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1.
Clin Rheumatol ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31902028

RESUMO

OBJECTIVE: To investigate cognitive dysfunction in adult patients with systemic sclerosis (SSc) who had no known clinical neurological manifestations and to relate it with other disease severity parameters. METHODS: In the present study, 20 SSc consecutive female patients, who met the 2013 American College of Rheumatology SSc criteria, were compared with 20 healthy age-, gender-, and educational status-matched volunteer hospital workers. Mean age and duration of illness were 41.8 ± 12.52 and 6.9 ± 5.4 years respectively. Mini-Mental State Examination (MMSE), Wechsler Adult Intelligence scale (WAIS-III), and P300 component of event-related potentials (ERPs) were used to evaluate cognitive function in SS subjectively and objectively respectively. RESULTS: Sixty-five percent (13 out of 20) of SSc patients had MMSE score < 25, and cognitive impairment. Despite the lack of clinically apparent neurological manifestations, SSc patients had significantly low MMSE score, high Deterioration Index (DI), and prolonged P300 latency compared with that of the control group (P = 0.0001; 0.010 and 0.008 respectively). A significant positive association was found between (DI) and the Medsger severity vascular score (r = 0.518; P = 0.012).There were few differences between limited and diffuse SSc. CONCLUSIONS: To our knowledge, few studies highlighted that subclinical cognitive impairment can occur in the course of SSc disease. Early diagnosis of cognitive impairment should be investigated either subjectively (using psychometrics tests as MMSE or WAIS-III) or objectively using P300 evoked related potentials. Medsger severity vascular score seems to be closely related to cognitive impairment.Key points• Cognitive impairment can be associated with Medsger Vascular severity score and the duration of illness.• Further larger studies will be needed to estimate the effect of disease activity on cognitive function, to further delineate the differences between limited and diffuse SSc in this area, and to understand the underlying pathophysiological mechanisms causing cognitive impairment in patients with SSc.• To investigate impaired cognitive function in patients with SSc, even in the absence of clinically apparent neurological and vascular disease.

2.
Arthritis Rheumatol ; 72(1): 125-136, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31342624

RESUMO

OBJECTIVE: T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS: In this 12-month, randomized, double-blind, placebo-controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets. RESULTS: Among 88 participants, the adjusted mean change in the MRSS at 12 months was -6.24 units for those receiving abatacept and -4.49 units for those receiving placebo, with an adjusted mean treatment difference of -1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal-like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively. CONCLUSION: In this phase II trial, abatacept was well-tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

3.
Ann Rheum Dis ; 79(2): 268-275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31848144

RESUMO

OBJECTIVES: Familial aggregation of primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and co-aggregation of these autoimmune diseases (ADs) (also called familial autoimmunity) is well recognised. However, the genetic predisposition variants that explain this clustering remains poorly defined. METHODS: We used whole-exome sequencing on 31 families (9 pSS, 11 SLE, 6 RA and 5 mixed autoimmunity), followed by heterozygous filtering and cosegregation analysis of a family-focused approach to document rare variants predicted to be pathogenic by in silico analysis. Potential importance in immune-related processes, gene ontology, pathway enrichment and overlap analyses were performed to prioritise gene sets. RESULTS: A range from 1 to 50 rare possible pathogenic variants, including 39 variants in immune-related genes across SLE, RA and pSS families, were identified. Among this gene set, regulation of T cell activation (p=4.06×10-7) and T cell receptor (TCR) signalling pathway (p=1.73×10-6) were particularly concentrated, including PTPRC (CD45), LCK, LAT-SLP76 complex genes (THEMIS, LAT, ITK, TEC, TESPA1, PLCL1), DGKD, PRKD1, PAK2 and NFAT5, shared across 14 SLE, RA and pSS families. TCR-interactive genes P2RX7, LAG3, PTPN3 and LAX1 were also detected. Overlap analysis demonstrated that the antiviral immunity gene DUS2 variant cosegregated with SLE, RA and pSS phenotypes in an extended family, that variants in the TCR-pathway genes CD45, LCK and PRKD1 occurred independently in three mixed autoimmunity families, and that variants in CD36 and VWA8 occurred in both RA-pSS and SLE-pSS families. CONCLUSIONS: Our preliminary results define common genetic characteristics linked to familial pSS, SLE and RA and highlight rare genetic variations in TCR signalling pathway genes which might provide innovative molecular targets for therapeutic interventions for those three ADs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31794028

