Hydroxychloroquine Treatment Research Articles

P39 Primary antiphospholipid syndrome before development of severe systemic lupus erythematosus – a case report

Abstract Introduction Antiphospholipid syndrome (APS) has long been associated with systemic lupus erythematosus (SLE). Graham Hughes first reported APS in 1983 in cohorts of SLE patients with recurrent thrombosis. We present a case of a young man who developed severe manifestations of SLE 7 years after the diagnosis of primary APS and we look at the literature for predictors in primary APS to develop into SLE. Case description A 28 year old Caucasian male with Turkish ancestry was diagnosed with triple positive primary APS at the age of 21 when he presented with bilateral pulmonary embolisms. He was stable on warfarin with target INR between 3-4. He had been having occasional mouth ulcers, lethargy, mild paraesthesia of his feet and headaches for 2 months. He then presented in February 2024 with short history of pleuritic chest pain and marked breathlessness. Initial cross sectioning imaging did not reveal pulmonary embolism. A week later, echocardiogram demonstrated large global pericardial effusion and small pleural effusions. Ejection fraction was preserved. Interval MRI scan showed pericarditis without evidence of myocarditis. Almost 600 mls of heavily blood stained pericardial fluid was drained. Analysis of the pericardial fluid showed inflammatory processes with macrophages, neutrophil and lymphocytes. Culture was negative including for tuberculosis and cytology negative for malignancy. Immunology revealed ANA 1:160, ENA normal, dsDNA was initially negative but upon interval testing was high at 27.5 IU/mL, IgG 13.1 g/L, C3 1.2 g/L, C4 <0.1 g/L, CRP 143, ESR 30. He had anaemia, lymphopenia and positive direct antiglobulin test. ANCA and rheumatoid factor were unremarkable. Renal and joints were unaffected. Due to his Turkish ancestry, he was extensively investigated for the possibility of Behcet’s with normal femoral vein ultrasound and negative HLA-B51 genotype. His manifestations fulfilled the SLICC criteria to be diagnosed with SLE. His response to intravenous methylprednisolone infusions and subsequent oral steroid was marked. He was initiated on dual treatment of hydroxychloroquine and mycophenolate mofetil and is currently recovering. Discussion We relooked at this immunology when he was first diagnosed with primary APS in 2017. He was strongly positive for ANA at titre of 1:640 but did not have manifestations of SLE then. We researched literature on the predictors for primary APS to develop into SLE. Both disease spectrums have several overlapping manifestations including haemolytic anaemia, thrombocytopenia, lymphopenia, neurological symptoms, renal manifestations and livedo reticularis. Freire et al (1) retrospectively analysed 80 patients with primary APS and found 14 (17.5%) progressed to develop APS-SLE in 5.2 +/- 4 years. ANA positivity was found in 100% those who eventually developed APS-SLE. Other specific autoantibodies including anti-dsDNA, anti-ribosomal P, anti-Ro, anti-La and anti-U1RNP are found more commonly in the cohort too. In their APS-SLE cohort, they also found a correlation with younger age at the time of diagnosis of APS and the duration of the disease. Andreoli L et al (2) demonstrated anti-nucleosome antibody (anti-NCS) was frequently found in their cohort of APS-SLE patients but no relationship between clinical-serological was found, except for a weak correlation between anti-dsDNA antibodies. 2 of their primary APS who developed severe SLE had displayed high titres of anti-NCS years before. Tarr T et al (3) found 4 of their primary APS who developed SLE all presented with cerebrovascular events as the thrombotic manifestation. Key learning points • Primary APS has been associated with the development of SLE • Certain antibody profile such as ANA, anti-nucleosome antibody may predict the development of SLE in primary APS patients • Younger age, cerebrovascular events as thrombotic manifestation at diagnosis of primary APS and the length of duration of primary APS may be associated with the development of SLE at a later stage

Careers of chloroquine and hydroxychloroquine as “miraculous” anti-Covid-19 drugs

