms worsened, her medication was changed to tocilizumab (TCZ), and her symptoms improved. However, one year and six months later, she was referred to our hospital because of fever, cervical and para-aortic lymphadenopathy, and massive lesions of the liver/spleen. She was diagnosed with clinical stage IVB mixed cellularity classical Hodgkin lymphoma (cHL) on the basis of right cervical lymph node biopsy. Immunohistochemically, Hodgkin cells were positive for CD20, CD30, PAX-5, LMP-1, PD-L1, and EBER and were negative for CD5, CD15, and EBNA2. Her fever and lymphadenopathy did not improve after the discontinuation of TCZ. Therefore, she was administered ABVd therapy and achieved complete remission (CR) after six cycles of ABVd therapy. She was found to be alive and in CR on regular follow up till February 2021. To the best of our knowledge, there are limited reports of immunodeficiency-related lymphoproliferative disorders associated with TCZ in literature, and our case may be a valuable report on the association of TCZ with the development of cHL in patients with RA.


Assuntos
Artrite Reumatoide , Doença de Hodgkin , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Metotrexato/uso terapêutico , Vimblastina/uso terapêutico
2.
Trials ; 22(1): 764, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732237

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with the primary clinical symptoms of joint swelling and pain. Early detection of erosion and synovial inflammation at an active stage resulting from RA can prevent damage to the joints and activity restriction. However, there are still many patients who do not respond to these treatments; the development of newer, safer drugs is urgently needed. Compared to Western medicine, Guizhi-Shaoyao-Zhimu decoction has equal or higher efficacy and safety for RA patients. With the widespread use of musculoskeletal ultrasound (MSUS), this technology holds great value for the degree of joint damage in RA patients, guiding the clinical selection of treatments, and assessing of prognosis. Therefore, we designed a double-blinded randomized controlled clinical trial to measure the safety and efficacy of Guizhi-Shaoyao-Zhimu decoction in treating early-stage RA using MSUS. METHODS: This study is a randomized, double-blinded, parallel group, placebo-controlled trial. A total of 152 adult participants with early RA will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be Guizhi-Shaoyao-Zhimu decoction plus the conventional medicine methotrexate and the control intervention will be placebo plus the conventional drug methotrexate for 3 months. In addition, both groups will receive folic acid during treatment to prevent side effects from methotrexate. The primary outcomes are the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hepatic and renal function, visual analog scale, disease activity score in 28 joints, measurement scale for TCM symptoms, and 7-joint ultrasound score. DISCUSSION: We designed this double-blinded randomized controlled clinical trial to evaluate the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in RA patients using MSUS. The results of this trial may provide insights into how to improve the clinical symptoms of RA patients and delay further joint destruction. We hope that this trial may provide preliminary evidence of the efficacy of Guizhi-Shaoyao-Zhimu decoction in treating RA patients and that these results aid researchers, practitioners, and patients alike. AIM: The main aim of the study is to clarify the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in patients with early RA. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2000036141 . Registered on 21 August 2020 (retroactively registered).


Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Metotrexato/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Ultrassom
3.
Pan Afr Med J ; 40: 15, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34733383

RESUMO

Introduction: ankylosing spondylitis (AS) is a progressive disease, which can result in disability. The purpose of this study is to describe the epidemiological, diagnostic, therapeutic and evolutionary features of AS in the Department of Rheumatology of the Hospital Center University Aristide Le Dantec, Dakar. Methods: we conducted a descriptive and analytical cross-sectional study. Data were collected on a prospective and retrospective basis over a period of 8 years, between January 2012 and December 2020. Patients were diagnosed with AS on the basis of ESSG (European Seronegative Spondylarthropathy Group) and Amor diagnostic criteria, ASAS (Assessment of Spondyloarthritis International Society) criteria and modified New York criteria. Data were collected by a structured questionnaire and analyzed using the SPSS25 (Statistical Package for the Social Sciences) software. Results: six hundred forty-seven patients met the inclusion criteria (414 women and 233 men) with a sex ratio of 1.77F/1M. Different symptomatic cases were found: axial disease (55.65%), mixed disease (44.35%) and systemic disease with extra-articular manifestations including uveitis (12.21%), aortic insufficiency (5.71%) and fibrobullous lung disease (3.86%). Sixty percent of patients were receiving non-steroidal anti-inflammatory drugs (NSAIDs), 47% methotrexate, and 0.92% biotherapy. Disease activity index, functional index and quality of life index enabled disease monitoring. Conclusion: our results show that there was predominance in women. Patients were mostly affected by axial spondyloarthritis. More than half of our patients were treated with anti-inflammatory, 47% with methotrexate and 0.92% with biotherapy. This study highlights that the features of ankylosing spondylitis (AS) are a burden to the patient with spondyloarthritis and disease progression over time.


