Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 354
Filtrar
1.
Rev Med Suisse ; 16(676-7): 12-15, 2020 Jan 15.
Artigo em Francês | MEDLINE | ID: mdl-31961075

RESUMO

Giant cell arteritis (GCA) is the most common vasculitis in adults over 50 years, which requires an urgent treatment with corticosteroids to reduce ischemic complications. Because of their side-effects, a valid diagnosis is necessary. Histological confirmation remains the gold-standard but non-invasive imaging along specific clinical criteria can nowadays diagnose GCA, particularly temporal artery ultrasound. Alternatives to corticosteroids are being studied and recently, the addition of tocilizumab to corticosteroids has been validated by international institutions and is approved by Swissmedic. Similarly to tocilizumab, methotrexate has been shown to decrease the total dose of corticosteroids and the number of relapses. We will also discuss newer potential therapies (abatacept and ustekinumab).


Assuntos
Arterite de Células Gigantes , Abatacepte/uso terapêutico , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Ultrassonografia
2.
Life Sci ; 243: 117243, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31917994

RESUMO

The present study aimed to evaluate the healing process of ulcers in the jugal mucosa of Wistar rats treated with abatacept. The rats were randomly assigned to four groups: saline-treated control (0.3 mL/kg) abatacept-treated groups at dosages of 3.2, 8.0 and 20.0 mg/kg/week. After two weeks of subcutaneous (SC) administration, ulcers were introduced into the left jugal mucosa with an 8-mm diameter punch. SC administration was continued until euthanasia (after 1, 3, 7, 14 and 21 days of ulceration), and ulcers were clinically measured and animals weighed. Histological slides were evaluated (healing scores and polymorphonuclear, mononuclear, vessel, and fibroblast/myofibroblast counts). We also performed collagenesis analysis (Picrosirius Red) and immunohistochemistry (induced nitric oxide synthase (iNOS), interleukin (IL)-1beta (1ß), -6, -10, plus the analysis of CD8 and CD30). The experiment was repeated to perform a vascular permeability assay. ANOVA 1-way or 2-way/Bonferroni and Kruskal-Wallis/Dunn tests were used for statistical analysis (GraphPad Prism 5.0®, p < 0.05). Abatacept treatment reduced the ulcer diameter and the numbers of polymorphonuclear and mononuclear cells; reduced the CD8+/CD30+ ratio and vascular permeability; and increased collagenesis and IL-10 expression at the beginning of the protocol. At the highest dose, there was a delay in repair and vascular proliferation; a reduction in the number of fibroblasts/myofibroblasts; and prolongation of iNOS, IL- and IL- expression. We conclude that abatacept accelerates the healing of oral ulcers by reducing the migration of inflammatory cells, but overdose of abatacept leads to delayed repair and prolongation of proinflammatory cytokine expression.


Assuntos
Abatacepte/uso terapêutico , Antígenos CD8/imunologia , Imunossupressores/uso terapêutico , Interleucinas/metabolismo , Antígeno Ki-1/imunologia , Úlceras Orais/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Abatacepte/administração & dosagem , Abatacepte/farmacologia , Animais , Relação Dose-Resposta a Droga , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Úlceras Orais/imunologia , Úlceras Orais/metabolismo , Úlceras Orais/patologia , Ratos , Ratos Wistar
3.
Presse Med ; 48(9): 968-979, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31324351

