RESUMO
BACKGROUND: ConclusionFibromyalgia is a chronic pain disorder characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance and cognitive impairment. OBJECTIVE: A significant number of fibromyalgia patients do not respond adequately to the current drugs approved by the Food and Drug Administration (FDA) for fibromyalgia treatment including pregabalin, milnacipran, duloxetine. Thus, there is still a need for adjunctive therapies. METHOD: Naltrexone is an opioid receptor antagonist used to treat alcohol and opioid dependence. It is hypothesized that low dose naltrexone causes transient blockade of opioid receptors centrally resulting in a rebound of endorphin function which may attenuate pain in fibromyalgia. RESULTS: Two small prospective pilot studies have previously shown that treatment with low dose naltrexone may be an effective, safe, and inexpensive treatment for fibromyalgia. CONCLUSION: This prospective study lends further support to the preliminary body of evidence that naltrexone is a well tolerated and likely effective treatment option in the community setting. Further large prospective controlled trials are still needed.
Assuntos
Fibromialgia/tratamento farmacológico , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Since progranulin (PGRN) is a natural ligand of TNF receptors, we assessed whether serum PGRN levels predict and/or reflect responsiveness of RA patients to TNF-antagonist therapy. TNF-antagonist-naïve RA patients (N = 35) were started on TNF-antagonist therapy. At baseline and at follow-up visits, DAS28-ESR, DAS28-CRP, and CDAI were calculated, and venous blood was collected for serum PGRN determination. Disease activity and clinical response were based on EULAR criteria. Baseline serum PGRN levels varied considerably and correlated with ESR and CRP. DAS28-ESR, DAS28-CRP, and CDAI were greater in "PGRN-high" than in "PGRN-low". Baseline serum PGRN levels did not predict clinical responsiveness to TNF-antagonist therapy. Nevertheless, changes in serum PGRN levels at 274+ days following initiation of TNF-antagonist therapy correlated with changes in ESR, CRP, DAS28-ESR, DAS28-CRP, and CDAI. At this time, DAS28-ESR, DAS28-CRP, and CDAI in PGRN-high and PGRN-low equalized, but serum PGRN levels remained greater in PGRN-high than in PGRN-low. To our knowledge, the present report is the first prospective study to longitudinally assess changes in serum PGRN levels following initiation of TNF-antagonist therapy. Although pre-treatment serum PGRN levels may not predict clinical responsiveness to TNF-antagonist therapy, changes in serum PGRN levels correlate with changes in disease metrics over time. By inference, administration of PGRN may represent an effective therapeutic option for development in RA patients.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Hispânico ou Latino , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Progranulinas , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
AIMS: To evaluate the association of financial conflicts of interest (FCOI) with the characteristics, outcome and reported methodological quality of fibromyalgia drug therapy randomized controlled trials (FM-RCTs). METHODS: A cross-sectional study of original, parallel-group, drug therapy FM-RCTs published between 1997 and 2011 from Medline and Cochrane Central Register of Controlled Trials was conducted. Two reviewers independently assessed each RCT for funding source, authors' FCOI(s), study characteristics, reporting of methodological measures important for internal validity and outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or non-positive). RESULTS: Forty-seven RCTs were eligible with funding source as: 26 (55.3%) industry; eight (17%) non-profit source(s); five (10.6%) mixed; and eight (17%) unspecified. Industry-funded RCTs were more likely to be multicenter and enroll greater number of patients. Reporting of key methodological measures was suboptimal; however, industry and non-profit funded RCTs did not differ in their reporting. Thirty (63.8%) RCTs had ≥ one author who disclosed an FCOI (receipt of research grant [21, 44.7%], industry sponsor employee [20, 42.6%], receipt of consultancy fee/honorarium [16, 34%] and stock ownership [11, 23.4%]). Although industry funding and certain authors' FCOIs (employment and receipt of consultancy fee/honorarium) were univariately associated with positive outcome, such association was not observed after adjusting for study sample size. CONCLUSIONS: The majority of FM-RCTs were industry-sponsored, and had at least one author with an FCOI. Reporting of key methodological measures was suboptimal. After adjusting for study sample size, no association of industry funding or author's FCOI with study outcome was seen.
