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1.
Reumatol Clin ; 2019 May 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31054806

RESUMO

In 2015 the Spanish Society of Rheumatology (Sociedad Española de Reumatología [SER]) published its position paper on biosimilar drugs. In this update, the SER, continues to manifest its unequivocal commitment to the sustainability of the health system of our country and is aligned with the measures that, without reducing quality of care, are aimed at ensuring its continuity. Since the publication of the previous position paper, the European Commission has authorized new biosimilar drugs, which provides an excellent opportunity to advance the efficiency of health care. In this new scenario of increased therapeutic offer of biologics, the SER considers it crucial to preserve the freedom of prescription of physicians who prescribe drugs based exclusively on the characteristics and individual circumstances of each patient, without forgetting the economic aspects there of.

2.
Expert Opin Ther Targets ; 23(7): 607-618, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074669

RESUMO

Introduction: The rising prevalence of musculoskeletal pathologies in developed countries has caused a dramatic impact on social welfare. Amidst these musculoskeletal pathologies is Rheumatoid arthritis (RA), a chronic systemic autoimmune disease that mostly affects the synovium. RA metabolic-associated alterations, including distorted adipokine production, enhance RA inflammatory environment. Among the altered adipokines, visfatin is particularly involved in RA inflammation and catabolism and stands out as an essential enzyme linked to critical cell features. Areas covered: We discuss the potential mechanism supporting the contribution of visfatin to RA and the association between RA and obesity. We discuss the repurposing of cancer-tested drugs to inhibit visfatin in the context of RA. Additionally, we address the possibility of combining these drugs with current RA therapy. Finally, we explore the future of visfatin as an RA biomarker or therapeutic target. Expert opinion: Inhibition of visfatin has become an interesting therapeutic approach for RA pathology. Such a feat has already been attained in oncology using small molecule inhibitors, which suggest that a similar course of action would be worth pursuing in the RA context. Visfatin will become an important biomarker and therapeutic target for RA.

3.
PLoS One ; 14(2): e0213073, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30818333

RESUMO

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Etanercepte/uso terapêutico , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Feminino , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos , Variantes Farmacogenômicos , Adulto Jovem
4.
Expert Rev Clin Immunol ; 15(4): 319-326, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30730220

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) is a complex disease in which different mechanisms are involved. Studies suggest a key role for aberrant pathways of T-cell activation in the initiation and perpetuation of disease. Abatacept is a fusion protein composed of the Fc region of the immunoglobulin G1 (IgG1) fused to the extracellular domain of cytotoxic T lymphocyte-associated antigen (CTLA4). It has the ability to modulate T-cell activation by interfering with co-stimulation of these cells, a necessary step to become activated. This suggests that abatacept may play a role in the progression and/or even the initiation of RA. Areas covered: a review of the different studies carried out during clinical development of abatacept was performed. Both formulations, intravenous (IV) and subcutaneous (SC), showed a similar and consistent efficacy and safety profile. Abatacept was effective both in RA patients not responding to methotrexate (MTX) and to tumor necrosis factor (TNF) inhibitors. Expert commentary: abatacept, with its unique mechanism of action, proved to be a useful therapeutic alternative in RA, also having an acceptable safety profile. Evidence points out that abatacept may be able to alter the RA disease course. Ongoing studies will clarify this issue.

