Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Arthritis Res Ther ; 21(1): 299, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870459

RESUMO

BACKGROUND: To determine the frequency and clinical characteristics of systemic sclerosis-related digital ulcers, and associated direct health care costs, quality of life, and survival. METHODS: Digital ulcers (DUs) were defined as an area with a visually discernible depth and a loss of continuity of epithelial coverage. DU severity was calculated based on the physician reported highest number of new DUs at clinical review (mild = 1-5 DUs, moderate 6-10 DUs, severe > 10 DUs). Healthcare use was captured through data linkage, wherein SSc clinical data captured prospectively in a dedicated clinical database were linked with health services databases to capture hospital admissions, emergency department (ED) presentations and ambulatory care (MBS) utilization and cost for the period 2008-2015. Healthcare cost determinants were estimated using logistic regression. RESULTS: Among 1085 SSc patients, 48.6% experienced a DU over a mean follow-up of 5.2 ± 2.5 years. Those who developed DUs were more likely to have diffuse disease subtype (34.9% vs 18.2%, p < 0.001), anti-Scl-70 antibody (18.9% vs 9.3%, p < 0.001), and a younger age at SSc onset (43.6 ± 13.9 vs 48.8 ± 14.0 years, p < 0.001) in addition to reduced health-related quality of life (HRQoL) measured by the SF-36 but without a significant impact on survival. SSc patients with a history of a DU utilized significantly more healthcare resources per annum than those without a DU, including hospitalizations, ED presentation, and ambulatory care services. Total healthcare services, excluding medications, were associated with an annual excess cost per DU patient of AUD$12,474 (8574-25,677), p < 0.001, driven by hospital admission and ED presentation costs. CONCLUSION: DUs place a large burden on the patient and healthcare system through reduced HRQoL and increased healthcare resource utilization and associated cost.

2.
BMC Pulm Med ; 19(1): 226, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775705

RESUMO

BACKGROUND: To quantify the financial cost of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc). METHODS: Healthcare use was captured through data linkage, wherein clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with hospital, emergency department (ED) and ambulatory care databases (MBS) for the period 2008-2015. PAH was diagnosed on right heart catheter according to international criteria. Determinants of healthcare cost were estimated using logistic regression. RESULTS: Total median (25th-75th) healthcare cost per patient (including hospital, ED and MBS cost but excluding medication cost) for our cohort during 2008-2015 was AUD$37,685 (18,144-78,811) with an annual per patient healthcare cost of AUD$7506 (5273-10,654). Total healthcare cost was higher for SSc-PAH patients compared with those without PAH with a total cost per patient of AUD$70,034 (37,222-110,814) vs AUD$34,325 (16,093 - 69,957), p < 0.001 respectively with an annual excess healthcare cost per PAH patient of AUD$2463 (1973-1885), p < 0.001. The cost of SSc-PAH occurs early post PAH diagnosis with 89.4% utilizing a healthcare service within the first 12 months post PAH diagnosis with an associated cost per patient of AUD$4125 (0-15,666). PAH severity was the main significant determinant of increased healthcare cost (OR 2.5, p = 0.03) in our PAH cohort. CONCLUSIONS: Despite SSc-PAH being a low prevalence disease, it is associated with significant healthcare resource utilization and associated economic burden, predominantly driven by the severity of PAH.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31740961

RESUMO

OBJECTIVE: To quantify the burden of interstitial lung disease (ILD) in SSc. METHODS: Clinical data for SSc patients enrolled in the Australian Scleroderma Cohort Study were linked with healthcare databases for the period 2008-2015. ILD was defined by characteristic fibrotic changes on high-resolution CT (HRCT) lung, while severity was defined by the extent lung involvement on HRCT (mild <10%, moderate 10-30%, severe >30%). Determinants of healthcare cost were estimated using logistic regression. RESULTS: SSc-ILD patients utilized more healthcare resources, including hospitalization, emergency department presentation and ambulatory care services, than those without ILD with a total cost per patient of AUD$48 368 (26 230-93 615) vs AUD$33 657 (15 144-66 905), P<0.001) between 2008-2015. Healthcare utilization was associated with an annual median (25th-75th) excess cost per SSc-ILD patient compared with those without ILD of AUD$1192 (807-1212), P<0.001. Increasing ILD severity was associated with significantly more healthcare utilization and costs with an annual excess cost per patient with severe ILD compared with mild ILD of AUD$2321 (645-1846), P<0.001. ILD severity and the presence of coexistent PAH were the main determinants of overall healthcare cost above median for this SSc-ILD cohort (OR 5.1, P<0.001, and OR 2.6, P=0.01, respectively). Furthermore, SSc-ILD patients reported worse physical HRQoL compared with those without ILD [34.3 (10.5) vs 39.1 (10.8), P<0.001], with a progressive decline with increasing ILD severity (P=0.002). CONCLUSION: SSc-ILD places a large burden on the healthcare system and the patient through poor HRQoL in addition to incremental healthcare resource utilization and associated direct cost.