RESUMO

Glucocorticoids (GC) remain the gold standard of the treatment of giant cell arteritis provided objectives of GC-tapering are accurately followed: 15 to 20mg/day at 3 months, 10mg/day at 6 months, 5mg/day at 9-12 months and withdrawal between 12 and 18 months. In case of corticodependance at ≥7.5 mg/day of prednisone or intolerance to GC, a GCsparing therapy has to be introduced, mainly methotrexate or tocilizumab. Individual characteristics of each patient, data about the efficacy of the treatment, its cost and how easy the follow-up under this treatment is are important factors to consider for choosing the right GC-sparing therapy. For all these reasons, except particular situations, we prefer using methotrexate before tocilizumab. Prevention of cardiovascular events is an important aspect of the treatment of GCA. We recommend using aspirin (75-100mg/day) during the first month of treatment or longer in case of occurrence of an ischemic complication. Each patient treated for GCA should receive a prevention of osteoporosis with respect of usual recommendations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/uso terapêutico , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Abatacepte/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Azatioprina/uso terapêutico , Esquema de Medicação , Arterite de Células Gigantes/complicações , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/uso terapêutico , Leflunomida/uso terapêutico , Ustekinumab/uso terapêutico
5.
Clin Rheumatol ; 38(9): 2451-2459, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31102087

RESUMO

OBJECTIVE: To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. METHODS: A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(-)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period. RESULTS: Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(-)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (- 1.35/- 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52 weeks. CONCLUSION: In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX. KEY POINTS: • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in 'real-world' settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Metotrexato/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
6.
Int J Rheum Dis ; 22(6): 1138-1144, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30938065

RESUMO

AIM: Telomere is a component of chromosomes that protects their ends from various stresses. The telomeres shorten during cell division, and their length is maintained by telomerase. The telomerase activity of lymphocytes was shown to be upregulated on lymphocyte activation, and abatacept was found to suppress the activation of T lymphocytes involved in pathogenesis of rheumatoid arthritis. Therefore, we investigated the effect of abatacept on lymphocyte telomerase activity in patients with rheumatoid arthritis. METHOD: This study included 11 patients diagnosed with rheumatoid arthritis based on American College of Rheumatology 2010 criteria, who received abatacept treatment from August 2012 to August 2013. We collected their clinical data and obtained peripheral blood samples before starting abatacept, and 1, 3, 6, and 12 months after treatment. Peripheral blood mononuclear cells were extracted using Ficoll density gradient centrifugation, and T and B lymphocytes were sorted by magnetic beads. The telomerase activity of lymphocytes was determined using the telomeric repeat amplification protocol. RESULTS: The telomerase activity of T lymphocytes declined from 0.357 to 0.161 (P < 0.01) at 12 months after abatacept treatment, and that of B lymphocytes declined from 0.554 to 0.202 (P < 0.01). The telomerase activity of B lymphocytes, but not that of T lymphocytes, was also significantly downregulated 1 month after treatment. CONCLUSION: Abatacept suppressed the telomerase activity of both T and B lymphocytes, although that of B lymphocytes was downregulated before T lymphocytes. These findings imply that the clinical efficacy of abatacept during the early phase depends on the suppression of B lymphocytes.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Linfócitos B/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Telomerase/metabolismo , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/enzimologia , Linfócitos B/enzimologia , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/enzimologia , Fatores de Tempo , Resultado do Tratamento
7.
Reumatismo ; 71(1): 24-30, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932440

RESUMO

We performed a retrospective analysis to evaluate the survival on first line biologic drug of rheumatoid arthritis (RA) patients with potential occult HBV infection (pOBI). We analysed longitudinal data of 486 consecutive RA patients starting a first biological drug in a time frame from 1st January 2008 to 31st December 2014. Demographic and disease related characteristics were collected at baseline and at the last observation visit. Baseline serological markers of HBV infection and causes of treatment discontinuation were also recorded. Primary endpoint was the influence of pOBI on drug survival, estimated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs) of drug discontinuation, adjusted for disease characteristics, biological drug class and HBcAb status were computed by Cox-regression models. The retention rate was significantly lower in pOBI positive patients (58.2%) when compared to pOBI negative ones (67.8%) and this data was confirmed also when only discontinuation due to ineffectiveness was considered (pOBI positive 66.4% vs pOBI negative 75.3%, long rank 7.93, p=0.005). Cox regression models showed a significant association between HBcAb-neg (HR 0.58, 0.41-0.84), higher ESR-DAS28 at baseline (HR 1.07, 1.03-1.11) or RF/ACPA-neg (HR 1.46, 1.04-2.06) and drug discontinuation. Occult HBV infection seems to influence negatively the effectiveness of biological therapies in RA patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Hepatite B/complicações , Imunossupressores/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Abatacepte/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Citrulinação , DNA Viral/sangue , Etanercepte/uso terapêutico , Feminino , Glucocorticoides/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos
8.
Drugs Aging ; 36(6): 493-510, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30953327