RESUMO

OBJECTIVE: Idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) significantly increases morbidity and mortality. Lung ultrasound B-lines and Krebs von den Lungen-6 (KL-6) are identified as new sonographic and serum markers of ILD, respectively. The aim of our work was to assess the role of B-lines and KL-6 as markers of the severity of IIM-ILD. For this purpose, the correlation among B-lines score, serum KL-6 levels, high-resolution CT (HRCT) score, and pulmonary function tests were investigated in IIM-ILD patients. METHODS: Thirty-eight patients with IIM-ILD underwent chest HRCT scans, lung ultrasound and pulmonary function tests (independently performed within 1 week) examination. To assess severity and extent of ILD at HRCT, the Warrick score was used. The B-lines score denoting the extension of ILD was calculated by summing the number of B-lines on a total of 50 scanning sites. Serum KL-6 levels (U/ml) was measured by chemiluminescent enzyme immunoassay. RESULTS: A significant correlation was found between the B-lines score and serum KL-6 levels (r = 0.43, P < 0.01), and between the Warrick score and serum KL-6 levels (r = 0.45, P < 0.01). A positive correlation between B-lines score and the Warrick score (r = 0.87, P < 0.0001) was also confirmed. Both B-lines score and KL-6 levels inversely correlated to diffusion capacity for carbon monoxide (r = -0.77, P < 0.0001 and r = -0.42, P < 0.05, respectively) and total lung capacity (r = -0.73, P < 0.0001 and r = -0.36, P < 0.05, respectively). Moreover, B-lines correlated inversely with forced vital capacity (r = -0.73, P < 0.0001), forced expiratory volume in 1 s (r = -0.69, P < 0.0001). CONCLUSION: B-lines score and serum KL-6 levels correlate with HRCT findings and pulmonary function tests, supporting their use as measures of IIM-ILD severity.

5.
Drug Saf ; 42(12): 1499-1506, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31696432

RESUMO

INTRODUCTION: The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Rheumatology Common Toxicity Criteria (RCTC) version 2.0 was published in 2007 by the OMERACT Drug Safety Working Group, building on limited experience with RCTC version 1.0, to facilitate standardization of assessment (grading) and reporting of adverse events (AEs) commonly seen in rheumatic disease clinical trials (Woodworth et al. in J Rheumatol 34:1401-1414, 2007). OBJECTIVES: The objectives of this study were to (1) report the real-world performance of RCTC 2.0; (2) report immediately correctable errors in RCTC 2.0, and provide a revised RCTC 2.1; and (3) begin to identify the need for a comprehensive revision of RCTC 2.0. METHODS: Safety data outputs for several large rheumatic/autoimmune disease clinical trials in which RCTC 2.0 was used were evaluated for accuracy of reporting and the ability to assess differences among treatments. We examined RCTC 2.0 tables for errors, as well as for omission of terms for AEs that commonly occur in more recent rheumatology clinical trials. We also considered recommendations from recent US Food and Drug Administration (FDA) and international initiatives such CDISC (Clinical Data Interchange Standards Consortium) to improve the consistency of safety data collection and interpretability of safety data analyses. RESULTS: RCTC 2.0 enabled comparisons of safety data across treatment groups, including grading. However, we discovered inaccuracies in laboratory results grading and omission of AE terms now recognized to occur in rheumatic disease clinical trials. CONCLUSION: The RCTC 2.0 performed as intended, although some inaccuracies and omissions were found. We provide a corrected version, RCTC 2.1, and also recommend further revision of the RCTC within OMERACT guidances to include AEs that have been reported in rheumatology clinical trials since RCTC 2.0 was published. Ideally, a revised RCTC 3.0 would not only facilitate standardized assessment and reporting of AEs, but would also expand and encourage accurate comparison of the safety profiles of treatments for rheumatic/autoimmune diseases.