In early January 2024, a widely publicized article in the journal Biomedicine and Pharmacology estimated that approximately 17,000 COVID-19 patients in France, Italy, Spain, Turkey, and the US died as a result of hydroxychloroquine treatment. The publication of this article is a fitting closure to nearly three years of controversy about the possible use of chloroquine and hydroxychloroquine to treat COVID-19. Repurposed in early 2020 as miracle answers to the COVID-19 pandemic, they had a brief moment of worldwide celebrity, despite the doubts expressed by many experts. Hydroxychloroquine’s career ended in September 2020, when a series of clinical trials showed not only inefficacy to treat COVID-19 but also safety concerns. However, the use of chloroquine and hydroxychloroquine continued in Brazil, where the government continued to promote their use as the first therapeutic choice against COVID-19. Our study outlines the employ of these drugs in France and Brazil. Grounded in the methodology developed by social studies of science, our article reconstructs the trajectories of hydroxychloroquine in France and Brazil. It aims to elucidate the reasons for the Brazilian exception, illuminating the disastrous consequences of the exercise of a monolithic political power and of anti-democratic practices on drug regulation and proposes new reflections on a topic that has been visible in the media and widely discussed in society, but attracted much less attention in the academic sphere.

Inhibitory effect of hydroxychloroquine on glucocorticoid‐induced osteoporosis in lupus therapy

AbstractObjectivesSystemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first‐line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus.MethodsAn SLE IgG‐induced inflammation model was used to investigate the anti‐inflammatory effects of HCQ and dexamethasone (DXM). A glucocorticoid‐induced osteoporosis (GIOP) model was used to investigate the inhibitory effect of HCQ on osteoclastogenesis. Inflammation was assessed by haematoxylin and eosin staining. Bone metabolism was determined structurally via microcomputer tomography and in bone marrow‐derived osteoclast cultures.ResultsAn SLE IgG‐induced inflammation model demonstrated that HCQ could not ameliorate inflammation alone but could enhance the anti‐inflammatory effect of GCs by decreasing the expression of FcγRI on macrophages. HCQ inhibited osteoclastogenesis induced by GCs and RANKL by upregulating nuclear factor erythroid 2‐related factor 2 and limiting reactive oxygen species formation, which mitigated GC‐induced bone loss.ConclusionThe results indicate that HCQ improved the anti‐inflammatory effects of GCs and inhibits the osteoclastogenesis in experimental lupus. This study offers valuable insights into the mechanisms underlying the combined treatment of lupus with HCQ and GCs.

Effects of Hydroxychloroquine on Maternal and Fetal Outcomes in Pregnant Patients with Lupus: A Systematic Review and Meta-Analysis

Background: The effects of hydroxychloroquine (HCQ) on maternal and fetal outcomes in pregnant patients with systemic lupus erythematosus (SLE) have not been fully elucidated in recent research. This study aimed to provide a more comprehensive evaluation of the efficacy and safety of HCQ in pregnant patients with SLE. Methods: A systematic search of relevant articles was conducted using Medline, Embase, Scopus, Web of Science, and the Cochrane Library from inception to October 4th, 2023. The risk of bias in the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane's Quality Assessment Form. Data on maternal and fetal outcomes of the HCQ treatment groups (HCQ+) and control groups (HCQ–) were extracted, analyzed and evaluated. Pooled odds ratios (ORs), pooled relative risks (RRs), and weighted mean differences with 95% confidence intervals (95% CIs) were calculated for the meta-analysis using Stata/MP V.18. Results: This meta-analysis included 17 studies, involving a total of 2238 pregnant patients with SLE. Compared to the HCQ– groups, the HCQ+ groups exhibited a significant reduction in the incidence of preeclampsia (RR = 0.51, 95% CI: 0.37–0.71), high lupus activity (RR = 0.77, 95% CI: 0.64–0.92), gestational hypertension (OR = 0.41, 95% CI: 0.18–0.91), premature delivery (RR = 0.71, 95% CI: 0.60–0.84), and fetal growth restriction (OR = 0.61, 95% CI: 0.43–0.85). Additionally, the HCQ+ groups exhibited a significant increase in fetal birth weight of 0.21 kg (95% CI: 0.09–0.33). No significant differences were revealed in the other 15 pregnancy outcomes between the two groups. Conclusions: Despite the presence of a certain heterogeneity among the included studies, this study provides a more comprehensive evaluation of the efficacy and safety of HCQ in pregnant patients with SLE.

