ABSTRACT
Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterised by the presence of autoantibodies towards nuclear antigens, immune complex deposition, and chronic inflammation at classic target organs such as skin, joints, and kidneys. Despite substantial advances in the diagnosis and management of SLE, the burden of disease remains high. It is important to appreciate the typical presentations and the diagnostic process to facilitate early referral and diagnosis for patients. In most patients, constitutional, mucocutaneous, and musculoskeletal symptoms represent the earliest complaints; these symptoms can include fatigue, lupus-specific rash, mouth ulcers, alopecia, joint pain, and myalgia. In this Seminar we will discuss a diagnostic approach to symptoms in light of the latest classification criteria, which include a systematic evaluation of clinical manifestations (weighted within each domain) and autoantibody profiles (such as anti-double-stranded DNA, anti-Sm, hypocomplementaemia, or antiphospholipid antibodies). Non-pharmacotherapy management is tailored to the individual, with specific lifestyle interventions and patient education to improve quality of life and medication (such as hydroxychloroquine or immunosuppressant) adherence. In the last decade, there have been a few major breakthroughs in approved treatments for SLE and lupus nephritis, such as belimumab, anifrolumab, and voclosporin. However the disease course remains variable and mortality unacceptably high. Access to these expensive medications has also been restricted across different regions of the world. Nonetheless, understanding of treatment goals and strategies has improved. We recognise that the main goal of treatment is the achievement of remission or low disease activity. Comorbidities due to both disease activity and treatment adverse effects, especially infections, osteoporosis, and cardiovascular disease, necessitate vigilant prevention and management strategies. Tailoring treatment options to achieve remission, while balancing treatment-related comorbidities, are priority areas of SLE management.
Subject(s)
Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/therapy , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/complications , Immunosuppressive Agents/therapeutic use , AutoantibodiesABSTRACT
OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
Subject(s)
Azathioprine , Lupus Erythematosus, Systemic , Humans , Azathioprine/therapeutic use , Tacrolimus/therapeutic use , Rituximab/therapeutic use , Methotrexate/therapeutic use , Lupus Erythematosus, Systemic/complications , Immunosuppressive Agents/therapeutic use , Cyclophosphamide/therapeutic use , Hydroxychloroquine/therapeutic use , Glucocorticoids/therapeutic use , Enzyme Inhibitors/therapeutic useABSTRACT
OBJECTIVE: To identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). METHODS: Urine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. RESULTS: Systems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). CONCLUSION: In addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.
Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Lupus Nephritis/diagnosis , Lupus Nephritis/genetics , Insulin-Like Growth Factor Binding Protein 2 , Proteomics , Cross-Sectional Studies , Endothelial Cells , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/genetics , Biomarkers , Kidney , Gene Expression ProfilingABSTRACT
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.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Biological Products , Herpes Zoster , Neoplasms , Humans , Female , Middle Aged , Male , Tumor Necrosis Factor Inhibitors/therapeutic use , Biological Products/adverse effects , Retrospective Studies , Hong Kong/epidemiology , Antirheumatic Agents/adverse effects , Tumor Necrosis Factor-alpha , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/complications , Herpes Zoster/chemically induced , Herpes Zoster/epidemiology , Janus Kinases , Registries , Neoplasms/chemically inducedABSTRACT
BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/drug therapy , Adult , Antibodies, Monoclonal, Humanized/adverse effects , Azathioprine/therapeutic use , Creatinine/urine , Cyclophosphamide/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Enzyme Inhibitors/therapeutic use , Female , Glomerular Filtration Rate , Humans , Immunosuppressive Agents/adverse effects , Infusions, Intravenous , Intention to Treat Analysis , Lupus Nephritis/mortality , Male , Mycophenolic Acid/therapeutic use , Remission InductionABSTRACT
RATIONALE & OBJECTIVE: Belimumab improved kidney outcomes in patients with active lupus nephritis (LN) in BLISS-LN, leading to its approval in the United States and the European Union. As data on treatment of East Asian patients with LN are limited, we evaluated the efficacy and safety of belimumab in the BLISS-LN East Asian subgroup. STUDY DESIGN: Prespecified subgroup analysis of BLISS-LN, a phase 3, placebo-controlled, randomized 104-week trial. SETTING & PARTICIPANTS: Adults with biopsy-proven, active LN were randomized (1:1) to belimumab or placebo, plus standard therapy. INTERVENTION: Patients were administered intravenous belimumab 10mg/kg, or placebo, plus standard therapy (oral glucocorticoids and either cyclophosphamide for induction followed by azathioprine for maintenance, or mycophenolate mofetil for both induction and maintenance). At the investigator's discretion, 1-3 intravenous pulses of methylprednisolone, 500-1,000mg each, could be administered during induction. OUTCOMES: The primary end point was primary efficacy renal response (PERR; ie, urinary protein-creatinine ratio≤0.7g/g, estimated glomerular filtration rate no more than 20% below preflare value or≥60mL/min/1.73m2, and no treatment failure) at week 104. Key secondary end points included complete renal response (CRR; urinary protein-creatinine ratio<0.5g/g, estimated glomerular filtration rate no more than 10% below preflare value or≥90mL/min/1.73m2, and no treatment failure) at week 104; PERR at week 52; time to kidney-related event or death; and safety. ANALYTICAL APPROACH: PERR and CRR were analyzed using a logistic regression model, and time to a kidney-related event or death was analyzed using a Cox proportional hazards regression model. RESULTS: 142 patients from mainland China, Hong Kong, South Korea, and Taiwan were included (belimumab, n=74; placebo, n=68). At week 104, more belimumab than placebo patients achieved PERR (53% vs 37%; OR, 1.76 [95% CI, 0.88-3.51]) and CRR (35% vs 25%; OR, 1.73 [95% CI, 0.80-3.74]). At week 52, more belimumab than placebo patients achieved PERR (62% vs 37%; OR, 2.74 [95% CI, 1.33-5.64]). Belimumab reduced the risk of a kidney-related event or death compared with placebo at any time (HR, 0.37 [95% CI, 0.15-0.91]). Safety was similar across treatment groups. LIMITATIONS: Small sample size and lack of formal significance testing. CONCLUSIONS: Safety and efficacy profiles were consistent with BLISS-LN overall population, supporting benefits of belimumab treatment in the East Asian subgroup with LN. FUNDING: This study was funded by GSK (GSK study no. BEL114054). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01639339.
Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Adult , Humans , Lupus Nephritis/drug therapy , Immunosuppressive Agents/therapeutic use , Creatinine , East Asian People , Treatment OutcomeABSTRACT
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.
ABSTRACT
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.
Subject(s)
Arthritis, Rheumatoid , Cardiovascular Diseases , Humans , Case-Control Studies , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , Methotrexate/therapeutic use , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Inflammation/complications , Risk FactorsABSTRACT
The relationship between viral infection and onset of autoimmune diseases such as systemic lupus erythematosus remains uncertain. During the COVID-19 pandemic, organ-specific and multisystemic autoimmune phenomena temporally related to the viral infection have been described. Immune dysregulation triggered by the SARS-CoV-2 virus leading to hyperactivation of both the innate and adaptive immune systems contributes to the excessive production of pro-inflammatory cytokines, autoantibodies, and subsequent autoimmune manifestations. We report two patients without known autoimmune diseases who developed lupus nephritis shortly after a documented mild SARS-CoV-2 infection. Together with other similar cases in the literature, the observation supports a viral trigger of the development of systemic lupus erythematosus in susceptible individuals.
Subject(s)
Autoimmune Diseases , COVID-19 , Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Lupus Nephritis/etiology , COVID-19/complications , Pandemics , SARS-CoV-2ABSTRACT
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.
Subject(s)
Leukopenia , Lupus Erythematosus, Systemic , Humans , Female , Young Adult , Adult , Middle Aged , Male , Cross-Sectional Studies , Antibodies, Antiphospholipid , PrognosisABSTRACT
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.
Subject(s)
Dermatomyositis , Lung Diseases, Interstitial , Humans , Middle Aged , Dermatomyositis/complications , Autoantibodies , Retrospective Studies , Lung Diseases, Interstitial/etiology , Interferon-Induced Helicase, IFIH1 , Survival Rate , L-Lactate Dehydrogenase , FeverABSTRACT
BACKGROUND: Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known. METHODS: International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity. RESULTS: Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: ß 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: ß 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: ß -9.37, 95% CI -12.24, -6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity. CONCLUSIONS: HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician's communication with decision-making regarding the use of HCQ for SLE management.
Subject(s)
Antirheumatic Agents , Hydroxychloroquine , Lupus Erythematosus, Systemic , Patient Reported Outcome Measures , Adult , Antirheumatic Agents/therapeutic use , Cross-Sectional Studies , Databases, Factual , Female , Humans , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged , Quality of LifeABSTRACT
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.
Subject(s)
Immunosuppressive Agents/therapeutic use , Induction Chemotherapy/methods , Lupus Nephritis/drug therapy , Mycophenolic Acid/therapeutic use , Tacrolimus/therapeutic use , Adult , Azathioprine/therapeutic use , Enzyme Inhibitors/therapeutic use , Female , Humans , Maintenance Chemotherapy/methods , Male , Middle Aged , Prednisolone/therapeutic use , Symptom Flare Up , Time , Treatment OutcomeABSTRACT
OBJECTIVES: To study the prevalence of herpes zoster infection in patients with biopsy-confirmed lupus nephritis undergoing immunosuppressive therapies. METHODS: Patients who had histologically active lupus nephritis between 2004 and 2018 were retrospectively reviewed. Clinical and laboratory data at baseline and six months post-therapy were collected. The incidence of herpes zoster reactivation within two years of lupus nephritis treatment was calculated. Risk factors for herpes zoster reactivation were studied by logistic regression. RESULTS: Patients (N = 251) with 311 episodes of lupus nephritis were studied (92% women; age 34.2 ± 14.2 years; histological classes III/IV ± V (69%)). Within two years of therapy, 55 (18%) episodes of lupus nephritis were complicated by herpes zoster infection (incidence 8.84/100 patient-years). Fourteen episodes (25%) of herpes zoster were treated by intravenous anti-viral drugs in hospital but disseminated disease or mortality was not reported. Significant post-herpetic neuralgia developed in 9% of the episodes. Patients with herpes zoster reactivation, compared with those without, were more likely to have first-time renal disease and a shorter systemic lupus erythematosus duration at lupus nephritis than those without. Disease activity, treatment response and other clinical/laboratory parameters were not significantly different between patients with and without herpes zoster reactivation. Herpes zoster-infected patients had been treated with a significantly higher dose of prednisolone as induction therapy. Logistic regression revealed that first-time renal disease, peak daily mycophenolate mofetil dose and cumulative cyclophosphamide dose during induction therapy were significantly associated with herpes zoster reactivation. CONCLUSIONS: Herpes zoster reactivation is common in lupus nephritis patients but unpredictable from clinical parameters. Although adverse outcomes of herpes zoster infection are uncommon, using the minimally effective doses of mycophenolate mofetil and cyclophosphamide during induction therapy may help reduce the risk of herpes zoster infection.
Subject(s)
Cyclophosphamide/adverse effects , Herpes Zoster/epidemiology , Immunosuppressive Agents/adverse effects , Lupus Nephritis/complications , Mycophenolic Acid/adverse effects , Prednisolone/adverse effects , Adult , Antiviral Agents/administration & dosage , Female , Herpes Zoster/drug therapy , Hong Kong/epidemiology , Humans , Incidence , Logistic Models , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , Young AdultABSTRACT
OBJECTIVES: To study the safety and immunogenicity of a live-attenuated herpes zoster (HZ) vaccine in patients with systemic lupus erythematosus (SLE). METHODS: Adult SLE patients having a SLEDAI <6 and stable immunosuppressive treatment for ≥6 months were recruited. Participants were randomly assigned to receive HZ vaccine (Zostavax) or placebo injection. Anti-varicella zoster virus (VZV) IgG reactivity (baseline and week 6) was measured by an enzyme-linked fluorescence assay. Cell-mediated response was assessed by a VZV-stimulated interferon-gamma (IFN-γ) enzyme-linked ELISPOT assay. Adverse events and immune responses of the two groups were compared. RESULTS: 90 SLE patients were recruited (age 45.6±14.1 years; 93% women) and assigned to Zostavax or placebo (in 1:1 ratio). Baseline clinical parameters were similar between the two groups. The change in anti-VZV IgG from week 0 to 6 was +59.8% in the vaccine and -2.1% in the placebo group. Week 6 anti-VZV IgG was significantly higher in vaccinated than placebo-treated patients, after adjustment for baseline (4.16±1.26 vs 3.32±1.01; p<0.001). The number of IFN-γ secreting T-cell spots decreased in the placebo-treated patients (-17%) but increased in vaccinated patients (+42%). The T-cell spots number at week 6 was significantly higher in vaccine-than placebo-treated patients after adjustment for baseline (38.1±78.2 vs 23.1±47.9; p=0.02). Significantly more vaccinated patients reported self-limiting injection site reaction than controls (31% vs 7%; p<0.01). Two vaccinated patients (4.4%) and one (2.2%) placebo-treated patient had mild/moderate SLE flares but no patients developed HZ eruption within 6 weeks postvaccination. CONCLUSIONS: In patients with stable SLE not receiving intensive immunosuppression, Zostavax was well-tolerated and provoked an immune response. TRIAL REGISTRATION NUMBER: US ClinicalTrials.gov registry (NCT02477150).
Subject(s)
Herpes Zoster Vaccine/administration & dosage , Herpesvirus 3, Human/immunology , Lupus Erythematosus, Systemic/drug therapy , Vaccination/methods , Vaccines, Attenuated/administration & dosage , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Humans , Immunoglobulin G/immunology , Injections, Subcutaneous , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVES: To study the effect of the metabolic syndrome (MetS) on organ damage and mortality in patients with SLE. METHODS: Consecutive patients who fulfilled ≥4 ACR criteria for SLE were assessed for the MetS in October 2010. The MetS was defined by the updated joint consensus criteria, using the Asian criteria for central obesity. Longitudinal data on organ damage and mortality were retrieved. The association between MetS and new damage and mortality was studied by logistic regression. RESULTS: A total of 577 SLE patients were followed (93% women; age 41.2±13.4 years; SLE duration 9.3±7.2 years) and 85 (14.7%) patients qualified the MetS. After a follow-up of 66.3±1.8 month, new organ damage and vascular events developed in 128(22%) and 23(4.0%) patients, respectively. Thirty-nine (6.8%) patients succumbed. Patients with the MetS, compared to those without, had significantly more SLICC damage score accrual (0.70±1.0 vs 0.26±0.6; p<0.001), new vascular events (11% vs 2.8%; p=0.001), all-cause (14% vs 5.5%; p=0.003) and vascular (7.1% vs 0.2%; p<0.001) mortality. Logistic regression revealed that the MetS was significantly associated with new damage in the renal (OR 5.48[2.06-14.6]; p=0.001) and endocrine system (OR 38.0[4.50-321]; p=0.001), adjusted for age, sex, SLE duration, ever smoking, antiphospholipid antibodies and the new use of glucocorticoids or hydroxychloroquine since recruitment. Moreover, the presence of the MetS also significantly increased the risk of new vascular events (OR 3.38[1.31-8.74];p=0.01) and vascular mortality (OR 28.3[3.24-247]; p=0.002) after adjustment for the same covariates. CONCLUSION: In this longitudinal study, the MetS is significantly associated with new organ damage, vascular events and mortality in patients with SLE.
Subject(s)
Cardiovascular Diseases/epidemiology , Lupus Erythematosus, Systemic/epidemiology , Metabolic Syndrome/epidemiology , Mortality , Adult , Atherosclerosis/epidemiology , Cardiovascular Diseases/mortality , Case-Control Studies , Cause of Death , Endocrine System Diseases/epidemiology , Eye Diseases/epidemiology , Female , Gastrointestinal Diseases/epidemiology , Gonadal Disorders/epidemiology , Humans , Immunosuppressive Agents/therapeutic use , Infections/mortality , Kidney Diseases/epidemiology , Logistic Models , Longitudinal Studies , Lung Diseases/epidemiology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Vasculitis, Central Nervous System/epidemiology , Male , Middle Aged , Musculoskeletal Diseases/epidemiology , Neoplasms/epidemiology , Neoplasms/mortality , Skin Diseases/epidemiology , Stroke/mortalityABSTRACT
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.
Subject(s)
Glucocorticoids/administration & dosage , Immunosuppressive Agents/administration & dosage , Takayasu Arteritis/therapy , Vascular Surgical Procedures , Adult , Asian People , Computed Tomography Angiography , Diagnosis, Differential , Disease Progression , Female , Glucocorticoids/adverse effects , Hong Kong/epidemiology , Humans , Immunosuppressive Agents/adverse effects , Magnetic Resonance Angiography , Male , Middle Aged , Positron-Emission Tomography , Predictive Value of Tests , Retrospective Studies , Takayasu Arteritis/diagnostic imaging , Takayasu Arteritis/ethnology , Takayasu Arteritis/mortality , Time Factors , Treatment Outcome , Vascular Surgical Procedures/adverse effects , Vascular Surgical Procedures/mortality , Young AdultABSTRACT
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E-13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.