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Introduction: Hydroxychloroquine (HCQ) exerts a large reduction of cardiovascular risk in patients with inflammatory diseases, but the mechanisms are not fully known. The aim of this study was to study potential mechanisms for this., Methods: This interventional study (EudraCT 2014-005418-45) in 30 patients (23 with rheumatoid arthritis, 7 with systemic lupus erythematosus) investigates the effects of HCQ on cardiovascular risk factors and arterial stiffness in patients with inflammatory disease. Blood lipids, blood pressure, blood glucose, glycated haemoglobin (HbA1c) and arterial stiffness was assessed at initiation, after four weeks of treatment and after eight weeks of treatment with 200 mg HCQ daily., Results: After four weeks of treatment with HCQ, total cholesterol had decreased from 5.4 mmol/L to 5.1 mmol/L (p<0.001), low-density lipoproteins from 3,0 mmol/L to 2.7 mmol/L (p<0.001) and apolipoprotein B from 0.96 g/L to 0.90 g/L (p<0.01). Those levels remained unchanged after eight weeks of treatment with HCQ. Levels of triglycerides, high-density lipoproteins and apolipoprotein A1 remained unchanged during the study. HbA1c decreased in most patients, especially in patients with high levels at start of HCQ, but increased HbA1c was seen in patients with low levels at start of treatment with HCQ. No significant effect was seen on blood pressure or any measure of arterial stiffness., Conclusion: This study does not identify the mechanisms of cardiovascular risk reduction from HCQ. Arterial stiffness is not affected by HCQ. The impact of HCQ on HbA1c and blood lipids is rapid, but of modest magnitude, and these effects do not fully explain the reduced risk of cardiovascular disease seen in observational studies. The mechanisms of cardiovascular risk reduction from HCQ are yet not completely known., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wahlin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

PD-1/PD-L1 inhibitors have increasingly been associated with the occurrence of subacute cutaneous lupus erythematosus (SCLE), but the clinical characteristics and outcomes remain under-explored. Literature on PD-1/PD-L1 inhibitors induced SCLE was retrieved from Chinese and English databases until June 31, 2024, and clinical data of patients were extracted for retrospective analysis. Twenty-nine patients participated, with a median age of 63 years (range 43, 80). The most frequently reported drugs were Nivolumab (51.7%) and pembrolizumab (31.0%). The median time from treatment initiation to SCLE onset was 3 months (range 0.5, 47). Cutaneous manifestations presented primarily as papulosquamous lesions (65.5%) and erythema annulare (31.0%), predominantly occurring on the trunk (51.7%) and arms (51.7%). Serological analysis revealed positive anti-Ro antibodies in 91.7% of patients, positive antinuclear antibodies in 75.0%, and positive anti-La antibodies in 50.0%. Skin biopsies showed interface dermatitis in 65.5% of cases and lymphocyte infiltration in 82.8%. Treatment with topical corticosteroids, systemic corticosteroids, and hydroxychloroquine led to gradual improvement or resolution of the rash, with a median recovery time of 1 month (range 0.5, 11). As the use of PD-1/PD-L1 inhibitors in oncology increases, SCLE should be recognized as a rare cutaneous adverse effect. Histological and serological evaluations play a critical role in diagnosing SCLE. Typically, SCLE resolves on its own with appropriate local and systemic treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rationale: Podocyte infolding glomerulopathy (PIG) is a rare glomerular disease, its diagnosis mainly depends on pathological manifestations of the kidney. Few clinical cases of PIG have been reported, but it is sometimes associated with connective tissue diseases. Here we describe a case of systemic lupus erythematosus (SLE) with PIG and undertake a review of the literature., Patient Concerns: A 34-year-old female patient was admitted to our hospital in August 2019 with repeated facial erythema and proteinuria for more than 10 years. The patient was previously diagnosed with SLE., Diagnosis: Systemic lupus erythematosus., Interventions: Renal biopsy was performed to investigate ongoing proteinuria and the results were consistent with PIG. Treatment with methylprednisolone, hydroxychloroquine sulfate, mycophenolate mofetil, and candesartan ester., Outcomes: Improved the patient's condition and resolved the proteinuria., Lessons: This study reported a case of PIG and SLE. The patient was diagnosed according to biopsy, and the disease remain stable after immunosuppressive therapy. It is recommended to carefully study renal biopsies from patients with proteinuria and underlying autoimmune diseases to identify additional cases., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Pulmonary arterial hypertension is a life-threatening progressive disorder characterised by high blood pressure (hypertension) in the arteries of the lungs (pulmonary artery). Although treatable, there is no known cure for this rare disorder, and its exact cause is unknown. Mutations in the bone morphogenetic protein receptor type-2 (BMPR2) are the most common genetic cause of familial pulmonary arterial hypertension. This study represents the first-ever trial of treatments aimed at directly rescuing the BMPR2 pathway, repurposing two drugs that have shown promise at restoring levels of BMPR2 signalling: hydroxychloroquine and phenylbutyrate., Methods: This three-armed phase II precision medicine study will investigate BMPR2 target engagement and explore the efficacy of two repurposed therapies in pulmonary arterial hypertension patients with BMPR2 mutations. Patients will be stratified based on two BMPR2 mutation classes: missense and haploinsufficient mutations. Eligible subjects will be randomised to one of the three arms (two active therapy arms and a placebo arm, all plus standard of care) following a Bayesian response-adaptive design implemented independently in each stratum and updated in response to a novel panel of primary biomarkers designed to assess biological modification of the disease., Discussion: The results of this trial will provide the first randomised evidence of the efficacy of these therapies to rescue BMPR2 function and will efficiently explore the potential for a differential response of these therapies per mutation class to address causes rather than consequences of this rare disease., Trial Registration: The study has been registered with ISRCTN (ISRCTN10304915, 22/09/2023)., (© 2024. The Author(s).)