Assuntos
Qualidade de Vida , Espondilite Anquilosante/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Terapia Biológica/métodos , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Senegal , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/terapia , Adulto Jovem
4.
BMC Musculoskelet Disord ; 22(1): 953, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34781952

RESUMO

BACKGROUND: Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis. METHODS: Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. DISCUSSION: This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124.


Assuntos
Osteoartrite , Sinovite , Austrália , Canadá , Método Duplo-Cego , Humanos , Metotrexato/uso terapêutico , Estudos Multicêntricos como Assunto , Osteoartrite/diagnóstico por imagem , Osteoartrite/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Resultado do Tratamento
5.
J Med Invest ; 68(3.4): 286-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759146

RESUMO

BACKGROUND: PCNSL is mainly treated with HD-MTX-based chemotherapy with or without WBRT. However, As WBRT is associated with delayed neurotoxicity leading to dementia in the elderly, many institutes reported benefits of intensive chemotherapy or high-dose chemotherapy with ASCT. We investigated whether treatment with HD-MTX and rituximab, followed by continued-maintenance HD-MTX monotherapy (3.5g / m2), improves overall survival (OS). METHODS: In this retrospective, single-center trial 52 immunocompetent patients with newly diagnosed PCNSL were included. All were treated between January 2005 and December 2017. The controls were 18 patients who, between 2005 and 2011, had received 3 cycles of HD-MTX and then adjuvant treatment with WBRT. In 2011 we started HD-MTX continued-maintenance therapy to treat 34 PCNSL patients. In the induction phase, these patients received HD-MTX every 14 days until a complete response (CR) was observed. When CR was obtained, maintenance therapy with HD-MTX (3.5g / m2) was delivered every three months. RESULTS: In 3-year overall survival (OS) there was a statistically significant difference between the two groups [controls : 33.1% (95%, CI 12.4 - 55.7%) ; maintenance group : 74.9% (95%, CI 55.6 - 86.7%) (p < 0.02)]. Conclusion : The induction of HD-MTX based chemotherapy followed by continued-maintenance HD-MTX monotherapy improved OS compared with chemoradiotherapy consisting of HD-MTX followed by WBRT. J. Med. Invest. 68 : 286-291, August, 2021.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma não Hodgkin , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/uso terapêutico , Estudos Retrospectivos
6.
Zhonghua Fu Chan Ke Za Zhi ; 56(11): 782-787, 2021 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-34823291

RESUMO

Objective: To study the clinical characteristics of cornual pregnancy and compare the effects of various surgical methods on the outcomes. Methods: This was a single-center retrospective study. The clinical records of patients with cornual pregnancy who underwent surgery in Peking Union Medical College Hospital from June 2012 to December 2020 were collected. Surgical interventions included curettage (guided by ultrasound or monitored by laparoscope), and cornuostomy/cornectomy (the surgical approach by laparoscopy or laparotomy). The baseline data, perioperative treatment and whether persistent ectopic pregnancy (PEP) occurred after surgery were collected and analyzed statistically. Results: A total of 109 patients with cornual pregnancy diagnosed by surgical treatment were included in this study, whose average age was (32.9±4.8) years. Among them, the incidence of postoperative PEP was 16.5% (18/109). The risk of PEP in multipara was significantly higher than that in nulliparous women (OR=7.639, 95%CI: 2.063-28.279, P=0.001). The risk of PEP in patients with the maximum diameter of lesion<1.5 cm was significantly higher than that in patients with the maximum diameter of lesion≥1.5 cm (OR=8.600, 95%CI: 2.271-32.571, P=0.002). Among all surgical approaches for cornual pregnancy, the proportion of PEP in curettage under ultrasound monitoring was the highest (56.0%, 14/25), which was higher than that in curettage under laparoscope monitoring (1/10; χ2=6.172,P=0.013); the proportion of PEP in curettage group (42.9%, 15/35) was higher than that in cornuostomy/cornectomy group (4.1%, 3/74; χ2=25.950,P<0.01). Neither salpingectomy in the operation nor the routine use of methotrexate (MTX) in perioperative period could significantly reduce the incidence of PEP (all P>0.05). Conclusions: Among the patients with cornual pregnancy, multipara, the maximum diameter of lesion<1.5 cm and ultrasound-guided curettage are the risk factors of PEP after operation. Cornuostomy or cornectomy is recommended for patients with cornual pregnancy. If the patients would perform the curettage operation, laparoscopic monitoring is recommended. For patients with possible satisfactory operation outcome, it is not recommended to use MTX as a routine preventing measure.


