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1.
Clin Exp Rheumatol ; 38(1): 122-128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31498068

RESUMO

OBJECTIVES: To study circulating MFAP4 in rheumatoid arthritis (RA) and its associations with clinical phenotype. METHODS: Early RA (ERA): 47 patients with newly diagnosed, treatment naïve RA were included. Serum MFAP4, clinical and laboratory disease variables were recorded serially during 12 months of intensive synovitis suppressive treatment. Long-standing RA (LRA): 317 patients participated, all receiving DMARD treatment. Disease activity, autoantibody status, extra-articular manifestations and cardiovascular morbidity were recorded. Paired serum and synovial fluid samples were obtained from 13 untreated ERA patients. Healthy blood donors served as reference points. MFAP4 was quantified by AlphaLISA immunoassay. Univariate, multivariate and mixed effects regression models were applied in the statistical analysis. RESULTS: ERA: MFAP4 increased from baseline and was significantly elevated at the 12-month follow-up, 17.8 U/l [12.6;24.1] vs. healthy controls, 12.7 U/l [9.5;15.6], p<0.001. MFAP4 did not correlate with joint counts or C-reactive protein. LRA: MFAP4 was increased, 25.9 U/l [20.4;33.7] vs. healthy controls, 17.6 U/l [13.7;21.2], p<0.0001, but did not correlate with disease activity measures or presence of extra-articular manifestations. Notably, MFAP4 correlated inversely with smoking (p<0.0001) and presence of antibodies against cyclic citrullinated peptides (anti-CCP), p=0.005. There was a positive association with systolic blood pressure, p=0.001 and co-occurrence of three cardiovascular events and/or risk factors, p<0.0001. The serum:synovial fluid MFAP4 ratio was 2:1. CONCLUSIONS: MFAP4 increases from diagnostic baseline despite intensive treatment but does not associate with synovitis at early or late stages of RA. Correlation patterns indicate that increased MFAP4 may reflect enhanced RA-related vascular remodelling.


Assuntos
Artrite Reumatoide/sangue , Proteínas de Transporte/sangue , Proteínas da Matriz Extracelular/sangue , Glicoproteínas/sangue , Sinovite/sangue , Artrite Reumatoide/patologia , Autoanticorpos , Comorbidade , Humanos , Peptídeos Cíclicos/imunologia , Líquido Sinovial , Sinovite/patologia
2.
Ann Rheum Dis ; 76(10): 1707-1715, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28611080

RESUMO

OBJECTIVES: To examine whether MRI assessed inflammation and damage in the wrist of patients with early rheumatoid arthritis (RA) are associated with patient-reported outcomes (PROs). METHODS: Wrist and hand MRIs of 210 patients with early RA from two investigator-initiated, randomised controlled studies (CIMESTRA/OPERA) were assessed according to the Outcome Measures in Rheumatology RA MRI score (RAMRIS) for synovitis, tenosynovitis, osteitis, bone erosions and joint space narrowing (JSN) at baseline, 1 and 5 years follow-up. These features, and changes therein, were assessed for associations with health assessment questionnaires (HAQ), patient global visual analogue scales (VAS-PtGlobal) and VAS-pain using Spearman's correlations, generalised estimating equations and univariate/multivariable linear regression analyses. MRI features were further tested for trends against specific hand-related HAQ items using Jonckheere trend tests. RESULTS: MRI inflammation, but not damage, showed statistically significant associations with HAQ, VAS-PtGlobal and VAS-pain for status and change scores, independently of C reactive protein and swollen joint count. MRI-assessed synovitis was most consistently associated with PROs, particularly VAS-PtGlobal and VAS-pain. MRI-assessed synovitis and tenosynovitis mean scores were positively associated with patient-reported difficulty to cut meat and open a milk carton (p<0.01), and similar patterns were seen for other hand-related HAQ items. Incorporating metacarpophalangeal joints in the analyses did not strengthen the associations between MRI pathology and PROs. CONCLUSIONS: MRI-assessed inflammation, but not damage, in early RA wrists is associated with patient-reported physical impairment, global assessment of disease activity and pain and influences the physical function in the hand. TRIAL REGISTRATION NUMBER: NCT00660647.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Imageamento por Ressonância Magnética , Articulação do Punho/diagnóstico por imagem , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/metabolismo , Método Duplo-Cego , Feminino , Inquéritos Epidemiológicos , Humanos , Inflamação/sangue , Estudos Longitudinais , Masculino , Articulação Metacarpofalângica/diagnóstico por imagem , Pessoa de Meia-Idade , Dor Musculoesquelética/diagnóstico por imagem , Osteíte/sangue , Osteíte/diagnóstico por imagem , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Radiografia , Índice de Gravidade de Doença , Sinovite/sangue , Sinovite/diagnóstico por imagem , Tenossinovite/sangue , Tenossinovite/diagnóstico por imagem
4.
Rheumatology (Oxford) ; 54(12): 2156-65, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26175471