Objectives: To evaluate the risk of liver fibrosis and associated factors with the non-invasive fibrosis score-4 (FIB-4) index in patients with inflammatory arthritis using methotrexate (MTX)., Methods: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who were followed up in the rheumatology outpatient clinic, who were on methotrexate only and for whom FIB-4 index was could be calculated at methotrexate initiation and follow-up were included. The FIB-4 index was calculated according to the following formula: age (years) × AST(IU/L)/(platelet count(10 (9)/L) × √ALT(IU/L)). The patients' demographics, comorbidities, other treatments, cumulative MTX dose, and reasons for MTX cessation were assessed. For the multivariate analysis, possible factors associated with intermediate-high risk FIB-4 index at last visit were determined., Results: A total of 107 patients were enrolled in the study, of whom 82 (76.6%) had RA and 25 (23.4%) had PsA. At the initiation of MTX, 24 (22.4%) patients had intermediate-high risk FIB-4 index. Comorbidities and the rate of ≥3-4 Charlson comorbidity index were more common in patients with intermediate-high risk FIB-4 index. A total of 37 (34.5%) patients had intermediate-high risk FIB-4 index at the last visit after median 3.6 (0.3-22.06) years follow-up. The median cumulative MTX dose was 2550 mg (1050-13.991). Cumulative MTX dose [OR 1.18 (1.01-1.33), p = .03] and diabetes mellitus [OR 4.60 (1.74-12.50), p = .002] were associated factors with intermediate-high risk FIB-4 index. The concomitant use of hydroxychloroquine (HCQ) was found to be a low-risk factor for FIB-4 index [OR 0.28 (0.10-0.78) p = .015]., Conclusion: The FIB-4 index is a non-invasive method that can be used in daily rheumatology practice for the evaluation and follow-up of patients who will use methotrexate. Comorbidities and cumulative MTX dose seem to be related with the risk of liver fibrosis. Concomitant use of HCQ with MTX may reduce the risk of liver fibrosis., (© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Preclinical models of pancreatic cancer (PDAC) suggest a synergistic role for combined MEK and autophagy signaling inhibition, as well as MEK and CDK4/6 pathway targeting. Several case reports implicate clinical activity of the combination of either trametinib and hydroxychloroquine (HCQ) in patients with KRAS-mutant PDAC or trametinib with CDK4/6 inhibitors in patients with KRAS and CDKN2A/B alterations. However, prospective data from clinical trials is lacking. Here, we aim to provide clinical evidence regarding the use of these experimental regimens in the setting of dedicated precision oncology programs., Methods: In this retrospective case series, PDAC patients who received either trametinib/HCQ (THCQ) or trametinib/palbociclib (TP) were retrospectively identified across 11 participating cancer centers in Germany., Results: Overall, 34 patients were identified. 19 patients received THCQ, and 15 received TP, respectively. In patients treated with THCQ, the median duration of treatment was 46 days, median progression-free survival (PFS) was 52 days and median overall survival (OS) was 68 days. In the THCQ subgroup, all patients evaluable for response (13/19) had progressive disease (PD) within 100 days. In the TP subgroup, the median duration of treatment was 60 days, median PFS was 56 days and median OS was 195 days. In the TP subgroup, 9/15 patients were evaluable for response, of which 1/9 showed a partial response (PR) while 8/9 had PD. One patient achieved a clinical benefit despite progression under TP., Conclusion: THCQ and TP are not effective in patients with advanced PDAC harboring KRAS mutations or alterations in MAPK/CDKN2A/B., (© 2024. The Author(s).)

Background: There is a dearth of studies investigating the efficacy of hydroxychloroquine in the treatment of either anogenital lichen sclerosus or extragenital lichen sclerosus, a condition that, if left untreated, could lead to a greater degree of scarring and malignant transformation., Objective: This study aims to analyze the demographic characteristics, clinicopathological features, treatment response, and outcomes of patients diagnosed with either anogenital or extragenital lichen sclerosus who received hydroxychloroquine therapy., Methods: A retrospective analysis was conducted involving 70 patients diagnosed with lichen sclerosus who underwent treatment with hydroxychloroquine at our institution between 2018 and 2023., Results: Among the cohort, 67 patients were female, and 3 were male. Extragenital lichen sclerosus was diagnosed in 23 patients, with 16 exhibiting concomitant morphea overlap. Itching was the predominant clinical presentation (67%). A notable proportion of patients (36%) had a connective tissue disorder, prompting hydroxychloroquine therapy. Among the 30 patients treated solely for lichen sclerosus, 21 demonstrated response and 9 had no response. From a broader comparison of response to hydroxychloroquine, the overall anogenital response rate was 84.6% as opposed to 50% in extragenital lichen sclerosus. The median time to initial response was 4 months. Adverse effects, predominantly mild, were observed in 10 (14.3%) patients., Limitation: This study is constrained by its retrospective nature and reliance on data from a single center, resulting in a limited sample size., Conclusion: Hydroxychloroquine demonstrates promise as a therapeutic option for anogenital lichen sclerosus because of its favorable response rates and low incidence of adverse effects. However, further investigations, including larger-scale or prospective studies, are imperative to ascertain its definitive efficacy., (© 2024 the International Society of Dermatology.)

