RESUMO
OBJECTIVES: Fatigue is a disabling symptom in people with RA. This study aims to describe the prevalence, risk factors and longitudinal course of fatigue in early RA. METHODS: Demographic, clinical, quality of life (QoL), comorbidities and laboratory data were from the Early RA Network (ERAN), a UK multicentre inception cohort of people with RA. Fatigue was measured using the vitality subscale of the 36-item Short Form Health Survey, where higher values represent better QoL. Baseline prevalences of fatigue classifications were age and sex standardized. Linear regression, hierarchical growth curve modelling and group-based trajectory modelling (GBTM) were utilized. RESULTS: At baseline (n = 1236, 67% female, mean age 57 years), the mean vitality was 41 (s.d. 11) and disease duration was 11 months (interquartile range 7-18). Age- and sex-standardized prevalence rates of fatigue and severe fatigue were 44% (95% CI 39, 50) and 19% (95% CI 15, 23), respectively. Fatigue changed little over 3 years and five measurement occasions ß = -0.13 (95% CI -0.23, -0.02). GBTM identified two subgroups, which we named 'Fatigue' (53%) and 'No-fatigue' (47%). Female sex, worse pain, mental health and functional ability were associated with greater fatigue and predicted Fatigue group membership (area under the receiver operating characteristics curve = 0.81). Objective measures of inflammation-swollen joint count and ESR-were not significantly associated with fatigue. CONCLUSIONS: Fatigue is prevalent and persistent in early RA. Diverse characteristics indicative of central mechanisms are associated with persistent fatigue. Management of fatigue might require interventions targeted at central mechanisms in addition to inflammatory disease modification. People who require such interventions might be identified at presentation with early RA.
Assuntos
Artrite Reumatoide , Qualidade de Vida , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Feminino , Humanos , Inflamação/complicações , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Fatores de RiscoRESUMO
OBJECTIVES: To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. METHODS: Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. RESULTS: This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. CONCLUSION: Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.
Assuntos
Antirreumáticos , Artrite Reumatoide , Feminino , Humanos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Avaliação da Deficiência , Fadiga/tratamento farmacológico , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To estimate the incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies utilising different testing criteria, and review the clinical details of a series of patients with associated autoimmune myopathy. METHODS: The incidence of anti-HMGCR antibodies in 2019 from 3 groups, South West London, Berkshire/Surrey and Southampton, were compared in the adult population. Anti-HMGCR antibodies were measured by commercial chemiluminescent and immunodot assays. The case notes of patients with anti-HMGCR antibodies were reviewed for the case series. RESULTS: The estimated incidence of anti-HMGCR antibodies in the first 2 groups was 1.94 per million adults per year, and in the third group 10.3 per million adults per year. In the first 2 groups the test criteria restricted analysis to specific clinician request for anti-HMGCR. In the third group test criteria included cases with less specific clinical features or a cytoplasmic indirect immunofluorescence anti-nuclear antibody pattern. The latter strategy had a positive predictive value of 66.1% for anti-HMGCR associated myopathy. A case series of 27 patients with anti-HMGCR antibodies revealed 19 with myopathy, oesophageal involvement in 26% and median peak CK 8000 IU/L. Response to treatment, including intravenous immunoglobulin, was good with CK normalising after median 5.5 months. In 8 cases there was no evidence of autoimmune muscle disease, 7 not statin exposed. CONCLUSIONS: Varying criteria result in a 5-fold difference in estimated incidence of anti-HMGCR antibodies, revealing positive cases without evidence of myopathy. Patients with anti-HMGCR myopathy respond well to immune suppression, supporting wider testing for these antibodies amongst patients with myopathy.
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Doenças Autoimunes , Hidroximetilglutaril-CoA Redutases , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Musculares , Miosite , Adulto , Autoanticorpos , Doenças Autoimunes/complicações , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/epidemiologia , Coenzima A/uso terapêutico , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Músculo Esquelético , Oxirredutases/uso terapêuticoRESUMO
This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7-13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status.