RESUMO

OBJECTIVES: To estimate the prevalence of Danish RA patients currently on biologic monotherapy and compare the effectiveness and drug adherence of biologic therapies applied as monotherapy. METHODS: All RA patients registered in the Danish biologics database (DANBIO) as receiving biologic DMARD (bDMARD) treatment as monotherapy without concomitant conventional synthetic DMARDs (csDMARDs) during the study period 1 May, 2011 through 30 April 2013 were eligible for inclusion. All patient files were checked to ensure that they were in accordance with the treatment registration in DANBIO. Descriptive statistics for prevalence, effectiveness and drug adherence of bDMARD monotherapy were calculated. RESULTS: Of the 775 patients on bDMARD monotherapy, adalimumab (21.3%), etanercept (36.6%) and tocilizumab (15.3%) were the most prevalent biologic agents administered. At the 6-month follow-up, the overall crude clinical disease activity index remission rate in patients still on a biologic drug was 22%, the 28-joint DAS remission rate was 41% and the response rate of those with a 50% improvement in ACR criteria was 28%. At the 6-month follow-up, the drug adherence rates were similar for the different bDMARDs, with the exception of infliximab, which had significantly poorer drug adherence (P < 0.001). The overall drug adherence (except for infliximab) was approximately 70% after 2 years. CONCLUSION: Nearly one in five (19%) biologic treatments for RA was prescribed in Denmark as monotherapy, of which 70% were on monotherapy from bio-initiation and 30% were on monotherapy after cessation of a concomitant csDMARD. Acceptable drug adherence and remission rates were achieved with bDMARDs. With the exception of infliximab, no statistically significant differences were observed between anti-TNFs and biologics with other modes of action.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Adalimumab/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/epidemiologia , Dinamarca/epidemiologia , Etanercepte/uso terapêutico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Rheumatology (Oxford) ; 53(11): 2100-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24939677

