Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 584
Filtrar
1.
J Rheumatol ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649067

RESUMO

This article summarizes sessions that dealt with axial psoriatic arthritis (axPsA) at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 virtual meeting. The summary includes the symposium, which comprised a plenary presentation by Dr. Dafna Gladman from Toronto, Canada, as well as a panel discussion with Dr. Philip Helliwell, Dr. Denis Poddubnyy, and Dr. Gladman, moderated by Dr. Philip Mease. In addition, the paper also summarizes Dr. Mease's "Meet the Expert" session, which focused on axPsA.

2.
J Rheumatol ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649070

RESUMO

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Working Group provided updates at the 2020 GRAPPA annual meeting on its work toward developing a core outcome set for PsA. Working groups were set up for the 4 prioritized domains: enthesitis, fatigue, structural damage, and physical function. Two instruments for measurement of physical function were provisionally endorsed: (1) the Health Assessment Questionnaire-Disability Index and (2) the physical functioning domain in the Medical Outcomes Study 36-item Short Form survey.

3.
Arthritis Res Ther ; 23(1): 94, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33766074

RESUMO

BACKGROUND: In psoriatic arthritis (PsA), further understanding of the relationships between clinical measures and patient-reported outcomes (PROs) is needed. This post hoc analysis evaluated associations between minimal disease activity (MDA) as a continuous outcome (termed ScoreMDA) or Psoriatic Arthritis Disease Activity Score (PASDAS) with selected PROs not included in the composite measures. METHODS: Data from two phase 3 studies of tofacitinib in PsA (OPAL Broaden [NCT01877668; N = 422]; OPAL Beyond [NCT01882439; N = 394]) were included. MDA (binary outcome) was defined as meeting ≥5/7 criteria. For ScoreMDA, each criterion was assigned a value (1 = true; 0 = false; score range, 0-7; scores ≥5 indicated MDA). For PASDAS (score range, 0-10), higher scores indicated worse disease activity. PROs analyzed included Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Patient's Assessment of Arthritis Pain visual analog scale (Pain VAS), and EuroQoL-Five Dimensions-Three Level Health Questionnaire visual analog scale (EQ-5D-3L VAS) and utility index. Relationships were evaluated using repeated measures regression models. RESULTS: Similar, approximately linear relationships were confirmed between PASDAS or ScoreMDA and PROs in both studies. In OPAL Broaden and OPAL Beyond, a one-point difference in PASDAS was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (- 6.7 mm, - 6.9 mm), Pain VAS (9.9 mm, 10.7 mm), and FACIT-F (- 2.8, - 3.3). A one-point difference in ScoreMDA was associated with clinically relevant differences in PROs, including EQ-5D-3L VAS (5.0 mm, 5.5 mm) and FACIT-F (1.9, 2.7) in OPAL Broaden and OPAL Beyond, respectively. CONCLUSIONS: Linear associations between PASDAS or ScoreMDA and PROs provide interpretable and quantifiable metrics between composite clinical measures and PROs, highlighting the importance of these measures in understanding the relevance of treat-to-target goals in PsA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01877668 . Registered on June 12, 2013. ClinicalTrials.gov, NCT01882439 . Registered on June 18, 2013.