Objective: 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., Methods: 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., Results: 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)., Conclusion: 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., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The studies regarding prevalence, outcomes, and predictors of prolonged corrected QT (QTc) among COVID-19 patients not on QTc-prolonging medication are not available in the literature. In this retrospective cohort study, the QTc of 295 hospital-admitted COVID-19 patients was analyzed and its association with in-hospital mortality was determined. The QTc was prolonged in 14.6% (43/295) of the study population. Prolonged QTc was seen in patients with older age (P = 0.018), coronary artery disease (P = 0.001), congestive heart failure (P = 0.042), elevated N-terminal-pro-B-type natriuretic peptide (NT-ProBNP) (P < 0.0001), and on remdesivir (P = 0.046). No episode of torsades de pointes arrhythmia or any arrhythmic death was observed among patients with prolonged QTc. The mortality was significantly high in patients with prolonged QTc (P = 0.003). The multivariate logistic regression analysis showed coronary artery disease (odds ratio (OR): 4.153, 95% CI 1.37-14.86; P = 0.013), and NT-ProBNP (ng/L) (OR: 1.000, 95% CI 1.000-1.000; P = 0.007) as predictors of prolonged QTc. The prolonged QTc was associated with the worst in-hospital survival (p by log-rank 0.001). A significant independent association was observed between prolonged QTc and in-hospital mortality in multivariate cox-regression analysis (adjusted hazard ratio: 3.861; (95% CI 1.719-6.523), P < 0.0001). QTc was found to be a marker of underlying comorbidities among COVID-19 patients. Prolonged QTc in hospitalized COVID-19 patients was independently associated with in-hospital mortality., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Having a low complement level is associated with clinical systemic lupus erythematosus (SLE) disease activity and future organ damage. We studied the association of hydroxychloroquine (HCQ) whole blood levels with changes in complement level., Methods: We performed two analyses on data prospectively collected from an SLE cohort. In the first (a "new starts on HCQ" analysis), we compared changes in complement level between those starting HCQ and those not starting it. The second analysis evaluated the association between HCQ whole blood levels and low complement level in all cohort visits using conditional logistic regression., Results: In the "new starts on HCQ" analysis, a higher percentage of patients starting HCQ (as reflected in HCQ blood levels >50) experienced a normalization of C4 level compared to those not starting HCQ (23 of 57 [40%] vs. 9 of 56 [13%]; P = 0.011), as well as a significantly greater increase in both C3 and C4 level (P = 0.048 and P = 0.017, respectively). In the "all cohort visits" analysis, there was a statistically significant higher probability of having normal C4 levels in visits with higher HCQ whole blood levels (odds ratio 1.8-2.6 depending on the levels). This relationship was most pronounced for whole blood HCQ levels of 200 ng/mL or more., Conclusion: We observed significant improvement in complement levels when HCQ was started and among those with higher whole blood levels of HCQ, particularly with respect to C4. Modulating the pathogenic mechanisms that lead to complement consumption may be one mode by which HCQ prevents poor outcomes in SLE., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Competing Interests: Conflicts of interest None disclosed.

This case report describes a case of retinal vasculitis in a patient with Rhupus, which has not been reported earlier in the literature. A 39-year-old female patient with a history of Rhupus presented with sudden vision loss in her left eye. The patient was treated earlier, for her polyarthritis, with oral corticosteroids, hydroxychloroquine, and oral methotrexate, which were discontinued after 1 year of treatment. At presentation, fundus examination of the left eye revealed mild vitritis, perivenous sheathing, and hemorrhagic periphlebitis. The patient was administered three doses of pulse corticosteroid, resulting in a reduction in retinal vasculitis and macular edema. The patient was continued on oral corticosteroids and started on oral methotrexate and hydroxychloroquine. At 6-week follow-up, the patient's vision had improved to 6/9, and fundus examination revealed resolving phlebitis and retinal hemorrhages. This case also highlights the importance of prompt diagnosis and treatment of retinal vasculitis in patients with Rhupus.

Objectives: This study aims to explore the treatment pattern of systemic lupus erythematosus (SLE) in Aotearoa/New Zealand., Methods: SLE patients were linked to the pharmaceutical dispensing data. The use of publicly funded anti-malarials, immunomodulators, biologics, glucocorticoids and bisphosphonates were compared by gender, ethnicity, age group, socioeconomic status and year of SLE identification. Adherence to hydroxychloroquine was examined using the medication possession ratio (MPR), with a MPR of ≥0.8 considered as high adherence., Results: Of the 2631 SLE patients, 73.8% used hydroxychloroquine, 64.1% used immunomodulators/biologics and 68.0% used 5 mg or more prednisone daily for at least 90 days. Women were more likely to use hydroxychloroquine than men. Asian patients had a different treatment pattern than other ethnic groups, and Māori were less likely to use hydroxychloroquine. The proportions of patients using different treatments decreased with age. Of the patients using hydroxychloroquine, 54.5% had high adherence. For patients over 40 years old and on long term prednisone, 47.3% had bisphosphonates and this figure was 17.8% for patients under the age of 40 years old. Patients with better socioeconomic status had a higher probability of using bisphosphonates than patients with lower socioeconomic status., Conclusions: Adherence to hydroxychloroquine in these patients varied and was lower in men and in Māori. Prednisone is commonly prescribed and used long term. Half of those over the age of 40 years old co-administered bisphosphonate. Further research is needed to identify the reasons for these discrepancies on SLE treatments by gender, ethnicity, age and socioeconomic status., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: We sought to determine the impact of hydroxychloroquine (HCQ) dose on the risk of hospitalizations for systemic lupus erythematosus (SLE)., Methods: We conducted a case-crossover study within an academic health system, including patients with SLE who used HCQ and had ≥1 hospitalization for active SLE between January 2011 and December 2021. Case periods ended in hospitalization for SLE, whereas control periods did not. The exposures were the average weight-based HCQ dose, categorized as ≤5 or >5 mg/kg/day, and non-weight-based HCQ dose, categorized as <400 or 400 mg/day, assessed during each six-month case or control period. Odds ratios (ORs) were calculated using conditional logistic regression and adjusted for prior disease activity, kidney function, glucocorticoid use, and other immunosuppressant use., Results: Of 2,974 patients with SLE who used HCQ (mean age 36.5 years; 92% female), 584 had ≥1 hospitalization with primary discharge diagnosis of SLE. Of these, 122 had ≥1 hospitalization for active SLE while using HCQ and had ≥1 control period with HCQ use during the study period. Lower HCQ weight-based dose (≤5 vs >5 mg/kg/day) and non-weight-based dose (<400 vs 400 mg/day) were each associated with increased hospitalizations for active SLE (adjusted OR 4.20, 95% confidence interval [CI] 1.45-12.19, and adjusted OR 3.39, 95% CI 1.31-8.81)., Conclusion: The use of lower doses of HCQ was associated with an increased risk of hospitalizations for active SLE. Although the long-term risk of HCQ retinopathy must be acknowledged, this must be balanced with the short-term and cumulative risks of increased SLE activity., (© 2024 American College of Rheumatology.)