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Artrite Reumatoide , Fator Reumatoide , Articulação do Tornozelo , Artrite Reumatoide/cirurgia , Feminino , Humanos , Articulações/cirurgia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Articulação do Punho/cirurgiaRESUMO
Autoantibodies to the 75-kDa and 100-kDa subunits of the PM/Scl nucleolar protein complex are associated with an overlap syndrome, manifesting with clinical features of systemic sclerosis and idiopathic inflammatory myopathy. We describe the diverse clinical features in a series of 4 cases with anti-PM/Scl-75 and/or anti-PM/Scl-100 antibodies, including severe proximal muscle weakness, oesophageal dysfunction, respiratory weakness requiring mechanical ventilation, Raynaud's, calcinosis cutis, sclerodactyly and critical digital ischaemia. Despite the severity of striated and oesophageal muscle weakness, all patients responded very well to immune suppression, and calcinosis cutis in one case regressed substantially. We highlight the efficacy of Rituximab and intravenous immunoglobulin therapy (IVIg) in these cases, enabling return to normal muscle function within six months. Rituximab was preferentially chosen for cases with hyper-gammaglobulinemia and multiple autoantibodies in addition to anti-PM/Scl, and IVIg was utilised for cases where a rapid onset of effect was required, such as severe ventilator-dependent respiratory muscle weakness and oesophageal dysfunction.
Assuntos
Antirreumáticos/administração & dosagem , Imunoglobulinas Intravenosas/administração & dosagem , Miosite/tratamento farmacológico , Rituximab/administração & dosagem , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Autoanticorpos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Miosite/complicações , Escleroderma Sistêmico/complicações , Adulto JovemRESUMO
Ankle arthritis is a useful clinical signpost to differential diagnosis in rheumatic disease. Biomechanical features and differences in cartilage physiology compared with the knee may confer protection of the ankle joint from factors predisposing to certain arthritides. The prevalence of ankle OA is low, and usually secondary to trauma. Primary OA of the ankle should be investigated for underlying causes, especially haemochromatosis. New presentations of inflammatory mono/oligo arthritis involving the ankle are more likely due to undifferentiated arthritis or spondyloarthritis than RA, and gout over CPPD. The ankle is often involved in bacterial and viral causes of septic arthritis, especially bacterial, chikungunya and HIV infection, but rarely tuberculosis. Periarticular hind foot swelling can be confused with ankle arthritis, exemplified by Lofgren's syndrome and hypertrophic osteoarthropathy where swelling is due to subcutaneous oedema and osteitis respectively, and the ankle joint is rarely involved.
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Articulação do Tornozelo/patologia , Artrite/patologia , Artrite/diagnóstico , Artrite/etiologia , Diagnóstico Diferencial , HumanosRESUMO
OBJECTIVE: Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE. METHODS: Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria). RESULTS: Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE. CONCLUSION: Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Espondilite Anquilosante/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVES: To examine secular trends in the progression of clinical and patient-reported outcomes in early RA. METHODS: A total of 2701 patients recruited to the Early Rheumatoid Arthritis Study or Early Rheumatoid Arthritis Network with year of diagnosis from 1986 to 2011. The 5-year progression rates for patients diagnosed at different points in time were modelled using mixed-effects regression; 1990, 2002 and 2010, were compared. Clinical markers of disease included the 28-joint count DAS and the ESR. Patient-reported markers included the HAQ, visual analogue scale of pain and global health, and the Short-Form 36. RESULTS: Statistically significant improvements in both 28-joint count DAS and ESR were seen over the 5 years in patients diagnosed with RA compared with those diagnosed earlier. By 5 years, 59% of patients with diagnosis in 2010 were estimated to reach low disease activity compared with 48% with diagnosis in 2002 and 32% with diagnosis in 1990. Whilst HAQ demonstrated statistically significant improvements, these improvements were small, with similar proportions of patients achieving HAQ scores of ≤1.0 by 5 years with a diagnosis in 1990 compared with 2010. Levels of the visual analogue scale and the Mental Component Scores of the Short-Form 36 indicated similar, statistically non-significant levels over the 5 years, irrespective of year diagnosed. CONCLUSION: This study demonstrates improvements in inflammatory markers over time in early RA, in line with improved treatment strategies. These have not translated into similar improvements in patient-reported outcomes relating to either physical or mental health.