RESUMO

OBJECTIVE: The aim of this study was to describe dose regimens, dose escalation and clinical outcomes in TNF-α inhibitor (TNFi)-naive patients with PsA treated with infliximab in routine rheumatology care. METHODS: We conducted an observational cohort study based on the nationwide Danish Rheumatologic Database (DANBIO) and Center for Rheumatology Research (ICEBIO) registries. Stratified by country, characteristics of patients treated with ≤3 mg infliximab/kg body weight, 3-5 mg/kg or ≥5 mg/kg every 8 weeks were described. Outcomes were evaluated by ACR 20%, 50% and 70% (ACR20/50/70) responses and European League Against Rheumatism good response after 6 months, disease activity after 12 months, Kaplan-Meier plots and regression analyses. RESULTS: Four hundred and sixty-two patients (376 Danish, 86 Icelandic) received treatment with infliximab. In Danish patients, the starting dose was ≤3 mg/kg in 110 patients (29%), 3-5 mg/kg in 157 (42%), ≥5 mg/kg in 38 (10%) and unregistered in 71 (19%). In Icelandic patients, corresponding numbers were 64 (74%), 17 (27%), 0 (0%) and 5 (6%). Patients with a higher body weight received lower doses per kilogram. Danish patients received higher doses than Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P < 0.05] and after 12 months [3.3 (3.0-4.5) vs 2.9 (2.2-3.5) mg/kg, P < 0.0001]. After 12 months, 58% of Danish and 66% of Icelandic patients maintained treatment. Danish patients had shorter drug survival than Icelandic patients (1183 vs 483 days). In univariate analyses stratified by country, time until dose escalation, response rates, drug survival and 1-year's disease activity were independent of starting dose. Drug survival was shorter among patients not receiving concomitant MTX. CONCLUSION: In clinical practice, > 70% of Icelandic and Danish PsA patients treated with infliximab received sustained doses below the 5 mg/kg every 8 weeks recommended in international guidelines. Lower starting doses did not affect drug survival or response.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Sistema de Registros , Adulto , Antirreumáticos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Infliximab , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
Arthritis Rheum ; 65(5): 1213-23, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23460467

RESUMO

OBJECTIVE: To describe the frequency of treatment switching and outcomes among patients with psoriatic arthritis (PsA) who switched tumor necrosis factor α inhibitor (TNFi) agents in routine care. METHODS: We conducted an observational cohort study based on the Danish nationwide DANBIO registry. Treatment outcomes were evaluated using the American College of Rheumatology criteria for 20% improvement (ACR20)/ACR50/ACR70, European League Against Rheumatism (EULAR) response criteria for good response, and the 28-joint count Disease Activity Score (DAS28) (remission). Kaplan-Meier and regression analyses were used for drug survival analyses and to identify predictors of outcome after treatment switching. RESULTS: Of 1,422 patients starting TNFi agents, 548 patients (39%) switched to a second biologic drug during up to 10 years of followup. Median followup was 2.3 years (interquartile range [IQR] 1.0-4.3 years). Switchers were more frequently women (56% versus 45%), had a shorter disease duration (3 versus 4 years), a higher median Health Assessment Questionnaire (HAQ) score (1.1 [IQR 0.6-1.6] versus 0.9 [IQR 0.5-1.4]), DAS28 (4.8 [4.0-5.7] versus 4.4 [3.6-5.2]), pain score on a visual analog scale (VAS) (65 mm [46-77] versus 62 mm [40-75]), and fatigue score on a VAS (69 mm [50-83] versus 64 mm [42-80] mm) (all P < 0.05 at start of first TNFi). During the first and second treatment, HAQ, DAS28, and VAS scores and C-reactive protein levels had decreased after 6 months (all P < 0.05), and median drug survival was 2.2 versus 1.3 years (P < 0.001). Lower fatigue score increased survival of the second TNFi. After switching, the proportions of patients achieving a sustained ACR20, ACR50, ACR70, EULAR good response, and DAS28 remission after 3-6 months were 22% (number needed to treat [NNT] 4.5), 13% (NNT 7.9), 5% (NNT 20), 19% (NNT 5.3), and 34% (NNT 2.9), respectively. Response rates were lower during the second treatment (all P < 0.01 versus first TNFi). At the 2-year visit, 47% of switchers had achieved an ACR20 response. No differences between drug-drug combinations were found. CONCLUSION: Thirty-nine percent of the patients with PsA switched TNFi agents. Response rates and drug survival were lower after switching; however, half of the switchers had an ACR20 response 2 years after starting the first TNFi.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Artrite Psoriásica/fisiopatologia , Estudos de Coortes , Dinamarca , Substituição de Medicamentos , Feminino , Nível de Saúde , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Sistema de Registros , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento
7.
Ann Rheum Dis ; 72(7): 1149-55, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22941767