Objective: To evaluate whether hydroxychloroquine (HCQ) or chloroquine (CQ) are effective for the treatment of oral lichen planus (OLP)., Materials and Methods: A literature search was conducted in four databases. Clinical studies investigating the effect of HCQ/CQ in patients with OLP were included., Results: Eleven studies were included. Four were RCTs and seven quasi-experimental studies. The studies included 390 patients diagnosed with OLP, of which 326 and 7 received HCQ and CQ, respectively. 46 patients received topical dexamethasone, 5 placebo and 6 griseofulvin as controls. Five studies assessed pain, and all of them obtained pain reduction with the use of HCQ. Six studies reported objective clinical improvement of OLP with the use of HCQ. Five studies that used a subjective scale obtained that 24%-100% of the patients achieved a complete/almost complete improvement of OLP lesions and its symptomatology. The most frequent side effects were vision problems, gastric discomfort, rash, nauseas, headaches, skin pigmentation, and elevated kidney function. 17 patients had to withdraw from the studies., Conclusions: Current evidence is scarce to confirm HCQ as a therapeutic option for OLP. More RCTs are needed to compare its efficacy with topical corticosteroids and to evaluate whether HCQ reduces relapses of OLP., (© 2024 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Objective: To assess treatment patterns and the association between long-term glucocorticoid (GC) and hydroxychloroquine (HCQ) use and damage accrual in patients with systemic lupus erythematosus (SLE)., Methods: A retrospective study including patients with SLE using the computerised database of a large health maintenance organisation. Patients were matched with subjects from the general population. Multivariable logistic regression models were used to assess the association between GC cumulative daily doses, HCQ and comorbidities: Osteoporosis, cardiovascular disease (CVD), hypertension and diabetes mellitus. Models were adjusted for age, sex, socioeconomic status, smoking, disease duration and HCQ use., Results: A total of 1073 patients with SLE were included, 87.79% were women. The age at first diagnosis was 37.23±14.36 and the SLE disease duration was 12.89±6.23 years. Initiation of HCQ within 12 months of SLE diagnosis increased from 51.02% in 2000 to 83.67% in 2010 and 93.02% in 2018. The annual usage of GC gradually decreased from 45.34% in 2000 to 30.76% in 2020. CVD and osteoporosis were more prevalent in SLE than in the general population. Multivariable logistic regression models revealed increased odds for comorbidities in patients receiving a mean daily dose of prednisone of more than 5 mg/day compared with those receiving 5 mg/day or less., Conclusions: CVD and osteoporosis were more prevalent in SLE than in the general population. The dose and frequency of GC treatment in patients with SLE have decreased over the years. Prednisone usage in doses exceeding 5 mg/day is associated with significantly increased odds of osteoporosis and CVD., Competing Interests: Competing interests: RY, IL and ME are employees of AstraZeneca. TE and DP received consultant fees from AstraZeneca., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, we report a preanalytical challenge noted in our laboratory on plasma samples from a critically ill COVID-19 patient treated with hydroxychloroquine. This is significant because, in critically ill COVID-19 patients on hydroxychloroquine, plasma samples can have a high measured haemolysis index in the absence of haemolysis, with the impact on reporting the results for potassium and other analytes., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hydroxychloroquine (HCQ) has proved ineffective in treating patients hospitalised with Coronavirus Disease 2019 (COVID-19), but uncertainty remains over its safety and efficacy in chemoprevention. Previous chemoprevention randomised controlled trials (RCTs) did not individually show benefit of HCQ against COVID-19 and, although meta-analysis did suggest clinical benefit, guidelines recommend against its use., Methods and Findings: Healthy adult participants from the healthcare setting, and later from the community, were enrolled in 26 centres in 11 countries to a double-blind, placebo-controlled, randomised trial of COVID-19 chemoprevention. HCQ was evaluated in Europe and Africa, and chloroquine (CQ) was evaluated in Asia, (both base equivalent of 155 mg once daily). The primary endpoint was symptomatic COVID-19, confirmed by PCR or seroconversion during the 3-month follow-up period. The secondary and tertiary endpoints were: asymptomatic laboratory-confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection; severity of COVID-19 symptoms; all-cause PCR-confirmed symptomatic acute respiratory illness (including SARS-CoV-2 infection); participant reported number of workdays lost; genetic and baseline biochemical markers associated with symptomatic COVID-19, respiratory illness and disease severity (not reported here); and health economic analyses of HCQ and CQ prophylaxis on costs and quality of life measures (not reported here). The primary and safety analyses were conducted in the intention-to-treat (ITT) population. Recruitment of 40,000 (20,000 HCQ arm, 20,000 CQ arm) participants was planned but was not possible because of protracted delays resulting from controversies over efficacy and adverse events with HCQ use, vaccine rollout in some countries, and other factors. Between 29 April 2020 and 10 March 2022, 4,652 participants (46% females) were enrolled (HCQ/CQ n = 2,320; placebo n = 2,332). The median (IQR) age was 29 (23 to 39) years. SARS-CoV-2 infections (symptomatic and asymptomatic) occurred in 1,071 (23%) participants. For the primary endpoint the incidence of symptomatic COVID-19 was 240/2,320 in the HCQ/CQ versus 284/2,332 in the placebo arms (risk ratio (RR) 0.85 [95% confidence interval, 0.72 to 1.00; p = 0.05]). For the secondary and tertiary outcomes asymptomatic SARS-CoV-2 infections occurred in 11.5% of HCQ/CQ recipients and 12.0% of placebo recipients: RR: 0.96 (95% CI, 0.82 to 1.12; p = 0.6). There were no differences in the severity of symptoms between the groups and no severe illnesses. HCQ/CQ chemoprevention was associated with fewer PCR-confirmed all-cause respiratory infections (predominantly SARS-CoV-2): RR 0.61 (95% CI, 0.42 to 0.88; p = 0.009) and fewer days lost to work because of illness: 104 days per 1,000 participants over 90 days (95% CI, 12 to 199 days; p < 0.001). The prespecified meta-analysis of all published pre-exposure RCTs indicates that HCQ/CQ prophylaxis provided a moderate protective benefit against symptomatic COVID-19: RR 0.80 (95% CI, 0.71 to 0.91). Both drugs were well tolerated with no drug-related serious adverse events (SAEs). Study limitations include the smaller than planned study size, the relatively low number of PCR-confirmed infections, and the lower comparative accuracy of serology endpoints (in particular, the adapted dried blood spot method) compared to the PCR endpoint. The COPCOV trial was registered with ClinicalTrials.gov; number NCT04303507., Interpretation: In this large placebo-controlled, double-blind randomised trial, HCQ and CQ were safe and well tolerated in COVID-19 chemoprevention, and there was evidence of moderate protective benefit in a meta-analysis including this trial and similar RCTs., Trial Registration: ClinicalTrials.gov NCT04303507; ISRCTN Registry ISRCTN10207947., Competing Interests: NJW and LvS are members of the PLOS Medicine Editorial Board. The rest of the authors have declared that no competing interests exist., (Copyright: © 2024 Schilling et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This review discusses the pathophysiology of diabetes in pregnancy in relation to the placental function. We review the potential use of hydroxychloroquine in improving pregnancy outcomes affected by diabetes. The review focuses on the mechanism of action of hydroxychloroquine and its potential effects on diabetes. There are several pathways in which hydroxychloroquine mediates its effects: through the inflammasome complex, inflammatory cytokines, oxidative stress, modulatory effects, and antihyperglycemic effects. As a safe drug to be used in pregnancy, it is worth exploring the possible use hydroxychloroquine as an adjunct treatment to the current therapy of diabetes in pregnancy.