5.
Rheumatol Int ; 39(3): 509-515, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30353269

RESUMO

The retention rate of a biological drug (percentage of patients remaining on treatment over time) provides an index of a drug's overall effectiveness. The golimumab retention rate as first-line biological therapy was high in clinical trial extensions lasting 5 years. Real-world studies also indicate good retention rates but have been of shorter duration. The probability of retention with golimumab treatment was assessed, as any line of anti-tumor necrosis factor-alpha therapy, for up to 5 years in patients with rheumatoid arthritis (RA), axial spondyloarthritis (SpA) or psoriatic arthritis (PsA), associated factors were analyzed. A retrospective database analysis of the Spanish registry of patients with rheumatic disorders receiving biological drugs (BIOBADASER) was performed. Among 353 patients, 29.8% had RA, 41.6% SpA and 28.6% PsA. Golimumab was the first biological drug in 40.1% of patients, second in 30.1% and third/later in 29.8%. The overall probability of retention of golimumab at years 1, 2, 3, 4 and 5 was 85.9% (95% confidence interval 81.4-89.5%), 73.7% (67.1-79.1%), 68.5% (60.5-75.1%), 60.6% (50.2-69.5%) and 57.1% (44.9-67.5%), respectively. Retention was similar across indications (p = 0.070) but was greater when golimumab was used as the first biological agent compared with later therapy lines (p < 0.001). Factors associated with higher retention of golimumab treatment (Cox regression) were use as a first-line biological and concomitant methotrexate treatment; corticosteroid need was associated with lower retention. The long-term probability of golimumab retention was high in this real-world study of patients with rheumatic diseases, especially when used as the first biological drug.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Espondiloartropatias/tratamento farmacológico , /uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Espanha
6.
Arthritis Rheumatol ; 71(3): 331-339, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30277011

RESUMO

OBJECTIVE: Recognition of a new type of rheumatoid arthritis (RA)-specific autoantibody, the anti-carbamylated protein antibodies (anti-CarP), has provided an opportunity to improve the management and understanding of RA. The current study was undertaken to assess the relationship between anti-CarP antibodies and HLA-DRB1 alleles in RA. METHODS: Serum samples were obtained from 3 different collections, comprising a total of 1,126 RA patients. Serum reactivity against in vitro carbamylated fetal calf serum proteins was determined by enzyme-linked immunosorbent assay. HLA-DRB1 alleles were determined using either hybridization techniques or imputation from HLA-dense genotypes. Results of these analyses were combined in a meta-analysis with data from 3 previously reported cohorts. The carrier frequencies of the common HLA-DRB1 alleles were compared between the antibody-positive RA subgroups and the double-negative subgroup of RA patients stratified by anti-citrullinated protein antibody (ACPA)/anti-CarP antibody status, and also between the 4 RA patient strata and healthy controls. RESULTS: Meta-analysis was conducted with 3,709 RA patients and 2,305 healthy control subjects. Results revealed a significant increase in frequency of HLA-DRB1*03 carriers in the ACPA-/anti-CarP+ subgroup as compared to ACPA-/anti-CarP- RA patients and healthy controls; this was consistently found across the 6 sample collections. This association of HLA-DRB1*03 with ACPA-/anti-CarP+ RA was independent of the presence of the shared allele (SE) and any other confounders analyzed. No other allele was specifically associated with the ACPA-/anti-CarP+ RA patient subgroup. In contrast, frequency of the SE was significantly increased in the ACPA+/anti-CarP- and ACPA+/anti-CarP+ RA patient subgroups, without a significant distinction between them. Furthermore, some alleles (including HLA-DRB1*03) were associated with protection from ACPA+ RA. CONCLUSION: These findings indicate a specific association of HLA-DRB1*03 with ACPA-/anti-CarP+ RA, suggesting that preferential presentation of carbamylated peptides could be a new mechanism underlying the contribution of HLA alleles to RA susceptibility.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Cadeias HLA-DRB1/imunologia , Carbamilação de Proteínas/imunologia , Adulto , Alelos , Anticorpos Anti-Proteína Citrulinada/sangue , Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/sangue , Autoanticorpos/sangue , Feminino , Genótipo , Cadeias HLA-DRB1/sangue , Humanos , Masculino , Pessoa de Meia-Idade
7.
Am J Ophthalmol ; 195: 181-190, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30081019