RESUMO

OBJECTIVE: To investigate frequencies and reasons for switching, treatment responses and drug survival in patients with ankylosing spondylitis (AS) switching tumour-necrosis-factor-α inhibitor (TNFi) treatment in routine clinical care. METHODS: AS patients were identified in the Danish nationwide DANBIO registry. Disease activity, treatment responses (50% or 20 mm reduction in Bath AS Disease Activity Index (BASDAI)), duration and rates of drug survival and predictors thereof were studied in patients receiving ≥2 different biological drugs. RESULTS: Of 1436 AS patients starting TNFi treatment, 432 patients (30%) switched to a second and 137 (10%) to a third biological drug. Compared with non-switchers, switchers were more frequently women (33%/22%), had shorter disease duration (3 years/5 years) and higher BASDAI (62(52-76) mm/56(43-69) mm (median(interquartile-range))), Bath AS Functional Index (BASFI) (54(39-71) mm/47(31-65) mm) and visual-analogue-scale (VAS) global, pain and fatigue scores when they started the first TNFi (all p<0.01). Main reason for switching was lack of response (56%). During the first, second and third treatment BAS- and VAS scores had decreased after 6 months' treatment (all p<0.05). Median drug survivals were 3.1, 1.6 and 1.8 years respectively (p<0.001). After 2 years of treatment 52% of switchers and 63% of non-switchers had achieved response (number needed to treat 1.9 and 1.6, respectively, p=0.01). Drug survivals were similar regardless of the reason for switching. Male gender and low BASFI predicted drug survival of the second TNFi. CONCLUSIONS: Nearly one-third of AS patients in clinical practice switched biological treatment. Response rates and drug survivals were lower among switchers, however, half of switchers achieved treatment response.


Assuntos
Antirreumáticos/uso terapêutico , Substituição de Medicamentos/estatística & dados numéricos , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Dinamarca , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Medição da Dor , Receptores do Fator de Necrose Tumoral/uso terapêutico , Sistema de Registros , Resultado do Tratamento
8.
Clin Rheumatol ; 42(12): 3275-3281, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37553551

RESUMO

The objective of this pilot study was to assess the impact of a salivary gland ultrasound (SGUS) atlas for scoring parenchymal changes in Sjögren's syndrome by assessing the reliability of the scoring system (0-3), without and with the use of the SGUS atlas. Ten participants with varying experience in SGUS contributed to the reliability exercise. Thirty SGUS images of the submandibular and parotid gland with abnormalities ranging from 0 to 3 were scored using the written definitions of the OMERACT SGUS scoring system and using the SGUS atlas based on the OMERACT scoring system. For intra-reader reliability, two rounds were performed without and with the atlas-in the 2nd round the 30 images were rearranged in random order by a physician not included in the scoring. Inter-reader reliability was also determined in both rounds. Without using the atlas, the SGUS OMERACT scoring system showed fair inter-reader reliability in round 1 (mean kappa 0.36; range 0.06-0.69) and moderate intra-reader reliability (mean kappa 0.55; range 0.28-0.81). With the atlas, inter-reader reliability improved in round 1 to moderate (mean kappa 0.52; range 0.31-0.77) and intra-reader reliability to good (mean kappa 0.69; range 0.46-0.86). Higher intra-reader reliability was noted in participants with previous SGUS experience. The SGUS atlas increased both intra- and inter-reader reliability for scoring gland pathology in participants with varying SGUS experience suggesting a possible future role in clinical practice and trials. Key Points • Ultrasonography can detect parenchymal changes in salivary glands in patients with Sjögren's disease. • An ultrasound atlas may improve reliability of scoring parenchymal changes in salivary glands.