Competing Interests: Competing interests: None declared.

Osteoporosis remains incurable. The most widely used antiresorptive agents, bisphosphonates (BPs), also inhibit bone formation, while the anabolic agent, teriparatide, does not inhibit bone resorption, and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects. Thus, there is an unmet need to develop dual antiresorptive and anabolic agents to prevent and treat osteoporosis. Hydroxychloroquine (HCQ), which is used to treat rheumatoid arthritis, prevents the lysosomal degradation of TNF receptor-associated factor 3 (TRAF3), an NF-κB adaptor protein that limits bone resorption and maintains bone formation. We attempted to covalently link HCQ to a hydroxyalklyl BP (HABP) with anticipated low antiresorptive activity, to target delivery of HCQ to bone to test if this targeting increases its efficacy to prevent TRAF3 degradation in the bone microenvironment and thus reduce bone resorption and increase bone formation, while reducing its systemic side effects. Unexpectedly, HABP-HCQ was found to exist as a salt in aqueous solution, composed of a protonated HCQ cation and a deprotonated HABP anion. Nevertheless, it inhibited osteoclastogenesis, stimulated osteoblast differentiation, and increased TRAF3 protein levels in vitro. HABP-HCQ significantly inhibited both osteoclast formation and bone marrow fibrosis in mice given multiple daily PTH injections. In contrast, HCQ inhibited marrow fibrosis, but not osteoclast formation, while the HABP alone inhibited osteoclast formation, but not fibrosis, in the mice. HABP-HCQ, but not HCQ, prevented trabecular bone loss following ovariectomy in mice and, importantly, increased bone volume in ovariectomized mice with established bone loss because HABP-HCQ increased bone formation and decreased bone resorption parameters simultaneously. In contrast, HCQ increased bone formation, but did not decrease bone resorption parameters, while HABP also restored the bone lost in ovariectomized mice, but it inhibited parameters of both bone resorption and formation. Our findings suggest that the combination of HABP and HCQ could have dual antiresorptive and anabolic effects to prevent and treat osteoporosis., (© 2024. The Author(s).)

Background: Membranoproliferative glomerulonephritis is a rare entity which can be a result from autoimmune diseases, caused by various medications and infections., Case Presentation: We herein present the case of a 62-year-old male patient who presented with fatigue and was found to have severe anemia, impaired renal function, and nephrotic syndrome. A renal biopsy revealed membranoproliferative glomerulonephritis (MPGN) of the immune complex type with activation of the classical complement pathway. Further investigations led to the diagnosis of a chronic Coxiella burnetii-infection (Q fever), likely acquired during cycling trips in a region known for intensive sheep farming. Additionally, the patient was found to have a post endocarditic destructive bicuspid aortic valve caused by this pathogen. Treatment with hydroxychloroquine and doxycycline was administered for a duration of 24 months. The aortic valve was replaced successfully and the patient recovered completely., Conclusions: Early detection and targeted treatment of this life-threatening disease is crucial for complete recovery of the patient., (© 2024. The Author(s).)