RESUMO

The prevalence of rheumatoid arthritis (RA), the most common autoimmune inflammatory arthritis, is increasing, partly due to the aging of the general population. RA is an independent risk factor for the development of cardiovascular disease (CVD). Older adults and elderly patients with RA develop CVD at a younger age compared with their general population peers. Both the traditional cardiovascular risk factors (age, sex, smoking, diabetes mellitus, hypertension), and systemic inflammation (i.e. high disease activity) are contributors to accelerated CVD in people with RA. Of the disease-modifying antirheumatic drugs (DMARDs) used for RA treatment, methotrexate, triple combination oral therapy (methotrexate, sulfasalazine, and hydroxychloroquine), tumor necrosis factor inhibitor biologicals, and abatacept have the strongest data in favor of the reduction of cardiovascular events in patients with RA. A treat-to-target strategy should be employed in older adults and elderly patients with RA to ensure appropriate reduction in cardiovascular risk, which can also prevent short- and long-term musculoskeletal disability. Our review findings are in line with the 2016 European League Against Rheumatism guideline recommendations, specifically: (1) RA disease activity should be controlled with an optimal DMARD regimen using a treat-to-target approach; (2) the lipid profile should be assessed and monitored in every older adult and elderly RA patient; (3) CVD risk factors, including smoking cessation, blood pressure, and blood glucose control, should be optimized; (4) RA treatment should be initiated as soon as possible; and (5) shared decision making regarding the treatment of patients with RA should include a discussion on the potential amelioration of increased cardiovascular risk.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Abatacepte/uso terapêutico , Idoso , Produtos Biológicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Ther Drug Monit ; 41(2): 243-248, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30883517

RESUMO

BACKGROUND: There is an unmet need for reliable minimally invasive diagnostic biomarkers for immunological allograft monitoring and for the detection of acute kidney transplant rejection. Here, targeted proteomic analysis was applied to compare 92 proteins in sera of belatacept-treated patients who had biopsy-proven, acute T-cell-mediated rejection (aTCMR) with patients without aTCMR. METHODS: Proximity extension immunoassay was used to measure 92 inflammation-related protein concentrations in the prerejection and rejection sera of 11 patients with aTCMR and 9 patients without aTCMR. This assay uses 2 matched oligonucleotide-labeled antibody probes for each protein and polymerase chain reaction to measure normalized protein expression values. RESULTS: Five proteins (CD5, CD8A, NCR1, TNFRSF4, and TNFRSF9) were expressed significantly higher in samples with aTCMR compared with samples without aTCMR (adjusted P-value < 0.014) and had a good predictive capacity for aTCMR [area under the curve in a receiver-operator curve ranged from 0.83 to 0.91 (P < 0.014)]. These proteins are associated with CD8 cytotoxic T-cell and NK cell functions. Nonhierarchical clustering analysis showed distinct clustering of samples with aTCMR and samples without aTCMR. This clustering was not found in prerejection samples (1 month after transplantation). In prerejection samples, IFN-γ was expressed at a significantly lower level (normalized protein expression value median -0.15, interquartile range: -0.27 to 0.04) than in samples of patients without rejection (median 0.13, interquartile range: -0.07 to 0.15, adjusted P-value = 0.00367). CONCLUSIONS: Targeted proteomic analysis with proximity extension immunoassay is a promising minimally invasive technique to diagnose aTCMR in kidney transplant recipients.