4.
Lupus ; : 9612033211004714, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33779380

RESUMO

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

5.
Artigo em Inglês | MEDLINE | ID: mdl-33662177

RESUMO

BACKGROUND: The existing guidelines for lupus nephritis (LN) recommend initial prednisone doses of 0.3-1mg/kg/day. However, recent studies reported non-inferior outcomes with lower doses. The aim of this study was to compare the complete renal response rates in LN patients treated with prednisone ≤30mg/day or ≥40mg/day. PATIENTS-METHODS: Patients with new-onset LN and standard immunosuppressive treatment were followed for at least 12 months, divided into medium (≤30mg/day) and high prednisone groups (≥40mg/day) and matched (propensity score) based on the baseline differences. Complete renal response was defined as proteinuria <0.5g/day and no worsening in renal function. Glucocorticoid-related damage was also assessed. RESULTS: High prednisone patients (n=103, mean dose 48.6±12.3 mg/day) achieved better rates of complete response compared to the medium group (n=103, mean dose 24.2±4.6 mg/day) [61.8% vs. 38.2%, p=0.024] at 12 months. The difference in response rates was reproduced for several subgroups (concomitant immunosuppressive treatment, proliferative/non-proliferative LN). Complete remission rates were higher at two [67.8% vs. 39%, p=0.002] and three years [64.9% vs. 49.1%, p=0.025] after LN diagnosis. Cumulative glucocorticoid dose was comparable at two and three years. Glucocorticoid-related damage was accelerated in both groups for the same period. CONCLUSION: Higher initial prednisone doses (median 45mg/day) achieved significantly better rates of complete renal response at 12 months in new-onset LN. Cumulative glucocorticoid dose and damage accrual was not different at 2 and 3 years after LN. Damage was more prominent in the late phases of LN in both groups, underlining the importance of rapid tapering and the need to implement alternative strategies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33662181

RESUMO

OBJECTIVE: We aimed to determine whether the presence of depression or anxiety is associated with the achieving sustained minimal disease activity (MDA) in patients with psoriatic arthritis (PsA). METHODS: Adult patients satisfying CASPAR criteria prospectively followed from 2008 to 2017 were included. A standard protocol including physician assessment and patient-reported outcomes defined whether patients achieved sustained MDA, defined when MDA criteria were met for two or more consecutive visits. The presence of depression/anxiety was determined using three definitions: 1) a score of <=38 on the Mental Component Summary score of the SF-36 questionnaire; 2) a score of <=56 on the Mental Health sub-scale score; and 3) rheumatologist's report of a diagnosis or treatment for depression/anxiety. A discrete time-to-event analyses was conducted based on a proportional odds model to identify factors associated with achieving sustained MDA. RESULTS: 743 patients were included in the study. The number of patients identified as having depression/anxiety at baseline was: Definition 1- 331 (44.54%), 2- 364 (48.99%), and 3- 211 (28.4%). 337 patients (45.36%) failed to achieve sustained MDA. The presence of depression/anxiety was associated with reduced probability of achieving sustained MDA with OR=0.30, p <0.0001, OR=0.34, p <0.0001, and OR=0.47, p <0.0001 for Definitions 1, 2 and 3, respectively. Other variables associated with a reduced probability of achieving sustained MDA included the Charlson comorbidity index and fibromyalgia. CONCLUSION: Symptoms of anxiety/depression reduce the probability of achieving sustained MDA in PsA. Comprehensive management of PsA should include measures for addressing these comorbidities.

7.
Semin Arthritis Rheum ; 51(2): 464-468, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33774593

RESUMO

BACKGROUND/PURPOSE: A universally accepted definition of axial psoriatic arthritis (axPsA) is lacking. We aimed to 1) assess the presence of axial involvement as defined by "at least unilateral grade 2 sacroiliitis (Uni2SI)" and 2) assess the radiographic progression of Uni2SI and identify risk factors for progression. METHODS: PsA patients participating in a prospective observational cohort were classified according to their highest sacroiliitis grade. The baseline features of patients with Uni2SI were compared to patients meeting the radiographic criteria of the modified New York Ankylosing Spondylitis (mNY AS) criteria. Risk factors were examined for progression from Uni2SI in a sub-group of patients with >1 follow-up radiographs. Logistic regression and a survival analysis were carried out and identified risk factors associated with radiographic mNY AS compared to Uni2SI. RESULTS: Axial disease defined as ≥Uni2SI was detected in 612/1354 patients (45%). mNY AS sacroiliitis was observed in 477 patients (35%). Radiographic progression of Uni2SI was assessed in 154 patients, 80 (52%) progressed to mNY AS criteria within 5.5 years. At baseline, progressors were diagnosed at a younger age (35.6 vs. 38.9, p = 0.05), had less degenerative disc disease (OR = 0.47, p = 0.02), worse peripheral radiographic damage (OR=1.02, p = 0.03) and worse psoriasis (OR = 1.09, p = 0.01) compared to non-progressors. Patients with an elevated erythrocyte sedimentation rate were more likely to progress (HR = 1.83, p = 0.02), while patients with longer disease duration were less likely to progress (HR = 0.95, p = 0.02). CONCLUSION: The radiographic mNY AS criteria appear to be suitable for defining axial PsA according to radiographs. MRI definitions are needed as well for the most appropriate definition of axial PsA.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33555325

RESUMO

OBJECTIVES: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10-36 nmol/l), T2 (37-60 nmol/l) and T3 (61-174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels. RESULTS: Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased HDL were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. CONCLUSIONS: MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.