Drug induced lupus associated with Trastuzumab emtansine in a patient with metastatic breast cancer

Introduction Ado-trastuzumab emtansine (T-DM1) is employed in the treatment of patients with HER2-positive breast cancer. The most common side effects are fatigue, diarrhoea, anaemia, transaminase elevation and drug-induced thrombocytopenia. This report describes a patient with metastatic breast cancer who developed drug-induced lupus due to T-DM1. Case Report A 54-year-old woman was diagnosed with breast cancer in March 2018. She underwent modified radical mastectomy and axillary lymph node dissection (pT2N1aM0). Following supraclavicular lymph node metastasis in May 2018, she received 8 cycles of docetaxel, trastuzumab, and pertuzumab. In December 2020, the patient presented with axillary and intra-abdominal lymph node metastases, along with bone metastases observed on PET/CT scan. Treatment with T-DM1 and zoledronic acid was initiated. After 18 months on T-DM1, she developed drug-induced lupus. Her symptoms resolved with hydroxychloroquine treatment and discontinuation of T-DM1. Discussion Drug-induced lupus is a clinical syndrome that shares similar features with systemic lupus erythematosus (SLE). The majority of patients present with symptoms such as arthralgia and myalgia. Hydralazine and procainamide are high-risk drugs for drug-induced lupus. Symptoms usually develop after months or years of use, but may also develop suddenly. Our patient also received TDM-1 treatment for 18 months. We present a case of TDM-1-associated drug-induced lupus in a patient with metastatic breast cancer. This is the first case of TDM-1-related drug-induced lupus reported in the literature.

Autophagy unrelated transcriptional mechanisms of hydroxychloroquine resistance revealed by integrated multi-omics of evolved cancer cells

ABSTRACT Hydroxychloroquine (HCQ) and chloroquine are repurposed drugs known to disrupt autophagy, a molecular recycling pathway essential for tumor cell survival, chemotherapeutic resistance, and stemness. We pursued a multi-omic strategy in OVCAR3 ovarian cancer and CCL218 colorectal cancer cells. Two genome-scale screens were performed. In the forward genetic screen, cell populations were passaged for 15 drug pulse-chases with HCQ or vehicle control. Evolved cells were collected and processed for bulk RNA-seq, exome-seq, and single-cell RNA-seq (scRNA-seq). In the reverse genetic screen, a pooled CRISPR-Cas9 library was used in cells over three pulse-chases of HCQ or vehicle control treatments. HCQ evolved cells displayed remarkably few mutational differences, but substantial transcriptional differences. Transcriptomes revealed multiple pathways associated with resistance to HCQ, including upregulation of glycolysis, exocytosis, and chromosome condensation/segregation, or downregulation of translation and apoptosis. The Cas9 screen identified only one autophagy gene. Chromosome condensation and segregation were confirmed to be disrupted by HCQ in live cells and organelle-free in vitro extracts. Transcriptional plasticity was the primary mechanism by which cells evolved resistance to HCQ. Neither autophagy nor the lysosome were substantive hits. Our analysis may serve as a model for how to better position repurposed drugs in oncology.

Decreased Autophagic Activity in Triple-Negative Breast Cancer Cells upon Hydroxychloroquine and Thymoquinone Combination Treatment

Objective: Autophagy plays a significant role in breast cancer tumorigenesis, including triple-negative breast cancer. Research indicates that hydroxychloroquine and thymoquinone modulate autophagy, potentially suppressing its activity. However, their combined effects on autophagy in triple-negative breast cancer remain unexplored. In this study, we investigated the potential anti-cancer and autophagy-modulating effects of hydroxychloroquine-thymoquinone combination on triple-negative breast cancer cells in vitro. Material and Method: The viability of MDA-MB-231 cells was evaluated after treatment with hydroxychloroquine (10-210 µM) and thymoquinone (5-45 µM) for 24 and 48 hours using the WST-1 assay. Combination effects were analyzed using the Chou-Talalay method with CompuSyn (v.10). Autophagic vesicles were visualized using an Autophagy Detection Kit and fluorescence microscopy to investigate their role in the decrease in cell viability. Statistical analysis was performed with GraphPad Prism (v.8.3.0). Results: At both 24- and 48-hour intervals post-treatment, a significant decrease in viability was observed for both hydroxychloroquine and thymoquinone treatments individually (p1). At 24 hours, favorable dose reduction effects were evident (dose reduction index >1), while the 48-hour results showed an unfavorable reduction (dose reduction index