4.
Sci Rep ; 9(1): 14834, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619697

RESUMO

Fibrosis across different organs and tissues is likely to share common pathophysiological mechanisms and pathways. Recently, a polymorphism (rs12979860) near the interferon lambda gene (IFNL3) was shown to be associated with fibrosis in liver across multiple disease etiologies. We determined whether this variant is a risk factor for pulmonary fibrosis (PF) and worsening cutaneous fibrosis in systemic sclerosis (SSc). Caucasian patients with SSc (n = 733) were genotyped to test for association with the presence of PF and worsening of skin fibrosis. Serum IFN-λ3 levels from 200 SSc cases were evaluated. An association of the IFNL3 polymorphism with PF was demonstrated (OR: 1.66 (95% CI: 1.142-2.416, p = 0.008). The IFNL3 variant was not a risk factor for worsening of skin fibrosis. Functionally, IFN-λ3 serum levels were higher among subjects with PF compared to those unaffected (P < 0.0001). In conclusion, IFNL3 serum levels and the genetic variant known to be associated with liver fibrosis are similarly linked to PF, but not to worsening of skin fibrosis in SSc. These data highlight both common fibrosis pathways operating between organs, as well as differential effects within the same disease.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31539207

RESUMO

OBJECTIVE: To quantify the burden of cancer in systemic sclerosis (SSc). METHODS: Standardized incidence ratios (SIR) and mortality ratios (SMR) relative to the general Australian population were derived. Cox proportional hazards regression was used to estimate survival in SSc patients with cancer compared to those without. Determinants of cancer were identified using logistic regression. Healthcare cost was quantified through cross-jurisicational data linkage. RESULTS: This SSc cohort of 1,727 had cancer incidence of 1.3% per annum and prevalence of 14.2%, with SIR of 2.15 (93%CI 1.84-2.49). The most common cancers were breast, melanoma, hematological and lung. RNAP III antibody was associated with increased risk of cancer (OR 2.9. p=0.044), diagnosed within five years of SSc disease onset. Calcium channel blockers were associated with a higher risk of overall cancer (OR 1.47,p=0.016), breast cancer (OR 1.61, p=0.051) and melanoma (OR 2.01, p=0.042). Interstitial lung disease (ILD) was associated with lung cancer (OR 2.83, p=0.031). Incident SSc cancer patients had more than a two-fold increased mortality compared to SSc patients without cancer [HR 2.85 (95%CI 1.51-5.37), p=0.001). SSc cancer patients utilized more healthcare than those without cancer with an excess annual healthcare cost of AUD$1,496 (p<0.001). CONCLUSION: SSc carries an increased risk of developing cancer, particularly lung cancer associated with ILD, and breast cancer and melanoma occurring close to SSc disease onset in association with RNAP III antibodies. Compared to those without cancer, SSc cancer patients had higher mortality and increased healthcare cost with an annual excess per patient cost of AUD$1,496 (p<0.001).