Assuntos
Laparoscopia , Gravidez Cornual , Gravidez Ectópica , Adulto , Feminino , Humanos , Metotrexato , Gravidez , Gravidez Cornual/epidemiologia , Gravidez Cornual/cirurgia , Gravidez Ectópica/epidemiologia , Gravidez Ectópica/cirurgia , Estudos Retrospectivos
7.
Ann Palliat Med ; 10(10): 10652-10660, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763513

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease dominated by chronic inflammation of the synovium of the joints. Methotrexate (MTX) is the most widely used in the treatment of RA. This study systematically evaluated the clinical efficacy of MTX on RA and provided a theoretical basis for the clinical treatment of RA. METHODS: Four English databases (PubMed, Embase, Medline, and Web of Sciences) were searched for randomized controlled trials (RCTs) on MTX treatment of RA published from the date of establishment of the database to 2021. The Cochrane Handbook 5.0.2 was used to perform risk bias evaluation and Review Manager 5.3 was used to conduct a meta-analysis. RESULTS: A total of eight articles were included. The meta-analysis showed that, compared to the control group, the number of patients with DAS28-ESR ≤2.6 [erythrocyte sedimentation rate (ESR)] in the MTX alone or MTX combined treatment groups was higher, and the incidence of adverse events was also higher. However, there was no significant difference in the level of alanine aminotransferase (ALT) after treatment versus the control group. DISCUSSION: MTX alone or MTX combined treatment can better control the condition of RA patients without causing damage to the patient's blood system or liver and kidney function, but may increase the probability of adverse events.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Resultado do Tratamento
8.
BMJ Case Rep ; 14(11)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764105

RESUMO

A 30-year-old nulliparous woman was referred with suspected left ovarian ectopic pregnancy. She had undergone laparoscopic left salpingectomy for ruptured tubal ectopic pregnancy 3 weeks earlier, following treatment with medications for ovulation induction. Sonological examination revealed a left ovarian ectopic pregnancy corresponding to 8 0/7 weeks with cardiac activity. She underwent ultrasound-guided intrasac therapy with intrasac instillation of 3 mEq of potassium chloride followed by 50 mg of methotrexate. She was followed with weekly measurements of serum beta human Chorionic Gonadotropin (hCG) which returned to baseline after 65 days of the intrasac therapy. This case not only highlights the need for continued follow-up of the serum beta hCG after definitive management of an ectopic pregnancy in cases with multiple ovulations, but also the option of medical management in cases of advanced ovarian ectopic pregnancy. It also accentuates the necessity for adequate counselling to avoid conception in a multiple ovulation cycle.


Assuntos
Gravidez Ectópica , Gravidez Tubária , Adulto , Gonadotropina Coriônica Humana Subunidade beta , Feminino , Humanos , Metotrexato/uso terapêutico , Gravidez , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/tratamento farmacológico , Gravidez Tubária/diagnóstico por imagem , Gravidez Tubária/cirurgia , Salpingectomia
9.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639104

RESUMO

The interactions of two conformers of newly synthesized photoswitchable azobenzene analogue of methotrexate, called Phototrexate, with two cavitand derivatives, have been investigated in dimethyl sulfoxide medium. Photoluminescence methods have been applied to determine the complex stabilities and the related enthalpy and entropy changes associated to the complex formation around room temperature. Results show opposite temperature dependence of complex stabilities. The structure of the upper rims of the host molecules and the reordered solvent structure were identified as the background of the opposite tendencies of temperature dependence at molecular level. These results can support the therapeutic application of the photoswitchable phototrexate, because the formation of inclusion complexes is a promising method to regulate the pharmacokinetics of drug molecules.