Importance: Anti-double-stranded DNA (dsDNA) antibody has been reported to have a close relationship with systemic lupus erythematosus (SLE) flares and participates in the pathogenesis of lupus nephritis (LN) as well as causing damage to other organs. However, whether early use of mycophenolate mofetil (MMF) could prevent SLE flares is not clear., Objective: To assess the efficacy and safety of MMF plus prednisone and hydroxychloroquine sulfate compared with prednisone and hydroxychloroquine sulfate alone in patients with SLE., Design, Setting, and Participants: This investigator-initiated, multicenter, observer-blinded randomized clinical trial enrolled 130 participants aged 18 to 65 years and was conducted in 3 hospitals across China. Treatment-naive patients with newly diagnosed SLE, a high titer of anti-dsDNA antibody, and no major organ involvement were included. The study was started September 1, 2018, and the follow-up was completed September 30, 2021. Data were analyzed from December 1, 2021, to March 31, 2022., Interventions: Patients were randomized 1:1 to receive oral prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) (control group) or prednisone (0.5 mg/kg/d) and hydroxychloroquine sulfate (5 mg/kg/d) plus MMF (500 mg twice daily) (MMF group) for 96 weeks., Main Outcomes and Measures: The primary outcome was the proportion of patients presenting with flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare Index. The secondary outcomes included the proportion with lupus low disease activity state at week 96, 36-Item Short Form Health Survey scores before and after treatment, proportion of adverse events (AEs), and changes in SLEDAI-2000 scores and prednisone doses., Results: Among 130 randomized patients (mean [SD] age, 34.5 [12.5] years; 112 [86.2%] women), 119 (91.5%) completed the follow-up. The risk of severe flare was significantly lower in the MMF group (7 of 65 [10.8%]) vs the control group (18 of 65 [27.7%]) (relative risk [RR], 0.39 [95% CI, 0.17-0.87]; P = .01). Additionally, 1 of 65 patients in the MMF group (1.5%) and 9 of 65 in the control group (13.8%) manifested LN (RR, 0.11 [95% CI, 0.01-0.85]; P = .008). Most common serious study drug-related AEs were infections (20 of 65 [30.8%] in the control group and 22 of 65 [33.8%] in the MMF group)., Conclusions and Relevance: The findings of this randomized clinical trial suggest that MMF may reduce the rate of severe flare and lower the incidence of LN in patients with new-onset SLE and a high titer of anti-dsDNA antibody without major organ involvement., Trial Registration: Chinese Clinical Trial Registry: ChiCTR1800017540.

Objective: To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA)., Methods: Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study., Results: At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05)., Conclusion: In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Competing Interests: S.K.F.: Sling (Consultant), Viridian (Consultant), WL Gore (Consultant), Poriferous (Consultant), Medtronic (Consultant), ASPEN/Third Rock (consultant), Lassen (consultant), Immunovant (consultant), and Thieme and Springer (textbook royalties). The other authors have no financial or conflicts of interest to disclose.

We report a 67-year-old man who presented with poor dietary intake and fatigue. Laboratory tests showed leukopenia, antinuclear antibody (ANA) positivity, anti-dsDNA antibody (A-dsDNA) and anti-Smith antibody (anti-Sm) negativity, decreased C3 and C4, elevated serum immunoglobulin G (IgG), IgG4, and creatinine, and 1.25 g urinary protein at 24 hours. As his condition worsened, re-examination showed thrombocytopenia and A-dsDNA positivity, and renal biopsy pathology showed IgG4-related tubulointerstitial nephritis. The final diagnosis was IgG4-related disease (IgG4-RD) with systemic lupus erythematosus (SLE). His condition improved with glucocorticoid (GC) combined with hydroxychloroquine (HCQ) and mycophenolate mofetil (MMF) treatment. This case highlights that IgG4-RD and SLE may occur successively or co-exist and may convert into each other.

Background: Immunity 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., Methods: 245 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., Results: The 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, Eta 2 = 0.052), anti-ENA (p = 0.016, Eta 2 = 0.030), ANA (p = 0.035, Eta 2 = 0.022), and LA (p = 0.016, Eta 2 = 0.028). Furthermore, the recurrence rate of the HCQ treatment group was lower than that of the control group (p = 0.024)., Conclusions: Co-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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg -1 ·d -1 ) or hydroxychloroquine (50 mg·kg -1 ·d -1 ) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg -1 ·d -1 ) was more effective than hydroxychloroquine (50 mg·kg -1 ·d -1 ). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

This text addresses the implications of misinformation during the COVID-19 pandemic, focusing on the use of hydroxychloroquine (HCQ) and other drugs based on a specific publication. The article titled "Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate," published in 2024 in the journal Biomedicine and Pharmacotherapy, reveals 17 000 deaths associated with the inappropriate use of HCQ in 6 countries, excluding Brazil and India. The dissemination of ineffective drugs, the persistence in recommending HCQ in Brazil, and the lack of an effective response from academia underscore the fragility of public health systems under pressure. Transparent communication between the scientific community and the public is vital, particularly considering studies, such as the one published in Nature Communications in 2021, which warns of the risks of chloroquine. The text highlights the influence of social media in spreading unverified information and emphasizes the need for criminal liability for those contributing to the spread of misinformation. It concludes by underlining the importance of learning from past mistakes to build a more resilient and informed future in the field of public health., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Study Question: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?, Summary Answer: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages., What Is Known Already: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL., Study Design, Size, Duration: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals., Participants/materials, Setting, Methods: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth., Main Results and the Role of Chance: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01)., Limitations, Reasons for Caution: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered., Wider Implications of the Findings: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system., Study Funding/competing Interest(s): The research received no specific funding, and the authors declare no competing interests., Trial Registration Number: clinicaltrial.gov NCT05557201., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

This mini-review explores glucocorticoids, mycophenolate mofetil (MMF), and hydroxychloroquine (HCQ) in IgA nephropathy (IgAN). It discusses conflicting findings from pivotal trials like TESTING and STOP-IgAN regarding glucocorticoid efficacy, emphasizing reduced-dose protocols as potentially safer options. MMF's effectiveness varies among populations, demonstrating promise in Chinese cohorts but yielding inconclusive results elsewhere. HCQ shows potential in reducing proteinuria, with ongoing trials investigating its long-term benefits., (© 2024 Asian Pacific Society of Nephrology.)