Assuntos
Aloenxertos/imunologia , Rejeição de Enxerto/sangue , Transplante de Rim , Valor Preditivo dos Testes , Proteômica/estatística & dados numéricos , Linfócitos T/imunologia , Abatacepte/uso terapêutico , Biomarcadores/sangue , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Projetos Piloto
10.
Transplant Proc ; 51(2): 517-521, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879580

RESUMO

OBJECTIVE: We aim to report our experience managing cases of recurrent focal segmental glomerulosclerosis (FSGS) in a group of pediatric renal transplant recipients. METHODS: This study was a retrospective chart review of pediatric patients who had their first kidney transplant at King Faisal Specialist Hospital & Research Center between 2014 and 2016. RESULTS: We reviewed the files of 6 patients, 3 of whom were male. The median age of the children was 2.75 years (range, 2-4 years) at disease onset, with an average time of progression to end-stage renal disease of 19 months (range, 8-30 months). Five of the patients received a living related donor transplant, and 1 received a living nonrelated donor transplant. Patients had FSGS recurrence at varying intervals (1 to 3 days) post transplant. All cases had plasmapheresis prior to receiving abatacept or rituximab. The therapeutic strategy in 4 patients involved switching tacrolimus to cyclosporine. A complete response was observed in 5 of the 6 patients (83.3%), and treatment was well tolerated in 5 patients. Patient 1 had severe oliguria and required intermittent hemodialysis during the first 3 weeks post transplant. He showed minimal response to the therapeutic plasma exchange and rituximab and was subsequently treated with abatacept. However, he died 8 months post transplant of pneumonia and sepsis. CONCLUSION: Rituximab and switching tacrolimus to cyclosporine, in conjunction with plasmapheresis, appeared to be effective and safe in children with recurrent FSGS. Conversely, abatacept did not appear to provide clinical benefit.


Assuntos
Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Rim , Abatacepte/uso terapêutico , Adolescente , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Humanos , Masculino , Plasmaferese , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Tacrolimo/uso terapêutico , Transplantados
11.
Autoimmun Rev ; 18(5): 501-509, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30844558

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is burdened by a significant increase in cardiovascular disease (CVD) risk. Amongst CVD risk factors, endothelial dysfunction and arterial stiffness represent powerful predictors of atherosclerosis and cardiovascular events in the general population and in RA patients. METHODS: A systematic review of the literature was performed to identify the available data on the effect of non-TNF-targeted biologics licensed for the treatment of RA on endothelial function, arterial stiffness or subclinical atherosclerosis. MedLine (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science (WOS) databases were searched using a predefined strategy to identify relevant articles. RESULTS: The search strategy initially retrieved 389 records. After screening titles and abstracts, a total of 362 studies were excluded. Amongst the remaining 27 studies selected for final examination, 16 articles were included in the systematic literature review. Included studies demonstrated a significant effect of abatacept, anakinra, rituximab and tocilizumab in improving endothelial dysfunction associated with RA; the effect on arterial stiffness was less consistent and deserves further investigation. No significant effect of non-TNF-targeted biologics was observed for measures of subclinical atherosclerosis. CONCLUSION: Non-TNF-targeted biologics have been associated with favorable effects on endothelial dysfunction as already demonstrated for TNF inhibitors. Future studies are needed to ascertain the impact of this mediations on arterial stiffness in RA patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Vasculares/tratamento farmacológico , Abatacepte/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/complicações , Fatores Biológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Rituximab/uso terapêutico , Doenças Vasculares/etiologia
12.
Clin Rheumatol ; 38(5): 1413-1424, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30790095

