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1.
Artigo em Inglês | MEDLINE | ID: mdl-32221602

RESUMO

OBJECTIVES: To study the clinical phenotypes, determined based on cumulative disease activity manifestations, and sociodemographic factors associated with depression and anxiety in SLE. METHODS: Patients attending a single centre were assessed for depression and anxiety. SLE clinical phenotypes were based on the organ systems of cumulative 10-year SLE Disease Activity Index 2000 (SLEDAI-2K), prior to visit. Multivariable logistic regression analyses for depression, anxiety, and coexisting anxiety and depression were performed to study associated SLE clinical phenotypes and other factors. RESULTS: Among 341 patients, the prevalence of anxiety and depression was 34% and 27%, respectively, while 21% had coexisting anxiety and depression. Patients with skin involvement had significantly higher likelihood of anxiety compared with patients with no skin involvement [adjusted odds ratio (aOR) = 1.8; 95% CI: 1.1, 3.0]. Patients with skin involvement also had higher likelihood of having coexisting anxiety and depression (aOR = 2.0, 95% CI: 1.2, 3.9). Patients with musculoskeletal (MSK) (aOR = 1.9; 95% CI: 1.1, 3.5) and skin system (aOR = 1.8; 95% CI: 1.04, 3.2) involvement had higher likelihood of depression compared with patients without skin or musculoskeletal involvement. Employment status and fibromyalgia at the time of the visit, and inception status were significantly associated with anxiety, depression, and coexisting anxiety and depression, respectively. CONCLUSION: SLE clinical phenotypes, specifically skin or MSK systems, along with fibromyalgia, employment and shorter disease duration were associated with anxiety or depression. Routine patient screening, especially among patients with shorter disease duration, for these associations may facilitate the diagnosis of these mental health disorders, and allow for more timely diagnosis.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32191334

RESUMO

OBJECTIVES: To examine for latent patterns of SLE disease activity trajectories that associate with specific latent patterns of health-related quality of life (HRQoL; Medical Outcomes Study Short Form-36), and to determine baseline predictors of class membership. METHODS: In this retrospective longitudinal inception cohort of 222 SLE adults over 10 years, trajectories of three outcomes were studied jointly: Short Form-36 physical (PCS) and mental (MCS) component summaries and adjusted mean SLEDAI-2000 (AMS). Group-based joint trajectory modelling was used to model latent classes; univariable and multivariable analyses were used to identify predictors of class membership. RESULTS: Four latent classes were identified: Class 1 (C1) (24%) had moderate AMS, and persistently low PCS and MCS; C2 (26%) had low AMS, moderate PCS and improved then worsened MCS; C3 (38%) had moderate AMS, and persistently high PCS and MCS; and C4 (11%) had high AMS, moderate-low PCS and improving MCS. Baseline older age was associated with lower HRQoL trajectories. Higher AMS trajectories did not associate with a particular pattern of HRQoL trajectory. A higher prevalence of fibromyalgia (44% in C1) was associated with worse HRQoL trajectories. Disease manifestations, organ damage and cumulative glucocorticoid were not differentially distributed across the latent classes. CONCLUSION: High disease activity did not necessarily associate with low HRQoL. More patients with worse HRQoL trajectories had fibromyalgia. Older age at diagnosis increased the probability of belonging to a class with low HRQoL trajectories. The care of SLE patients may be improved through addressing fibromyalgia in addition to disease activity.