Assuntos
Artrite Reumatoide/patologia , Secularismo , Índice de Gravidade de Doença , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/psicologia , Biomarcadores/análise , Avaliação da Deficiência , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Análise de RegressãoRESUMO
OBJECTIVES: To examine associations between function, quality of life and structural outcomes in patients achieving remission vs low disease activity in early RA. METHODS: Demographic, clinical and radiographic variables were collected at baseline and then annually from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts in routine care from 1986 to 2012. Disease activity was categorized: mean DAS28 score between years 1 and 5: remission [mean remission DAS (mRDAS) <2.6] or low [mean low DAS (mLDAS) 2.6-3.2]; sustained low/remission DAS28 (sLDAS/sRDAS) at years 1 and 2; and sustained Boolean remission (sBR) at years 1 and 2. Changes in HAQ and Short Form 36 Health Survey Questionnaire [SF-36; physical (PCS) and mental (MCS) component score]) and total Sharp van der Heijde (SvdH) scores for each disease activity category were modelled using multi-level models. Covariates included year of onset, age, gender and DMARD use at first visit. RESULTS: Of 2701 patients, 562 (21%) were categorized mRDAS, 330 (12%) mLDAS, 279 (10%) sRDAS, 203 (7.5%) sLDAS and 93 (3%) sBR. Patients categorized as mRDAS had increasingly divergent improved HAQ, SF-36 PCS, MCS and total SvdH scores compared with mLDAS (P-values 0.001 to <0.0001, all time points). Patients categorized as sRDAS had better HAQ, SF-36 PCS and MCS scores (P-values 0.05 to <0.0001, all time points) and SvdH scores (P = 0.05, years 3-5) over sLDAS. sBR was associated with better HAQ, and SF-36 PCS and MCS scores over sLDAS (P-values 0.002 to <0.0001, all time points). CONCLUSION: These findings from routine care support ACR/EULAR guidelines that remission is a preferable goal over low disease activity in early RA.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Qualidade de Vida/psicologia , Adulto , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/psicologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de DoençaAssuntos
COVID-19 , Pérnio , Humanos , Pérnio/diagnóstico , Pérnio/epidemiologia , Pérnio/etiologia , Pandemias , SARS-CoV-2 , PesquisaAssuntos
Artrite Juvenil , Miosite , Reumatologia , Adolescente , Adulto , Criança , Humanos , Miosite/diagnóstico , Miosite/terapiaRESUMO
OBJECTIVES: The optimal treatment for active rheumatoid arthritis (RA) is unresolved, particularly in early RA. We used data from an observational cohort to develop the simple predictor algorithm and evaluated its application in two completed clinical trials in early and established RA. We assessed whether using a simple algorithm can identify patients who have persisting active disease despite treatment with disease-modifying drugs (DMARDs). We also examined if patients who have lower likelihoods of persisting active RA are likely to benefit from intensive treatment. METHODS: We developed a simple predictive score for persisting disease activity using conventional clinical assessments in an observational cohort of patients with early RA (ERAN). It was tested in two trials in early (CARDERA) and established (TACIT) RA. Persistent disease activity was defined as disease activity score for 28 joints (DAS28) >3.2 at both 6 and 12 months. RESULTS: Regression modelling identified three main predictors of persisting active disease in ERAN; tender joint counts, health assessment questionnaire (HAQ) scores and ESR. We dichotomised these predictors (≥6 tender joint counts, ≥1.0 HAQ ≥20 mm/h ESR) in a four-point prediction score. This simple prediction score predicted persisting active disease in the ERAN cohort and both CARDERA and TACIT trials. Patients with high scores were more likely to have persistently active disease at 6 and 12 months. The relationship was weaker in TACIT because no patients were without any predictive factors. CONCLUSIONS: Combining tender joint counts, ESR and HAQ in a simple predictive score prospectively identifies patients with higher risks of persistent disease activity over the next 12 months. More patients with all three risk factors had persistent active disease than those with none or one risk factor.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Adulto , Idoso , Algoritmos , Artrite Reumatoide/diagnóstico , Sedimentação Sanguínea , Ensaios Clínicos como Assunto , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Articulações/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Seleção de Pacientes , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