RESUMO

OBJECTIVES: Evaluate abatacept retention over 2 years in the AbataCepT In rOutiNe clinical practice (ACTION) study. METHOD: ACTION was an international, observational study of patients with moderate-to-severe rheumatoid arthritis (RA) who initiated intravenous abatacept. Crude abatacept retention rates over 2 years were estimated using Kaplan-Meier analyses in biologic-naive and -failure patients. Clinically relevant risk factors and significant prognostic factors for retention were evaluated using a Cox proportional hazards multivariable model. RESULTS: Overall, 2350/2364 enrolled patients were evaluable; 673 (28.6%) were biologic naive and 1677 (71.4%) had prior biologic failure (1 biologic, 728/1677 [43.4%]; ≥ 2 biologics, 949/1677 [56.6%]). Abatacept retention rate (95% confidence interval [CI]) at 2 years was 47.9% (45.7, 50.0): 54.5% (50.4, 58.3) for biologic-naive vs 45.2% (42.7, 47.7) for biologic-failure patients (log-rank P < 0.001). For patients with 1 and ≥ 2 prior biologic failures, respectively, retention rates (95% CI) were 50.2% (46.3, 53.9) vs 41.3% (38.0, 44.6; log-rank P < 0.001). Main reasons for discontinuation (biologic-naive vs biologic-failure, respectively) were lack of efficacy (61.4 vs 67.7%) and safety (21.3 vs 21.2%). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) double positivity versus negativity were predictive of higher retention in both biologic-naive (hazard ratio [HR] [95% CI] 0.71 [0.53, 0.96]; P = 0.019) and biologic-failure patients (HR [95% CI] 0.76 [0.62, 0.94]; P = 0.035). CONCLUSIONS: Abatacept initiation as earlier vs later line of therapy in RA may achieve higher 2-year retention rates. RF and anti-CCP seropositivity could predict increased abatacept retention, irrespective of treatment line. TRIAL REGISTRATION: NCT02109666.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Corticosteroides/uso terapêutico , Idoso , Estudos de Coortes , Quimioterapia Combinada , Feminino , Humanos , Internacionalidade , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fator Reumatoide/sangue , Resultado do Tratamento
13.
Exp Clin Transplant ; 17(Suppl 1): 178-180, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30777550

RESUMO

Primary focal segmental glomerulosclerosis recurrence occurs in 10% to 50% of recipients after kidney transplant and may affect both children and adults. Treatment after recurrence with plasma exchange and immunosuppression is quite variable and challenging, and those who do not respond usually progress to allograft failure. Podocyte injury and B7-1 expression and subsequently its blockade (abatacept) have been reported to be associated with complete remission of proteinuria in 4 patients with focal segmental glomerulosclerosis recurrence after kidney transplantation and in 1 patient with focal segmental glomerulosclerosis in native kidney. Here, we report our experience of successfully treating 3 consecutive patients with focal segmental glomerulosclerosis recurrence after kidney transplant with abatacept, which induced proteinuria remission.


Assuntos
Abatacepte/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/diagnóstico , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Recidiva , Resultado do Tratamento , Adulto Jovem
14.
Intern Med ; 58(12): 1703-1712, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30799358

RESUMO

Objective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear. This study was performed to evaluate the association of the use of different bDMARDs with new-onset or worsening of RA-AD/ILD. Methods We performed a retrospective cohort study of RA patients who received bDMARDs and assessed their AD/ILD before and after drug initiation in our hospital over the past 10 years. We evaluated the serial changes in computed tomography (CT), classified patients according to AD/ILD progression, and analyzed associations between clinical characteristics and outcomes. Results We enrolled 49 patients. Thirty patients received tumor necrosis factor inhibitors (TNFis), 12 received abatacept (ABT), and the remaining 7 received tocilizumab (TCZ). Seventeen patients had ILD, 10 had AD, and 6 had both AD and ILD before the initiation of bDMARDs. New emergence or exacerbation of AD/ILD was observed in 18 patients after drug initiation, while the remaining 31 remained stable or improved. Multiple logistic regression analyses revealed that pre-existing AD was an independent risk factor against the emergence or exacerbation of RA-AD/ILD, and ABT use was a protective factor against it. Conclusion Our study showed that pre-existing RA-AD is associated with future worsening of RA-AD/ILD, and ABT over other bDMARDs was associated with a better prognosis. Future studies to confirm our results are needed.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Abatacepte/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa/uso terapêutico
15.
Ann Rheum Dis ; 78(4): 456-464, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30679153