3.
Semin Arthritis Rheum ; 50(1): 84-94, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31303437

RESUMO

OBJECTIVES: To systematically review and synthesize literature on 1) the overall prevalence of depression and anxiety in SLE patients in identified studies, and 2) the pooled prevalence per metrics of depression and anxiety in adult SLE patients. METHODS: This review used (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) PRISMA guidelines and in-depth searches in four databases (1954-2016; Ovid-based Medline, Embase, PsycINFO and CINAHL) to identify articles on the prevalence of depression and/or anxiety in adult SLE patients. Included studies were critically appraised and analyzed. The prevalence of depression and anxiety was studied for all included studies, and whenever possible, pooled prevalence (PP) was determined for more commonly used metrics. Statistical and publication bias was assessed using funnel plots. RESULT: A total of 3103 references were identified, 226 were selected for detailed review and 72 were included in the final analysis. OVERALL PREVALENCE: The depression PP, obtained from 69 studies representing 23,386 SLE patients, was 35.0% (95% CI: 29.9%-40.3%). The anxiety PP, obtained from 38 studies representing 4439 SLE patients, was 25.8% (95% CI: 19.2%-32.9%). PREVALENCE PER METRICS USED: The more commonly used instruments included the Centre for Epidemiological Studies - Depression (CES-D), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Hospital Anxiety and Depression Scales (HADS-A/D), and Hamilton Rating Scales for Depression/Anxiety (HAM-D/A)]. The CES-D was utilized in 13 studies including 1856 SLE patients; depression PP was 41.5% (95% CI: 35.1%-48.1%). The BDI was utilized in 14 studies including 1355 SLE patients and the BAI in 3 studies including 489 patients; depression PP was 39.9% (95% CI: 31.1%-49.1) and anxiety PP was 38.4% (95% CI: 34.2%-42.8%). The HADS-D was utilized in 14 studies including 1238 SLE patients and the HADS-A in 12 studies including 1099 patients respectively; its depression PP was 24.4% (95% CI: 19.1%-30.1%) and anxiety PP was 38.3% (95% CI: 29.1%-47.9%). The HAM-D was utilized in 4 studies including 267 SLE patients and the HAM-A in 4 studies including 213 patients respectively; its depression PP was 40.0% (95% CI: 23.0%-59.0%) and anxiety PP was 39.0% (95% CI: 32.0%-45.0%). CONCLUSION: There was high variability in the prevalence of depression and anxiety, ranging from 8.7%-78.6% and 1.1%-71.4%, respectively. This could be attributed to the lack of consistency in the metrics used and its definition for depression and anxiety in SLE. Studies that used a specific metric, such as the CES-D, BDI or HAM-D, yielded similar depression prevalence. The HADS-D had the lowest prevalence. All metrics of anxiety yielded similar anxiety prevalence.

4.
Rheumatology (Oxford) ; 59(1): 90-98, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31236574

RESUMO

OBJECTIVE: LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). METHODS: Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed <18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. RESULTS: Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). CONCLUSION: We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31628718

RESUMO

BACKGROUND: Screening for Cognitive Impairment (CI) in Systemic Lupus Erythematosus (SLE) conventionally relies on the American College of Rheumatology (ACR) Neuropsychological Battery (NB), which is not universally available. To develop a more accessible screening approach, we assessed validity of the Automated Neuropsychological Assessment Metrics (ANAM). Using the ACR-NB as the gold standard for CI classification, the objectives were to (a) measure overall discriminative validity of the ANAM for CI vs. non-CI, (b) identify ANAM subtests and scores that best differentiate CI from non-CI patients, and (c) derive an ANAM composite indices and cut-offs. METHODS: 211 consecutive adult, female/male SLE patients were administered the ANAM and NB. (a) For overall discriminative validity of the ANAM, we compared CI vs non-CI patients on 4 scores. (b) Six ANAM models using different scores were developed and the most discriminatory subtests were selected using logistic regression analyses. The Area Under the receiver operating characteristics Curve (AUC) was calculated to establish ANAM validity against NB. (c) ANAM composite indices and cut-offs were derived for the best model(s), and sensitivities/specificities calculated. RESULTS: Patients with non-CI performed better on most ANAM subtests, supporting ANAM's discriminative validity. CI could be accurately identified by selected ANAM subtests with top models demonstrating excellent AUCs of 81% and 84%. Derived composite indices and cut-offs demonstrated sensitivity of 78-80% and specificity of 70%. CONCLUSION: This study provides support for ANAM's discriminative validity for CI and utility for cognitive screening in adult SLE. Derived composite indices and cut-offs enhance clinical applicability.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31560454