Assuntos
Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico por imagem , Projetos Piloto , Reprodutibilidade dos Testes , Glândulas Salivares/diagnóstico por imagem , Ultrassonografia/métodos
9.
PLoS One ; 17(12): e0265057, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36508457

RESUMO

OBJECTIVES: To investigate whether ultrasound findings of major salivary glands are correlated with serological markers, autoantibodies, patient- or doctor-reported disease activity in a Danish cohort of patients with primary Sjögren's Syndrome (pSS). METHODS: In all, 49 patients at Odense University Hospital with pSS diagnosed according to the 2002 American-European Consensus Group (AECG) classification criteria were included. Patients were characterized using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI, score of systemic complications) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), serologic markers, Schirmer's test and salivary test. Salivary gland ultrasound (SGUS) was performed of the submandibular and parotid glands and scored according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) semi-quantitative scoring system. RESULTS: More patients with abnormal SGUS had antinuclear antibodies (ANA) (p = 0.002), anti-Ro52 (p = 0.001), anti-Ro60 (p<0.001), anti-La (p<0.001) and IgM-RF (p<0.001). Titers for ANA (p = 0.02) and anti-Ro52 (p = 0.03) were higher in patients with abnormal SGUS. Twenty-three of the pSS patients had no pathological findings on SGUS. There was no correlation between SGUS severity and ESSDAI- or ESSPRI-scores. CONCLUSIONS: Abnormal SGUS findings are associated with autoantibodies of high specificity for pSS but not with ESSDAI, ESSPRI or inflammatory markers.


Assuntos
Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Autoanticorpos , Glândulas Salivares/diagnóstico por imagem , Glândulas Salivares/patologia , Ultrassonografia , Glândula Parótida/diagnóstico por imagem , Anticorpos Antinucleares
10.
Arthritis Res Ther ; 19(1): 80, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28446218

RESUMO

BACKGROUND: Undifferentiated arthritis (UA) is a label applied to patients with joint complaints which cannot be classified according to current criteria, which implies a need for precision diagnostic technologies. We studied serum galectin-3, a proinflammatory mediator, and seromarkers of structural joint elements in patients with early, UA and their associations with disease profile and biochemical and imaging findings. METHODS: One hundred and eleven UA patients were followed-up for at least 12 months and reclassified according to appropriate criteria (TUDAR). At baseline, demographics and laboratory and clinical disease measures, as well as wrist magnetic resonance imaging (MRI) synovitis, erosion, and bone marrow edema scorings, were recorded. Galectin-3, the type IIA collagen N-terminal propeptide (PIIANP), which is a marker of regenerative cartilage formation, and hyaluronan (HYA), which is prevalent in synovial tissue swellings, were measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curve analysis was carried out to assess the discriminant capacity of galectin-3 against arthritis subsets. RESULTS: Galectin-3 was increased in pre-rheumatoid arthritis (RA) (4.6 µg/l, interquartile range (IQR) 3.8-5.5) versus non-RA (4.0 µg/l, IQR 3.1-4.9; p = 0.03) and controls (3.8 µg/l, IQR 3.0-4.8; p = 0.009). PIIANP was equally depressed in either subset (p < 0.01). Galectin-3 in non-RA and HYA in UA did not differ from healthy controls. In the entire UA cohort, galectin-3 correlated with the MRI bone marrow edema score, while PIIANP correlated with the MRI erosion score, and HYA with the synovitis and erosion scores. ROC curve analysis showed that baseline galectin-3 discriminated well between pre-RA and non-RA with univariate area under the curve (AUC) of 0.64 (95% confidence interval (CI) 0.53-0.76) while AUC for galectin-3 + anti-CCP increased to 0.71 (95% CI 0.59-0.83). CONCLUSIONS: Galectin-3 in serum was increased in patients with early UA of pre-RA origin. Cartilage remodeling assessed by PIIANP was diminished in UA irrespective of subsequent clinical differentiation, while HYA did not differ from controls. ROC analysis showed a potential for galectin-3 to discriminate between pre-RA and non-RA. TRIAL REGISTRATION: KF 11 315829. Registered 25 July 2006.