Assuntos
Compostos Azo/química , Éteres Cíclicos/química , Metotrexato/química , Resorcinóis/química , Compostos Azo/metabolismo , Éteres Cíclicos/metabolismo , Isomerismo , Metotrexato/metabolismo , Modelos Moleculares , Estrutura Molecular , Resorcinóis/metabolismo , Temperatura , Termodinâmica
10.
BMJ Case Rep ; 14(10)2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645625

RESUMO

Induction of remission in biologic-experienced individuals with moderate to severe Crohn's disease (CD) can be a challenge. We hereby present a case of CD with secondary non-response to infliximab. Adding methotrexate and switching to ustekinumab plus methotrexate did not stop the inflammatory process. Therefore, combination therapy with two classes of biologics consisting of ustekinumab and adalimumab plus methotrexate was initiated. He achieved clinical remission in 4 weeks and remained on triple therapy for 6 months which was subsequently tailored to adalimumab/methotrexate combination therapy due to insurance restriction on ustekinumab. He remained in remission for the duration of follow-up, 14 months after initiation of triple therapy and 8 months after switching to methotrexate/adalimumab biologic monotherapy. Triple therapy with anti-TNF, IL-12/23 inhibitor and methotrexate could potentially be an option for induction of remission in biologic-experienced individuals with good initial clinical response to anti-TNF agents.


Assuntos
Produtos Biológicos , Doença de Crohn , Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Infliximab , Masculino , Metotrexato/uso terapêutico , Indução de Remissão , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Ustekinumab/uso terapêutico
11.
Medicina (Kaunas) ; 57(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34684087

RESUMO

Background and Objectives: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to define methotrexate drug survival and reasons for discontinuation, along with factors associated with drug survival, in a cohort of adult patients with moderate-to-severe plaque psoriasis. Materials and Methods: Data on methotrexate treatment were extracted from our institutional registry. Drug survival was estimated by Kaplan-Meier analysis, and predictors of drug survival were analyzed by Cox proportional hazards regression. Results: We included 133 patients treated with methotrexate. Due to significant effects of the year of treatment initiation, drug survival analysis was performed for 117 patients who started methotrexate in 2010 or later. Median methotrexate drug survival was 11.0 months. Overall, 89% of patients discontinued treatment, with over half of these (51%) due to lack of efficacy. Significantly longer drug survival was seen for patients who discontinued treatment due to lack of efficacy versus drug safety (p = 0.049); when stratified by sex, this remained significant only for women (p = 0.002). The patient ABCC2 rs717620 genotype was significantly associated with drug survival in both univariate log-rank and multivariate Cox regression analyses, with variant T allele associated with longer drug survival (hazard ratio, 0.606; 95% confidence interval, 0.380-0.967; p = 0.036). Conclusions: We have identified the novel association of patient ABCC2 rs717620 genotype with methotrexate drug survival. This pharmacogenetic marker might thus help in the management of psoriasis patients in daily practice.


Assuntos
Preparações Farmacêuticas , Psoríase , Adulto , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Metotrexato/uso terapêutico , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Psoríase/tratamento farmacológico , Psoríase/genética , Resultado do Tratamento
12.
In Vivo ; 35(6): 3245-3251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34697155

RESUMO

BACKGROUND/AIM: Using a rat model of collagen-induced arthritis (CIA), we evaluated the therapeutic effects of HM71224 (BTKi), as well as the drug-drug interactions in combined therapy with methotrexate (MTX) based on both drugs' pharmacological role in immune regulation and antiinflammation. MATERIALS AND METHODS: Arthritis in rats was induced using type II collagen and incomplete Freund's adjuvant. The therapeutic effects of HM71224 (alone or in combination with MTX) were evaluated by arthritis score, paw volume, body weight, and histopathological examination (H&E and Safranin-O staining). The drug-drug interactions between HM71224 and MTX were investigated by measuring plasma, liver enzyme and creatinine levels and blood cell counts. RESULTS: HM71224 reduced the clinical signs of arthritis, paw volume, and body weight loss in CIA rats. ED50 and ED90 were 1.0 and 2.5 mg/kg, respectively. HM71224 combined with MTX decreased the arthritis score, bone erosion, synovitis, and cartilage degradation without apparent interaction. CONCLUSION: The combination of HM71224 and MTX improved the therapeutic effect with no drug-drug interactions in RA.