Inter-eye asymmetry of microvascular density in patients on hydroxychloroquine therapy by optical coherence tomography angiography

AimsTo explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA). Methods40 subjects were enrolled in this cross-sectional study, including 20 systemic lupus erythematasus patients currently treated with HCQ (40 eyes) and 20 age- and sex-matched normal controls (NCs, 40 eyes). OCTA images were obtained to measure macular and peripapillary mircrovasculatures and microstructures, including vessel density, retinal nerver fiber layer thickness, and peripapillary ganglion cell-inner plexiform layer thickness. The absolute values of the difference between right and left eyes were taken as a measure of inter-eye asymmetry. ResultsMacular whole image vessel density (wiVD-M) and perifoveal vessel density (pfVD) of superficial capillary plexus (SCP) were notably reduced in both the right and left eyes of the HCQ treatment group compared with NCs. Specifically, SLE patients treated with HCQ have higher inter-eye asymmetry of wiVD-M of SCP (2.28 ± 1.03 vs 1.27 ± 0.79, p < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, p = 0.04) compared with NCs. There were no significant differences in inter-eye asymmetry of structure parameters. Inter-eye asymmetry of wiVD-M of SCP (AUC = 0.80, p < 0.01) and pfVD of SCP (AUC = 0.71, p = 0.02) exhibited greater discrimination power. ConclusionSLE Patients treated with HCQ exhibited a notably higher inter-eye vessel density asymmetry compared to that of NCs. Thus, inter-eye vessel density asymmetry could be used to screen for HCQ retinal toxicity.

Insights into Long COVID: Unraveling Risk Factors, Clinical Features, Radiological Findings, Functional Sequelae and Correlations: A Retrospective Cohort Study

BackgroundThe long-term symptomatology of COVID-19 has yet to be comprehensively described. The aim of the study was to describe persistent COVID-19 symptoms in a cohort of hospitalized and home-isolated patients. MethodsA retrospective cohort study was conducted on long COVID patients. Long COVID symptoms were identified, and patients were divided into hospitalized (in-patients) and home-isolated (out-patients) as well as according to the number of symptoms. Patients were examined by a multydisciplinary medical team. Blood tests, high resolution chest computed tomography (CT), physical and infectious examination were performed. Finally, in-patients were evaluated at two time-points: on hospital admission (T0) and after three months from discharge (Tpost). ResultsThree hundred and sixty-four COVID-19 patients were enrolled. 82% of patients reported at least one or more symptoms. The most reported symptom was fatigue. Chest CT showed alteration in 76% of patients and pulmonary function alterations were observed in 44.7% of patients.A higher risk of presenting at least one symptom was seen in patients treated with corticosteroid and a higher risk of presenting chest CT residual lesion was observed in hospitalized patients and in patients that received hydroxychloroquine treatment. Moreover, a higher risk of altered pulmonary function was observed in older patients. ConclusionLong-term sequelae are present in a remarkable number of long COVID patients and pose a new challenge to the healthcare system to identify long-lasting effects and improve patients’ wellbeing. Multi-disciplinary teams are crucial to develop preventive measures, and clinical management strategies.

Treatment of Lichen Planopilaris and Frontal Fibrosing Alopecia: A Retrospective, Real-Life Analysis in a Tertiary Center in Germany.