9.
J Rheumatol ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589551

RESUMO

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held its annual meeting in 2020 in an online format due to travel restrictions during the coronavirus disease 2019 (COVID­19; caused by SARS-CoV-2) pandemic. The virtual meeting was attended by 351 rheumatologists, dermatologists, representatives of biopharmaceutical companies, and patient research partners. Similar to previous years, GRAPPA's annual meeting focused on the 3 overlapping missions of education, research, and clinical care of psoriatic disease. Trainee sessions this year included the annual trainee symposium and a grant-writing workshop. Plenary sessions included updates on COVID-19 and psoriatic disease from multispecialty and patient perspectives, and updates on pustular psoriasis and associated musculoskeletal manifestations. Progress on research and updates were presented for the following groups: Collaborative Research Network, Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Working Group, International Dermatology Outcome Measures, Composite Measures, Education Committee, and Treatment Guidelines. New this year were 3 concurrent workshops on ultrasound assessment of joints and entheses, magnetic resonance imaging of psoriatic arthritis, and pustular psoriasis efficacy endpoints; 6 "Meet the Expert" sessions; and facilitated "poster tours." In our prologue, we introduce the papers that summarize this meeting.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33571391

RESUMO

OBJECTIVES: To assess the incidence and risk factors for heart failure (HF) in patients with psoriatic disease (PsD) and describe their electrocardiographic and echocardiographic findings. METHODS: A cohort analysis was conducted involving patients with PsD followed prospectively from 1978 to 2018. Participants were assessed according to a standard protocol every 6 to 12-months. The primary outcome was the time to first event of HF, further classified into ischemic and non-ischemic HF (secondary outcomes). The association between cardiovascular risk factors, measures of disease activity and HF events was assessed using Cox proportional hazards regression. Electrocardiographic and echocardiographic findings associated with HF events were described. RESULTS: A total of 1994 patients with PsD were analyzed with 64 incident HF events (38 ischemic, 26 non-ischemic). The incidence rate of first HF event was 2.85 per 1000 patient years. In all events, most common electrocardiographic findings were atrial fibrillation (22%) and bundle branch blocks (29%). Echocardiogram revealed 37% reduced ejection fraction and 63% preserved ejection fraction. In multivariable analysis, independent risk factors for all HF events were ischemic heart disease, adjusted mean (AM)-tender joint count, AM-swollen joint count, AM-erythrocyte sedimentation rate, AM-C-reactive protein, and physical function (by health assessment questionnaire) (all p<0.05). Minimal disease activity state was protective for all HF (p<0.05). CONCLUSIONS: Increased risk of HF is associated with a combination of known cardiovascular risk factors and measures of disease activity, particularly in non-ischemic HF. The effect of inflammation on HF may be partially independent of atherosclerotic disease.