Introduction: The association of outer foveal microdefect and LES or hydroxychloroquine use has not been established in current literature., Case Report: We present the first reported case of bilateral outer foveal microdefect ina a patient with systemic lúpus erythematosus using hydroxycloroquine., Discussion/conclusion: While it is not possible to definitively attribute the described findings in our patient to HCQ use, it is important to be aware of the possibility that the outer foveal microdefect may be caused by this medication. Therefore, patients on chronic HCQ therapy should be informed about the risk of potential visual adverse effects, so that appropriate interventions can be implemented if necessary., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Politicization and misinformation or disinformation of unproven COVID-19 therapies have resulted in communication challenges in presenting science to the public, especially in times of heightened public trepidation and uncertainty., Objective: This study aims to examine how scientific evidence and uncertainty were portrayed in US news on 3 unproven COVID-19 therapeutics, prior to the development of proven therapeutics and vaccines., Methods: We conducted a media analysis of unproven COVID-19 therapeutics in early 2020. A total of 479 discussions of unproven COVID-19 therapeutics (hydroxychloroquine, remdesivir, and convalescent plasma) in traditional and online US news reports from January 1, 2020, to July 30, 2020, were systematically analyzed for theme, scientific evidence, evidence details and limitations, safety, efficacy, and sources of authority., Results: The majority of discussions included scientific evidence (n=322, 67%) although only 24% (n=116) of them mentioned publications. "Government" was the most frequently named source of authority for safety and efficacy claims on remdesivir (n=43, 35%) while "expert" claims were mostly mentioned for convalescent plasma (n=22, 38%). Most claims on hydroxychloroquine (n=236, 79%) were offered by a "prominent person," of which 97% (n=230) were from former US President Trump. Despite the inclusion of scientific evidence, many claims of the safety and efficacy were made by nonexperts. Few news reports expressed scientific uncertainty in discussions of unproven COVID-19 therapeutics as limitations of evidence were infrequently included in the body of news reports (n=125, 26%) and rarely found in headlines (n=2, 2%) or lead paragraphs (n=9, 9%; P<.001)., Conclusions: These results highlight that while scientific evidence is discussed relatively frequently in news reports, scientific uncertainty is infrequently reported and rarely found in prominent headlines and lead paragraphs., (©Sara Watson, Tyler J Benning, Alessandro R Marcon, Xuan Zhu, Timothy Caulfield, Richard R Sharp, Zubin Master. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 29.08.2024.)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: 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., Objective: To evaluate the association between hydroxychloroquine and the risk of myocardial infarction (MI), stroke, and other thromboembolic events (OTEs) in patients with SLE., Design, Setting, and Participants: 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., Exposures: 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., Main Outcomes and Measures: 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., Results: 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., Conclusions and Relevance: 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.

Competing Interests: The authors report no conflicts of interest.

Background: Amid concerns about severe COVID-19 in patients with autoimmune rheumatic disease (AIRD) during the outbreak, it is crucial to explore behavioural changes, whether healthy or unhealthy, arising from this patient population in response to the changing healthcare environment., Aim: To investigate COVID-19-driven behavioural changes in patients with AIRD., Methods: This observational study invited patients who attended the rheumatology clinic of the Korle Bu Teaching Hospital from 1 August 2020 to 1 July 2021, to respond to a survey questionnaire distributed on the patient's WhatsApp platform. Variables observed were changes in patient behaviour and decision-making related to medication, healthcare service utilisation and clinical advice., Results: Results for 233 patients were analysed in the study, the majority (89.7%) of whom were women. The most significant behavioural changes were a reduction in hydroxychloroquine (HCQ) dosage, adoption of telemedicine for clinical consultation and keen adherence to protective/preventive health measures. Patients also expressed anxiety regarding the risk of contracting COVID-19 (52.5%), infecting their families (66.5%) and losing income (50.2%) due to the pandemic. Women and students were more likely to engage in self-isolation/shielding behaviour. Employed participants practised social distancing more, reduced HCQ dosage and had more fear of losing income. Having mixed connective tissue disease is associated with being anxious about the risk of COVID-19 infection., Conclusion: The COVID-19 pandemic has resulted in behaviour changes among patients with AIRD. Despite the perceived risk, most of these patients continue to adhere to their prescribed medication regimens, especially maintaining the dosage of traditional immunosuppressive agents., (© 2024 Royal Australasian College of Physicians.)

Objective: This paper presents an analysis of the pregnancy trajectory and therapeutic regimen documentation of a primigravida with APSN. It aims at communicating the therapeutic approach and preventive measures for APSN in pregnancy., Case Presentation: This paper reports the trajectory and therapeutic regimen documentation of a primigravida with APSN. The APSN was discovered in a primigravida woman aged 26 years at 11 weeks of gestation. The initial therapy regimen consists of daily administration of prednisone 10 mg, hydroxychloroquine 200 mg, dapparin 5000 IU, and aspirin 50 mg. At a gestational age of 20 + 3 weeks, the dosage of dapparin was modified to 5000 IU/other day, along with a significant rise in urinary protein level seen at 30 + 3 weeks of gestational age. The initial dosage of dapanin sodium was renewed. The patient delivered at 38 + 3 weeks of gestation without other complications., Conclusion: It is imperative to acknowledge that altering the dosage and administration of medication should not be done haphazardly during pregnancy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: We studied whether the use of hydroxychloroquine (HCQ) for COVID-19 resulted in supply shortages for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)., Methods: We used US claims data (IQVIA PHARMETRICS® Plus for Academics [PHARMETRICS]) and hospital electronic records from Spain (Institut Municipal d'Assistència Sanitària Information System [IMASIS]) to estimate monthly rates of HCQ use between January 2019 and March 2022, in the general population and in patients with RA and SLE. Methotrexate (MTX) use was estimated as a control., Results: More than 13.5 million individuals (13,311,811 PHARMETRICS, 207,646 IMASIS) were included in the general population cohort. RA and SLE cohorts enrolled 135,259 and 39,295 patients, respectively, in PHARMETRICS. Incidence of MTX and HCQ were stable before March 2020. On March 2020, the incidence of HCQ increased by 9- and 67-fold in PHARMETRICS and IMASIS, respectively, and decreased in May 2020. Usage rates of HCQ went back to prepandemic trends in Spain but remained high in the United States, mimicking waves of COVID-19. No significant changes in HCQ use were noted among patients with RA and SLE. MTX use rates decreased during HCQ approval period for COVID-19 treatment., Conclusion: Use of HCQ increased dramatically in the general population in both Spain and the United States during March and April 2020. Whereas Spain returned to prepandemic rates after the first wave, use of HCQ remained high and followed waves of COVID-19 in the United States. However, we found no evidence of general shortages in the use of HCQ for both RA and SLE in the United States., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