Background: Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia characterized by an irreversible destruction of the hair follicle resulting in its permeant destruction. The clinical presentation of LPP is a progressive patchy scarring alopecia. A variety of systemic agents is used to treat LPP with varying success. The aim of this retrospective, real-life analysis was to evaluate the treatment of hydroxychloroquine for LPP. Method: In this retrospective, single-center study, we analyzed 110 patients with LPP and frontal fibrosing alopecia (FFA) who received treatment over a 12-month period from March 2014 to March 2021 at the Department of Dermatology, University of Mainz Medical Center. Patient records were analyzed for response to treatment, co-morbidities, disease progression-free survival (DPFS), and safety. Clinical parameters associated with treatment response were determined with Cox regression modelling and logistic regression. Results: Overall, 77 of 110 patients were treated with a systemic agent. There was a clear association between LPP and the occurrence of Hashimoto thyroiditis. Topical treatment with corticosteroids did not improve clinical symptoms in the majority of patients (15 out of 101). In 71% of patients treated with systemic cyclosporine A and 62% of patients treated with hydroxychloroquine, we observed a significant resolution of the inflammatory process, which correlated with a robust durable clinical response (p < 0.001). Toxicity was observed in 17% (n = 9) of patients receiving systemic treatment with hydroxychloroquine and correlated with the duration of systemic treatment (p < 0.001). Treatment discontinuation was associated with a flare-up of clinical symptoms (29%), which required the re-initiation of second-line therapy in 13 out of 51 patients. Overall, the initiation of second-line treatment, either hydroxychloroquine or Cyclosporine A (CsA), yielded positive results, especially in the patient cohort treated with hydroxychloroquine (overall response rate, ORR = 100%), who showed disease progression during CsA or retinoids. Conclusions: Our results from this contemporary cohort of patients with LPP and FFA indicate that hydroxychloroquine and cyclosporine are effective systemic agents in decreasing clinical symptoms. However, our data also show that the discontinuation of treatment is often associated with the exacerbation of clinical symptoms. Response rates to second-line treatment were especially favorable in the patient cohort with hydroxychloroquine.

Hydroxychloroquine and Pre-eclampsia in a Diverse Cohort of Women With Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) are at risk for pregnancy complications such as pre-eclampsia and eclampsia. These clinically important complications are associated with maternal morbidity, mortality, and postpartum cardiovascular disease. Some studies suggest that hydroxychloroquine (HCQ) may reduce pre-eclampsia risk in lupus pregnancy. Using a cohort of pregnant patients with prevalent SLE at Kaiser Permanente Northern California (KPNC), we investigated whether HCQ treatment in early pregnancy reduced the risk of pre-eclampsia or eclampsia. Among pregnant patients with SLE from 2011 to 2020, we assessed HCQ treatment from three months before pregnancy through the first trimester. HCQ exposure was defined multiple ways to account for adherence and duration of treatment. Propensity scores accounted for multiple confounders and modified Poisson models estimated risk ratios (RRs) and 95% confidence intervals of the association between HCQ treatment and pre-eclampsia or eclampsia. Effect modification by pregestational hypertension, history of nephritis, and antiphospholipid antibody (aPL) status was investigated through stratified analysis. There were 399 pregnancies among 324 patients with SLE at KPNC between 2011 and 2020. Considering multiple exposure definitions, we consistently found a null association between HCQ and pre-eclampsia or eclampsia. The RRs were consistently lower among nullipara patients, and RRs were consistently protective but not statistically significant among the high-risk subgroup of patients with a history of nephritis, aPL positivity, or pregestational hypertension (for both nullipara and multipara patients). Although this study found no reduced risk of HCQ on pre-eclampsia or eclampsia, residual confounding may be attenuating the effect despite an integrated health care delivery system setting with detailed clinical data.

The evaluation of the short-term and long-term hydroxychloroquine therapy on ECG parameters.

Amidst the COVID-19 pandemic, hydroxychloroquine (HCQ) was widely administered despite limited data on its safety and efficacy. This study assesses the acute and chronic impacts of HCQ on electrocardiography (ECG) parameters alongside the effects of azithromycin and levofloxacin coadministration in patients with COVID-19. A comprehensive analysis was conducted on 109 COVID-19 patients receiving HCQ, with or without Azithromycin and/or Levofloxacin, and 51 long-term HCQ-treated Sjogren's syndrome (SS) patients. ECG parameters, including QTc interval, were meticulously evaluated against a control group of 109 COVID-19 patients without HCQ treatment. HCQ monotherapy, in combination with Levofloxacin, significantly prolonged the QTc interval in COVID-19 patients compared to controls. Notably, the combination of HCQ and Azithromycin demonstrated a mitigated impact on QTc prolongation. Long-term HCQ use in SS patients did not significantly affect QTc intervals, illustrating a distinct safety profile from short-term use in COVID-19 treatment. HCQ's impact on QTc prolongation is influenced by therapeutic context, coadministered drugs, and patient demographics. The findings underscore the necessity of cautious HCQ use, particularly in acute settings like COVID-19, where monitoring and consideration of drug interactions and patient-specific factors are critical.