RESUMO

A project towards new SLE classification criteria supported by both EULAR and the ACR is based on weighted criteria that include both laboratory and clinical items. Combinations of certain symptoms may occur commonly in SLE, which would argue against independently counting these items. However, these interrelationships have not been formally investigated. OBJECTIVES: To evaluate the interrelationship between candidate criteria items in an international early SLE cohort and in the Euro-Lupus cohort. METHODS: The international early SLE cohort included 389 patients, who were diagnosed within the last 3 years. Data on ACR 1997, SLICC 2012 and 30 additional items were collected. To evaluate the inter-relationship of criteria, a tetrachoric correlation was used to assess the degree of association between different manifestations of the same organ-system. The correlations identified in the international early SLE cohort were validated in the Euro-Lupus cohort. RESULTS: A few relevant correlations were observed among specific clinical cutaneous manifestations (in particular, malar rash correlated with photosensitivity, alopecia, and oral ulcers) and serologic manifestations (anti-Sm and anti-dsDNA and anti-RNP, anti-Ro with anti-La, and between anti-phospholipid antibodies), and these results were validated in the Euro-Lupus cohort. The associations within the mucocutaneous domain, hematologic and the specific autoantibodies suggest that within a single domain only the highest ranking item should be counted to avoid overrepresentation. CONCLUSIONS: Some of the candidate SLE criteria do cluster within domains. Given these interrelationships, multiple criteria within a domain should not be independently counted. These results are important for the structure of new SLE classification criteria.

7.
Ann Rheum Dis ; 78(9): 1151-1159, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383717

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.

8.
Arthritis Rheumatol ; 71(9): 1400-1412, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31385462

RESUMO

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.


Assuntos
Lúpus Eritematoso Sistêmico/classificação , Reumatologia/normas , Adulto , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Coortes , Proteínas do Sistema Complemento/análise , Técnicas de Apoio para a Decisão , Técnica Delfos , Europa (Continente) , Feminino , Humanos , Cooperação Internacional , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Sociedades Médicas , Estados Unidos
9.
J Rheumatol ; 46(6): 653, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31154447
10.
Semin Arthritis Rheum ; 49(2): 260-266, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30940467

RESUMO

OBJECTIVES: This study aimed to: 1) determine the prevalence of depression and anxiety in SLE patients using the Center for Epidemiological Studies-Depression Scale [CES-D], Hospital Anxiety and Depression Scale [HADS], and Beck Anxiety Inventory [BAI] questionnaires; 2) study the criterion validity, interpretability, and test-retest reliability of CES-D, HADS and BAI; and 3) evaluate their diagnostic accuracy when compared to the assessment of an independent psychiatric assessment using the Mini-International Neuropsychiatric Interview (MINI). METHODS: 159 consecutive SLE participants were screened for depression and anxiety using the CES-D, HADS, and BAI, and underwent the MINI. Sensitivity and specificity were evaluated against the MINI. Test-retest reliability was studied. Receiver operator characteristic (ROC) curves were utilized to determine the cut-off scores for CES-D, HADS and BAI. RESULTS: The prevalence of depression ranged from 29% (HADS-D) to 52% (CES-D) and the prevalence of anxiety ranged from 45% (BAI) to 50% (HADS-A). ROC showed similar performance for CES-D and HADS-D. The diagnostic accuracy of HADS-A outperformed BAI. Furthermore, these self-reported questionnaires demonstrated good to excellent test-retest reliability. Analyses exhibited optimal cut-offs for CES-D (26), BAI (19), HADS-A (6), and HADS-D (8) that optimized their sensitivity and specificity as screening metrics for depression and anxiety in SLE patients. CONCLUSIONS: Anxiety and depression are highly prevalent in patients with SLE. Patient-reported outcome questionnaires such as the CES-D, HADS, and BAI may be useful tools to screen for depression and anxiety in SLE. Our results suggest that SLE-specific cut-offs may improve diagnostic accuracy of current screening metrics in patients with lupus.