11.
Ann Rheum Dis ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568386

RESUMO

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

12.
Semin Arthritis Rheum ; 51(2): 367-386, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33601193

RESUMO

BACKGROUND: Structural damage is as an important outcome in the Psoriatic Arthritis (PsA) Core Domain Set and its assessment is recommended at least once in the development of a new drug. OBJECTIVES: To conduct a systematic review (SR) to identify studies addressing the measurement properties of radiographic outcome instruments for structural damage in PsA and appraise the evidence through the Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Framework Instrument Selection Algorithm (OFISA). METHODS: A SR was conducted using search strategies in EMBASE and MEDLINE to identify full-text English studies which aimed to develop or assess the measurement properties of radiographic outcome instruments in PsA. Determination of eligibility and data extraction was performed independently by two reviewers with input from a third to achieve consensus. Two reviewers assessed the methodology and results of eligible studies and synthesized the evidence using OMERACT methodology. RESULTS: Twelve articles evaluating radiographic instruments were included. The articles assessed nine peripheral (hands, wrists and/or feet) and six axial (spinal and/or sacroiliac joints) radiographic instruments. The peripheral radiographic instruments with some evidence for reliability, cross-sectional construct validity and longitudinal construct validity were the Ratingen and modified Sharp van der Heijde scores. No instruments had evidence for clinical trial discrimination or thresholds of meaning. There was limited evidence for the measurement properties of all identified axial instruments. CONCLUSION: There are significant knowledge gaps in the responsiveness of peripheral radiographic instruments. Axial radiographic instruments require further validation, and the need to generate novel instruments and utilise other imaging modalities should be considered.

13.
Ann Rheum Dis ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452003

RESUMO

OBJECTIVE: To determine the ominosity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Systemic Lupus Erythematosus Classification Criteria by determining its predictive role for disease severity in the first 5 years following diagnosis. METHODS: 867 patients with systemic lupus erythematosus (SLE) from the Toronto Lupus Clinic were included (all first 12 months after SLE diagnosis). The EULAR/ACR criteria score was calculated based on baseline information. To determine disease severity in the first 5 years after diagnosis, adjusted mean SLE Disease Activity Index 2000 (AMS), flares, remission and immunosuppressive treatment were used as outcomes. The Systemic Lupus International Collaborating Clinics (SLICC) registry comprised the validation cohort. RESULTS: Based on receiver operating characteristic analysis, a EULAR/ACR score of 20 was used as a threshold to compare outcomes between groups. In the first 5 years of disease course, patients with a score of ≥20 had higher AMS scores (p<0.001) and were more likely to ever experience a flare (p<0.001). These patients had lower probabilities of achieving remission and higher requirements for immunosuppressives. Results were confirmed in the SLICC validation cohort. Patients with a score of ≥20 had higher AMS during the first 5 years of disease (5.4 vs 3.1% and ≥20 vs <20 respectively, p≤0.001). The score correlated with AMS (r=0.43, p≤0.001) in the same time frame. CONCLUSION: A EULAR/ACR score of ≥20 is an indicator of ominosity in SLE. Patients with a score of ≥20 were characterised by a more active disease course throughout the first 5 years. These criteria provide prognostic information regarding disease severity in the first 5 years following diagnosis.

14.
Arthritis Res Ther ; 23(1): 29, 2021 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-33451338

RESUMO

OBJECTIVES: Type I interferons (IFNs) play an important role in the pathophysiology of systemic lupus erythematosus (SLE). While cross-sectional data suggest an association between IFN-induced gene expression and SLE disease activity, interest in this as a biomarker of flare has been tempered by a lack of fluctuation with disease activity in the majority of patients. This led us to question whether IFN-induced gene expression might instead be a biomarker of overall disease severity, with patients with high levels spending more time in an active disease state. METHODS: Levels of five interferon-responsive genes were measured in the whole peripheral blood at baseline visit for 137 SLE patients subsequently followed for 5 years. Log transformed values were summed to yield a composite IFN5 score, and the correlation with various disease outcomes examined. Receiver operator characteristic analyses were performed for outcomes of interest. Kaplan-Meier curves were generated to compare the proportion of flare-free patients with high and low IFN5 scores over time. RESULTS: The baseline IFN5 score was positively correlated with the adjusted mean SLE disease activity index-2000, number of flares, adjusted mean prednisone dose, and number of new immunosuppressive medications over the subsequent 5 years. Optimal cut-offs for the IFN5 score were determined using Youden's index and predicted more severe outcomes with 57-67% accuracy. A high baseline IFN5 level was associated with a significantly increased risk of subsequent flare. CONCLUSIONS: Measurement of the type I IFN signature is a useful tool for predicting the subsequent disease activity course.

15.
J Am Acad Dermatol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33422626

RESUMO

OBJECTIVE: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic. STUDY DESIGN: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted. RESULTS: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus. LIMITATIONS: The evidence behind many guidance statements is variable in quality and/or quantity. CONCLUSIONS: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge.