The KDIGO Update 2024 was supplemented by new "Clinical Practice Points", which were derived from the current evidence but are not necessarily comprehensively proven by prospective controlled studies. The most significant change in the Update 2024 for Lupus nephritis concerns the recommendations for induction therapy for lupus nephritis classes III and IV. The basis is still high-dose glucocorticoid treatment and the use of hydroxychloroquine. The 2 new developments in the 2024 Update concerning ANCA-associated nephritis are based on the studies on the use of the C5a receptor inhibitor Avacopan and the increasing data on induction protocols with reduced glucocorticoid dosage. Due to the inconsistency and variability of the conditions under which blood pressure measurements are carried out in practice, an international consensus statement was issued which defines 4 steps to achieve sufficient validity of the measurement results. CKD-MBD Controversies Conference 2023: The update for CKD-MBD, which was discussed in the Controversies Conference 2023, is in progress and has not been released yet. However, there were no serious contradictions between the 2023 data and the 2017 guidelines - the risk assessment regarding calcium-containing phosphate binders may have been put into perspective., Competing Interests: M.K. erhielt Vortrags- und Beraterhonorare von Amgen, AstraZeneca, BMS, Boehringer Ingelheim, CSL Vifor, Kyowa Kirin und Pfizer. M.K. war Mitglied des KDIGO Executive Committees von 2020–2023 und Ko-Vorsitzender der KDIGO Controversies Conference zum Thema „CKD-MBD“ im Oktober 2023 in Madrid., (Thieme. All rights reserved.)

The 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus (SLE) faced several tasks: the newly approved medications anifrolumab and voclosporin as well as the additional approval of belimumab for lupus nephritis had to be conceptionally fitted into the management of SLE. Novel data on hydroxychloroquine and glucocorticoids, additional results for the treat-to-target goals remission and low disease activity and experience with respect to vaccinations and infections had to be considered. Additionally, EULAR specified a slightly modified structure. The update was further developed with 5 overarching principles and 13 recommendations. An SLE activity score is required for each patient visit. All SLE patients should receive hydroxychloroquine at a target dose of 5 mg/kg body weight. Glucocorticoids should only be used if necessary and reduced to not more than 5 mg prednisone equivalent daily in the long-term or, even better, tapered off. If the target of remission or low disease activity is not reached, methotrexate, azathioprine, mycophenolate and/or belimumab or anifrolumab should be used. For lupus nephritis, Euro-Lupus cyclophosphamide or mycophenolate are options for induction therapy and mycophenolate or azathioprine for maintenance. In the case of severe nephritis, the addition of belimumab or a calcineurin inhibitor (voclosporin or tacrolimus) should be considered. It is important that treatment should be continued for at least 3 years. This review article describes the details of the new recommendations against the background of relevant studies in recent years and classifies them in the clinical context., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Aim: 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., Methods: 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)., Results: 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)]., Conclusions: The study indicates that there is no significant association between the use of HCQ and the risk of osteoporosis in patients with RA., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort., Methods: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological and treatment variables. Antimalarial use was approached as (i) users vs no users, (ii) according to prevalent vs incident use regarding the LN flare and (iii) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression., Results: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73 m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92) and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect of antimalarials on these outcomes was modified by the presentation eGFR, histological class and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7% and 8.8% by 3, 5 and 7 years of continued antimalarial use, respectively., Conclusion: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Q fever is a worldwide zoonosis due to Coxiella burnetii, responsible for endocarditis and endovascular infections. Since the 1990s, the combination hydroxychloroquine + doxycycline has constituted the curative and prophylactic treatment in persistent focalized Q fever. This combination appears to have significantly reduced the treatment's duration (from 60 to 26 months), yet substantial evidence of effectiveness remains lacking. Data are mostly based on in vitro and observational studies. We conducted a literature review to assess the effectiveness of this therapy, along with potential alternatives. The proposed in vitro mechanism of action describes the inhibition of Coxiella replication by doxycycline through the restoration of its bactericidal activity (inhibited in acidic environment) by alkalinization of phagolysosome-like vacuoles with hydroxychloroquine. So far, the rarity and heterogeneous presentation of cases have made it challenging to design prospective studies with statistical power. The main studies supporting this treatment are retrospective cohorts, dating back to the 1990s-2000s. Retrospective studies from the large Dutch outbreak of Q fever (>4000 cases between 2007 and 2010) did not corroborate a clear benefit of this combination, notably in comparison with other regimens. Thus, there is still no consensus among the medical community on this issue. However insufficient the evidence, today the doxycycline + hydroxychloroquine combination remains the regimen with the largest clinical experience in the treatment of 'chronic' Q fever. Reinforcing the guidelines' level of evidence is critical. We herein propose the creation of an extensive international registry, followed by a prospective cohort or ideally a randomized controlled trial., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Systemic lupus erythematosus (SLE) is an autoimmune disease with variable clinical presentation and organ involvement. Early diagnosis and rapid achievement of low disease activity or remission reduces organ damage and improves prognosis. Therapeutic principles can be divided into so-called basic measures and immunosuppressive treatment. Novel drugs have been developed in recent years, with new classes of agents being added for the treatment of SLE. These include biologic therapies and approved therapeutic options for the treatment of lupus nephritis. In light of improved treatment options, good disease control can now frequently be achieved; with savings on glucocorticoids, combination therapies are increasingly being used. Of great importance is the consistent use of basic measures, which include the use of hydroxychloroquine, optimization of cardiovascular risk factors, UV protection, bone-protective measures, and the implementation of vaccinations. In the treatment of lupus nephritis, conservative therapeutic measures for nephroprotection play a crucial role in renal prognosis. Finally, non-pharmacological therapy options such as exercise therapy are of great importance for improving quality of life., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)