6.
Rheumatol Ther ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754941

RESUMO

INTRODUCTION: Patients with rheumatoid arthritis (RA) are at an increased risk of developing malignancies, but it is unclear whether this increased risk is the result of disease pathobiology or immunosuppressant treatments for RA. This analysis evaluated the potential risk of malignancy in patients with RA treated with rituximab (MabThera®/Rituxan®) a CD20+ B-cell depleting agent manufactured by F. Hoffmann-La Roche Ltd. METHODS: Malignancy rates were obtained from the rituximab global company safety database for adverse event reporting and from the rituximab global clinical trial program for RA consisting of eight randomized clinical trials, two long-term open-label extensions, and one open-label prospective study. Global company safety database searches were performed using the standard Medical Dictionary for Regulatory Activities (MedDRA) queries "Malignant tumors wide" and "Skin malignant tumors wide" up to April 30, 2017. Age- and sex-specific comparator values from the general population were obtained from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: For the 409,706 patients with RA in the rituximab global company safety database since first market approval in 2006, 1739 cumulative malignant events were reported, with an overall malignancy reporting rate of approximately 4.2 events per 1000 patients. No evidence of increased risk of malignancy, of any organ-specific type, was found following rituximab treatment. The rate of malignancies from rituximab-treated patients in RA clinical trials was 7.4 per 1000 patient-years. This is within the expected range, with no evidence for increased risk over time or with additional rituximab courses. CONCLUSIONS: Analyses of the global postmarketing safety database and long-term clinical trial data showed no evidence of an increased risk of malignancy of any type following rituximab treatment in patients with RA. FUNDING: F. Hoffmann-La Roche Ltd.

7.
Eur J Intern Med ; 70: 43-49, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31540806

RESUMO

BACKGROUND: Renal Resistive Index (RRI), reflects changes in both renal vascular and tubular-interstitial compartments and in systemic vascular compliance related to age and comorbidities. OBJECTIVES: a) To investigate determinants of RRI in SSc population, b) its association with SSc-related features and c) to test its prognostic impact on organ specific worsening or death. METHODS: 380 SSc patients ≥18 years were enrolled after giving informed consent. Baseline data on RRI, laboratory, instrumental and therapeutic features were retrospectively collected. Age-SSc adjusted cut-offs were created by dividing the population in age quartiles and considering RRI values >75th percentile as pathologic. Clinical follow-up was performed until last available visit or the development/worsening of specific internal organ involvement or death. RESULTS: RRI was independently predicted by age and systolic pulmonary arterial pressure on Echo. Therefore, we created Age-SSc adjusted pathologic RRI cut-offs, which were significantly associated with various disease related skin and lung fibrotic manifestations, as well as vasculopathic complications. After a mean follow-up of 3.6 ±â€¯2.6 years, RRI was one of the independent predictors (together with modified Rodnan skin score, interstitial lung disease, presence of dyspnoea and late nailfold-videocapillaroscopy pattern) for mortality, with 0.68 as best cut-off (sensitivity 88.5%, specificity 50.9%). CONCLUSION: If corroborated, Renal Resistive Index cut-offs might be used to evaluate renal and extrarenal involvement in SSc and could serve as predictors of mortality.

8.
J Rheumatol ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31474594

RESUMO

OBJECTIVE: Through a systemic literature research (SLR) and meta-analysis, to determine maternal and foetal outcomes in SSc pregnancies, to analyse the effect of pregnancy on disease activity and to explore predictors of foetal and maternal outcomes. METHODS: A SLR was performed for articles on SSc and pregnancy published between 1950 and 1st February 2018. Reviewers double extracted articles to obtain agreement on>95% of pre-defined critical outcomes. RESULTS: 461 publications were identified, 16 were included in the meta-analysis. The metanalysis showed that SSc pregnancies were at higher risk of miscarriages (OR 1.6,CI95% 1.22-2.22), foetuses with intrauterine growth retardation (IUGR) (OR 3.2,CI95% 2.21-4.53), preterm births (OR 2.4,CI95% 1.14-4.86) and newborns with low birth weight (OR 3.8,CI95% 2.16-6.56). SSc patients had 2.8 times higher chance of developing gestational hypertension (OR 2.8,CI95% 2.28-3.39) and 2.3 times higher chance of having Caesarean delivery compared to controls (OR 2.3,CI95% 1.37-3.8). The definitions of disease worsening/new visceral organ involvement were too inexact to have any confidence in the results although there were said to be worsening or new disease manifestations during pregnancy in 44/307(14.3%) cases and during the 6-months post-partum in 32/306(10.5%) cases. The data did not permit definition of predictors of disease progression and of maternal and foetal outcomes. CONCLUSION: SSc pregnancies have increased frequency of miscarriages, IUGR, pre-term deliveries and newborns with low birth weight compared to healthy controls. SSc women were more prone to develop gestational hypertension and to undergo Caesarean section. Disease manifestations seem to remain stable or improve in most patients.