16.
Semin Arthritis Rheum ; 51(1): 144-149, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33383290

RESUMO

OBJECTIVES: To estimate the prevalence and incidence of malignancy and its types in psoriatic arthritis (PsA) and psoriasis without arthritis (PsC) patients, in comparison to the general population, and to identify the predictive factors for developing cancer in psoriatic disease (PsD). METHODS: PsA patients followed prospectively since 1978 and PsC patients followed since 2006 at 6-to-12 month intervals according to a standard protocol were included. Malignancies were recorded prospectively and linkages with Cancer Care Ontario and the Death Registry were carried out to confirm the presence and type of malignancy up to December 2016. Standardized incidence ratios (SIR) were calculated for overall cancers and by age and sex. Cox regression analysis was conducted to identify risk factors associated with the development of malignancy after the diagnosis of PsD. RESULTS: 2051 patients (PsD) were included of whom 228 (11%) developed cancer. 168 patients developed cancer after first clinic visit and are included in this report. Overall SIR for malignancy was 0.83 (0.68, 1.00), SIR for females was 1.06 (0.80, 1.37), and for males was 0.67 (0.50, 0.88). The most common malignancies were skin, breast, and hematological. Skin cancer was the only specific cancer that had a higher incidence than the general population with SIR = 3.37 (1.84, 5.66). There was insufficient evidence to suggest an increased risk of malignancy associated with biologics use. CONCLUSIONS: In this long-term prospective follow-up of patients with PsA and PsC the overall malignancy risk was not found to be higher than the general population, while skin cancer increased.

17.
J Rheumatol ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259331

RESUMO

OBJECTIVE: Lupus nephritis (LN) may lead to end-stage kidney disease (ESKD) in 22% of patients over 15 years with the risk being particularly higher in diffuse proliferative forms. The rate of kidney function decline varies. However, a catastrophic course leading to ESKD within a few years from onset is uncommon. The aim of the present study was to assess the factors associated with rapid progression to ESKD in LN patients. METHODS: Patients from the Toronto Lupus Clinic with biopsy-proven LN at presentation and eGFR≥60ml/min/1.73m2 who developed ESKD within three years were retrieved. Pathology reports were reviewed with particular emphasis on distinct histopathologic features. Demographic, clinical, laboratory and therapeutic variables were also analyzed. RESULTS: Ten patients (1.8% of the total LN population) developed ESKD within three years of diagnosis. Their mean age was 34.2±7.3 years, mean time to ESKD 19.2±12.4 months, initial eGFR=90.2±24.9ml/min/1.73m2, proteinuria 2.7±1.04 grams/24h. The rate of kidney function decline was more than 43ml/min/1.73m2/year (median). One patient had LN class III, five had LN class IV, two membranous LN (class V) and another two had mixed IV/V. Moreover, two patients had extensive thrombotic microangiopathy, one collapsing glomerulonephritis and one concomitant anti-glomerular basement membrane (anti-GBM) nephropathy. Four patients showed no unusual kidney pathology; all of them had severe non-compliance (discontinued all medications to follow alternative treatment). CONCLUSION: Catastrophic progression to ESKD is uncommon in LN. The major associated factors are poor compliance and distinct histopathologic features such as thrombotic microangiopathy, collapsing glomerulopathy and concomitant anti-GBM nephropathy.