RESUMO

OBJECTIVE: To demonstrate the efficacy of the anti-interleukin-6 receptor monoclonal antibody tocilizumab in patients with moderate-to-severe corticosteroid-resistant Graves orbitopathy (GO). DESIGN: Double-masked randomized clinical trial. METHODS: Setting and Participants: Thirty-two adults with moderate-to-severe corticosteroid-resistant GO from 10 medical centers in Spain were randomized (1:1). INTERVENTION: Randomization to either 8 mg/kg body weight tocilizumab or placebo administered intravenously at weeks 0, 4, 8, and 12, and follow-up for an additional 28 weeks. Main Outcomes and Measures: The primary outcome was the proportion of patients with a change from baseline to week 16 of at least 2 in the clinical activity score (CAS). RESULTS: The primary outcome was met by 93.3% (95% confidence interval [CI] 70.1%-98.8%) of the patients receiving tocilizumab and 58.8% (36%-78.3%) receiving placebo (P = .04; odds ratio, 9.8 [CI 1.3-73.2]). A significant difference was also observed in the proportion of patients achieving a CAS < 3 (86.7% [CI 62.1%-96.2%] vs 35.2% [CI 17.3%-58.7%], P = .005; OR 11.9 [CI 2.1-63.1]) at week 16. Additionally, a larger proportion of patients with improvement in the European Group on GO-proposed composite ophthalmic score at week 16 (73.3% [CI 48%-89.1%] vs 29.4% [CI 13.2%-53.1%]; P = .03), and exophthalmos size change from baseline to week 16 (-1.5 [-2.0 to 0.5] mm vs 0.0 [-1.0 to 0.5] mm; P = .01) were seen with tocilizumab. One patient experienced a moderate increase in transaminases at week 8; another had an acute pyelonephritis at week 32 in the tocilizumab-treated group. CONCLUSION: Tocilizumab offers a meaningful improvement in activity and severity in corticosteroid-resistant GO. This trial justifies further studies to characterize the role of tocilizumab in GO.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Metilprednisolona/uso terapêutico , Adulto , Método Duplo-Cego , Resistência a Medicamentos , Feminino , Oftalmopatia de Graves/fisiopatologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-6/imunologia , Resultado do Tratamento
8.
RMD Open ; 4(1): e000669, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018799

RESUMO

Objective: The Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) clinical trial programme findings demonstrated that apremilast, an oral phosphodiesterase 4 inhibitor, is effective for treating psoriatic arthritis (PsA). Enthesitis and dactylitis are difficult-to-treat features of PsA leading to disability and affecting quality of life. PALACE 1, 2 and 3 data were pooled to assess the efficacy of apremilast on enthesitis and dactylitis outcomes in patients with these conditions at baseline. Methods: Patients with enthesitis (n=945) or dactylitis (n=633) at baseline were analysed after receiving double-blind treatment with placebo, apremilast 30 mg two times per day or apremilast 20 mg two times per day up to 52 weeks and continuing up to 5 years. Data were analysed through 156 weeks. Enthesitis was evaluated by Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and dactylitis via dactylitis count. Results: At week 24, patients receiving apremilast 30 mg two times per day demonstrated a significantly greater mean change in enthesitis (-1.3 vs -0.9; p<0.05) and dactylitis (-1.8 vs -1.3; p<0.01) vs placebo. Patients in the 30 mg dose group showed significantly greater mean (-23.6% vs -7.0%; p<0.05) and median (-50.0% vs -21.1%; p<0.05) per cent changes in MASES; mean and median per cent changes in dactylitis count were numerically, but not significantly, different for either apremilast dose in patients with dactylitis. In the patient population remaining on apremilast, observed mean and median improvements in both conditions were sustained through 156 weeks. Conclusion: Apremilast is effective for the treatment of active PsA, including improvements in enthesitis and dactylitis up to 3 years. Trial registration numbers: NCT01172938, NCT01212757 and NCT01212770.

9.
Sci Rep ; 8(1): 7342, 2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743634

RESUMO

About 70 genetic studies have already addressed the need of biomarkers to predict the response of patients with rheumatoid arthritis (RA) to methotrexate (MTX) treatment. However, no genetic biomarker has yet been sufficiently validated. Here, we aimed to replicate a selection of 25 SNPs in the largest collection of patients up to date, which consisted of 915 patients treated with MTX. The change in disease activity (measured as ΔDAS28) from baseline was considered the primary outcome. In addition, response according to widely used criteria (EULAR) was taken as secondary outcome. We considered consistency between outcomes, P values accounting for the number of SNPs, and independence from potential confounders for interpretation of the results. Only the rs1801394 SNP in MTRR fulfilled the high association standards. Its minor allele was associated with less improvement than the major allele according to ΔDAS28 (p = 0.0016), and EULAR response (p = 0.004), with independence of sex, age, baseline DAS28, smoking, seropositivity, concomitant corticosteroid use or previous treatments. In addition, previous evidence suggests the association of this SNP with response to MTX in another autoimmune disease, juvenile idiopathic arthritis, and with high intracellular folate levels, which could contribute to poor response.