11.
J Rheumatol ; 46(9): 1192-1197, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30770500

RESUMO

OBJECTIVE: To develop definitions for the assessment of magnetic resonance imaging (MRI) pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis. METHODS: An Outcome Measures in Rheumatology (OMERACT) consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists. RESULTS: Two domains, inflammation and structural, were identified. Definitions for bone marrow edema, joint space inflammation, capsulitis, and enthesitis were derived for joint inflammation; sclerosis, erosion, fatty lesion, and ankylosis were defined for assessing structural joint changes. CONCLUSION: Preliminary consensus-driven definitions for inflammation and structural elements have been derived, underpinning the ongoing development of the OMERACT Juvenile Arthritis MRI SIJ scoring system (OMERACT JAMRIS-SIJ).

12.
Artigo em Inglês | MEDLINE | ID: mdl-30666173

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune, multisystem rheumatic disease with significant impact on health-related quality of life (HRQoL). Patient-reported outcomes (PROs) provide valuable data on patient perceptions across a variety of domains, such as HRQoL, pain, fatigue, and depression. The measurement and results of PROs with respect to HRQoL in randomized controlled trials (RCTs) on belimumab (B-lymphocyte stimulator inhibitor) in SLE are reviewed here, including BLISS-52 and BLISS-76, as well as publications related to belimumab trials that included HRQoL data. Other trials that evaluated belimumab did not include HRQoL data and were therefore not included in the analysis. The BLISS-52 and BLISS-76 RCTs met their primary endpoints and demonstrated improvements in PROs, measured by the 36-item Short Form Health Survey, EuroQol 5 Dimensions, and Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Belimumab was shown overall to improve PROs in adult autoantibody-positive lupus patients.

13.
Arthritis Care Res (Hoboken) ; 71(6): 822-828, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30055090

RESUMO

OBJECTIVE: A recent study conducted by our clinical group demonstrated that low disease activity (LDA), defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤2, maintained for 12 months, confers the same risk for damage accrual as complete remission after 2 years. The aim of the present study was to assess the validity of these findings in the long term (10 years). METHODS: Patients in the inception cohort of the Toronto Lupus Clinic, who had a minimum follow-up of 10 years and no interval >18 months between consecutive visits, were included in the analysis. Prolonged clinical remission was defined based on a SLEDAI-2K score of 0 (serology excluded), achieved within the first 5 years of enrollment and maintained for ≥10 years. Prolonged LDA was defined as SLEDAI-2K score ≤2 (serology excluded) with the same time frame restrictions. RESULTS: Of 267 patients, 27 (10.1%) achieved prolonged clinical remission and 48 (18%) attained prolonged LDA. There were no differences regarding demographic, clinical, and immunologic variables at any time. The mean prednisone dose at enrollment was higher in patients in whom remission was achieved, while patients with prolonged LDA were taking antimalarials more frequently, both at enrollment and after the 10-year time period. Cumulative damage and flare rate after 10 years, and mortality throughout follow-up were comparable. SLE in patients in the prolonged LDA group was in complete remission for 76% of the follow-up time. CONCLUSION: Prolonged clinical remission and LDA were demonstrated in 10.1% and 18% of our patients, respectively, and comparable outcomes were demonstrated in the long term, rendering sustained LDA an acceptable treat-to-target outcome in SLE.


Assuntos
Antimaláricos/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Antimaláricos/efeitos adversos , Bases de Dados Factuais , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Ontário , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Arthritis Rheumatol ; 71(1): 91-98, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30035365

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) presents with nonspecific signs and symptoms that are also found in other conditions. This study aimed to evaluate manifestations at disease onset and to compare early SLE manifestations to those of diseases mimicking SLE. METHODS: Academic lupus centers in Asia, Europe, North America, and South America collected baseline data on patients who were referred to them during the previous 3 years for possible SLE and who had a symptom duration of <1 year. Clinical and serologic manifestations were compared between patients diagnosed as having SLE and those diagnosed as having SLE-mimicking conditions. Diagnostic performance of the 1997 American College of Rheumatology (ACR) SLE classification criteria and the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria was tested. RESULTS: Data were collected on 389 patients with early SLE and 227 patients with SLE-mimicking conditions. Unexplained fever was more common in early SLE than in SLE-mimicking conditions (34.5% versus 13.7%, respectively; P < 0.001). Features less common in early SLE included Raynaud's phenomenon (22.1% versus 48.5%; P < 0.001), sicca symptoms (4.4% versus 34.4%; P < 0.001), dysphagia (0.3% versus 6.2%; P < 0.001), and fatigue (28.3% versus 37.0%; P = 0.024). Anti-double-stranded DNA, anti-ß2 -glycoprotein I antibodies, positive Coombs' test results, autoimmune hemolytic anemia, hypocomplementemia, and leukopenia were more common in early SLE than in SLE-mimicking conditions. Symptoms detailed in the ACR and SLICC classification criteria were significantly more frequent among those with early SLE. Fewer patients with early SLE were not identified as having early SLE with use of the SLICC criteria compared to the ACR criteria (16.5% versus 33.9%), but the ACR criteria demonstrated higher specificity than the SLICC criteria (91.6% versus 82.4%). CONCLUSION: In this multicenter cohort, clinical manifestations that could help to distinguish early SLE from SLE-mimicking conditions were identified. These findings may aid in earlier SLE diagnosis and provide information for ongoing initiatives to revise SLE classification criteria.


Assuntos
Doenças Autoimunes/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome de Sjogren/diagnóstico , Adulto , Anemia Hemolítica Autoimune/etiologia , Anticorpos Antinucleares , Síndrome Antifosfolipídica/diagnóstico , Artrite Reumatoide/diagnóstico , Autoanticorpos/imunologia , Estudos de Coortes , Proteínas do Sistema Complemento/imunologia , Teste de Coombs , DNA/imunologia , Transtornos de Deglutição/etiologia , Diagnóstico Diferencial , Feminino , Febre de Causa Desconhecida/etiologia , Hepatite Autoimune/diagnóstico , Humanos , Leucopenia/etiologia , Doenças Pulmonares Intersticiais/diagnóstico , Lúpus Eritematoso Sistêmico/classificação , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença de Raynaud/etiologia , Escleroderma Sistêmico/diagnóstico , Síndrome de Sjogren/etiologia , Tireoidite Autoimune/diagnóstico , Doenças do Tecido Conjuntivo Indiferenciado/diagnóstico , Adulto Jovem , beta 2-Glicoproteína I/imunologia
15.
J Rheumatol ; 46(1): 43-56, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30008458

RESUMO

OBJECTIVE: As part of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound working group, we performed a systematic review of the literature to assess the evidence and knowledge gaps in scoring instruments of enthesitis in psoriatic arthritis (PsA). METHODS: A systematic search of PubMed, EMBase, and Cochrane databases was performed. The search strategy was constructed to find original publications containing terms related to ultrasound, enthesitis, spondyloarthritis (SpA) or PsA. Data extraction focused on the properties of the sonographic enthesitis instruments used in each study following components of the Outcome Measures in Rheumatology (OMERACT) filter: feasibility, test-retest reliability, construct validity as related to clinical assessment of enthesitis, biomarkers of inflammation and imaging of enthesitis by other modalities, discriminative validity, and responsiveness to treatment. RESULTS: Fifty-one of 310 identified manuscripts were included. Only 1 scoring instrument of enthesitis was specifically developed and validated in patients with PsA. Only 18 (35%) of the studies involved patients with PsA, while the remaining studies focused on SpA. In PsA, construct validity was assessed using biomarkers and clinical examination in 1 (2%) and 11 (21.5%) of the studies, respectively, whereas no studies used imaging for the same purpose. Only 2 (4%) of the studies assessed discriminative validity in PsA. Responsiveness to treatment was assessed in 7 studies, none of which included patients with PsA. CONCLUSION: Although sonographic enthesitis scoring instruments have been developed for SpA, only a few have been validated in PsA. None of them passed the OMERACT filter in patients with PsA. Additional research is required before endorsing a specific instrument for the assessment of enthesitis in patients with PsA.

16.
Curr Rheumatol Rev ; 15(2): 90-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30255761

RESUMO

BACKGROUND: Depression and anxiety are common neuropsychiatric complaints in patients with Systemic Lupus Erythematosus (SLE). While numerous studies have been performed to investigate the prevalence, impact, and associated factors of depression and anxiety, current literature presents mixed results. In particular, the prevalence of anxiety and depression varies substantially between studies due to methodological limitations, and heterogeneity in defining anxiety and depression, patient selection, and metrics used. Moreover, there is a lack of studies evaluating the validity, reliability, and interpretability of commonly used screening tools for depression and anxiety in SLE patients. RESULT AND CONCLUSION: Further investigations should aim to reach a consensus surrounding the role of controversial associated factors in depression and anxiety of SLE patients, while also focusing on the identification of novel factors that have not yet been highlighted in the literature.


Assuntos
Ansiedade/epidemiologia , Ansiedade/etiologia , Depressão/epidemiologia , Depressão/etiologia , Lúpus Eritematoso Sistêmico/psicologia , Adulto , Ansiedade/diagnóstico , Depressão/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
17.
J Rheumatol ; 45(10): 1426-1439, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30173152

RESUMO

OBJECTIVE: To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada. METHODS: Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online. RESULTS: There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination. CONCLUSION: These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.


Assuntos
Diretrizes para o Planejamento em Saúde , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Programas de Rastreamento , Adulto , Canadá , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Criança , Feminino , Pessoal de Saúde , Hepatite C/diagnóstico , Hepatite C/etiologia , Humanos , /etiologia , Lúpus Eritematoso Sistêmico/complicações , Masculino , Osteonecrose/diagnóstico , Osteonecrose/etiologia , Osteoporose/diagnóstico , Osteoporose/etiologia , Período Periparto/sangue , Gravidez , Reumatologistas , Medição de Risco , Índice de Gravidade de Doença , Revisão Sistemática como Assunto , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/etiologia , Vacinação
18.
Lancet ; 392(10155): 1330-1339, 2018 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-30249507

RESUMO

BACKGROUND: Ustekinumab is a monoclonal antibody targeting interleukin (IL)-12 and IL-23 and is approved for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. IL-12 and IL-23 have been implicated in systemic lupus erythematosus. We aimed to assess the efficacy and safety of ustekinumab for the treatment of systemic lupus erythematosus in patients with moderate-to-severe disease activity despite conventional treatment. METHODS: This was a multicentre, double-blind, phase 2, randomised, controlled trial of adult patients with active, seropositive systemic lupus erythematosus, done at 44 private practices and academic centres in Argentina, Australia, Germany, Hungary, Mexico, Poland, Spain, Taiwan, and the USA. Eligible adults were aged 18-75 years, weighed at least 35 kg, and had a diagnosis of systemic lupus erythematosus at least 3 months before the first administration of study drug. Eligible patients were randomly assigned (3:2) to the ustekinumab or placebo group using an interactive web response system with stratification by skin biopsy, lupus nephritis presence, baseline systemic lupus erythematosus medications and systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score combined factor, site, region, and race. Patients and investigators were masked to treatment allocation. Patients received an intravenous infusion of ustekinumab (260 mg for patients weighing 35-55 kg, 390 mg for patients weighing >55 kg and ≤85 kg, and 520 mg for patients weighing >85 kg) followed by subcutaneous injections of ustekinumab 90 mg every 8 weeks or intravenous infusion of placebo at week 0 followed by subcutaneous injections of placebo every 8 weeks, both in addition to standard-of-care therapy. The primary endpoint was the proportion of patients achieving a SLEDAI-2K responder index-4 (SRI-4) response at week 24. Efficacy analyses were done in a modified intention-to-treat population of patients who received at least one dose (partial or complete, intravenous or subcutaneous) of their randomly assigned study treatment. Safety analyses were done in all patients who received at least one dose of study treatment, regardless of group assignment. This study is registered at ClinicalTrials.gov, number NCT02349061. FINDINGS: Between Oct 6, 2015, and Nov 30, 2016, 166 patients were screened, of whom 102 were randomly assigned to receive ustekinumab (n=60) or placebo (n=42). At week 24, 37 (62%) of 60 patients in the ustekinumab group and 14 (33%) of 42 patients in the placebo group achieved an SRI-4 response (percentage difference 28% [95% CI 10-47], p=0·006). Between week 0 and week 24, 47 (78%) of 60 patients in the ustekinumab group and 28 (67%) of 42 patients in the placebo group had at least one adverse event. Infections were the most common type of adverse event (27 [45%] in the ustekinumab group vs 21 [50%] in the placebo group). No deaths or treatment-emergent opportunistic infections, herpes zoster, tuberculosis, or malignancies occurred between weeks 0-24. INTERPRETATION: The addition of ustekinumab to standard-of-care treatment resulted in better efficacy in clinical and laboratory parameters than placebo in the treatment of active systemic lupus erythematosus and had a safety profile consistent with ustekinumab therapy in other diseases. The results of this study support further development of ustekinumab as a novel treatment in systemic lupus erythematosus. FUNDING: Janssen Research & Development, LLC.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ustekinumab/administração & dosagem , Ustekinumab/farmacologia , Adulto , Anticorpos Monoclonais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Interleucina-12/imunologia , Interleucina-12/metabolismo , Interleucina-23/imunologia , Interleucina-23/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Ustekinumab/efeitos adversos
19.
J Rheumatol ; 45(10): 1448-1461, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30111638

RESUMO

OBJECTIVE: To identify the effect of disease activity and damage, measured by validated indices, on mortality and damage accrual, in order to inform upcoming Canadian systemic lupus erythematosus (SLE) recommendations. METHODS: Following GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to fill in evidence-to-decision tables to create recommendations for "minimal investigations needed to monitor SLE patients at baseline and subsequent visits," a systematic literature review was performed. The effect of disease activity and damage, measured by validated metrics, on mortality and damage was systematically reviewed, with metaanalyses performed when available. RESULTS: A title/abstract screen of 5599 articles identified 816 articles for full paper review, with 102 meeting inclusion criteria and 53 with extractable data. Thirty-three articles describing outcomes related to disease activity and 20 articles related to damage were identified. Mortality was associated with higher SLE Disease Activity Index-2000 scores in 6 studies (HR 1.14, 95% CI 1.06-1.22) and higher Systemic Lupus International Collaborating Clinics/ACR Damage Index scores in 6 studies (HR 1.53, 95% CI 1.28-1.83). Higher SLE Activity Measure scores were associated with increased risk of damage in 3 studies (OR 1.06, 95% CI 1.04-1.08). British Isles Lupus Assessment Group was associated with mortality in 1 study with HR of 1.15. CONCLUSION: Active SLE disease and damage are associated with and predict greater mortality and damage. The use of validated disease activity and damage metrics is important in the assessment of disease activity and damage and will inform upcoming Canadian recommendations for the assessment of SLE.


Assuntos
Lúpus Eritematoso Sistêmico/mortalidade , Índice de Gravidade de Doença , Adulto , Canadá , Criança , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica , Reumatologistas , Inquéritos e Questionários , Adulto Jovem
20.
Immunotherapy ; 10(13): 1163-1173, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30105936

RESUMO

Systemic lupus erythematosus is a chronic autoimmune disease with various clinical manifestations, organ involvement and laboratory findings. The disease can involve any organ including skin, joints, kidneys, central and peripheral nervous system, cardiovascular system and more. Currently, the cornerstone of treatment includes antimalarial and immunosuppressive medications and glucocorticosteroids. Recently, great effort has been invested in finding more targeted drugs for achieving better control of the disease with less adverse events. Intravenous belimumab was the first and only biologic drug to be approved by the US FDA and Health Canada for lupus over the last 50 years, and recently was studied in subcutaneous form. This paper will review the major belimumab trials with a focus on the subcutaneous form.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fator Ativador de Células B/imunologia , Linfócitos B/fisiologia , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Linfócitos B/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Infusões Subcutâneas , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
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