RESUMO

OBJECTIVE: To investigate the rate of serious bacterial, viral or opportunistic infection in patients with rheumatoid arthritis (RA) starting tocilizumab (TCZ) versus tumour necrosis factor inhibitors (TNFi) or abatacept. METHODS: Using claims data from US Medicare from 2010 to 2015, and IMS and MarketScan from 2011 to 2015, we identified adults with RA who initiated TCZ or TNFi (primary comparator)/abatacept (secondary comparator) with prior use of ≥1 different biologic drug or tofacitinib. The primary outcome was hospitalised serious infection (SI), including bacterial, viral or opportunistic infection. To control for >70 confounders, TCZ initiators were propensity score (PS)-matched to TNFi or abatacept initiators. Database-specific HRs were combined by a meta-analysis. RESULTS: The primary cohort included 16 074 TCZ PS-matched to 33 109 TNFi initiators. The risk of composite SI was not different between TCZ and TNFi initiators (combined HR 1.05, 95% CI 0.95 to 1.16). However, TCZ was associated with an increased risk of serious bacterial infection (HR 1.19, 95% CI 1.07 to 1.33), skin and soft tissue infections (HR 2.38, 95% CI 1.47 to 3.86), and diverticulitis (HR 2.34, 95% CI 1.64 to 3.34) versus TNFi. An increased risk of composite SI, serious bacterial infection, diverticulitis, pneumonia/upper respiratory tract infection and septicaemia/bacteraemia was observed in TCZ versus abatacept users. CONCLUSIONS: This large multidatabase cohort study found no difference in composite SI risk in patients with RA initiating TCZ versus TNFi after failing ≥1 biologic drug or tofacitinib. However, the risk of serious bacterial infection, skin and soft tissue infections, and diverticulitis was higher in TCZ versus TNFi initiators. The risk of composite SI was higher in TCZ initiators versus abatacept.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Infecções Oportunistas/induzido quimicamente , Abatacepte/efeitos adversos , Abatacepte/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/epidemiologia , Infecções Bacterianas/induzido quimicamente , Infecções Bacterianas/epidemiologia , Produtos Biológicos/uso terapêutico , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Medição de Risco/métodos , Estados Unidos/epidemiologia , Viroses/induzido quimicamente , Viroses/epidemiologia
16.
Biol Blood Marrow Transplant ; 25(4): 673-682, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30610925

RESUMO

CTLA4Ig attenuates T cell activation by co-stimulation blockade, but natural killer (NK) cells are not only resistant to CTLA4Ig, they also may demonstrate better antileukemia effect in the presence of CTLA4Ig. To explore this phenomenon we used sequential CTLA4Ig primed donor lymphocyte infusion (DLI) after post-transplant cyclophosphamide-based haploidentical transplantation. Thirty patients (CTLA4Ig-DLI group) with advanced leukemia received CTLA4Ig on day -1 and subsequently on days +7, +21, and +35, followed 12hours later by DLI of 1 to 10 × 106 CD3+ T cells/kg containing .1 to 3.27 × 106/kg CD56+ NK cells, with low dose cyclosporine for 60days. The incidences of acute graft-versus-host disease (GVHD), chronic GVHD and nonrelapse mortality (NRM) were 6.7%, 21%, and 4.5 %, respectively, with disease progression of 23.3% and overall survival of 79% at 18 months. Patients without disease progression had a significant early surge in CD56dimCD16+NK cells with lower NKG2A expression. CTLA4Ig primed DLI was associated with an upregulation of CD86 in mature NK cells that was not witnessed with CTLA4Ig administration alone. Thus, CTLA4Ig primed DLI resulted in early proliferation of mature NK cells with cytotoxic potential enabling early institution of adoptive immunotherapy to mitigate the risk of relapse in advanced leukemia with reduced GVHD and NRM.