This following is a review of the factors that influence the outcome of biologic agents in the treatment of adult RA and, when synthesized into the clinical decision-making process, enhance optimization. Adiposity can exacerbate inflammatory diseases; patients with high BMI have worse outcomes from RA, including TNF inhibitors (TNFis), whereas the efficacy of abatacept and tocilizumab is unaffected. Smoking adversely affects TNFi outcomes but has less or no effect on the efficacy of rituximab and tocilizumab, and the effect on abatacept is unknown. Patients who are positive for ACPA and RF have better efficacy with rituximab and abatacept than those who are seronegative, whereas the influence of serotype is less significant for tocilizumab and more complex for TNFis. All biologics seem to do better when co-prescribed with MTX, whereas in monotherapy, tocilizumab is superior to adalimumab and prescription of a non-MTX DMARD has advantages over no DMARD for rituximab and adalimumab. Monitoring of TNFi drug levels is an exciting new field, correlating closely with efficacy in RA and PsA, and is influenced by BMI, adherence, co-prescribed DMARDs and anti-drug antibodies. The measurement of trough levels provides a potential tool for patients who are not doing well to determine early whether to switch within the TNFi class (if levels are low) or to a biologic with an alternative mode of action (if levels are normal or high). Conversely, the finding of supratherapeutic levels has the potential to enable individual patient selection for dose reduction without the risk of flare.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Medicina de Precisão/métodos , Antirreumáticos/administração & dosagem , Produtos Biológicos/administração & dosagem , Índice de Massa Corporal , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Humanos , Participação do Paciente , Sorogrupo , Fumar/efeitos adversos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: To investigate factors associated with joint damage in early RA, and how comorbid OA might influence patient assessment and outcomes. METHODS: Baseline radiographs of hands and feet from 512 participants in the Early RA Network cohort, and after 3 (±1) years, 166 of those participants yielded complete scores for RA [erosions, joint space narrowing (JSN)] and OA [JSN, osteophytes (OST)] using validated atlases. DAS28-P is the proportion of DAS28 attributed to patient-reported factors. Adjusted odds ratios were calculated using logistic regression. RESULTS: OA was common at baseline in early RA (40% hand and 48% foot) and associated with RA radiographic score. Higher baseline RA scores were associated with increasing age and ESR, and lower DAS28-P. OST scores were associated with higher age. DAS28 and patient-reported outcomes improved, whereas RA and OA radiographic scores deteriorated by follow-up. Erosive progression was predicted by higher baseline erosions, female gender, better mental health and lower DAS28-P. Hand OST progression was predicted by baseline OST scores. Inflammatory disease activity was associated with erosive, but not with OA progression. Baseline hand OA predicted worse physical function at follow-up, but radiographic progression did not explain changes in patient-reported outcomes. CONCLUSION: OA is a common comorbidity that might confound radiographic and clinical assessment, but does not fully explain erosive progression or patient-reported outcomes in early RA. Early RA management should address psychosocial factors and comorbidities, as well as joint inflammation.