6.
Artigo em Inglês | MEDLINE | ID: mdl-31421031

RESUMO

OBJECTIVE: To evaluate the association between patient-reported symptoms and changes in disease activity over time in systemic sclerosis (SSc). METHODS: Using data from 1,636 patients enrolled in the Australian Scleroderma Cohort Study, we used generalised estimating equations to determine the relationship between patient-reported worsening of Raynaud phenomenon (RP), skin involvement and breathlessness in the month preceding each study visit and features of disease activity in the corresponding organ systems. The associations between the following parameters were analysed: patient-reported worsening RP and the presence of new-onset digital pitting and digital ulcers; patient-reported worsening skin involvement and increasing modified Rodnan skin score (mRSS), new areas of skin involvement and new-onset joint contractures; patient-reported worsening breathlessness and deteriorating respiratory functions tests (RFTs), indicated by 10% decrease in forced vital capacity (FVC) and 15% decrease in diffusing capacity of carbon monoxide (DLCO), new-onset interstitial lung disease (ILD) and new-onset pulmonary arterial hypertension (PAH). RESULTS: We found a significant association between patient-reported worsening RP and the presence of digital ulcers (OR 1.53; 95%CI:0.60-0.93); patient-reported worsening skin involvement and increasing mRSS (OR 2.10; 95%CI:1.54-2.86); and worsening patient breathlessness and deteriorating RFTs (FVC OR 2.12; 95%CI:1.70-2.65; DLCO OR 1.97; 95%CI:1.34-2.02), new-onset ILD (OR 1.91; 95%CI:1.40-2.61) and new-onset PAH (OR 5.08; 95%CI:3.59-7.19). CONCLUSION: These results demonstrate that patient-reported symptoms are associated with clinically meaningful changes in disease activity in SSc patients. This suggests that when objective measures of change in disease status are unavailable, patient-reported symptoms could be used to indicate a change in SSc-disease activity.

7.
Arthritis Res Ther ; 21(1): 57, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764870

RESUMO

BACKGROUND: Up to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality. METHODS: Clinical data were obtained from 5 centres in the Australian Scleroderma Cohort Study (ASCS). ANCA positive was defined as the presence of any one or combination of cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), atypical ANCA, anti-myeloperoxidase (anti-MPO) or anti-proteinase-3 (anti-PR3). Associations of demographic and clinical features with ANCA were investigated by logistic or linear regression. Survival analysis was performed using Kaplan-Meyer curves and Cox regression models. RESULTS: Of 1303 patients, 116 (8.9%) were ANCA positive. Anti-PR3 was more common than anti-MPO (13.8% and 11.2% of ANCA-positive patients, respectively). Only 3 ANCA-positive patients had AAV. Anti-Scl-70 was more common in ANCA positive vs ANCA negative (25% vs 12.8%, p < 0.001), anti-MPO positive vs anti-MPO negative (38.5% vs 13.6%, p = 0.006) and anti-PR3 positive vs anti-PR3 negative patients (44.4% vs 13.4%, p < 0.001). A higher prevalence of interstitial lung disease (ILD) was found in the ANCA positive (44.8% vs 21.8%, p < 0.001) and the anti-PR3 positive groups (50.0% vs 23.4%, p = 0.009). In multivariable analysis, ANCA-positive status remained associated with ILD after adjusting for anti-Scl-70 antibodies. Pulmonary embolism (PE) was more common in ANCA-positive patients (8.6% vs 3.0%, p = 0.002) and anti-PR3-positive patients (16.7% vs 3.3%, p = 0.022). ANCA-positive status remained associated with PE in a multivariable analysis adjusting for anti-phospholipid antibodies. Kaplan-Meier analysis revealed increased mortality in ANCA-positive patients (p = 0.006). In Cox regression analysis, ANCA was associated with increased mortality, after adjusting for age and sex. CONCLUSIONS: ANCA is associated with increased prevalence of ILD and PE in SSc. ANCA should be tested in SSc, as it identifies individuals with worse prognosis who require close monitoring for adverse outcomes.

9.
Clin Exp Rheumatol ; 36 Suppl 113(4): 126-134, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30277869

RESUMO

OBJECTIVES: The role of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in systemic sclerosis (SSc) remains controversial. We sought to evaluate the relationship between clinical features of SSc and raised inflammatory markers and to determine if changes in ESR and CRP reflect changes in other disease features over time. METHODS: One thousand, five hundred and forty-five patients enrolled in the Australian Scleroderma Cohort Study were observed over a mean 3.52±2.91 years and assessed at 6,119 study visits. Generalised estimating equations were used to determine the relationship between ESR≥20mm/hr and CRP≥5mg/L and features of disease. The associations between change in inflammatory markers and change in skin scores and respiratory function tests were analysed. RESULTS: Overall, there was a significant association between raised ESR and forced vital capacity (FVC)<80% predicted, diffusing capacity of the lung (DLCO)<80% predicted, pulmonary arterial hypertension (PAH), body mass index (BMI), proximal muscle strength, anaemia, and hypocomplementaemia (p<0.05). Raised CRP was significantly associated with modified Rodnan Skin Score>20, FVC<80%, DLCO<80%, PAH, digital ulcers, BMI, synovitis, tendon friction rub, anaemia, and hypocomplementaemia (p<0.05). A significant deterioration in respiratory function tests (RFTs) was associated with a 2-fold increase in both ESR and CRP (p<0.05). CONCLUSIONS: Raised inflammatory markers are associated with pulmonary, cutaneous and musculoskeletal manifestations of SSc. Rising inflammatory markers are correlated with declining respiratory function tests. This suggests inflammatory markers have a role in the assessment of SSc disease activity.