9.
Ann Rheum Dis ; 78(10): 1371-1378, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31391177

RESUMO

OBJECTIVE: In the randomised scleroderma: Cyclophosphamide Or Transplantation (SCOT trial) (NCT00114530), myeloablation, followed by haematopoietic stem cell transplantation (HSCT), led to improved clinical outcomes compared with monthly cyclophosphamide (CYC) treatment in systemic sclerosis (SSc). Herein, the study aimed to determine global molecular changes at the whole blood transcript and serum protein levels ensuing from HSCT in comparison to intravenous monthly CYC in 62 participants enrolled in the SCOT study. METHODS: Global transcript studies were performed at pretreatment baseline, 8 months and 26 months postrandomisation using Illumina HT-12 arrays. Levels of 102 proteins were measured in the concomitantly collected serum samples. RESULTS: At the baseline visit, interferon (IFN) and neutrophil transcript modules were upregulated and the cytotoxic/NK module was downregulated in SSc compared with unaffected controls. A paired comparison of the 26 months to the baseline samples revealed a significant decrease of the IFN and neutrophil modules and an increase in the cytotoxic/NK module in the HSCT arm while there was no significant change in the CYC control arm. Also, a composite score of correlating serum proteins with IFN and neutrophil transcript modules, as well as a multilevel analysis showed significant changes in SSc molecular signatures after HSCT while similar changes were not observed in the CYC arm. Lastly, a decline in the IFN and neutrophil modules was associated with an improvement in pulmonary forced vital capacity and an increase in the cytotoxic/NK module correlated with improvement in skin score. CONCLUSION: HSCT contrary to conventional treatment leads to a significant 'correction' in disease-related molecular signatures.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31280935

RESUMO

BACKGROUND: There has been a significant increase in financial support of clinical research by the pharmaceutical industry. METHODS: We performed a comprehensive systematic literature review to determine whether there is publication bias for rheumatoid arthritis (RA) studies between industry-funded and non-industry funded randomized controlled trials (RCTs), and between RCTs with positive results (PRs) and those with negative results (NRs) of FDAapproved biological and small molecule drug therapy for RA. Each RCT was classified as having either a PR or a NR, and as having received commercial funding or not. RESULTS: Most (297/349, 85.18%) of the RCTs were commercially funded. There was no significant difference in PRs or association with publication between commercially and noncommercially funded RCTs. Sample size was significantly larger in commercially funded RCTs and in those with PRs, and it was the only significant parameter that predicted publication in higher impact factor journals in the field of RA. CONCLUSION: There is no significant association between commercial funding and the publication of positive results or the publication of an RCT in higher impact factor journals.

12.
Arthritis Res Ther ; 21(1): 135, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164157

RESUMO

The triggers and pathogenesis of axial spondyloarthritis (axSpA) are not yet completely understood. However, therapeutic agents targeting tumor necrosis factor-α and interleukin-17 inflammatory pathways have proven successful in suppressing many of the clinical symptoms and signs of axSpA, giving us an indication of which pathways are responsible for initiating and maintaining the inflammation. The mechanisms that eventuate in syndesmophytes and ankyloses are less clear. This review addresses these two critical pathways of inflammation, discussing their nature and these factors that may activate or enhance the pathways in patients with axSpA. In addition, genetic and other markers important to the inflammatory pathways implicated in axSpA are explored, and prognostic biomarkers are discussed. Treatment options available for the management of axSpA and their associated targets are highlighted.