Assuntos
Artrite Experimental , Metotrexato , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Quimioterapia Combinada , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Ratos
13.
Medicine (Baltimore) ; 100(40): e27450, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622865

RESUMO

RATIONALE: Adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are caused by HTLV-1, but the coexistence of both disorders is rare. The estimated incidence is approximately 3%. PATIENT CONCERNS: A 54-year-old man was unable to stand up because of spastic paraparesis 1 month after the onset. He developed lymphadenopathy in the left supraclavicular fossa 5 months after the onset. The spastic paraplegia and sensory symptoms below the thoracic spinal cord level worsened. DIAGNOSES: Both blood and cerebrospinal fluid (CSF) tests were positive for anti-HTLV-1 antibodies. The patient was diagnosed with rapidly progressive HAM/TSP. He was also diagnosed with lymphoma-type ATL by the biopsy specimen of the lymph node. CSF examination at the time of symptom exacerbation showed abnormal lymphocytes, suggesting central infiltration of the ATL in the central nervous system. INTERVENTIONS: Methylprednisolone pulse therapy and oral prednisolone maintenance therapy were administered for rapidly progressive HAM/TSP. Intrathecal injection of methotrexate was administered for the suggested central infiltration of the ATL. OUTCOMES: Methylprednisolone pulse therapy and intrathecal injection of methotrexate did not improve the patient's exacerbated symptoms. Five months later, clumsiness and mild muscle weakness of the fingers appeared, and magnetic resonance imaging showed swelling of the cervical spinal cord. Clonality analysis showed monoclonal proliferation only in the DNA of a lymph node lesion, but not in the CSF and peripheral blood cells. LESSONS: This was a case of rapidly progressive HAM/TSP associated with lymphoma-type ATL that was refractory to steroids and chemotherapy. The pathogenesis was presumed to involve ATL cells in the brain and spinal cord because of the presence of abnormal lymphocytes in the CSF, but DNA analysis could not prove direct invasion. This case suggests that when we encounter cases with refractory HAM/TSP, it should be needed to suspect the presence of ATL in the background.


Assuntos
Leucemia-Linfoma de Células T do Adulto/complicações , Paraparesia Espástica Tropical/complicações , Feminino , Glucocorticoides/administração & dosagem , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/tratamento farmacológico
14.
Mol Syst Biol ; 17(11): e10396, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34709727

RESUMO

Treatment options for COVID-19, caused by SARS-CoV-2, remain limited. Understanding viral pathogenesis at the molecular level is critical to develop effective therapy. Some recent studies have explored SARS-CoV-2-host interactomes and provided great resources for understanding viral replication. However, host proteins that functionally associate with SARS-CoV-2 are localized in the corresponding subnetwork within the comprehensive human interactome. Therefore, constructing a downstream network including all potential viral receptors, host cell proteases, and cofactors is necessary and should be used as an additional criterion for the validation of critical host machineries used for viral processing. This study applied both affinity purification mass spectrometry (AP-MS) and the complementary proximity-based labeling MS method (BioID-MS) on 29 viral ORFs and 18 host proteins with potential roles in viral replication to map the interactions relevant to viral processing. The analysis yields a list of 693 hub proteins sharing interactions with both viral baits and host baits and revealed their biological significance for SARS-CoV-2. Those hub proteins then served as a rational resource for drug repurposing via a virtual screening approach. The overall process resulted in the suggested repurposing of 59 compounds for 15 protein targets. Furthermore, antiviral effects of some candidate drugs were observed in vitro validation using image-based drug screen with infectious SARS-CoV-2. In addition, our results suggest that the antiviral activity of methotrexate could be associated with its inhibitory effect on specific protein-protein interactions.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Descoberta de Drogas , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Proteoma/efeitos dos fármacos , SARS-CoV-2/fisiologia , COVID-19/virologia , Reposicionamento de Medicamentos , Humanos , Espectrometria de Massas , Metotrexato/farmacologia , Proteômica , Replicação Viral/efeitos dos fármacos
15.
Rheum Dis Clin North Am ; 47(4): 619-641, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635295