18.
Sci Rep ; 10(1): 21703, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303908

RESUMO

Biological therapies have dramatically improved the therapeutic landscape of psoriatic arthritis (PsA); however, 40-50% of patients are primary non-responders with response rates declining significantly with each successive biological therapy. Therefore, there is a pressing need to develop a coherent strategy for effective initial and subsequent selection of biologic agents. We interrogated 40 PsA patients initiating either tumour necrosis factor inhibitors (TNFi) or interleukin-17A inhibitors (17Ai) for active PsA. Patients achieving low disease activity according to the Disease Activity Index for PsA (DAPSA) at 3 months were classified as responders. Baseline and 3-month CD4+ transcript profiling were performed, and novel signaling pathways were identified using a multi-omics profiling and integrative computational analysis approach. Using transcriptomic data at initiation of therapy, we identified over 100 differentially expressed genes (DEGs) that differentiated IL-17Ai response from non-response and TNFi response from non-response. Integration of cell-type-specific DEGs with protein-protein interactions and further comprehensive pathway enrichment analysis revealed several pathways. Rho GTPase signaling pathway exhibited a strong signal specific to IL-17Ai response and the genes, RAC1 and ROCKs, are supported by results from prior research. Our detailed network and pathway analyses have identified the rewiring of Rho GTPase pathways as potential markers of response to IL17Ai but not TNFi. These results need further verification.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33326187

RESUMO

OBJECTIVES: To determine bone mineral density (BMD) in psoriatic arthritis (PsA) patients, factors associated with undergoing BMD testing, and the effect of PsA clinical activity on BMD. METHODS: Patients attending the University of Toronto PsA Clinic with a BMD from cohort inception to January 2019 were included. Descriptive statistics summarized lumbar spine, femoral neck and total hip T-scores. Cox proportional hazard regression identified predictors for BMD testing. Logistic regression analysis determined odds of having normal (T-score ≥ -1.0) versus osteoporotic range BMD (T-score ≤ -2.5). A multi-state model determined factors associated with BMD state changes over time. RESULTS: Of the 1479 patients, 214 had BMDs. Mean T-scores at the lumbar spine, femoral neck and total hip were -0.30±0.32, -1.10±1.04 and -0.45±0.42 respectively. Osteopenia and osteoporosis occurred in 45.27% and 12.94% of patients. Increasing age, menopause, elevated acute phase reactants, biologic, methotrexate and systemic glucocorticoid use were associated with a higher chance of undergoing BMD testing. Increased BMI and biologic use were associated with a lower chance of having osteoporotic range BMD. In multi-state analysis, polyarthritis may portend lower BMDs over time, although this did not achieve statistical significance due to low patient numbers. CONCLUSIONS: The prevalence of osteopenia and osteoporosis in the PsA cohort were similar to the general population. Clinicians are using osteoporosis risk factors and PsA disease severity markers to select patients for BMD testing. Polyarticular disease may portend worse BMDs. Biologic use and increased BMI appear to have a protective effect.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33140092

RESUMO

OBJECTIVES: Most randomized controlled trials (RCTs) in SLE have failed to reach their respective end points, with the rates of response to placebo (plus standard-of-care treatment) being unexpectedly high. The aim of this systematic review was to quantify the response to placebo in non-renal, non-neuropsychiatric lupus. METHODS: The PubMed database was searched (from 2000 to December 2019) for phase II/III RCTs assessing the efficacy and safety of biologics in non-renal, non-neuropsychiatric SLE. Data on the efficacy and safety of the placebo-treated patients were collected in a pre-established data retrieval form. Descriptive statistics were used. RESULTS: A total of 24 RCTs (n = 11 128 in total) were included. Placebo-treated patients (n = 3899) were mostly females (93.5%), Caucasians (60.2%), of mean age 39.7 years, and having a mean disease duration of 7.4 years. Their mean initial SLEDAI 2000 was 10.4, whereas 60.5% had positive anti-dsDNA antibodies, 41.9% low C3 and 35.6% low C4 at randomization. Standard-of-care treatment included glucocorticosteroids in 85.9%, antimalarials in 72.8% and immunosuppressives in 48.5%. The response to placebo was 36.2% for the primary end point (as defined in each study), 39.8% for the SLE Responder Index-4 (SRI-4), 29.2% for SRI-5, 28.4% for SRI-6 and 30.9% for BILAG-based Combined Lupus Assessment response. Regarding safety, there were serious adverse events in 16.3% of patients, serious infections in 5.5% and malignancies in 0.3%, and death occurred in 0.56% of patients. CONCLUSION: More than one-third of the placebo-treated patients achieved their respective primary end points in RCTs with biologics in non-renal, non-neuropsychiatric SLE. The response rate was higher for certain end points, such as the SRI-4, while it decreased with more stringent end points.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...