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Analgésicos/economia , Analgésicos/uso terapêutico , Conflito de Interesses/economia , Custos de Medicamentos , Indústria Farmacêutica/economia , Fibromialgia/tratamento farmacológico , Fibromialgia/economia , Organizações sem Fins Lucrativos/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Apoio à Pesquisa como Assunto/economia , Indústria Farmacêutica/ética , Fibromialgia/diagnóstico , Humanos , Organizações sem Fins Lucrativos/ética , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Apoio à Pesquisa como Assunto/ética , Resultado do TratamentoRESUMO
OBJECTIVE: Engagement of Fcγ receptor IIb (FcγRIIb) suppresses B cell activation and represents a promising target for therapy in autoimmunity. The aim of this study was to characterize B cell immunosuppression mediated by the Fc-engineered antibody, XmAb5871, which coengages FcγRIIb with the B cell antigen receptor (BCR) complex and that is currently in clinical development for the treatment of rheumatoid arthritis (RA). Because rheumatoid factor (RF) might interfere with the binding of XmAb5871 to FcγRIIb, we correlated RF titers with the potency of XmAb5871. METHODS: We analyzed the expression of CD19, FcγRIIb, and CD86 on naive and memory B cells from 50 patients with RA and 66 healthy donors, quantified XmAb5871-induced promotion of FcγRIIb phosphorylation and suppression of calcium flux in activated B cells, measured CD86 inhibition in whole blood, and correlated RF and anti-citrullinated protein antibody (ACPA) levels with drug potency. We engrafted RA peripheral blood mononuclear cells (PBMCs) into SCID mice, treated them with XmAb5871, and quantified human total IgG, total IgM, and anti-tetanus IgG antibody levels in vivo. RESULTS: B cells from all donors expressed CD19 and FcγRIIb, and the expression of FcγRIIb was higher on naive, but not memory, B cells from donors with RA compared with healthy donors. BCR-mediated calcium flux was suppressed by XmAb5871 and was associated with FcγRIIb phosphorylation. XmAb5871 inhibited CD86 induction, and the levels of RF and ACPAs did not affect efficacy. XmAb5871 suppressed B cell activation regardless of disease severity. In SCID mice engrafted with PBMCs from a patient with RA, XmAb5871 suppressed humoral responses. CONCLUSION: Coengagement of the BCR complex and FcγRIIb by XmAb5871 inhibits B cell activation and function. The similar potency in patients with RA and healthy donors and the absence of autoantibody interference suggest that XmAb5871 may represent a new therapeutic strategy to suppress autoreactive B cells in RA.
Assuntos
Anticorpos Anti-Idiotípicos/farmacologia , Antígenos CD19/imunologia , Artrite Reumatoide/patologia , Linfócitos B/efeitos dos fármacos , Receptores de Antígenos de Linfócitos B/efeitos dos fármacos , Receptores de IgG/efeitos dos fármacos , Animais , Anticorpos Anti-Idiotípicos/metabolismo , Antígenos CD19/metabolismo , Artrite Reumatoide/metabolismo , Linfócitos B/metabolismo , Linfócitos B/patologia , Antígeno B7-2/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Xenoenxertos , Humanos , Leucócitos Mononucleares/patologia , Camundongos , Camundongos SCID , Peptídeos Cíclicos/imunologia , Receptores de Antígenos de Linfócitos B/metabolismo , Receptores de IgG/metabolismoAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças do Sistema Nervoso Central/tratamento farmacológico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Esclerose Múltipla/diagnóstico , Sarcoidose/tratamento farmacológico , Adalimumab , Doenças do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Indução de Remissão , Sarcoidose/diagnóstico , Resultado do TratamentoRESUMO
Zoledronic acid is used in the treatment of osteoporosis. Giant cell artertitis may lead to vision loss. We report a case in which vision loss occurred after zoledronic acid infusion.
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Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Arterite de Células Gigantes/induzido quimicamente , Imidazóis/efeitos adversos , Osteoporose/tratamento farmacológico , Transtornos da Visão/induzido quimicamente , Visão Ocular/efeitos dos fármacos , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Feminino , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Imidazóis/administração & dosagem , Infusões Parenterais , Resultado do Tratamento , Transtornos da Visão/diagnóstico , Transtornos da Visão/fisiopatologia , Ácido ZoledrônicoAssuntos
Articulações dos Dedos/efeitos dos fármacos , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Urato Oxidase/uso terapêutico , Idoso , Biomarcadores/sangue , Doença Crônica , Progressão da Doença , Articulações dos Dedos/diagnóstico por imagem , Gota/sangue , Gota/diagnóstico , Humanos , Masculino , Radiografia , Resultado do Tratamento , Ácido Úrico/sangueAssuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Histiocitose de Células não Langerhans/tratamento farmacológico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Minociclina/uso terapêutico , Adalimumab , Quimioterapia Combinada , Histiocitose de Células não Langerhans/complicações , Histiocitose de Células não Langerhans/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Dermatopatias/etiologiaRESUMO
Psychosocial problems such as depression are present as long-term sequelae of breast cancer and its treatment in a substantial minority of patients. In general and patient populations, lifestyle factors such as obesity and physical activity have been associated with depression, and these and related characteristics may be associated with depression in breast cancer survivors. The purpose of this cross-sectional study was to examine factors associated with depression in overweight or obese women (n=85) who had been diagnosed and treated for early stage breast cancer. Depressive symptoms were measured with the Beck depression inventory (BDI), eating psychopathology was assessed with the eating disorder examination--questionnaire (EDE-Q), and physical activity was estimated with the seven-day physical activity recall. BDI was directly correlated with global EDE-Q score (r=0.56, P<0.01) and inversely associated with age (r=-0.22, P<0.05) in bivariate analysis. Controlling for body mass index, age, education and other factors, BDI was directly associated with global EDE-Q score (P<0.001) and inversely associated with level of physical activity (P<0.05) in a model that explained 61% of the variance. Eating attitudes and behaviors, and physical activity level, are independently associated with depressive symptoms in overweight or obese breast cancer survivors.