RESUMO

Childhood noninfectious uveitis leads to sight-threatening complications. Idiopathic chronic anterior uveitis and juvenile idiopathic arthritis-associated uveitis are most common. Inflammation arises from an immune response against antigens within the eye. Ophthalmic work-up evaluates anatomic involvement, disease activity, ocular complications, and disease course. Local and/or systemic glucocorticoids are initial treatment, but not as long-term sole therapy to avoid glucocorticoids-induced toxicity or persistent ocular inflammation. Children with recurrent, refractory, or severe disease require systemic immunosuppression with methotrexate and/or anti-tumor necrosis factor monoclonal antibody medications (adalimumab, infliximab). Goals of early detection and treatment are to optimize vision in childhood uveitis.


Assuntos
Artrite Juvenil , Uveíte , Adalimumab , Adolescente , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico , Artrite Juvenil/tratamento farmacológico , Criança , Humanos , Infliximab , Metotrexato , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/epidemiologia
16.
Adv Ther ; 38(12): 5649-5661, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636000

RESUMO

INTRODUCTION: To compare the economic benefit of upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy from improvements in health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA). METHODS: Data were analyzed from two trials of upadacitinib (SELECT-NEXT and SELECT-MONOTHERAPY) and one trial of tofacitinib (ORAL-Standard) that collected HRQOL measurements using the Short Form 36 (SF-36) Health Survey in patients with RA. Direct medical costs per patient per month (PPPM) for patients receiving upadacitinib 15 mg once daily and methotrexate were derived from observed SF-36 Physical (PCS) and Mental Component Summary (MCS) scores in the SELECT trials using a regression algorithm. Direct medical costs PPPM for patients receiving tofacitinib 5 mg twice daily were obtained from a published analysis of SF-36 PCS and MCS scores observed in the ORAL-Standard trial. Short-term (12-14 weeks) and long-term (48 weeks) estimates of direct medical costs PPPM were compared between upadacitinib and tofacitinib and between upadacitinib and methotrexate. RESULTS: Over 12 weeks, direct medical costs PPPM were $252 lower (95% CI $72, $446) for upadacitinib-treated patients versus tofacitinib-treated patients. Medical costs PPPM at weeks 24 and 48 and cumulative costs over the entire 48-week period (difference $1759; 95% CI $1162, $2449) were significantly lower for upadacitinib than for tofacitinib. Over 14 weeks, direct medical costs PPPM were $399 lower (95% CI $158, $620) for patients treated with upadacitinib monotherapy compared with those treated with methotrexate alone. Direct medical costs at week 48 and cumulative costs over the entire 48-week period (difference $2044; 95% CI $1221, $2846) were significantly lower for upadacitinib monotherapy compared with methotrexate alone. CONCLUSION: In the short and long term, upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy were associated with significantly lower direct medical costs for patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02675426, NCT02706951, and NCT00853385.


Assuntos
Antirreumáticos , Artrite Reumatoide , Compostos Heterocíclicos com 3 Anéis , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Compostos Heterocíclicos com 3 Anéis/economia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Metotrexato/economia , Metotrexato/uso terapêutico , Piperidinas/economia , Piperidinas/uso terapêutico , Pirimidinas/economia , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
RMD Open ; 7(3)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34663636

RESUMO

BACKGROUND: In SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1. METHODS: Patients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised. RESULTS: Consistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups. CONCLUSION: Efficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.


Assuntos
Antirreumáticos , Artrite Psoriásica , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Metotrexato/uso terapêutico
18.
Int J Clin Pharmacol Ther ; 59(12): 760-767, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34622769