Assuntos
Artrite Reumatoide/diagnóstico por imagem , Osteoartrite/diagnóstico por imagem , Idoso , Pessoas com Deficiência , Progressão da Doença , Feminino , Pé , Mãos , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Dor Musculoesquelética , Osteófito/diagnóstico por imagem , Radiografia , Fatores SexuaisRESUMO
Interstitial lung disease (ILD) is a very important complication of the idiopathic inflammatory myositides (IIM), with a prevalence of approximately 40 %. Characteristic HRCT changes, most commonly NSIP, together with a restrictive ventilatory defect and an associated decline in DLco support the presence of ILD. The strongest risk factors are the presence of the anti-amino-acyl-tRNA synthetases (ARS) and anti-MDA-5 antibodies, but a raised index of suspicion for ILD should also apply to IIM patients of black ethnicity. Overall, the prognosis of ILD in IIM is good; between 50 and 66 % of cases have a stable disease course over a substantial period of time. The remaining proportion will show signs of worsening lung disease within 12 months of diagnosis. Whereas ARS antibodies and black ethnicity have no influence on ILD prognosis, detection of the anti-MDA-5 antibody carries a poor ILD outcome, in which hyperferritinaemia appears to be an important diagnostic and prognostic feature.
Assuntos
Doenças Pulmonares Intersticiais/etiologia , Miosite/complicações , Biomarcadores/sangue , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Miosite/epidemiologia , Fenótipo , Prevalência , Prognóstico , Testes de Função Respiratória/métodos , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Outcomes in early Rheumatoid Arthritis (RA) may be improved by rapidly establishing a stable and effective disease modifying anti-rheumatic drug (DMARD) treatment regimen. We aimed to investigate whether baseline factors and initial treatment strategies are associated with changes to the first DMARD treatment, due to either Lack of Efficacy (LoE) or Adverse Drug Reaction (ADR) within 2 years of presentation. METHODS: Reasons for changes from initial DMARD therapy within 2 years of baseline, and associated factors, were examined using logistic regression in data from the Early RA Network (ERAN) inception cohort. RESULTS: Data were available for 766 participants. 410 (54%) changed their initial DMARD regime within 2 years, including 230 (56%) due to Lack of Efficacy (LoE) and 139 (34%) due to Adverse Drug Reaction (ADR). The first DMARD was recorded as methotrexate monotherapy in 336 (44%), sulphasalazine monotherapy in 273 (36%), or combined methotrexate/sulphasalazine/hydroxychlorquine in 52 (7%).Baseline predictors of changing DMARD (for all reasons) were HAQ-disability (aOR 1.44, 95% CI 1.12 - 1.86), poor mental health (aOR 1.44, 95% CI 1.16 - 1.78) and extra-articular disease (aOR 1.78, 95% CI 1.00 - 3.16). In this model, the triple combination therapy also predicted lower likelihood of DMARD change (aOR 0.30, 95% CI 0.12 - 0.79).Subgroup analyses showed that MTX monotherapy was associated with lower risk of change due to ADR. Combination therapy conferred lower risk of change due to LoE. Poor mental health was associated with change due to ADR, and extra-articular disease, HAQ-disability at baseline, and younger age predicted LoE. CONCLUSIONS: Our findings suggest that non-pharmacological interventions to improve disability and mental health, may reduce initial DMARD treatment failure.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Sulfassalazina/uso terapêutico , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Estudos de Coortes , Avaliação da Deficiência , Substituição de Medicamentos , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Nível de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Falha de Tratamento , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). METHODS: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). RESULTS: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (ß = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (ß = 0.24 [95% CI 0.14, 0.34]), less exercise (ß = 0.17 [95% CI 0.09-0.25]), and less education (ß = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. CONCLUSION: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.