Assuntos
Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Mediadores da Inflamação/sangue , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Idoso , Austrália , Biomarcadores/sangue , Progressão da Doença , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Índice de Gravidade de Doença , Fatores de Tempo
10.
Clin Rheumatol ; 37(6): 1563-1571, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29687288

RESUMO

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n = 15) had definite PAH; group 2 (n = 19) had interstitial lung disease (ILD); group 3 (n = 30) were SSc-controls; and group 4 (n = 34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0 ± 85.4 vs 380.4 ± 168.3 ng/mL, p = 0.136), SSc-controls (263.0 ± 85.4 vs 253.1 ± 98.0 ng/mL, p = 1.00), or healthy controls (263.0 ± 85.4 vs 201.8 ± 57.2 ng/mL, p = 0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2 ± 434.9 vs 1424.8 ± 527.6 ng/mL, p = 1.00) and SSc-controls (1476.2 ± 434.9 vs 1409.5 ± 341.1 ng/mL, p = 1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4 ± 134.0 vs 201.8 ± 57.2 ng/mL, p < 0.0001) and VCAM-1 compared to healthy controls (1432.7 ± 427.4 vs 1125.6 ± 273.4 ng/mL, p < 0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.


Assuntos
Hipertensão Pulmonar/etiologia , Molécula 1 de Adesão Intercelular/sangue , Escleroderma Sistêmico/complicações , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão Pulmonar/sangue , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/sangue , Adulto Jovem
11.
Ann Rheum Dis ; 77(4): 563-570, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29306872

RESUMO

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. TRIAL REGISTRATION NUMBER: NCT02339441.


Assuntos
Esclerodermia Difusa/diagnóstico , Índice de Gravidade de Doença , Testes Cutâneos/estatística & dados numéricos , Adulto , Área Sob a Curva , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Modelos Logísticos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , RNA Polimerase III/análise , Curva ROC , Esclerodermia Difusa/enzimologia , Esclerodermia Difusa/patologia , Pele/patologia
12.
Rheumatology (Oxford) ; 57(1): 73-83, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29155994

RESUMO

Objective: To evaluate work productivity and its economic burden in SSc patients. Methods: Consecutive SSc patients enrolled in the Australian Scleroderma Cohort Study were mailed questionnaires assessing employment (Workers' Productivity and Activity Impairment Questionnaire and a custom-made questionnaire) and health-related quality of life (HRQoL) (36-item Short Form Health Survey and Patient-Reported Outcomes Measurement Information System 29). Linear regression methods were used to determine factors associated with work productivity. Results: Among 476 patients submitting responses, 55.2% <65 years of age were employed. Unemployed patients were older at the time of survey completion (57.1 vs 53.7 years; P < 0.001) and had longer disease duration from first SSc clinical manifestation (16.2 vs 14.9 years; P = 0.01) than employed patients. The mean age at unemployment onset was 13.2 years below the average Australian retirement age. Of those working in the week prior to completing the survey, 16.0% reported missing work (absenteeism) due to their SSc, accounting for 32.9% of their working week. Reduced productivity while at work (presenteeism) accounted for 22% of their working week. Annual costs per patient as a consequence of unemployment and reduced productivity equated to a total of AUD$67 595.40. Factors independently associated with reduced work productivity were presence of synovitis and sicca symptoms, while tertiary education protected against work impairment. Patients with low HRQoL scores also had low work productivity. Conclusion: SSc is associated with considerable unemployment and reduced productivity, which in turn is associated with a substantial economic burden and poor HRQoL. Raising awareness and identifying modifiable factors are possible ways of reducing this burden.


Assuntos
Eficiência , Emprego/economia , Nível de Saúde , Qualidade de Vida , Escleroderma Sistêmico/economia , Idoso , Austrália , Estudos de Coortes , Efeitos Psicossociais da Doença , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Aposentadoria , Escleroderma Sistêmico/fisiopatologia , Fatores de Tempo , Desemprego
13.
Rheumatology (Oxford) ; 57(2): 370-381, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29207002

RESUMO

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.