RESUMO

OBJECTIVE: We aimed to assess the relative efficacy and safety of etanercept biosimilars and etanercept originators in patients with active rheumatoid arthritis (RA) who showed an inadequate response to methotrexate (MTX). MATERIALS AND METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of etanercept biosimilars vs. etanercept originators in patients with active RA despite treatment with MTX. RESULTS: Three RCTs involving 1,200 patients, including 4 types of biologics, were included. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that LBEC0101 had a high probability of being the better treatment in terms of the American College of Rheumatology 20 (ACR20) response rate (SUCRA = 0.744), followed by HD203 (SUCRA = 0.457), SB4 (SUCRA = 0.446), and etanercept (SUCRA = 0.352), although no difference in the ACR20 response rate between the biosimilars and etanercept groups was found. Although not statistically significant, there was a difference in the ranking probability of safety based on serious adverse events (SAEs) among interventions. Ranking probability based on SUCRA values indicated that LBEC0101 had the highest probability of being the safest treatment (SUCRA = 0.638), followed by SB4 (SUCRA = 0.495) and HD203 (SUCRA = 0.475), while etanercept had the lowest probability of being the safest treatment (SUCRA = 0.393). CONCLUSION: No significant difference was found between etanercept biosimilars and etanercept originators in patients with active RA despite treatment with MTX in terms of the ACR20 response rate and SAEs.


Assuntos
Antirreumáticos , Artrite Reumatoide , Medicamentos Biossimilares , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/efeitos adversos , Quimioterapia Combinada , Etanercepte/efeitos adversos , Humanos , Metotrexato/efeitos adversos , Metanálise em Rede , Resultado do Tratamento
19.
Clin Drug Investig ; 41(11): 929-939, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34657244

RESUMO

Allogeneic haematopoietic stem cell transplantation (alloHSCT) offers a potentially curative therapy for patients suffering from diseases of the haematopoietic system but requires a high level of expertise and is both resource intensive and expensive. A frequent and life-threatening complication is graft-versus-host disease (GvHD). Acute GvHD (aGvHD) generally causes skin, gastrointestinal and liver symptoms, but chronic GvHD (cGvHD) has a different pathophysiology and may affect nearly every organ or tissue of the body. In Europe, GvHD prophylaxis is generally a calcineurin inhibitor in combination with methotrexate, with high-dose systemic steroids used for advanced GvHD treatment. Between 39% and 59% of alloHSCT patients will develop aGvHD and around 36-37% will develop cGvHD. Steroid response decreases with increasing disease severity, which in turn leads to an increase in non-relapse mortality. GvHD imposes a financial burden on healthcare systems, significantly increasing post-alloHSCT costs. Increased GvHD disease severity magnifies this. Balancing immunosuppression to control the GvHD whilst maintaining a degree of immunocompetence against infection is critical. European GvHD guidelines acknowledge the lack of evidence to support a standard second-line therapy, and improved long-term outcomes and quality-of-life (QoL) remain an unmet need. Evidence generation for potential treatments is challenging. Issues to overcome include choice of comparator (extensive off-label usage); blinding; selection of relevant patient-reported outcome measures (PROMs); and rarity of the condition, which may infeasibly increase timescales to achieve clinical and statistical relevance.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Inibidores de Calcineurina , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Metotrexato , Qualidade de Vida
20.
Eur J Pharm Sci ; 167: 106039, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34644599

RESUMO

Stringent formulation requirements are defined to intrathecally administer drug substances, avoiding neurological complications. In case of pediatric patients, these are further complicated due to the limited volumes of the celebrospinal fluid and, therefore, high concentrated solutions of methotrexate (MTX), cytarabine and corticosteroids (i.e., methylprednisolone or hydrocortisone) are prepared based on the patient's age. This work aims to assess the chemical and physical stability of triple intrathecal mixtures differing in volume and composition by a bracketing approach and to identify possible stress causes and mitigation strategies. Low solubility of MTX was the main factor limiting the physical stability of triple mixtures. Regarding solutions containing methylprednisolone, the amount of MTX remaining was about 95% in the solution at highest concentrations with the concomitant formation of a visible particulate sizing bigger than 1 µm after 24 h of storage at 25 °C. This behavior was mainly driven by the pH reduction due to the pH value of the cytarabine solution used; the shear stress also induced drug precipitation. In the case of the hydrocortisone based mixtures, the precipitate formation occurred at a slow rate. To improve the physical stability, a better control of the mixture pH (optimal value ≈ 7) is required or, as an alternative, the addition of the cytarabine solution to a pre-mixed binary mixture containing MTX and a corticosteroid should be preferred.


Assuntos
Citarabina , Pediatria , Criança , Estabilidade de Medicamentos , Humanos , Hidrocortisona , Injeções Espinhais , Metotrexato
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