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Artrite Reumatoide , Humanos , Feminino , Masculino , Estudos de Coortes , Inflamação , Estilo de Vida , Apoio Social , Apoio FinanceiroRESUMO
In England and Wales, the National Institute for Health and Clinical Excellence (NICE) has provided guidance [technology appraisals (TAs) 130, 186, 195, 198 and 225] on the use of biologic drugs for the treatment of RA. This is based on an analysis of efficacy, safety and cost-effectiveness, and has resulted in a complex management pathway that restricts freedom to prescribe biologics according to their licensed indications. Specifically, TNF antagonists are the only class of biologics that can be used first line in DMARD-inadequate responders, and only in patients with a persistent 28-joint DAS score of ≥5.1. Alternative biologic agents are denied to those with contraindications to anti-TNF drugs and are also not supported following intolerance to TNF antagonists. Rituximab is the only class of biologic permitted after TNF antagonist inefficacy, in the absence of a contraindication to its use, whereas abatacept and tocilizumab are licensed and may be a more efficacious choice at this stage in some patient groups. Furthermore, for patients who demonstrate sequential inadequate responses, treatment is restricted to one TNF antagonist, rituximab and tocilizumab, whereas abatacept is only a permitted choice when rituximab is contraindicated or has been withdrawn because of an adverse event. In this review, we discuss the treatment algorithm published by NICE, and suggest alternatives where perceived deficiencies exist.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Guias de Prática Clínica como Assunto , Avaliação da Tecnologia Biomédica/métodos , Algoritmos , Medicina Baseada em Evidências/métodos , Humanos , Medicina Estatal/normas , Reino UnidoRESUMO
OBJECTIVE: Interstitial lung disease (ILD) is an important feature of idiopathic inflammatory myositis (IIM). Factors associated with its development and progression remain incompletely understood. The authors report ethnicity differences and lung function trends that characterize the predilection for and natural history of ILD in a group of British patients with IIM. METHODS: A 10-year retrospective analysis of patients with IIM at two hospitals was conducted. Demographic, clinico-radiological and laboratory features of cases with and without ILD were compared. Serial pulmonary function tests, including measurements of forced vital capacity, volume and diffusing capacity for carbon monoxide, were used to identify longitudinal patterns of lung disease. RESULTS: A total of 107 patients with IIM were identified. ILD was present in 37.4%, with non-specific interstitial pneumonia being the most common radiological pattern (75%). ILD was more common in IIM patients of Black ethnicity (OR 3.42), and in cases where ANA (OR 3.06) and anti-histidyl-tRNA synthetase (OR 3.2) antibodies were detected. In the ILD cohort, 50% deteriorated, defined as a drop in diffusing capacity of the lung for carbon monoxide by <15% or forced vital capacity <10% during the study period, occurring in all within a year of onset of ILD and significantly more frequently in those with a synchronous onset of IIM and ILD. Black ethnicity was not associated with poor lung function outcome. CONCLUSION: In IIM, the risk of developing ILD is significantly higher in patients of Black ethnicity. Progressive lung damage occurs in an appreciable subgroup of patients with IIM-ILD, heralded by functional lung decline at 1 year despite systemic immunomodulatory treatment.
Assuntos
Doenças Pulmonares Intersticiais/etnologia , Pulmão/fisiopatologia , Miosite/etnologia , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Inglaterra/epidemiologia , Feminino , Histidina-tRNA Ligase/imunologia , Humanos , Doenças Pulmonares Intersticiais/imunologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , Miosite/fisiopatologia , Prevalência , Testes de Função Respiratória , Estudos RetrospectivosRESUMO
BACKGROUND: Fifteen myositis-specific antibodies have been described and characterized over the past 40 years. Approximately two thirds of patients with idiopathic inflammatory myositis have a myositis-specific antibody and only rarely more than one. Assays to detect them are now widely available within clinical practice. CONTENT: We describe the original description and clinical phenotype of the myositis-specific antibodies, forming the antisynthetase syndrome group, anti-MDA-5 and rapidly progressive interstitial lung disease, anti-SRP/HMGCR and necrotizing myositis, anti-TIF-1γ/NXP-2 and malignancy, anti-SAE and esophageal disease, and anti-Mi-2 and classic dermatomyositis skin disease. SUMMARY: Clinical practice is likely to be refined, with diagnosis and classification of the idiopathic inflammatory myositides based primarily on myositis-specific antibody, rather than directed by muscle histology or the broader clinical characteristics of polymyositis and dermatomyositis. All patients newly presenting with idiopathic inflammatory myositis should be routinely screened for myositis-specific antibodies. A positive result will usefully provide diagnostic and prognostic information, guide selection of therapy, and prompt surveillance for potential organ involvement and other features, such as cancer, throughout the disease course.