Assuntos
Avaliação da Deficiência , Fadiga/fisiopatologia , Dor/fisiopatologia , Esclerodermia Difusa/fisiopatologia , Índice de Gravidade de Doença , Adulto , Efeitos Psicossociais da Doença , Europa (Continente) , Fadiga/etiologia , Feminino , Dedos , Força da Mão , Inquéritos Epidemiológicos , Humanos , Masculino , Dor/etiologia , Estudos Prospectivos , Esclerodermia Difusa/complicações , Úlcera Cutânea/etiologia , Úlcera Cutânea/fisiopatologia
14.
Clin Exp Rheumatol ; 35 Suppl 106(4): 198-207, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28869416

RESUMO

OBJECTIVES: Haematopoetic autologous stem cell transplantation (ASCT) has emerged as a treatment option for patients with refractory, severe autoimmune disease. This is a systematic review of the current literature on ASCT in adult patients with systemic sclerosis (SSc). METHODS: Original articles published between 2005 and 2016 that evaluated the use of ASCT in patients with SSc were reviewed with respect to the primary outcomes of overall and transplant related mortality (TRM) rates, and secondary outcomes of changes in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), progression/event free survival (P/EFS) and quality of life measures. We also focussed on patient characteristics, the ASCT conditioning and mobilisation regimens used, and their relationship to patient outcome in each study. RESULTS: Of the 155 articles found, only 9 articles were suitable for review. There were 2 placebo-controlled trials (RCTs), ASTIS and ASSIST, and 7 observational and cohort studies. In general, patients undergoing ASCT had diffuse SSc with mRSS >14, and interstitial lung disease. The 2 RCTs showed a benefit in P/EFS (80-81%), FVC and quality of life measures in ASCT compared to monthly cyclophosphamide. All the studies showed an improvement in mRSS. TRM rates varied among studies, from 0 to 23%, with a trend to higher mortality rates in studies using higher doses of cyclophosphamide or myeloablative conditioning regimens. CONCLUSIONS: We conclude that ASCT is beneficial in some patients with SSc and that patient selection and conditioning regimens are critical determinants of prognosis and mortality post-ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Escleroderma Sistêmico/terapia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Escleroderma Sistêmico/mortalidade , Escleroderma Sistêmico/fisiopatologia , Condicionamento Pré-Transplante , Transplante Autólogo , Capacidade Vital
15.
Clin Exp Rheumatol ; 35 Suppl 106(4): 130-137, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28516877

RESUMO

OBJECTIVES: To evaluate the construct validity of the Workers Productivity and Impairment Activity Index: Specific Health Problem (WPAI:SHP) in Australian systemic sclerosis (SSc) patients. METHODS: SSc patients, identified through the Australian Scleroderma Cohort Study database, completed the WPAI:SHP and a quality of life instrument (PROMIS-29) cross-sectionally. The construct validity of the WPAI:SHP was assessed by the correlations between the WPAI:SHP and a range of SSc health states. Non-parametric correlation, including Spearman's correlation (ρ), was used to test the validity of WPAI:SHP and ability to distinguish between different health states. RESULTS: A total of 476 completed questionnaires was returned, equating to a response rate of 63.7%. Among those under 65 years of age, 155 patients (55.2%) were in paid employment. Employed patients had a mean (± SD) age of 56.5 (9.8) years and were predominantly female (87.3%) with limited disease subtype (75.6%). The WPAI:SHP showed construct validity based on moderate to strong correlations with health status as assessed by a range of health outcome measures including disease activity (ρ=0.34-0.39, p=0.001), physical function (ρ=0.55-0.62, p=0.001), disease severity(ρ=0.55-0.62, p=0.001), fatigue (ρ= 0.62-0.63, p=0.001), pain (ρ=0.68-0.71, p=0.001), and breathlessness (ρ=0.39-0.46, p=0.001). Furthermore, according to the effect size, the WPAI:SHP scores have a large discriminative ability (d=1.26-1.47) for distinguishing SSc patients with different health outcomes. CONCLUSIONS: The WPAI is a valid questionnaire for assessing impairments in paid employment and social activities in SSc patients, and for measuring the relative differences between SSc patients with varying health states.