Assuntos
Artrite Reumatoide/genética , Metotrexato/uso terapêutico , Adulto , Idoso , Alelos , Antirreumáticos/uso terapêutico , Biomarcadores Farmacológicos/sangue , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Ferredoxina-NADP Redutase/genética , Ferredoxina-NADP Redutase/fisiologia , Frequência do Gene/genética , Humanos , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Índice de Gravidade de Doença , Resultado do Tratamento
10.
PLoS One ; 13(5): e0196793, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734345

RESUMO

Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Marcadores Genéticos/genética , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
11.
RMD Open ; 4(1): e000615, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29593881

RESUMO

Background: Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Methods: Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy ≥3 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 ≤3.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Results: Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. Conclusion: RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients.

12.
Rheumatol Int ; 38(5): 933, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29594329

RESUMO

In the original published article, the family name was incorrectly tagged for two co-authors. The correct family names of authors José Ramón Maneiro Fernández is Maneiro Fernández and Alejandro Souto Vilas is Souto Vilas.

13.
Ann Rheum Dis ; 77(5): 690-698, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29343507

RESUMO

OBJECTIVE: Evaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA. METHODS: Patients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52. RESULTS: Among 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast's safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0-24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo). CONCLUSIONS: In biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports. TRIAL REGISTRATION NUMBER: NCT01925768; Results.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Artrite Psoriásica/sangue , Artrite Psoriásica/fisiopatologia , Proteína C-Reativa/análise , Avaliação da Deficiência , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Talidomida/administração & dosagem , Resultado do Tratamento
14.
Rheumatol Int ; 38(3): 467-472, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29356882

RESUMO

To perform a transcultural adaptation and validation of a Spanish version of the compliance questionnaire in rheumatology (sCQR). In this transversal study of transcultural adaptation of the sCQR, validity was evaluated in patients with rheumatoid arthritis (RA) and a minimum 6-month follow-up by determining compliance with the electronic prescription system in consuming steroids or nonbiologic disease-modifying antirheumatic drugs. A two-week retest was proposed to all patients. All patients completed the health assessment questionnaire (HAQ), and the Morisky-Green test was also performed. Reliability was analyzed using Cronbach's alpha and the intraclass correlation coefficient (ICC). Convergent construct validity was tested in the electronic prescription system using discriminative analysis, and divergent construct validity was tested by comparing it to the HAQ. Sensitivity, specificity and ROC curves were evaluated for the sCQR and the Morisky-Green test. Of 123 recruited patients, 101 fulfilled the inclusion criteria, and 61 were on biologic therapy. 23 performed the retest. Test-retest reliability (ICC) was 0.76 (Cronbach's alpha 0.86). Multiple regression analysis showed correlation with each item of the sCQR as independent variables (r2 = 0.60). No correlation was seen between total score punctuation of the sCQR and the HAQ (r2 = 0.22). Discriminative analysis weighting each sCQR item showed a cutoff point of - 0.9991 (sensibility and 58.8%, specificity 98.3%). The likelihood ratio of the sCQR to detect ≤ 80% adherence with electronic prescriptions was 35.3. The Morisky-Green test revealed sensibility and specificity were 29.4 and 83.3%, respectively. This study validates the transcultural adaptation of sCQR in RA patients. A high reliability of sCQR for measuring adherence was found. Its predictive value suggests that it could be used as a screening instrument.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Características Culturais , Adesão à Medicação , Reumatologia/métodos , Esteroides/uso terapêutico , Inquéritos e Questionários , Tradução , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/psicologia , Análise Discriminante , Prescrição Eletrônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Espanha , Fatores de Tempo
15.
PLoS One ; 12(7): e0180144, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28672020