Abstract We056: Hydroxychloroquine cures autoimmune myocarditis by inhibiting innate immune via the CXCL16-CXCR6 axis between macrophages and T cells

Background: Myocarditis is a live-threatening inflammatory disease of the heart and is lack of effective treatment measures. Hydroxychloroquine (HCQ), a classic antimalarial drug, has been widely used in the treatment of rheumatic diseases. This study investigated whether HCQ can treat chronic autoimmune myocarditis. Methods and Results: Murine autoimmune myocarditis was induced, and therapeutic effects of oral HCQ on acute and chronic myocarditis were evaluated using echocardiography, cardiac catheterization, and analysis of inflammatory scores in cardiac tissue. Results showed that HCQ treatment significantly improved cardiac function, inhibited ventricle enlargement and reduced cardiac inflammation. Single-cell transcriptomic analysis in the heart showed that HCQ treatment significantly reduced infiltration of macrophage, neutrophiles and T-cells, inhibited inflammatory pathway, especially the secretion of CXCL16 from macrophages, thereby reducing the chemotaxis of T cells, especially NKT cells and Th17 cells. Finally, both in vitro and in vivo experiments confirm the inhibitory effect of HCQ on CXCL16-CXCR6 axis between macrophages and T cells. Additionally, treatment with anti-CXCL16 antibody can also improve cardiac function and attenuate cardiac fibrosis in myocarditis. Conclusions: HCQ treatments clinically cure mice with autoimmune myocarditis through inhibiting innate immune and infiltration of macrophages majorly via CXCL16-CXCR6 axis.

Hydroxychloroquine and risk of osteoporosis in patients with rheumatoid arthritis: A population-based retrospective study of 6408 patients.

Patients with rheumatoid arthritis (RA) are at a higher risk of osteoporotic fractures. Studies have shown that patients with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) experienced an increase in bone mineral density (BMD) after receiving hydroxychloroquine (HCQ) treatment, indicating a potential protective effect against osteoporosis. Therefore, this study is to examine the relationship between HCQ usage and the risk of osteoporosis in patients diagnosed with RA. The retrospective cohort study used data from Taiwan's National Health Insurance Research Database (NHIRD) covering the period from January 2010 to December 2018, which included 14 050 newly diagnosed RA patients, subsequently divided into two groups: HCQ users and non-users. Propensity score matching (PSM) based on sex, age, urbanization, insured unit type, insured area, and comorbidities was conducted to match the groups. The primary outcome assessed was the evaluation of the risk of osteoporosis by employing a multivariable Cox proportional hazard regression model to calculate the adjusted hazard ratio (aHR). After PSM, a total of 6408 RA patients were included in the analysis (3204 HCQ users and 3204 non-users). There was no significantly higher risk of osteoporosis in HCQ users compared with non-users, aHR = 0.99 (95% CI: 0.82-1.196). Additionally, different durations of HCQ usage demonstrated a neutral effect on the risk of osteoporosis [HCQ <90 days, aHR = 0.88 (95% CI: 0.585-1.324); HCQ 90-180 days, aHR = 0.941 (95% CI: 0.625-1.418); HCQ >180 days, aHR = 1.019 (95% CI: 0.832-1.249)]. The study indicates that there is no significant association between the use of HCQ and the risk of osteoporosis in patients with RA.