Assuntos
Eficiência , Emprego , Nível de Saúde , Escleroderma Sistêmico/fisiopatologia , Inquéritos e Questionários , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
16.
Int J Rheum Dis ; 20(4): 481-488, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28337853

RESUMO

OBJECTIVES: To assess the long-term efficacy and tolerability of mycophenolate mofetil (MMF) in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients enrolled in the Australian Scleroderma Cohort study with dcSSc and baseline modified Rodnan skin score (mRSS) ≥ 12 who were treated for a minimum of 12 months with MMF for the primary indication of skin disease were included and their prospectively collected data retrieved. Change in mRSS, the proportion with a clinically significant improvement (reduction in mRSS ≥ 5 from baseline) and adverse effects due to therapy were determined. RESULTS: Seventy-four participants treated with MMF were identified and of these, 42 met inclusion criteria. The mean age was 53 ± 12 years, with mean disease duration at MMF commencement of 4.8 ± 4.3 years. Twenty-one participants (50%) commenced MMF within 2 years of disease onset and the mean duration of therapy was 2.7 ± 1.7 years. The mean mRSS at baseline was 25.9 ± 9.2 with a reduction of 3.7 ± 7.1 (P = 0.07) after 1 year of therapy, 7.6 ± 8.3 after 2 years (P = 0.01) and 10.5 ± 10.3 after 5 years (P < 0.01). Response to treatment was not affected by disease duration at MMF commencement or baseline skin score. Eighteen participants (43%) demonstrated clinically significant improvement after 1 year, increasing to 92% after 4 years. Two participants (5%) ceased MMF due to adverse effects. CONCLUSION: MMF was associated with a modest improvement in mRSS and was well tolerated in the treatment of dcSSc. Given the natural history of dcSSc where skin involvement can spontaneously improve, randomized, placebo-controlled studies are required to confirm whether improvement can be attributed to MMF therapy.


Assuntos
Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Esclerodermia Difusa/tratamento farmacológico , Adulto , Austrália , Feminino , Humanos , Imunossupressores/efeitos adversos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Estudos Prospectivos , Indução de Remissão , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/imunologia , Fatores de Tempo , Resultado do Tratamento
17.
Ann Rheum Dis ; 76(7): 1207-1218, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28188239

RESUMO

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441.


Assuntos
Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Esclerodermia Difusa/tratamento farmacológico , Adulto , Anticorpos Antinucleares/imunologia , Autoanticorpos/imunologia , Estudos de Coortes , Intervenção Médica Precoce , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/imunologia , Estudos Prospectivos , RNA Polimerase III/imunologia , Esclerodermia Difusa/imunologia , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
18.
Arthritis Res Ther ; 18(1): 246, 2016 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-27770830

RESUMO

BACKGROUND: In some rheumatic diseases such as systemic lupus erythematosus (SLE), low serum complement ('hypocomplementaemia') is a feature of active disease. However, the role of hypocomplementaemia in systemic sclerosis (SSc) is unknown. We sought to determine the frequency, clinical associations and relationship to disease activity of hypocomplementaemia in SSc. METHODS: The study included 1140 patients fulfilling the 2013 American College of Rheumatology criteria for SSc. Demographic, serological and clinical data, obtained prospectively through annual review, were analysed using univariable methods. Linear and logistic regression, together with generalised estimating equations, were used to determine the independent correlates of hypocomplementaemia ever, and at each visit, respectively. RESULTS: At least one episode of hypocomplementaemia (low C3 and/or low C4) occurred in 24.1 % of patients over 1893 visits; these patients were more likely to be seropositive for anti-ribonucleoprotein (OR = 3.8, p = 0.002), anti-Ro (OR = 2.2, p = 0.002), anti-Smith (OR = 6.3, p = 0.035) and anti-phospholipid antibodies (OR = 1.4, p = 0.021) and were more likely to display features of overlap connective tissue disease, in particular polymyositis (OR = 16.0, p = 0.012). However, no association was found between hypocomplementaemia and either the European Scleroderma Study Group disease activity score or any of its component variables (including erythrocyte sedimentation rate) in univariate analysis. Among patients with SSc overlap disease features, those who were hypocomplementaemic were more likely to have digital ulcers (OR = 1.6, p = 0.034), tendon friction rubs (OR = 2.4, p = 0.037), forced vital capacity <80 % predicted (OR = 2.9, p = 0.008) and lower body mass index (BMI) (OR for BMI = 0.9, p < 0.0005) at that visit, all of which are features associated with SSc disease activity and/or severity. CONCLUSIONS: While hypocomplementaemia is not associated with disease activity in patients with non-overlap SSc, it is associated with some features of increased SSc disease activity in patients with overlap disease features.