13.
Arthritis Rheumatol ; 71(12): 2059-2067, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31233287

RESUMO

OBJECTIVE: To investigate the relationship between Krebs von den Lungen 6 (KL-6) and CCL18 levels and the severity and progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS: Patients enrolled in the Scleroderma Lung Study II (cyclophosphamide [CYC] versus mycophenolate mofetil [MMF]) were included. Baseline and 12-month plasma samples were analyzed by enzyme-linked immunosorbent assay to assess CCL18 and KL-6 levels. The forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLco) were measured every 3 months. Joint models were created to investigate the relationship between baseline CCL18 and KL-6 levels and the course of the FVC and DLco over 1 year according to treatment arm. RESULTS: Baseline KL-6 and CCL18 levels each correlated with the extent of radiographic fibrosis. Levels of both CCL18 and KL-6 declined significantly at 1 year. In both treatment arms (n = 71 for CYC, n = 62 for MMF), a higher baseline KL-6 level predicted progression of ILD based on the course of FVC (P = 0.024 for CYC; P = 0.005 for MMF) and DLco (P < 0.001 for CYC; P = 0.004 for MMF) over 1 year. A higher baseline CCL18 level predicted progression of ILD based on the course of the FVC (P < 0.001 for CYC; P = 0.007 for MMF) and DLco (P = 0.001 for CYC; P < 0.001 for MMF) over 1 year, as well as mortality (P = 0.0008 for CYC arm only). CONCLUSION: In a rigorously conducted clinical trial for SSc-related ILD, KL-6 and CCL18 levels correlated with ILD severity and declined with immunosuppression. Patients with higher baseline KL-6 and CCL18 levels were more likely to experience disease progression despite treatment. KL-6 and CCL18 levels could be used to identify patients with a progressive ILD phenotype who may benefit from a more aggressive initial treatment approach.

14.
J Rheumatol ; 46(9): 1173-1178, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31043547

RESUMO

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Safety Working Group objective was to identify harm domains from existing outcome measurements in rheumatology. METHODS: Systematically searching the MEDLINE database on January 24, 2017, we identified full-text articles that could be used for harm outcomes in rheumatology. Domains/items from the identified instruments were described and the content synthesized to provide a preliminary framework for harm outcomes. RESULTS: From 435 possible references, 24 were read in full text and 9 were included: 7 measurement instruments were identified. Investigation of domains/items revealed considerable heterogeneity in the grouping and approach. CONCLUSION: The ideal way to assess harm aspects from the patients' perspective has not yet been ascertained.

15.
Arthritis Res Ther ; 21(1): 95, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987675

RESUMO

BACKGROUND/OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease associated with immune abnormalities and widespread vascular lesions, including increased intimal and medial thickness. These changes may be reflected in early atherosclerosis and cardiovascular risks. We aimed in this study to examine the carotid artery intima-media thickness and MRI brain findings in SSc patients and compared them to a group of normal controls. A relationship between these parameters and clinical measures in SSc was also sought. METHODS: Seventy-two SSc patients with no central nervous system (CNS) symptoms and 42 healthy controls were included. Clinical and laboratory measures, Medsger's severity scale, and Doppler ultrasound common carotid artery intima-media thickness (CCA-IMT) were measured. Brain fluid-attenuated inversion recovery (FLAIR)-MRI and diffusion-weighted MRI (DWI) were also done. RESULTS: SSc patients had more CCA-IMT, higher CRP, and more brain MRI hyperintense lesions than controls (P < 0.05). Significant positive correlations existed between CCA-IMT and Medsger vascular (r = 0.7, P = 0.02). The FLAIR-MRI showed multiple hyperintense lesions in 24 patients (33%), ranging 0-36 lesions. SSc patients with more lesions (positive MRI) had longer disease duration (P = 0.001) and left and right carotid artery atheromata (P = 0.001, and 0.013, respectively) than SSc patients with negative MRIs; Medsger vascular score did not separate the SSc groups (P = 0.08). CONCLUSIONS: In systemic sclerosis patients without central nervous system symptoms, MRI lesion numbers correlated with CCA-IMT. MRI abnormalities were found more frequently if CRP was elevated, if the Medsger SSc Severity Scale was increased, or if there was thickened carotid IMT.

16.
RMD Open ; 5(1): e000840, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30997151

RESUMO

Objectives: To complete reporting of outcomes after total withdrawal of all rheumatoid arthritis (RA) therapy and re-treatment after flare in Assessing Very Early Rheumatoid arthritis Treatment study (NCT01142726). Methods: Patients with early RA were initially randomised to double-blind, weekly subcutaneous abatacept plus methotrexate, or abatacept or methotrexate monotherapy. At month 12, patients with Disease Activity Score (DAS)28 C reactive protein (CRP) <3.2 had all RA treatments rapidly withdrawn and were observed for ≤12 months or until flare. After ≥3 months' withdrawal, patients with protocol-defined RA flare received open-label abatacept plus methotrexate for 6 months (re-treatment). Results: Proportion of patients in DAS28-CRP-defined remission remained numerically higher in original abatacept plus methotrexate and abatacept arms versus methotrexate arm up to day 253 of withdrawal. At the end of the withdrawal period, few patients remained in remission across all arms: 9/73 (12.3%), 7/50 (14.0%) and 6/53 (11.3%), respectively. For patients entering re-treatment, after 6 months' re-treatment, 95/124 (76.6%) and 78/124 (62.9%) patients achieved DAS28-CRP <3.2 and <2.6, respectively; mean changes in DAS28-CRP and Health Assessment Questionnaire-Disability Index scores from re-treatment baseline were -2.87 and 0.76, respectively. Re-treatment was well tolerated; exposure-adjusted infection rates per 100 patient-years were lower with abatacept plus methotrexate during withdrawal (7.2) and re-treatment (17.2) versus initial treatment periods of months 0-6 (116.6) and 6-12 (64.6). Conclusions: Most patients flared within 6 months of therapy withdrawal and few sustained major responses for 1 year. Re-treatment with abatacept plus methotrexate was effective and well tolerated in this controlled setting.