Assuntos
Abatacepte/uso terapêutico , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Leucemia/terapia , Transfusão de Linfócitos/métodos , Transplante Haploidêntico/métodos , Abatacepte/farmacologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Imunossupressores/farmacologia , Células Matadoras Naturais , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
J Med Econ ; 22(4): 350-358, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30653389

RESUMO

AIMS: To estimate real world healthcare costs and resource utilization of rheumatoid arthritis (RA) patients associated with targeted disease modifying anti-rheumatic drugs (tDMARD) switching in general and switching to abatacept specifically. MATERIALS AND METHODS: RA patients initiating a tDMARD were identified in IMS PharMetrics Plus health insurance claims data (2010-2016), and outcomes measured included monthly healthcare costs per patient (all-cause, RA-related) and resource utilization (inpatient stays, outpatient visits, emergency department [ED] visits). Generalized linear models were used to assess (i) average monthly costs per patient associated with tDMARD switching, and (ii) among switchers only, costs of switching to abatacept vs tumor necrosis factor inhibitors (TNFi) or other non-TNFi. Negative binomial regressions were used to determine incident rate ratios of resource utilization associated with switching to abatacept. RESULTS: Among 11,856 RA patients who initiated a tDMARD, 2,708 switched tDMARDs once and 814 switched twice (to a third tDMARD). Adjusted average monthly costs were higher among patients who switched to a second tDMARD vs non-switchers (all-cause: $4,785 vs $3,491, p < .001; RA-related: $3,364 vs $2,297, p < .001). Monthly RA-related costs were higher for patients switching to a third tDMARD compared to non-switchers remaining on their second tDMARD ($3,835 vs $3,383, p < .001). Switchers to abatacept had significantly lower RA-related monthly costs vs switchers to TNFi ($3,129 vs $3,436, p = .021), and numerically lower all-cause costs ($4,444 vs $4,741, p = 0.188). Switchers to TNFi relative to abatacept had more frequent inpatient stays after switch (incidence rate ratio (IRR) = 1.85, p = .031), and numerically higher ED visits (IRR = 1.32, p = .093). Outpatient visits were less frequent for TNFi switchers (IRR = 0.83, p < .001) compared to switchers to abatacept. LIMITATIONS AND CONCLUSIONS: Switching to another tDMARD was associated with higher healthcare costs. Switching to abatacept, however, was associated with lower RA-related costs, fewer inpatient stays, but more frequent outpatient visits compared to switching to a TNFi.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Abatacepte/economia , Abatacepte/uso terapêutico , Adulto , Fatores Etários , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/economia , Artrite Reumatoide/fisiopatologia , Custos e Análise de Custo , Vias de Administração de Medicamentos , Substituição de Medicamentos/economia , Feminino , Gastos em Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Econométricos , Estudos Retrospectivos , Fatores Sexuais , Fatores Socioeconômicos , Fator de Necrose Tumoral alfa/economia , Fator de Necrose Tumoral alfa/uso terapêutico
18.
Joint Bone Spine ; 86(2): 173-183, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29635017