RESUMO

Patients with rheumatoid arthritis (RA) have an increased mortality rate that is associated with the presence of RA-specific autoantibodies in many studies. However, the relative role of rheumatoid factor (RF), anti-CCP antibodies and the most recently established RA-autoantibodies, directed against carbamylated proteins (anti-CarP antibodies), is unclear. Here, we have assessed the role of these three antibodies in 331 patients with established RA recruited from 2001 to 2009 and followed until November 2015. During this time, 124 patients died (37.5%). This death rate corresponds to a mortality rate 1.53 (95% CI 1.26 to 1.80) folds the observed in the reference population. We used for analysis of all-cause mortality the Cox proportional hazard regression model with adjustment for age, sex and smoking. It showed a trend for association with increased mortality of each of the three RA autoantibodies in antibody-specific analysis (hazards ratio (HR) from 1.37 to 1.79), but only the HR of the anti-CarP antibodies was significant (HR = 1.79, 95% CI 1.23 to 2.61, p = 0.002). In addition, the multivariate analysis that included all autoantibodies showed a marked decrease in the HR of RF and of anti-CCP antibodies, whereas the HR of anti-CarP remained significant. This increase was specific of respiratory system causes of death (HR = 3.19, 95% CI 1.52 to 6.69, p = 0.002). Therefore, our results suggest a specific relation of anti-CarP antibodies with the increased mortality in RA, and drive attention to their possible connection with respiratory diseases.


Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Adulto , Idoso , Artrite Reumatoide/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha
16.
Semin Arthritis Rheum ; 47(2): 149-156, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28284845

RESUMO

OBJECTIVE: To summarize and compare the risks of malignancies accompanying biologic DMARDs (b-DMARDs) and tofacitinib in rheumatoid arthritis (RA) in randomized clinical trials (RCTs) and long-term extension studies (LTEs). METHODS: Articles in Medline, Embase, Cochrane Library, and the Web of Science dated from 2000 to February 2015. Selection criteria were as follows: (1) focus on RCTs or LTEs in RA; (2) treatment with b-DMARDs or tofacitinib; (3) data on malignancies; and (4) a minimum follow-up of 12 weeks. Data included publication details, study design, risk of bias, number and types of malignancies, and patient characteristics and treatments. DATA SYNTHESIS: Of 113 articles and one updated report that were meta-analyzed, overall malignancies in RCTs showed odds ratio (95% confidence intervals) of 1.01 (0.72, 1.42) for all TNF antagonists, 1.12 (0.33, 3.81) for abatacept, 0.54 (0.20, 1.50) for rituximab, 0.70 (0.20, 2.41) for tocilizumab, and 2.39 (0.50, 11.5) for tofacitinib. Network meta-analysis of overall malignancies showed odds ratio (95% predictive intervals) of 1.68 (0.48-5.92) for infliximab, 0.79 (0.44-1.40) for etanercept, 0.93 (0.43-2.03) for adalimumab, 0.87 (0.28-2.75) for certolizumab, 0.87 (0.39-1.95) for golimumab, 1.04 (0.32-3.32) for abatacept, 0.58 (0.21-1.56) for rituximab, 0.60 (0.16-2.28) for tocilizumab, and 1.15 (0.24-5.47) for tofacitinib. Marginal numerical differences in the incidence rate of solid and hematological malignancies and non-melanoma skin cancers appeared in LTEs. CONCLUSIONS: In RCTs, treatment of RA with b-DMARDs or tofacitinib does not increase the risk for malignancies. Generalizability of the differences in the rate of specific malignancies encountered in LTEs requires continuous pharmacovigilance of real-world patients.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Neoplasias/induzido quimicamente , Piperidinas/efeitos adversos , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Meta-Análise em Rede , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Risco
17.
Nat Rev Rheumatol ; 13(2): 100-109, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28053336

RESUMO

Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes. Research on the regulation of different adipose tissues has provided important insights into the intricate network that links nutrition, metabolism and immune homeostasis. The neuroendocrine and immune systems communicate bi-directionally through common ligands and receptors during stress responses and inflammation, and control cellular immune responses in several pathological situations including immune-inflammatory rheumatic diseases. This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis.