Assuntos
Complemento C3/metabolismo , Complemento C4/metabolismo , Escleroderma Sistêmico/imunologia , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doenças Autoimunes/complicações , Complemento C3/imunologia , Complemento C4/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Clin Exp Rheumatol ; 34 Suppl 100(5): 129-136, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27214686

RESUMO

OBJECTIVES: Asymmetric dimethylarginine (ADMA) is a novel biomarker of endothelial cell dysfunction. In this proof of concept study, we sought to evaluate the role of ADMA as a screening biomarker for incident systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). METHODS: ADMA levels were measured using high performance liquid chromatography in 15 consecutive treatment-naive patients with newly-diagnosed SSc-PAH and compared with 30 SSc-controls without PAH. Logistic regression models were used to evaluate the independent association of ADMA with PAH. The optimal cut-point of ADMA for SSc-PAH screening was determined. NT-proBNP levels were previously measured in the same patients and the optimal cut-point of NT-proBNP of ≥210ng/mL was coupled with the optimal cut-point of ADMA to create a screening model that combined the two biomarkers. RESULTS: The PAH group had significantly higher mean ADMA levels than the control group (0.76±0.14 µM versus 0.59±0.07 µM; p<0.0001). ADMA levels remained significantly associated with PAH after the adjustment for specific disease characteristics, cardiovascular risk factors and other SSc-related vascular complications (all p<0.01). An ADMA level ≥0.7 µM had a sensitivity of 86.7%, specificity of 90.0% and AUC of 0.86 for diagnosing PAH. A screening model that combined an NT-proBNP ≥210ng/mL and/ or ADMA ≥0.7 ng/mL resulted in a sensitivity of 100% and specificity of 90% for the detection of SSc-PAH. CONCLUSIONS: In this small study, use of ADMA in combination with NT-proBNP produced excellent sensitivity and specificity for the non-invasive identification of SSc-PAH. The role of ADMA as a screening biomarker for SSc-PAH merits further evaluation.


Assuntos
Arginina/análogos & derivados , Pressão Arterial , Hipertensão Pulmonar/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Artéria Pulmonar/fisiopatologia , Escleroderma Sistêmico/complicações , Adulto , Área Sob a Curva , Arginina/sangue , Austrália , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Fatores de Risco , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico
20.
Clin Exp Rheumatol ; 34 Suppl 100(5): 170-176, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27049330

RESUMO

OBJECTIVES: To report the efficacy and tolerability of mycophenolate mofetil (MMF) and azathioprine (AZA) in the management of systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: Patients in the Australian Scleroderma Cohort Study treated with at least 3 months of MMF or AZA for SSc-ILD confirmed on high resolution computed tomography (HRCT) chest were identified and their pulmonary function tests (PFTs) retrieved. Individuals with available results for T-1 (12 months prior to treatment commencement), T0 (date of treatment commencement) and at least one subsequent time point were included in the drug efficacy analysis. The Wilcoxon signed-rank test was used to compare absolute FVC at T1, T0, 12 months (T1), 24 months (T2) and 36 months (T3). Analysis of drug tolerability included all identified patients treated with MMF or AZA. RESULTS: 18/22 patients treated with MMF and 29/49 treated with AZA had adequate PFTs for inclusion in the drug efficacy analysis. Median absolute FVC at T1 for MMF treatment was 2.50L, declining to 2.12L at T0 (p=0.02). Following MMF therapy, FVC results were stable at T1 (2.13L, p=0.86), T2 (2.17L, p=0.65) and T3 (2.25L, p=0.78). In the AZA group, a statistically significant decline did not occur prior to treatment, however FVC results remained stable at T1, T2 and T3.Adverse events leading to early discontinuation (<12 months treatment) were less common in the MMF group (4/22 vs. 13/49). Gastrointestinal complications were the main cause of discontinuation in both groups. CONCLUSIONS: In patients with SSc-ILD with declining pulmonary function, MMF therapy was associated with stability for up to 36 months. Early adverse events leading to discontinuation occurred less frequently in patients treated with MMF than in AZA treated patients.


Assuntos
Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pulmão/efeitos dos fármacos , Ácido Micofenólico/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Idoso , Austrália , Azatioprina/uso terapêutico , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Estudos Longitudinais , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Testes de Função Respiratória , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA