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OBJECTIVES: To compare the incidence of major adverse cardiovascular events (MACEs), cancer and infective complications in RA patients using Janus kinase (JAKis) and TNF (TNFis) inhibitors. METHOD: A retrospective analysis of data from the Hong Kong Biologics Registry 2008-2021 was performed. RA patients who had ever used JAKis or TNFis were included. The incidence of MACEs, cancer and infections were compared between the two groups, with adjustment for confounding factors. RESULTS: A total of 2471 courses of JAKis (n = 551) and TNFis (n = 1920) were used in 1732 RA patients (83.7% women, age 53.8 [12.5] years; follow-up 6431 patient-years). JAKi users had significantly older age, more atherosclerotic risk factors and higher frequency of past malignancies. A total of 15 and 40 MACEs developed in the JAKi and TNFi users, respectively (incidence 1.34 vs 0.75 per 100 patient-years; P = 0.22). There was no significant difference in the incidence of cancers between the two groups (0.81 [JAKi] vs 0.85 [TNFi] per 100 patient-years; P = 0.25). The adjusted hazard ratios of MACE and cancer in the JAKi users were 1.36 (95% CI: 0.62, 2.96) (P = 0.44) and 0.87 (95% CI: 0.39, 1.95) (P = 0.74), respectively. Rates of infections were significantly higher in the JAKi than TNFi users (16.3 vs 9.9 per 100 patient-years; P = 0.02), particularly herpes zoster (3.49 vs 0.94 per 100 patient-years; P < 0.001). CONCLUSIONS: In a real-life setting, there is no increase in MACEs or cancers in users of JAKis compared with TNFis. However, the incidence of non-serious infections, including herpes zoster, was increased in users of JAKis.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Herpes Zoster , Neoplasias , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Produtos Biológicos/efeitos adversos , Estudos Retrospectivos , Hong Kong/epidemiologia , Antirreumáticos/efeitos adversos , Fator de Necrose Tumoral alfa , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/complicações , Herpes Zoster/induzido quimicamente , Herpes Zoster/epidemiologia , Janus Quinases , Sistema de Registros , Neoplasias/induzido quimicamenteRESUMO
OBJECTIVES: To study the effect of SARS-CoV2 infection on flares of systemic lupus erythematosus (SLE). METHODS: Patients who fulfilled the ACR/SLICC criteria for SLE and had documented COVID-19 between February and November 2022 were identified retrospectively from our hospital COVID-19 registry. SLE controls who did not have SARS-CoV2 infection were randomly matched for age, sex and the time of infection in a 2:1 ratio with those infected. The primary outcome of interest was clinical flare of SLE within 90 days of COVID-19. The rate of SLE flares (mild/moderate or severe) was compared between SARS-CoV2-infected SLE patients and controls. RESULTS: 91 SLE patients with COVID-19 (age 48.6 ± 14.0 years; 95.6% women) and 182 SLE controls (age 48.7 ± 13.8 years; 95.6% women) were studied. Eleven of 91 (12.1%) SARS-CoV2-infected patients had serious manifestations. One (1.1%) patient died and 7(7.7%) developed severe complications. Within 90 days of SARS-CoV2 infection, 14(15.4%) patients developed mild/moderate clinical SLE flares and 2(2.2%) patients had severe SLE flares. The incidence of SLE flares in SARS-CoV2-infected patients was significantly higher than those without the infection (17.6% vs 5.5%; odds ratio 3.67[1.59-8.46]; p = 0.001). The changes in anti-dsDNA and complement levels, however, were not significantly different between the two groups. Among SARS-CoV2-infected SLE patients, those with clinical SLE flares had significantly lower C3 values (p = 0.004) before the infection than those without. CONCLUSION: Clinical flares within 90 days were significantly more common in SLE patients infected with SARS-CoV2 than matched non-infected SLE controls.
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OBJECTIVES: This study explored whether the excess cardiovascular (CV) disease (CVD) risk in RA could be ameliorated by suppression of inflammation using a treat-to-target (T2T) approach. We compared the CV event (CVE) incidence among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population and a historical RA cohort (HRA). METHODS: This was an observational study using the city-wide hospital data and the ERA registry. ERA patients received T2T management while HRA patients received routine care. Each ERA/HRA patient was matched to three non-RA controls according to age, gender and CV risk factors. Patients on antiplatelet/anticoagulant agents, with pre-existing CVD, chronic kidney disease or other autoimmune diseases were excluded. All subjects were followed for up to 5 years. The primary end point was the first occurrence of a CVE. RESULTS: The incidence of CVE in the ERA cohort (n = 261) and ERA controls were similar with a hazard ratio of 0.53 (95% CI 0.15, 1.79). In contrast, the incidence of CVE in the HRA cohort (n = 268) was significantly higher than that of the HRA controls with a hazard ratio of 1.9 (95% CI 1.16, 3.13). The incidence of CVE in the ERA cohort was significantly lower than that of the HRA cohort and the difference became insignificant after adjusting for inflammation, the use of methotrexate and traditional CV risk factors. CONCLUSION: ERA patients managed by a T2T strategy did not develop excess CVE compared with CV risk factor-matched controls over 5 years.
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Artrite Reumatoide , Doenças Cardiovasculares , Humanos , Estudos de Casos e Controles , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Metotrexato/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Inflamação/complicações , Fatores de RiscoRESUMO
OBJECTIVES: To study the relationship between the 2019 EULAR/ACR classification criteria and organ damage in patients with systemic lupus erythematosus (SLE). METHODS: Patients involved in a cross-sectional validation study of the EULAR/ACR criteria and judged by a panel of rheumatologists to be clinical SLE were studied. Those who fulfilled the EULAR/ACR criteria at their last clinic visit were stratified into 2 groups based on a cutoff score of 20. The last SLE International Collaborating Clinic (SLICC) Organ Damage Index (SDI) was compared between these two groups. Relationship among the domains of the EULAR/ACR criteria and SDI in all patients was studied by using Spearman's rank correlation. RESULTS: A total of 562 SLE patients were studied (93.6% women; age 36.5 ± 14.1 years; follow-up duration 11.6 ± 6.6 years). The mean and median EULAR/ACR criteria scores in those who fulfilled the EULAR/ACR criteria (N = 542) were 24.6 ± 7.3 and 24 (interquartile range 19-30), respectively. A total of 392 patients had EULAR/ACR scores of ≥20 (group 1), and 150 patients had scores of 10-19 (group 2). Group 1 patients had significantly higher prevalence of fever, alopecia, oral ulcers, acute lupus skin lesions, arthritis, serositis, seizure, hemolytic anemia, leukopenia, and renal disease and so were the anti-dsDNA, anti-Sm, antiphospholipid antibodies, and low complement state. Organ damage (SDI score of ≥1) occurred in 232 (42.8%) patients. Patients in group 1 had significantly higher SDI scores in the renal, cardiovascular, dermatological, and gonadal domains than group 2. The renal, neuropsychiatric, and antiphospholipid antibody domain scores of the EULAR/ACR criteria correlated positively with the total SDI. The renal domain of the EULAR/ACR criteria had the strongest correlation with renal damage (Rho 0.30; p < 0.001). Patients who scored 10 points in the renal domain had significantly higher renal damage score than those scored 8 points or 4 points. Gonadal damage score was also significantly more common in the 10-point than in the 8-point group. CONCLUSION: In addition to disease classification, the EULAR/ACR SLE criteria may have value in predicting prognosis.
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Leucopenia , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Anticorpos Antifosfolipídeos , PrognósticoRESUMO
OBJECTIVE: Anti-melanoma differentiation-associated protein 5 (MDA5)-positive DM is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors of mortality and RP-ILD. METHODS: Anti-MDA5-positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. RESULTS: Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed RP-ILD [hazard ratio (HR) 9.735 (95% CI 3.905, 24.272)], age >52 years [HR 4.750 (95% CI 1.692, 13.333)], ferritin level >2800 pmol/l [HR 3.042 (95% CI 1.323, 6.997)] and lactate dehydrogenase (LDH) >400 IU/l [HR 2.290 (95% CI 1.009, 5.198)] were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years [HR 2.640 (95% CI 1.277, 5.455)], LDH >300 IU/l [HR 3.189 (95% CI 1.469, 6.918)], fever [HR 1.903 (95% CI 0.956, 3.790)] and neutrophil:lymphocyte ratio >7.0 [HR 1.967 (95% CI 0.942, 4.107)]. We proposed a prediction model based on fever, LDH, age and white cell count (FLAW) to stratify the risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75%, respectively. CONCLUSIONS: Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The FLAW model maybe useful to predict the development of RP-ILD.
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Dermatomiosite , Doenças Pulmonares Intersticiais , Humanos , Pessoa de Meia-Idade , Dermatomiosite/complicações , Autoanticorpos , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/etiologia , Helicase IFIH1 Induzida por Interferon , Taxa de Sobrevida , L-Lactato Desidrogenase , FebreRESUMO
OBJECTIVES: To report the 10-year outcome of lupus nephritis (LN) treated with mycophenolate mofetil (MMF) or tacrolimus (TAC) induction in a randomised controlled trial. METHODS: Patients with active LN were treated with MMF or TAC combined with high-dose prednisolone. Responders were switched to azathioprine (AZA) at month 6. Clinical outcomes at 10 years (renal flares, renal function decline and mortality) were assessed. Factors affecting prognosis were studied by Cox regression. Urine protein-to-creatinine ratio (uPCr) and estimated glomerular filtration rate (eGFR) at different time points were evaluated for their prediction of a poor prognosis by receiver operating characteristic (ROC) analysis. RESULTS: 150 patients were studied (age 35.5±12.8 years). Complete renal response rate was similar between MMF (59%) and TAC-treated patients (62%; p=0.71). AZA maintenance was given to 79% patients. After 118.2±42 months, proteinuric and nephritic renal ï¬ares occurred in 34% and 37% of the MMF, and 53% and 30% of the TAC groups of patients, respectively (p=0.49). The cumulative incidence of a composite outcome of ↓eGFR ≥30%, chronic kidney disease stage 4/5 or death at 10 years was 33% in both groups (p=0.90). Factors independently associated with a poor renal prognosis were first-time LN (HR 0.12 (0.031 to 0.39); p=0.01), eGFR (HR 0.98 (0.96 to 0.99); p=0.008) and no response at month 6 (HR 5.18 (1.40 to 19.1); p=0.01). ROC analysis revealed an uPCr >0.75 and eGFR of <80 mL/min at month 18 best predicted a poor renal prognosis. CONCLUSIONS: Long-term data confirmed non-inferiority of TAC to MMF as induction therapy of LN. An uPCr≤0.75 and eGFR of ≥80 mL/min at month 18 best predicted a favourable 10-year outcome and may be suitable targets for induction/consolidation therapy. TRIAL REGISTRATION NUMBER: NCT00371319.
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Imunossupressores/uso terapêutico , Quimioterapia de Indução/métodos , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Azatioprina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Exacerbação dos Sintomas , Tempo , Resultado do TratamentoRESUMO
To study the clinical presentation, treatment and outcome of southern Chinese patients with Takayasu's arteritis (TA). This is a retrospective chart review study of 78 patients managed in 14 public hospitals in Hong Kong between the years 2000 and 2010. Patients were identified from the hospital registry using the ICD-10 diagnostic code of the disease. The classification of TA was based on the American College of Rheumatology (ACR) or modified Ichikawa's criteria. Demographic data, clinical presentation, angiographic findings, pattern of vascular involvement (Numano's classification), treatment and outcome of these patients were presented. 78 patients were studied (82% women, age at presentation 34.2 ± 14 years). The estimated point prevalence of TA was 11/million population. The commonest initial manifestations were hypertension (62%) and vascular ischemic symptoms (38%). Systemic symptoms occurred in nine (12%) patients only. The proportion of patients fulfilling the angiographic subtypes of the Numano's classification was: types I (13%), IIa (4%), IIb (12%), III (12%), IV (20%) and V (39%), respectively. Thirty-two patients (41%) were treated with high-dose glucocorticoids (GCs) and 22 patients (28%) received additional non-GC immunosuppressive drugs. Vascular complications occurred in 26 (33%) patients and revascularization surgery was performed in 23(29%) patients. Three (4%) patients died of vascular complication at a median of 8 years after disease onset. TA is rare in southern Chinese patients of Hong Kong. Most patients present with ischemic symptoms during the stenotic phase of the disease. Although mortality is low, a significant proportion of patients developed vascular stenosis that required surgical interventions. More awareness of TA as a differential diagnosis of non-specific systemic symptoms with elevated inflammatory markers in younger patients is needed for earlier diagnosis.
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Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Arterite de Takayasu/terapia , Procedimentos Cirúrgicos Vasculares , Adulto , Povo Asiático , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Progressão da Doença , Feminino , Glucocorticoides/efeitos adversos , Hong Kong/epidemiologia , Humanos , Imunossupressores/efeitos adversos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Estudos Retrospectivos , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/etnologia , Arterite de Takayasu/mortalidade , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidade , Adulto JovemRESUMO
OBJECTIVE: To compare the efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) for the initial therapy of lupus nephritis (LN). STUDY DESIGN: This is an open randomised controlled parallel group study. METHODS: Adult patients with biopsy-confirmed active LN (class III/IV/V) were randomised to receive prednisolone (0.6 mg/kg/day for 6 weeks and tapered) in combination with either TAC (0.06-0.1 mg/kg/day) or MMF (2-3 g/day) for 6 months. Good responders were shifted to azathioprine for maintenance. The primary outcome was the rate of complete renal response (CR) at 6 months and the secondary outcomes included partial renal response, renal flares and decline of renal function over time. RESULTS: 150 patients (92% women; aged 35.5±12.8 years; 81% class III/IV) were randomised (76 MMF, 74 TAC). At month 6, the rate of CR was 59% in the MMF and 62% in the TAC group (treatment difference: 3.0% (-12%, 18%); p=0.71). Major infective episodes occurred in 9.2% patients treated with MMF and in 5.4% patients treated with TAC (p=0.53). Maintenance therapy with azathioprine was given to 79% patients. After 60.8±26 months, proteinuric and nephritic renal flares developed in 24% and 18% of patients in the MMF group and 35% (p=0.12) and 27% (p=0.21) in the TAC group, respectively. The cumulative incidence of a composite outcome of decline of creatinine clearance by ≥30%, development of chronic kidney disease stage 4/5 or death was 21% in the MMF and 22% in the TAC group of patients (p=0.35). CONCLUSIONS: TAC is non-inferior to MMF, when combined with prednisolone, for induction therapy of active LN. With azathioprine maintenance for 5 years, a non-significant trend of higher incidence of renal flares and renal function decline is observed with the TAC regimen. TRIAL REGISTRATION NUMBER: Hospital Authority Research Ethics Committee Clinical Trial Registry (HARECCTR0500018; Hong Kong) and US ClinicalTrials.gov (NCT00371319).
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Imunossupressores/uso terapêutico , Quimioterapia de Indução/métodos , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Tacrolimo/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Azatioprina/uso terapêutico , Creatinina/sangue , Creatinina/urina , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/etiologia , Nefrite Lúpica/complicações , Nefrite Lúpica/fisiopatologia , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Prednisolona/uso terapêutico , Proteinúria/etiologia , Recidiva , Tacrolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: To evaluate the immunogenicity and safety of GARDASIL, a quadrivalent human papillomavirus (HPV) vaccine, in patients with systemic lupus erythematosus (SLE). METHODS: Women with SLE aged 18-35 years who had stable disease were recruited to receive GARDASIL vaccination and an equal number of age-matched healthy women were also vaccinated. Seroconversion rates of antibodies to HPV serotypes 6, 11, 16 and 18 at months 7 and 12 and adverse events (AEs) were compared between patients and controls. The rate of disease flares in SLE participants was compared with matched SLE controls. RESULTS: 50 patients with SLE and 50 healthy controls were studied. The mean age and disease duration of the patients was 25.8±3.9 years and 6.6±4.5 years, respectively. At month 12 the seroconversion rates of anti-HPV serotypes 6, 11, 16 and 18 in patients and controls were 82%, 89%, 95%, 76% and 98%, 98%, 98%, 80%, respectively. In patients with SLE there were no significant changes in the titres of anti-dsDNA, complements, anti-C1q and SLE Disease Activity Index scores from baseline to months 2, 7 and 12. There was one mild/moderate SLE flare at months 0-2, two mild/moderate flares at months 3-6 and six mild/moderate and two severe flares at months 7-12. Disease flares in patients with SLE occurred at a similar frequency to that of 50 matched SLE controls (0.22/patient/year vs 0.20/patient/year, p=0.81). Injection site reaction was the commonest AE (5%), and the incidence of AEs was comparable between patients with SLE and controls. CONCLUSIONS: The quadrivalent HPV vaccine is well tolerated and reasonably effective in patients with stable SLE and does not induce an increase in lupus activity or flares.
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Alphapapillomavirus/imunologia , Hospedeiro Imunocomprometido/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/efeitos adversos , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVES: The objective was to study the prevalence and risk factors of herpes zoster (HZ) infection in patients with rheumatic diseases. METHODS: Consecutive patients with rheumatic diseases not receiving biologic/targeted DMARDs who attended our rheumatology clinics between March and August 2019 were retrospectively reviewed. Episodes of HZ infection since their first clinic attendance were identified. Laboratory results (total white cell count, neutrophil-to-lymphocyte ratio (NLR), serum albumin, globulin, and creatinine) and use of immunosuppressive medications were compared between those with (preceding infection) and without (preceding last visit) HZ infection. Cox regression analysis was performed to identify factors associated with the first HZ infection in all patients. RESULTS: 1,479 patients were studied (88.3% women, age 45.0 ± 15.8 years). Systemic lupus erythematosus (SLE) (38.7%) and rheumatoid arthritis (28.3%) were the commonest rheumatic diseases. After a follow-up of 14,715 patient-years (9.9 ± 7.0 years), 219 (14.8%) patients developed 258 episodes of HZ infection, giving an overall prevalence of 1.75/100-patient years. The prevalence rates of HZ were highest in SLE and inflammatory myopathies (2.54 and 2.58 per 100 patient-years, respectively). Patients who experienced HZ reactivation were younger, more likely to have SLE, and had significantly lower serum albumin/globulin levels but higher NLR. Significantly more patients with HZ reactivation were using prednisolone and other immunosuppressive drugs in the visits preceding HZ infection. The cumulative risk of having HZ reactivation at 24 and 48 months was 4.9% and 7.6%, respectively. Cox regression analysis revealed that a diagnosis of SLE, increasing age, higher NLR, use of cyclophosphamide, and increasing doses of prednisolone, azathioprine, hydroxychloroquine and leflunomide were independently associated with HZ infection. CONCLUSIONS: Reactivation of HZ is fairly common in patients with rheumatic diseases. Underlying SLE, age, neutrophil/lymphocyte ratio, and immunosuppressive therapies are independent risk factors. Key Points ⢠Herpes zoster (HZ) infection is fairly common in patients with rheumatic diseases undergoing conventional DMARD or immunosuppressive therapies. ⢠Underlying SLE, increasing age, higher neutrophil/lymphocyte ratio and increasing dosages of immunosuppressive drugs are independent risk factors. ⢠Patients with rheumatic diseases, particularly SLE, should be encouraged to receive HZ vaccination.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Herpes Zoster , Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Prevalência , Herpes Zoster/complicações , Herpes Zoster/epidemiologia , Fatores de Risco , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Herpesvirus Humano 3 , Prednisolona/uso terapêutico , Produtos Biológicos/uso terapêutico , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologiaRESUMO
To study the relationship of serum PCSK9 and disease activity and major adverse cardiovascular events (MACEs) in systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥ 4 ACR criteria for SLE and consented for a biomarker study in 2009-2013 were included. Stored serum samples were assayed for PCSK9. PCSK9 levels were correlated with SLE disease activity scores. Patients were divided into two groups according to the median PCSK9 level and new MACEs over time were evaluated. The effect of PCSK9 level on MACEs and mortality was studied by Cox regression, adjusted for confounders. A total of 539 SLE patients were studied (93% women, age 41.9 ± 14.0 years). The median PCSK9 level at baseline was 220 ng/ml. Patients with higher PCSK9 (≥ 220 ng/ml; n = 269) had significantly higher SLE disease activity index (SLEDAI) than those with lower PCSK9 (< 220 ng/ml; n = 270). PCSK9 levels were significantly higher in patients with active renal than active non-renal SLE, which in turn were significantly higher than those with inactive SLE or healthy controls. PCSK9 level correlated with SLEDAI in the overall population (ρ = 0.30; p < 0.001). Over 91.3 ± 18.6 months, 29 patients developed 31 MACEs and 40 patients succumbed (25% for vascular events). The cumulative incidence of MACEs at 5 years was 4.8% in the higher PCSK9 and 1.1% in the lower PCSK9 group (HR2.51[1.11-5.70]; p = 0.03). Cox regression revealed higher PCSK9 was significantly associated with MACEs (HR1.003[1.000-1.005] per ng/ml; p = 0.02) independent of age, sex, renal function, baseline disease activity score, traditional atherosclerotic risk factors, antiphospholipid antibody and the use of aspirin/warfarin, statins and immunosuppressive drugs. PCSK9 level was also independently associated with all-cause (HR1.002[1.000-1.004] per ng/ml; p = 0.03) and vascular mortality (HR1.004[1.000-1.007]; p = 0.04). We concluded that serum PCSK9 level correlates with SLE disease activity. Higher serum PCSK9 levels are associated with increased risk of cardiovascular events and mortality in SLE.
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Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Pró-Proteína Convertase 9 , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , SubtilisinasRESUMO
Background: The aim of this study was to validate the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) in antinuclear antibody (ANA)-positive Chinese patients. Methods: Medical records of all adult patients who attended the rheumatology out-patient clinics between May and September 2019 were reviewed. Patients with ever ANA positive (titre ⩾1:80) were included and evaluated for the fulfilment of the 2019 EULAR/ACR, 2012 Systemic Lupus International Collaborating Clinics (SLICC) and 1997 ACR criteria for SLE classification. The performance of these criteria in predicting a clinical diagnosis of SLE as judged by an independent panel of rheumatologists was studied and compared in different subgroups. Results: A total of 1533 patients (88.2% women; age at first clinic attendance 45.5 ± 15.6 years) were studied and 562 patients were judged to be clinical SLE. The sensitivity and specificity of the EULAR/ACR (⩾10 points), SLICC and ACR criteria for a clinical diagnosis of SLE was 96.1%, 97.9% and 86.1%; and 85.8%, 86.3% and 94.3%, respectively. Applying the attribution rule to the non-SLE controls, the specificity of the three criteria increased to 95.0%, 92.5% and 98.8%, respectively. The specificity of the EULAR/ACR criteria was higher in male patients (97.9%), those aged >50 years (97.0%) and disease duration of ⩽3 years (97.6%). Using a cut-off of 12 points, the specificity of the EULAR/ACR criteria was further increased (96.6%) while a high sensitivity (95.0%) was maintained. Conclusion: In Chinese patients with a positive ANA, the EULAR/ACR criteria for clinical SLE perform equally well to the SLICC criteria. Both the EULAR/ACR and SLICC are more sensitive but less specific than the ACR criteria. The specificity of all the three criteria is enhanced by applying the attribution rule to controls. The specificity of the EULAR/ACR criteria is higher in certain patient subgroups or when the cut-off score is raised.
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OBJECTIVES: To study the efficacy of raloxifene in preventing bone mineral density (BMD) loss in women receiving long-term glucocorticoids (GC). The study took the form of a parallel-group randomised double-blinded placebo-controlled trial. METHODS: Postmenopausal women without hypercoagulability risk factors who were prevalent GC users were randomised to receive either raloxifene (60 mg/day) or placebo (1 tablet/day) on top of calcium (1000 mg/day) and calcitriol (0.25 µg/day). BMD of the hip and spine (primary outcome), bone turnover markers and new vertebral fractures (secondary outcomes) at month 12 were assessed. RESULTS: Between December 2006 and December 2008, 114 patients were recruited (age 55.3±7.7 years). The duration and dose of prednisolone received was 62.2±64 months and 6.7±5.9 mg/day, respectively. Baseline vertebral fracture was present in six (5%) patients. In all, 57 patients were allocated to each of the treatment arms. Demographic data, osteoporotic risk factors and BMD at various sites were similar between the two groups of patients. At month 12, a significant gain in the lumbar spine (+1.3±0.4%; p=0.004) and total hip BMD (+1.0±0.4%; p=0.01) was observed in patients treated with raloxifene but a significant decrease in BMD of the lumbar spine (-0.9±0.4%; p=0.045) and hip (-0.8±0.3%; p=0.01) occurred in the placebo group. The femoral neck BMD did not change significantly in favour of raloxifene. Three new fractures developed exclusively in the patients treated with placebo. Bone formation (serum osteocalcin and procollagen type I N-terminal) and resorption (urine deoxypyridinoline and type I collagen) markers decreased significantly in the raloxifene group but not in patients treated with placebo. Leg cramps were numerically more frequent in the raloxifene group (7% vs 0%) but thromboembolism was not reported in any patients. CONCLUSIONS: In postmenopausal women receiving long-term GCs, raloxifene is well tolerated and significantly increases spinal and hip BMD after 12 months of treatment.
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Conservadores da Densidade Óssea/uso terapêutico , Glucocorticoides/efeitos adversos , Osteoporose Pós-Menopausa/prevenção & controle , Cloridrato de Raloxifeno/uso terapêutico , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Articulação do Quadril/fisiopatologia , Humanos , Lipídeos/sangue , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/induzido quimicamente , Osteoporose Pós-Menopausa/fisiopatologia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Cloridrato de Raloxifeno/efeitos adversos , Doenças Reumáticas/tratamento farmacológicoRESUMO
Objectives: To revisit the trend of survival of systemic lupus erythematosus in a cohort of Chinese patients over 25 years. Methods: Patients who fulfilled the 1997 ACR criteria for SLE and were followed in our hospital since 1995 were included. Patients were stratified into two groups according to the year of diagnosis: (1) 1995-2004 and (2) 2005-2018. Survival of patients was studied by Kaplan-Meier analysis. Organ damage as assessed by the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) and causes of death in the first 10 years of SLE onset was compared between the two groups. Cox regression was used to study factors associated with survival. Results: A total of 1,098 SLE patients were registered in our database. After excluding 157 patients diagnosed outside the time period of 1995-2018, 941 patients were studied (92% women). All were ethnic Chinese. The mean age of SLE onset was 35.1 ± 14.4 years, and the mean duration of observation was 13.1 ± 6.6 years. Seventy-seven (8.2%) patients were lost to follow-up. Groups 1 and 2 consisted of 364 and 577 patients, respectively. The mean SDI score at 10 years of disease onset was significantly higher in group 1 than group 2 patients (1.01 ± 1.43 vs. 0.57 ± 0.94; p < 0.01), particularly in the neuropsychiatric, musculoskeletal, and gonadal domains. Within 10 years of SLE onset, 32 (8.8%) patients in group 1 and 25 (4.3%) patients in group 2 died (p = 0.005). The 5- and 10-year cumulative survival rates were 93.6 and 91.0% in group 1 and 96.5 and 94.2% in group 2 patients, respectively (log-rank test p = 0.048). Infection accounted for more than half of the deaths in both groups. More group 1 than group 2 patients died of vascular events, but the difference was not statistically significant. Cox regression showed that the age of SLE onset and damage score accrued at 10 years, but not the time period in which SLE was diagnosed, were significantly associated with mortality. Conclusions: The improvement in survival of our SLE patients is probably related to the accrual of less organ damage in the past 15 years.
RESUMO
OBJECTIVE: To study the bone mineral density (BMD) and body composition in men with systemic lupus erythematosus (SLE). METHODS: Consecutive male patients who fulfilled > or =4 ACR criteria for SLE and age-matched healthy men were recruited for measurement of BMD and body composition by DXA scan. Risk factors for low BMD in SLE patients were evaluated. RESULTS: 40 male SLE patients were studied (age 42.6+/-12 years; disease duration 84.7+/-79 months). 34 (85%) patients were treated with long-term glucocorticoids. Compared with 40 controls, SLE patients had a significantly lower BMD at the lumbar spine (0.96+/-0.16 vs 1.03+/-0.11 g/cm2; p=0.02) and the hip (0.87+/-0.14 vs 0.94+/-0.12 g/cm2; p=0.04). At the spine, 12 (30%) SLE patients had Z scores< - 2.0 and 2 (5%) had osteoporotic fractures. At the hip, 3 (7.5%) patients had Z scores< - 2.0 but none had hip fractures. The BMD Z scores at the femoral neck and spine were significantly lower in SLE patients than controls. The total lean body mass was also lower in patients than control subjects (46.4+/-7.3 vs 50.5+/-5.9 kg; p=0.01). Multiple regression revealed increasing age, habitual drinking, lower BMI and use of high-dose prednisolone were unfavorably associated with lower BMD at the spine in SLE patients. CONCLUSIONS: Reduced BMD and lean body mass are prevalent in men with SLE. Appropriate measures against osteoporosis should be undertaken, especially in older patients with low BMI who receive high-dose glucocorticoids.
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Composição Corporal/fisiologia , Densidade Óssea/fisiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Autoanticorpos/imunologia , Peso Corporal , Estudos de Casos e Controles , Quadril/fisiopatologia , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Obesidade/fisiopatologia , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Análise de Regressão , Coluna Vertebral/fisiopatologia , Magreza/fisiopatologiaRESUMO
We conducted the current study to compare the incidence and risk factors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis. We identified patients in whom lupus nephritis and non-lupus primary glomerulonephritis were diagnosed between 1993 and 2003 using our lupus cohort database and pathology registry. We analyzed the cumulative incidence of new arterial thromboembolic events since diagnosis by Kaplan-Meier plot, and studied risk factors by multivariate analysis. We studied 162 patients with lupus and 181 patients with non-lupus primary glomerulonephritis. After a mean observation of 8.1 years, 47 (14%) patients died, 23 (7%) were lost to follow-up, and 38 (11%) developed 42 arterial events (incidence, 15.1/1000 patient-years). Although patients with lupus nephritis were younger and had a significantly lower frequency of smoking, hypertension, obesity, and renal dysfunction, their cumulative risk of arterial event at 5 years was not significantly lower than that of patients with primary non-lupus glomerulonephritis (6.3% vs. 6.6%, p = 0.96). In a Cox regression model, lupus was found to be an independent risk factor for arterial thrombosis (hazard ratio 3.57 [1.07-11.9]; p = 0.04), in addition to increasing age (hazard ratio 1.04 per year; p = 0.02), low-density lipoprotein > or =2.6 mmol/L (hazard ratio 4.46; p = 0.002), and glomerular filtration rate <30 mL/min (hazard ratio 2.67; p = 0.04). We concluded that in immune-mediated glomerulonephritis, having systemic lupus increased the risk of arterial thromboembolism after adjustment for age, renal insufficiency, and other traditional risk factors.
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Nefrite Lúpica/epidemiologia , Tromboembolia/epidemiologia , Adulto , Fatores Etários , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Hiperlipidemias/epidemiologia , Incidência , Lipoproteínas LDL/sangue , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Insuficiência Renal/epidemiologia , Fatores de RiscoRESUMO
We conducted the current study to determine the prevalence and predictors of neuropsychiatric damage in a cohort of Chinese patients with systemic lupus erythematosus (SLE). Patients were those newly diagnosed as having SLE between 1990 and 2004 in our unit. Demographic data, presenting and cumulative clinical features, disease activity score at diagnosis, and serial damage scores were obtained. Neuropsychiatric (NP) manifestations were classified according to the American College of Rheumatology (ACR) nomenclature. NP damage was evaluated by the NP domain of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index. Factors predictive of NP damage were studied by regression models. We studied 282 patients who fulfilled > or =4 of the ACR criteria for SLE. The mean age of SLE onset was 31.8 +/- 14 years. After a mean follow-up of 6.7 years, 65 patients (23%) had at least 1 NP manifestation and 50 (18%) developed NP damage (SLICC/ACR Damage Index > or = 1). Cerebrovascular accident was the most common cause of NP damage (35%), followed by seizure (20%), psychosis (12%), cranial/peripheral neuropathy (12%), cognitive dysfunction (12%), and myelopathy (9%). In a multiple regression model, disease activity at diagnosis, cumulative non-NP damage, presence of antiphospholipid antibodies, and ever use of pulse methylprednisolone were independent factors associated with NP damage. New NP damage after the first year of diagnosis was predicted by longer disease duration and the use of pulse methylprednisolone in another multivariate model. Neither early nor cumulative NP damage predicted mortality. NP damage is prevalent in Chinese patients with SLE and is independently associated with more active disease at diagnosis, antiphospholipid antibodies and the use of pulse methylprednisolone therapy. Primary prevention for cerebrovascular disease in high-risk patients may reduce NP damage.
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Doenças do Sistema Nervoso Central/etiologia , Lúpus Eritematoso Sistêmico/complicações , Doenças do Sistema Nervoso Periférico/etiologia , Adulto , Doenças do Sistema Nervoso Central/epidemiologia , Distribuição de Qui-Quadrado , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Doenças do Sistema Nervoso Periférico/epidemiologia , PrevalênciaRESUMO
We conducted the current study to determine the clinical determinants of survival and the survival rates in an unselected cohort of Chinese patients with new-onset systemic lupus erythematosus (SLE), including all age-groups. Patients were those newly diagnosed as having SLE or referred within 6 months of diagnosis to the departments of medicine, geriatrics, and pediatrics at Tuen Mun Hospital, Hong Kong, between 1991 and 2003. Patients under the care of all specialists were included for analysis. We obtained demographic data, presenting and cumulative clinical features, disease activity, and serial damage scores. For patients who died or were lost to follow-up, data were censored at the last clinic visit. Survival over time was studied by the Kaplan-Meier method, and factors predictive of mortality were evaluated by the Cox proportional hazard model. We studied 285 new-onset SLE patients (92% women). All were ethnic Chinese and fulfilled at least 4 of the American College of Rheumatology criteria for SLE. The mean age of SLE onset was 30.0 +/- 13.5 years. Fifty (18%) patients had first onset of SLE before the age of 16 years (childhood onset), and 22 (8%) had disease onset after the age of 50 years (late onset); 213 (75%) patients had disease onset between the ages of 16 and 50 years (adult onset). Twenty-nine (10%) patients died (4 from the childhood-onset group, 6 from the late-onset group, and 19 from the adult-onset group) and 18 (6%) patients were lost to follow-up. The overall 5-, 10-, and 15-year survival rates were 92%, 83%, and 80%, respectively. Survival was significantly worse in late-onset patients: 5-, 10-, and 15-year survival rates were 66%, 44%, and 44%, respectively; p < 0.0001. Infection was the main cause of death (55%), followed by cardiovascular (17%) and cerebrovascular complications (14%). Unfavorable factors for survival on univariate analysis were increasing age, damage scores at 1 year, and the use of high-dose corticosteroids. Cox regression revealed that damage scores at 1 year and hematologic manifestations were independent predictors of mortality. Long-term survival of Chinese SLE patients is comparable to that reported for white patients in the 1990s. Late-onset SLE patients have the worst prognosis. Early damage predicts mortality.
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Lúpus Eritematoso Sistêmico/mortalidade , Adolescente , Corticosteroides/uso terapêutico , Adulto , Fatores Etários , Idade de Início , Doenças Cardiovasculares/mortalidade , Transtornos Cerebrovasculares/mortalidade , Criança , China/etnologia , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Previsões , Hong Kong/epidemiologia , Humanos , Infecções/mortalidade , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/classificação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de SobrevidaRESUMO
UNLABELLED: In this work we evaluate the prevalence of the antiphospholipid syndrome (APS) and its impact on survival in Chinese patients with systemic lupus erythematosus (SLE). We studied a prospective cohort of southern Chinese patients who fulfilled ≥4 American College of Rheumatology criteria for SLE. The cumulative rate of survival over time was calculated by the Kaplan-Meier method. APS was defined by the 2006 updated consensus criteria. We evaluated the prevalence and manifestations of APS, and compared the survival of patients with and without APS. We followed 679 patients with SLE (92% women; age of onset, 32.5 ± 14 yr) for 9.7 ± 7.3 years. Sixty-eight (10%) patients died and 33 (4.9%) patients were lost to follow-up. Forty-four (6.5%) patients met the criteria for APS, manifested by the following: ischemic stroke (55%), deep venous thrombosis (32%), obstetric morbidity (14%), cardiovascular events (9%), and peripheral vascular disease (9%). Nine (9/44 [20%]) APS patients died, which was more frequent than the non-APS patients (59/635 [9%]; p = 0.02). The cumulative mortality of patients with APS was 4.6% at 5 years, 7.8% at 10 years, and 22.2% at 15 years, which was not significantly higher than that of non-APS patients (5.4% at 5 years, 9.2% at 10 years, and 11.3% at 15 years; p = 0.14). However, if we considered only patients with APS caused by arterial thrombosis, the presence of APS was significantly associated with mortality (hazard ratio, 2.29; 95% confidence interval, 1.13-4.64; p = 0.02). We conclude that the presence of APS increases the mortality risk of Chinese patients with SLE, which is mainly contributed by arterial thrombotic events. CLINICAL SIGNIFICANCE: 1) APS is infrequent in southern Chinese patients with SLE compared to white patients. 2) Arterial thrombosis is a more common manifestation of APS than venous thrombosis in Chinese SLE patients. 3) APS related to arterial thrombosis is associated with increased mortality in Chinese patients with SLE.
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Síndrome Antifosfolipídica/etnologia , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/mortalidade , Adulto , Síndrome Antifosfolipídica/diagnóstico , Causas de Morte , China/epidemiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez/etnologia , Prevalência , Estudos ProspectivosRESUMO
OBJECTIVE: To determine whether there is any seasonal variation in the activity of systemic lupus erythematosus (SLE) overall and by individual organs. METHODS: The study group comprised 2102 patients with SLE who were followed in a prospective longitudinal cohort study. In this cohort, 92.3% of the patients were women. The mean ± SD age of the patients was 47.9 ± 13.9 years, 56.3% were white, 37.1% were African American, and 3.1% were Asian. Global disease activity was recorded by the Safety of Estrogens in Lupus Erythematosus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and the physician's global assessment. Activity of each organ was also recorded using SLEDAI terms and a visual analog scale (VAS; 0 to 3). RESULTS: There was significant seasonal variation in photosensitive rash (p < 0.0001), which was more frequent in the spring and summer months (p < 0.0001). There was significantly more arthritis activity in spring and summer, as measured by both SELENA-SLEDAI (p = 0.0057) and the joint VAS (p = 0.0047). A decrease in renal activity was found in the summer months compared to the rest of the year (p = 0.0397). Serositis recorded by VAS had higher activity from August to October (p = 0.0392). Anti-dsDNA levels were significantly higher during October and November (p < 0.0001). There was significant seasonal variation in antiphospholipid antibody levels (p < 0.0001) and lupus anticoagulant (p = 0.0003). We found a significant variation in activity through the year in global disease activity as measured by SELENA-SLEDAI (p = 0.048). CONCLUSION: In the Hopkins Lupus Cohort, skin and joint activity is increased during the spring and summer, but other organs have different patterns. These seasonal variations likely reflect environmental factors that influence disease activity, including ultraviolet light and infections.