Assuntos
Artrite Reumatoide/sangue , Cartilagem/metabolismo , Galectina 3/sangue , Sinovite/sangue , Adulto , Idoso , Artrite Reumatoide/classificação , Artrite Reumatoide/diagnóstico por imagem , Biomarcadores/sangue , Proteínas Sanguíneas , Cartilagem/diagnóstico por imagem , Feminino , Seguimentos , Galectinas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sinovite/diagnóstico por imagem , Adulto Jovem
11.
Am J Med ; 129(3): 299-306.e2, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26589484

RESUMO

BACKGROUND: Hyperuricemia and gout have been associated with increased cardiovascular risk. Allopurinol is an effective urate-lowering drug. Whether lowering of urate by allopurinol improves the cardiovascular risk in hyperuricemic patients remains to be established. OBJECTIVE: Our objective was to investigate the effect of allopurinol on cardiovascular outcomes in hyperuricemic patients in an observational setting. METHODS: We had access to a study population consisting of all patients from Funen County, Denmark with high urate levels (≥6 mg/dL) from 1992 to 2010. We linked 4 registries; all blood samples, all in- and outpatient contacts in hospitals, all reimbursed prescriptions and causes of death. We identified all incident allopurinol users and matched them 1:1 to nonusers of urate-lowering therapy, with similar urate levels, by using propensity scores. Hazard ratios were calculated using competing risk regression model, with respect to Antiplatelet Trialists' Collaboration composite outcome (myocardial infarction, stroke, or cardiovascular death) and all-cause mortality. RESULTS: Among 65,971 patients with hyperuricemia, we found 7127 patients on allopurinol treatment. In the propensity score-matched cohort we found a hazard ratio of 0.89 (95% confidence interval, 0.81-0.97) for the main outcome among allopurinol treated compared with nonusers of allopurinol. The corresponding hazard ratio for all-cause mortality was 0.68 (95% confidence interval, 0.62-0.74). CONCLUSION: Allopurinol treatment is associated with a decreased cardiovascular risk among hyperuricemic patients.


Assuntos
Alopurinol/uso terapêutico , Doenças Cardiovasculares/mortalidade , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Hiperuricemia/epidemiologia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Pontuação de Propensão , Sistema de Registros
12.
PLoS One ; 11(1): e0146172, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26751377

RESUMO

BACKGROUND: Gout gives rise to increased risk of cardiovascular events. Gout attacks can be effectively prevented with urate lowering drugs, and allopurinol potentially reduces cardiovascular risk. What target level of urate is required to reduce cardiovascular risk is not known. OBJECTIVES: To investigate the effect of achieving target plasma urate with allopurinol on cardiovascular outcomes in a case-control study nested within long-term users of allopurinol. METHODS: We identified long-term users of allopurinol in Funen County, Denmark. Among these, we identified all cases of cardiovascular events and sampled 4 controls to each case from the same population. The cases and controls were compared with respect to whether they reached a urate target below 0.36 mmol/l on allopurinol. The derived odds ratios were controlled for potential confounders available from data on prescriptions, laboratory values and in- and outpatient contacts. RESULTS: No association between treatment-to-target urate level and cardiovascular events were found (adjusted odds ratio of 1.01, 95% confidence interval 0.79-1.28). No significant effect was seen in any subgroup defined by age, gender, renal function, allopurinol dose or the achieved urate level. Overall, the doses of allopurinol used in this study were low (mean ≈ 140 mg/day). CONCLUSION: We were unable to demonstrate a link between achieved urate level in patients treated with allopurinol and risk of cardiovascular events. Possible explanations include that allopurinol doses higher than those used in this study are required to achieve cardiovascular risk reduction or that the cardiovascular effect of allopurinol is not mediated through low urate levels. It remains to be seen whether allopurinol has a dose-response relationship with cardiovascular events at higher doses.