Hydroxychloroquine and Cardiovascular Events in Patients With Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) predisposes individuals to early cardiovascular (CV) events. While hydroxychloroquine is thought to mitigate CV risk factors, its protective role against CV events, particularly arterial ones, remains to be confirmed. To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE. This cohort study using a nested case-control design was conducted within the National French Healthcare Database (SNDS), which represents 99% of the French population, from 2010 to 2020. Participants were the cohort of all patients with SLE recorded in the SNDS. Patients with SLE experiencing CV events during the study period were the case group; those without CV events were controls. The analysis period was from February 2022 to September 2023. Hydroxychloroquine use within 365 days prior to the index date, defined as current (within 90 days), remote (91-365 days), or no exposure within the previous 365 days. Outcomes of interest were MI, stroke, and OTE, analyzed individually and as a composite outcome (primary analysis). Controls were matched to patients with CV events by age, sex, time since SLE onset and entry into the SNDS database, index date, prior antithrombotic and CV medication, chronic kidney disease, and hospitalization. Multivariable conditional logistic regression was performed using hydroxychloroquine exposure as the main independent variable. The SLE cohort included 52 883 patients (mean [SD] age, 44.23 [16.09] years; 45 255 [86.6%] female; mean [SD] follow-up, 9.01 [2.51] years), including 1981 patients with eligible CV events and 16 892 matched control patients. There were 669 MI events, 916 stroke events, and 696 OTEs in the individual outcome studies. For current exposure to hydroxychloroquine, the adjusted odds were lower for composite CV events (odds ratio [OR], 0.63; 95% CI, 0.57-0.69) as well as for MI (OR, 0.72; 95% CI, 0.60-0.85), stroke (OR, 0.69; 95% CI, 0.60-0.81), and OTEs (OR, 0.58; 95% CI, 0.49-0.69) individually compared with no hydroxychloroquine exposure within 365 days. In this nationwide cohort study of patients with SLE, a protective association was found between the current use of hydroxychloroquine and the occurrence of CV events, but not between remote use of hydroxychloroquine and CV outcomes, highlighting the value of continuous hydroxychloroquine treatment in patients with SLE.

Hydroxychloroquine blood concentrations and effects in Chinese patients with IgA nephropathy.

Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). However, the relationship between HCQ blood concentration and the therapeutic effect for IgAN has not yet been defined. This study investigates the optimal and efficacious range of HCQ blood concentrations in Chinese patients with IgAN. Seventy-three patients with biopsy-proven IgAN who were at risk of progression were included in this study. Thirty-eight patients with IgAN were treated with HCQ plus an optimized renin-angiotensin-aldosterone system inhibitor (RAASi), and thirty-five patients received only RAASi. Blood HCQ concentration and 24-h proteinuria were examined at three and six months after treatment. The baseline proteinuria levels were comparable between the RAASi and HCQ groups. The HCQ group had lower 24-h proteinuria than the RAASi group three months after treatment, though the difference was not significant (p = 0.38). After six months, the median proteinuria level was significantly lower in the HCQ group than in the RAASi group (p < 0.05). The percentage reduction in 24-h proteinuria in the HCQ group was greater than that in the RAASi group at three (p < 0.05) and six months (p < 0.05). Hydroxychlorquine blood concentration and efficacy were positively correlated at three months (r = 0.428, p < 0.05) and six months (r = 0.48, p < 0.05). Moreover, the optimal blood concentration of HCQ for three-month efficacy was 418.96ng/mL and that for six-month efficacy was 582.48ng/mL. No serious adverse events were reported during HCQ treatment. Hydroxyhloroquine safely reduces proteinuria in Chinese patients with IgAN. The efficacy of HCQ is positively correlated with its blood concentration.

Antiphospholipid antibodies as potential prognostic indicators of recurrent ischemic stroke