RESUMO

OBJECTIVE: Obesity is a worldwide epidemic and a growing body of evidence suggests that it may affect the body's response to biologic agents. We investigated the influence of obesity on the efficacy of different biologic agents used to treat inflammatory diseases. METHODS: Medline, EMBASE and the Cochrane Database were searched using relevant MeSH and keyword terms for obesity and bDMARDs. Articles were selected if they reported a clinical response in obese subjects relative to other BMI categories. Response and remission outcomes were assessed using meta-analysis and all other reported outcomes were summarized. RESULTS: Among the 3850 records retrieved, 24 articles met the inclusion criteria, including 10 on rheumatoid arthritis (RA), 4 on axial spondyloarthritis (axSpA), 4 on Crohn's disease (CD), 4 on psoriasis (Ps) and 2 on psoriasic arthritis (PsA). Four biological disease-modifying anti-rheumatic drugs (bDMARDs) - anti-TNF agents, T cell co-stimulation inhibitor (abatacept), IL-6 inhibitor (tocilizumab), and B-cell depletion therapy (rituximab) - were involved. The meta-analysis showed that the odds to reach a good response or achieve remission were lower in obese (BMI>30kg/m2) than non-obese (BMI≤30kg/m2) patients who were treated with anti-TNF agents (good responder % in RA: OR 0.34, 95% CI 0.18-0.64; remission% in RA: OR 0.36, 95% CI 0.21-0.59; BASDAI50% in axSpA: OR 0.41, 95% CI 0.21-0.83), but no significant difference between obese and non-obese was found in patients treated with abatacept (good responder % in RA: OR 0.75, 95% CI 0.42-1.36; remission% in RA: OR 0.84, 95% CI 0.65-1.09) and tocilizumab (good responder % in RA: OR 1.08, 95% CI 0.44-2.63; remission% in RA: OR 0.91, 95% CI 0.50-1.66). CONCLUSION: Obesity hampered the effect of anti-TNF agents, but not those of abatacept and tocilizumab, suggesting that a personalized treatment strategy should be considered for obese patients with inflammatory diseases.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Inflamação/tratamento farmacológico , Obesidade/epidemiologia , Abatacepte/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Psoriásica/epidemiologia , Artrite Reumatoide/epidemiologia , Produtos Biológicos/farmacologia , Comorbidade , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , Humanos , Inflamação/epidemiologia , Masculino , Obesidade/diagnóstico , Prognóstico , Medição de Risco , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Resultado do Tratamento
19.
Mod Rheumatol ; 29(3): 413-417, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29798700

RESUMO

OBJECTIVE: To examine the deterioration of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with abatacept over the long-term. METHODS: We examined 131 patients with RA who had been treated with abatacept for more than 1 year. All patients underwent high-resolution computed tomographic (HRCT) scanning of the chest before administration of abatacept, and we examined deterioration of ILD over a follow-up period after administration of abatacept was initiated. RESULTS: Eleven patients (8.4%) showed deterioration of ILD over a mean follow-up period of 47.8 months. The factors related to ILD deterioration were use of methotrexate (MTX) [odds ratio 12.75, 95% confidence interval (CI) 1.09-148.77], and change in Krebs von-den Lungen-6 (odds ratio 1.00, 95% CI 1.00-1.01), according to multivariate logistic regression analysis. CONCLUSION: MTX in patients with RA treated with abatacept was a risk factor for deterioration of ILD. Discontinuation of MTX should be considered one of treatment reduction to prevent the deterioration of ILD.


Assuntos
Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Doenças Pulmonares Intersticiais/epidemiologia , Abatacepte/uso terapêutico , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Feminino , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
20.
Intern Med ; 58(1): 67-71, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30146566

RESUMO

Abatacept, a cytotoxic T lymphocyte antigen-4 immunoglobulin recombinant fusion protein, is an immunosuppressive agent indicated for rheumatoid arthritis. Although no significant increase in malignancy has been reported in abatacept-treated patients, whether or not abatacept accelerates tumor progression in specific cancer types remains unclear. We herein report a 66-year-old woman who showed unusually rapid progression of hepatocellular carcinoma following abatacept therapy for rheumatoid arthritis. Abatacept was speculated to have accelerated her hepatocellular carcinoma progression in the setting of her preexisting risk factors: autoimmune hepatitis and long-term methotrexate use. We propose close tumor surveillance be performed during abatacept therapy, especially for high-risk patients.


Assuntos
Abatacepte/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Imunossupressores/uso terapêutico , Neoplasias Hepáticas/patologia , Idoso , Antirreumáticos/uso terapêutico , Progressão da Doença , Feminino , Humanos , Metotrexato/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA