Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19.
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ABSTRACT:
SUBMITTER: Konig MF
PROVIDER: S-EPMC8258626 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:Baseline retinal examinations have long been recommended for patients beginning treatment with hydroxychloroquine (HCQ), but it is unknown how well this guideline is followed. We investigated baseline eye examinations among US SLE patients enrolled in Medicaid in whom HCQ treatment was newly initiated. METHODS:Using billing codes, we identified SLE patients ages 18-65 years who were enrolled in Medicaid and residing in the 29 most populated US states, from 2000 to 2010. New users of HCQ were identified by filled prescriptions, with none filled in the preceding 12 months. Retinal examinations that were performed within 30 days before to 1 year after the index prescription were identified. We examined the proportions of patients receiving retinal examinations over the study years and compared the characteristics of those who did and those who did not receive examinations, using bivariable and multivariable logistic regression models. RESULTS:Among 12,755 SLE patients newly starting HCQ treatment, 32.5% received baseline dilated eye examinations. The proportions of patients receiving baseline eye examinations did not significantly change from 2000 to 2010 (31.0-34.4%; P for linear trend = 0.12). Factors associated with an increased likelihood of having an examination included female sex, Asian versus white race, and a higher number of laboratory tests performed during the preceding year. Compared with white patients, lower proportions of black and Native American patients with SLE had baseline retinal examinations. CONCLUSION:Only one-third of patients with SLE enrolled in Medicaid and in whom HCQ was newly initiated received the recommended baseline retinal examinations, and this proportion did not significantly increase from 2000 to 2010. The sociodemographic variation in this recommended care has been observed for other recommended medical care in SLE and requires both further investigation and interventions to address it.
| S-EPMC6078826 | biostudies-literature
Project description:Cardiovascular (CV) morbidity and mortality are a challenge in management of patients with systemic lupus erythematosus (SLE). Higher risk of CV disease in SLE patients is mostly related to accelerated atherosclerosis. Nevertheless, high prevalence of traditional cardiovascular risk factors in SLE patients does not fully explain the increased CV risk. Despite the pathological bases of accelerated atherosclerosis are not fully understood, it is thought that this process is driven by the complex interplay between SLE and atherosclerosis pathogenesis. Hydroxychloroquine (HCQ) is a cornerstone in treatment of SLE patients and has been thought to exert a broad spectrum of beneficial effects on disease activity, prevention of damage accrual, and mortality. Furthermore, HCQ is thought to protect against accelerated atherosclerosis targeting toll-like receptor signaling, cytokine production, T-cell and monocyte activation, oxidative stress, and endothelial dysfunction. HCQ was also described to have beneficial effects on traditional CV risk factors, such as dyslipidemia and diabetes. In conclusion, despite lacking randomized controlled trials unambiguously proving the protection of HCQ against accelerated atherosclerosis and incidence of CV events in SLE patients, evidence analyzed in this review is in favor of its beneficial effect.
| S-EPMC5835241 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-03 | E-GEOD-46923 | biostudies-arrayexpress
Project description:ObjectiveHCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels.MethodsThis case-control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy.ResultsThe study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P < 0.001), height (P = 0.045), creatinine clearance (P < 0.001), haemoglobin concentration (P = 0.01), duration of HCQ intake, (P < 0.001), higher cumulative HCQ dose (P < 0.001) and geographical origin (West Indies and sub-Saharan Africa) (P = 0.007) were associated with the risk of retinopathy, while HCQ blood levels were not. In the multivariate analysis, only cumulative dose (P = 0.016), duration of intake (P = 0.039), creatinine clearance (P = 0.002) and geographical origin (P < 0.0001, odds ratio 8.7) remained significantly associated with retinopathy.ConclusionSLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.
| S-EPMC8186841 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-06-03 | GSE46923 | GEO
Project description:BackgroundHydroxychloroquine (HCQ) is the standard of care medication for most SLE patients, however nonadherence is common. We investigated longitudinal patterns and predictors of nonadherence to HCQ in a U.S. SLE cohort of HCQ initiators.MethodsWe used Medicaid data from 28 states to identify adults 18-65 years with prevalent SLE. We included HCQ initiators following ≥6 months without use, and required ≥1 year of follow-up after first dispensing (index date). We used the proportion of days covered (PDC) to describe overall HCQ adherence (<80% = nonadherent) and novel group-based trajectory models (GBTM) to examine monthly patterns (<80% of days/month covered = nonadherent), during the first year of use. Multivariable multinomial logistic regression models were used to examine predictors of nonadherence.ResultsWe identified 10,406 HCQ initiators with SLE. Mean age was 38 (±12) years, 94% were female, 42% black, 31% white; 85% had a mean PDC < 80%. In our 4-group GBTM, 17% were persistent adherers, 36% persistent nonadherers, and 47% formed two dynamic patterns of partial adherence. Adherence declined for most patients over the first year. Compared to persistent adherers, the odds of nonadherence were increased for blacks and Hispanics vs. whites and for younger ages vs. older; increased SLE-related comorbidities were associated with reduced odds of nonadherence for persistent nonadherers (0.95, 95% CI: 0.91-0.99).ConclusionsAmong HCQ initiators with SLE, we observed poor adherence which declined for most over the first year of use. HCQ adherence is a dynamic behavior and further studies of associated predictors, outcomes, and interventions should reflect this.
| S-EPMC6035896 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-01 | GSE250025 | GEO
Project description:Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.
2024-03-01 | GSE250024 | GEO
Project description:Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.
2024-03-01 | GSE250023 | GEO
Project description:Overexpression of membranous CD154 in T lymphocytes has been found previously in systemic lupus erythematosus (SLE). Because hydroxychloroquine (HCQ) has been used frequently in the treatment of lupus, we sought to identify the effects of HCQ on CD154 and a possibly regulatory mechanism.CD4+ T cells were isolated from the blood of lupus patients. After stimulation with ionomycin or IL-15 and various concentrations of HCQ, expression of membranous CD154 and NFAT and STAT5 signaling were assessed.HCQ treatment had significant dose-dependent suppressive effects on membranous CD154 expression in ionomycin-activated T cells from lupus patients. Furthermore, HCQ inhibited intracellular sustained calcium storage release, and attenuated the nuclear translocation of NFATc2 and the expression of NFATc1. However, CD154 expressed through IL-15-mediated STAT5 signaling was not inhibited by HCQ treatment.HCQ inhibited NFAT signaling in activated T cells and blocked the expression of membranous CD154, but not STAT5 signaling. These findings provide a mechanistic insight into SLE in HCQ treatment.
| S-EPMC5550984 | biostudies-other