Assuntos
Doenças do Sistema Imunitário/metabolismo , Inflamação/metabolismo , Leptina/fisiologia , Imunidade Adaptativa/fisiologia , Animais , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Humanos , Doenças do Sistema Imunitário/fisiopatologia , Imunidade Inata/fisiologia , Inflamação/fisiopatologia , Células Matadoras Naturais/fisiologia , Neutrófilos/fisiologia , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Receptores para Leptina/fisiologia
18.
Clin Rheumatol ; 36(5): 1167-1172, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28108800

RESUMO

The objective of the study was to analyze the impact of TNF antagonists (TNFa) on the total cholesterol and triglycerides on ankylosing spondylitis (AS) and psoriatic arthritis (PsA). In this single-centre observational study of AS and PsA patients, differences in triglyceride and total cholesterol levels and frequency of hypertriglyceridemia and hypercholesterolemia at 3 and 6 months were analysed in patients treated and not treated with TNFa. General estimation equations and linear regression analysis were used to investigate associations between disease activity and lipid levels and to identify predictors of change. One hundred fifty-seven patients treated, and 157 not treated with TNFa, were included in the study. A transient increase in cholesterol level from baseline to 3 months in TNFa-treated patients was the only statistically significant effect (P < 0.001). Persistent percentages of hypertriglyceridemia and hypercholesterolemia from baseline were significantly higher in not treated than in TNFa-treated patients (P = 0.009 and P = 0.001, respectively). Inverse associations between changes in cholesterol level and Bath Ankylosing Spondylitis Disease Activity Index (P = 0.011) and CRP (P < 0.001), but not Disease Activity Score in 28 Joints (P = 0.095) were found in the whole group. In AS and PsA patients treated with TNFa, mild and transient changes in cholesterol but not in triglyceride levels were associated with changes in disease activity.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Colesterol/sangue , Etanercepte/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/uso terapêutico , Artrite Psoriásica/sangue , Artrite Psoriásica/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Espanha/epidemiologia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/epidemiologia , Resultado do Tratamento , Triglicerídeos/sangue
19.
J Orthop Res ; 35(6): 1299-1303, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27472907

RESUMO

Osteoarthritis (OA) is a chronic systemic musculoskeletal disorder involving inflammation, immunity, and metabolic alterations. OA is commonly regarded as non-inflammatory disease; still inflammation is recognized as contributing to the symptoms and progression of OA. New evidence suggests that adipokines are involved in the pathophysiology of OA and might modulate the production of inflammatory mediators including in immune cells. However, the role of immune component in osteoarthritis is still poorly investigated. To gain further insights into the interaction of immune cells in OA and the role of adipokines on these cells, we performed experiments aimed to determine the cytokine profile in activated CD4+ T cells from OA patients. For completeness, we also explored the cross talk between T lymphocytes and chondrocytes in OA by co-culturing human primary chondrocytes with activated CD4+ T cells in two ways: the first by incubating the cells by direct contact (D.C.) or by transwell system. Our results show that the exposure of activated CD4+ T cells to adipokines modulates IL-6, IL-8, and CCL-3 production. In addition, the production of key macromolecules of ECM (aggrecan and collagen-2) and matrix metalloproteinase 13 (MMP-13) in co-cultured chondrocytes with activated CD4+ T cells was altered. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1299-1303, 2017.


Assuntos
Adiponectina/fisiologia , Linfócitos T CD4-Positivos/metabolismo , Leptina/fisiologia , Lipocalina-2/fisiologia , Osteoartrite/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Condrócitos/metabolismo , Técnicas de Cocultura , Humanos , Cultura Primária de Células
20.
J Rheumatol ; 44(2): 142-146, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27909081

RESUMO

OBJECTIVE: To report on the 5-year efficacy and safety results of the AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) monotherapy study (ClinicalTrials.gov: NCT00109408, NCT00720798). METHODS: Patients with rheumatoid arthritis for whom biologics had not failed or who did not discontinue methotrexate because of lack of efficacy or tolerability were followed up for 5 years to assess the efficacy and serious adverse events (SAE) of tocilizumab (TCZ) monotherapy. RESULTS: Longterm efficacy results showed that efficacy was maintained or improved for up to 264 weeks in patients receiving TCZ monotherapy. Serious infection was the most frequent SAE; no new safety signals were reported. CONCLUSION: Longterm monotherapy with TCZ demonstrated continuing efficacy and safety.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Método Duplo-Cego , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
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