Assuntos
Alopurinol/uso terapêutico , Doenças Cardiovasculares/sangue , Ácido Úrico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopurinol/efeitos adversos , Estudos de Casos e Controles , Dinamarca , Relação Dose-Resposta a Droga , Feminino , Gota/prevenção & controle , Supressores da Gota/efeitos adversos , Supressores da Gota/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento
13.
Immunol Res ; 64(1): 55-63, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26091722

RESUMO

Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte antigens is reported for multiple sclerosis. We speculate the possibility that recombinants or mixed viral particles are formed and that the resulting viruses stimulate the innate immune system, thereby initiating the autoimmune response.


Assuntos
Artrite Reumatoide/virologia , Diabetes Mellitus Tipo 1/virologia , Retrovirus Endógenos/genética , Loci Gênicos , Esclerose Múltipla/virologia , Proteínas Virais/genética , Artrite Reumatoide/genética , Autoimunidade , Diabetes Mellitus Tipo 1/genética , Feminino , Redes Reguladoras de Genes , Estudos de Associação Genética , Marcadores Genéticos/genética , Predisposição Genética para Doença , Genótipo , Humanos , Imunidade Inata , Masculino , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único
14.
Arthritis ; 2015: 784825, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25759761

RESUMO

Objective. To investigate if antibodies towards biological TNF-α inhibitors (anti-TNFi Abs) are present in patients with rheumatoid arthritis (RA) in clinical remission and to relate any anti-TNFi Abs to circulating level of TNF-α inhibitor (TNFi). Methods. Patients with RA, treated with infliximab or adalimumab, and in clinical remission (DAS28(CRP) < 2.6) were included from 6 out-patient clinics. In blood samples, presence of anti-TNFi Abs was determined by radioimmunoassay, and concentration of bioactive TNFi was measured by a cell-based reporter gene assay. Results. Anti-TNFi Abs were present in 8/44 patients (18%) treated with infliximab and 1/49 patients (2%) treated with adalimumab (p = 0.012). In the former group, anti-TNFi Abs corresponded with low levels of TNFi (p = 0.048). Anti-TNFi Ab-positive patients had shorter disease duration at initiation of TNFi therapy (p = 0.023) but were similar for the rest of the compared parameters. Conclusions. In RA patients in clinical remission, anti-TNFi Abs occur frequently in patients treated with infliximab, while they occur rarely in patients treated with adalimumab. Presence of anti-infliximab Abs is accompanied by low or undetectable levels of infliximab. These data suggest that continued infliximab treatment may be redundant in a proportion of RA patients treated with infliximab and in clinical remission.

15.
BMC Res Notes ; 7: 716, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25304972

RESUMO

BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA in a predominantly Caucasian population from Denmark using a case-control approach. FINDINGS: DNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology.We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis according to IgM rheumatoid factor (RF) and anti-cyclic citrinullated peptide (CCP) status suggested a significant association of sero-negative RA with the rs3775291 A allele and disease activity in this subset. CONCLUSION: These observations on a RA population of Danish ancestry suggest that variations in the TLR3 locus may be implicated in the pathogenesis of sero-negative RA. Since this TLR3 SNP has previously been associated with systemic lupus erythematous (SLE), the present findings support the notion that TLR3 genetic variants may represent a common risk factor in different chronic inflammatory conditions, including RA and SLE.


Assuntos
Artrite Reumatoide/genética , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like/genética , Estudos de Casos e Controles , Dinamarca , Humanos
16.
Arthritis Rheum ; 62(1): 22-32, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20039405

RESUMO

OBJECTIVE: To compare tumor necrosis factor alpha inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response. METHODS: The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score). RESULTS: Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28-2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20-1.80). CONCLUSION: Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adesão à Medicação , Adalimumab , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Dinamarca , Etanercepte , Feminino , Nível de Saúde , Humanos , Imunoglobulina G/uso terapêutico , Infliximab , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Sistema de Registros , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
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