18.
Clin Immunol ; 202: 59-75, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30738143

RESUMO

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory musculoskeletal condition with complex pathophysiology. In recent years, understanding of the pathogenesis of PsA has improved substantially. Several genetic and inflammatory factors have been identified and studied as targets for new biologic disease-modifying therapies. This review presents findings from a detailed literature assessment conducted to identify genes and biomarkers associated with PsA and its most common comorbidities. This literature assessment identifies genes and biomarkers that may be predictive of the onset and severity of PsA, places them in the context of our understanding of PsA pathogenesis, and explores potential connections between the pathways involved in PsA and current biologic therapeutics used to treat PsA. Knowledge of the genetics and inflammatory factors associated with disease pathogenesis can support the targeted development of new biologic therapies and biomarkers for PsA.

19.
J Rheumatol ; 46(10): 1316-1325, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30770517

RESUMO

OBJECTIVE: To compare safety and efficacy outcomes between the cyclophosphamide (CYC) arms of Scleroderma Lung Study (SLS) I and II. METHODS: Participants enrolled in the CYC arms of SLS I (n = 79) and II (n = 69) were included. SLS I and II randomized participants to oral CYC for 1 year and followed patients for an additional year off therapy (in SLS II, patients received placebo in Year 2). Eligibility criteria for SLS I and II were nearly identical. Outcomes included the forced vital capacity (FVC%)-predicted and DLCO%-predicted (measured every 3 mos) and quantitative radiographic extent of interstitial lung disease (measured at 1 and 2 yrs for SLS I and SLS II, respectively). Joint models were created to evaluate the treatment effect on the course of the FVC/DLCO over 2 years while controlling for baseline disease severity. RESULTS: SLS I and II CYC participants had similar baseline characteristics. After adjusting for baseline disease severity, there was no difference in the course of the FVC%-predicted (p = 0.535) nor the DLCO%-predicted (p = 0.172) between the SLS I and II CYC arms. In both groups, treatment with CYC led to a significant improvement in the FVC%-predicted from 3 to 12 months, but no significant improvement beyond this point. Treatment with CYC had no effect on the DLCO for either group. CONCLUSION: Treatment with 1 year of oral CYC led to similar improvements in lung function in both SLS I and II, although the effects were not sustained following cessation of CYC. These results suggest that increasing the duration of ILD therapy may improve outcomes for patients with systemic sclerosis-ILD.

20.
Clin Rheumatol ; 38(5): 1433-1436, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30746580

RESUMO

In the past decade, lung ultrasound (LUS) B-lines and serum Krebs von den Lungen-6 (KL-6) antigen have been recognized as biomarkers of the connective tissue disease-associated interstitial lung diseases (CTD-ILDs). Robust data have demonstrated that B-lines total numbers and KL-6 levels are correlated with high-resolution computed tomography findings, pulmonary function test, and some clinical parameters in CTD-ILDs. However, limited data are available regarding the use of these two biomarkers to follow CTD-ILDs. Herein, we report a case with anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis-associated ILD, successfully treated with high-dose methylprednisolone, cyclophosphamide, intravenous immunoglobulin, pirfenidone, and followed using lung ultrasound and KL-6.


Assuntos
Dermatomiosite/complicações , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Mucina-1/sangue , Adulto , Anticorpos Antinucleares/sangue , Biomarcadores/sangue , Dermatomiosite/sangue , Progressão da Doença , Feminino , Humanos , Helicase IFIH1 Induzida por Interferon/imunologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/etiologia , Testes de Função Respiratória , Ultrassonografia
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