BackgroundImmunity play a pivotal role in the risk of ischemic stroke, and studies have also shown a relationship between ischemic stroke and autoimmune diseases. In light of this we conducted a prospective cohort study to elucidate the impact of antiphospholipid antibodies (aPLs), antinuclear antibodies (ANA), and anti-extractable nuclear antigen autoantibodies (anti-ENA) on the prognosis of ischemic stroke. Methods245 stroke patients were recruited in this single-center study and followed up with for 3 years. Autoantibodies, including aPLs (ACA, anti-β2GPI, LA), ANA and anti-ENA were evaluated in recurrent ischemic stroke (RIS) and nonrecurrent ischemic stroke (nonRIS). Stroke severity was judged using the National Institutes of Health Stroke Scale (NIHSS). For preventive treatment, 42 IS patients with positive aPLs + ANA/anti-ENA were randomized 1:1 into a hydroxychloroquine (HCQ) treatment group and a control group, and the prognoses were compared. ResultsThe positive rate of ACA IgG (p = 0.018), anti-β2GPI IgG (p = 0.047), LA (p = 0.023), and aPLs + ANA/anti-ENA (p = 0.000) were significantly higher in patients with RIS compared to patients with nonRIS, and aPLs + ANA/anti-ENA (HR2.31, 95 % CI1.02-5.25, p = 0.046) and hypertension (HR2.50, 95 % CI1.17-5.35, p = 0.018) were the independent risk factors of recurrence. There were differences in NIHSS at month 36 between those positive and negative for aPLs + ANA/anti-ENA (p = 0.001, Eta2 = 0.052), anti-ENA (p = 0.016, Eta2 = 0.030), ANA (p = 0.035, Eta2 = 0.022), and LA (p = 0.016, Eta2 = 0.028). Furthermore, the recurrence rate of the HCQ treatment group was lower than that of the control group (p = 0.024). ConclusionsCo-positivity of aPLs and ANA/anti-ENA is an independent risk factor for RIS. However, HCQ therapy may reduce the recurrence rate of IS for these patients.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Autophagy, apoptosis, and inflammation response of Sebastiscus marmoratus to different concentrations of hydroxychloroquine

Hydroxychloroquine (HCQ) is an important public health therapeutic agent widely used in the prevention and treatment of malaria and autoimmune diseases, with some antiviral effects, as well as a common autophagy inhibitor. Its autophagy-inhibiting effect attracts great research interest in mammals but is still little studied in fish. We even have no idea about the effects of HCQ on different tissues of fish and what concentrations should be used for safety studies. This study investigated the effect of different concentration of HCQ treatments on the survival, tissue structure, and expressions of genes related to autophagy, apoptosis, and inflammation in the gill, spleen, testis, and ovary of Sebastiscus marmoratus. The results showed that the higher HCQ concentration (77.40 and 154.80 mg/mL) led to mass mortality within an hour. The half-lethal concentration (LC50, 24 h) of HCQ for S. marmoratus was approximately 48.95 mg/mL. When exposed to 30.96 mg/mL HCQ for 24 hours, autophagy was blocked as revealed by electron microscopy from gill, spleen and testis of fish. The expressions of autophagy-related genes (LC3/Cx43), apoptosis-related genes (Cas3/p53), and inflammation-related genes (TNF-α/IL8) exhibited tissue-specific and dose-dependent responses. The gonads showed preferential expression of all these genes and were found to be sensitive and regular after HCQ treatment. For example, at a concentration of 30.96 mg/mL, the testis demonstrated a regularity that suggests it is an ideal candidate tissue for studying the role of HCQ or autophagy. This study systematically revealed the response of S. marmoratus to different concentrations of HCQ and provided optional assay concentrations for key tissues, serving as an important reference for the future studies on HCQ and autophagy in S. marmoratus. Furthermore, the potential crosstalk between autophagy, apoptosis, and inflammatory pathways initially identified in this study could be helpful for the future research on autophagy regulation in marine fish.

Effect of Hydroxychloroquine Treatment on Kidney Allograft Rejection and Graft Failure

Kidney allograft rejection is a major issue because it causes graft failure and because immunosuppressive treatments used for its prevention increase the risk of infections and cancers. In systemic lupus patients, hydroxychloroquine is used to prevent immune flares with decreased doses of immunosuppressants. Hydroxychloroquine can be safely used in kidney transplant recipients when indicated for autoimmune disease, but its effect on allograft rejection is unknown. We hypothesized that it may prevent kidney allograft rejection. We conducted a nationwide retrospective propensity-matched study on kidney transplantations of patients treated with hydroxychloroquine in France between 2008 and 2018. We analyzed the incidence of allograft rejection or failure within the first year after transplantation. The rates of rejection or allograft failure were not different between the 188 patients treated with hydroxychloroquine at the time of transplantation and their propensity matched controls. Hydroxychloroquine treatment in association with standard immunosuppressive treatment does not prevent rejection in kidney allograft recipients.