RESUMEN

PURPOSE: To assess structural (optical coherence tomography, fundus autofluorescence) and functional (contrast sensitivity and visual field) test results which were used for detecting early retinal changes in patients using oral hydroxychloroquine. METHODS: Patients using oral hydroxychloroquine for at least one year were divided into two groups according to the duration of drug use. Groups 1 and 2 consisted of patients with drug use for more than 5 years and 1-5 years, respectively. The drug-using groups were compared with the control group. The mean retinal nerve fiber layer (RNFL), central macular thickness (CMT), ganglion cell-inner plexiform layer (GC-IPL), static 10-2 visual field, fundus autofluorescence (FAF) imaging, and contrast sensitivity tests were performed and statistically compared between groups. RESULTS: Median and temporal quadrant RNFL thicknesses were found to be statistically significantly lower in the drug groups. In the drug groups, the GC-IPL sectoral and mean thicknesses were found to be statistically lower in all quadrants. Central macular thickness was also found to be similar in all three groups. There was no significant difference between the groups in visual field parameters. Macular FAF images were significantly higher in the drug users, but there was no significant difference between the three groups in foveal FAF images. Contrast sensitivity measurements were significantly lower in the drug groups than in the control group at all spatial frequencies except 6 and 18 cycles/degree. CONCLUSIONS: The combined use of structural and functional tests in patients using hydroxychloroquine provides useful information in detecting early retinal changes.

Asunto(s)

Antirreumáticos , Sensibilidad de Contraste , Diagnóstico Precoz , Angiografía con Fluoresceína , Hidroxicloroquina , Mácula Lútea , Enfermedades de la Retina , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica , Campos Visuales , Humanos , Hidroxicloroquina/efectos adversos , Tomografía de Coherencia Óptica/métodos , Femenino , Masculino , Campos Visuales/fisiología , Campos Visuales/efectos de los fármacos , Persona de Mediana Edad , Antirreumáticos/efectos adversos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Mácula Lútea/efectos de los fármacos , Mácula Lútea/patología , Mácula Lútea/diagnóstico por imagen , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/efectos de los fármacos , Sensibilidad de Contraste/fisiología , Sensibilidad de Contraste/efectos de los fármacos , Angiografía con Fluoresceína/métodos , Adulto , Fibras Nerviosas/patología , Fibras Nerviosas/efectos de los fármacos , Agudeza Visual , Pruebas del Campo Visual/métodos , Anciano

RESUMEN

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.

Asunto(s)

Antirreumáticos , Artritis Reumatoide , Quimioterapia Combinada , Hidroxicloroquina , Metotrexato , Calidad de Vida , Humanos , Metotrexato/efectos adversos , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/sangre , Femenino , Antirreumáticos/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/uso terapéutico , Masculino , Resultado del Tratamiento , Persona de Mediana Edad , Adulto , Factores de Tiempo , Dimensión del Dolor , Biomarcadores/sangre , Anciano , Mediadores de Inflamación/sangre

RESUMEN

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.

Asunto(s)

Hidroxicloroquina , Lupus Eritematoso Sistémico , Ácido Micofenólico , Prednisona , Humanos , Ácido Micofenólico/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Femenino , Adulto , Masculino , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , Persona de Mediana Edad , Prednisona/uso terapéutico , Prednisona/efectos adversos , Quimioterapia Combinada , Adolescente , Inmunosupresores/uso terapéutico , Adulto Joven , China , Resultado del Tratamiento

RESUMEN

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.

Asunto(s)

Tratamiento Farmacológico de COVID-19 , COVID-19 , Cloroquina , Hidroxicloroquina , SARS-CoV-2 , Humanos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , Cloroquina/uso terapéutico , Cloroquina/efectos adversos , Método Doble Ciego , Femenino , Adulto , Masculino , COVID-19/prevención & control , COVID-19/epidemiología , Persona de Mediana Edad , Antivirales/uso terapéutico , Antivirales/efectos adversos , Resultado del Tratamiento , Adulto Joven

Asunto(s)

Arritmias Cardíacas , Enfermedades Autoinmunes , Cloroquina , Hidroxicloroquina , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/epidemiología , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Factores de Riesgo , Medición de Riesgo , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos

RESUMEN

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.

Asunto(s)

Azitromicina , Tratamiento Farmacológico de COVID-19 , Electrocardiografía , Hidroxicloroquina , Síndrome de QT Prolongado , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/administración & dosificación , Electrocardiografía/efectos de los fármacos , Femenino , Masculino , Persona de Mediana Edad , Azitromicina/uso terapéutico , Azitromicina/efectos adversos , Azitromicina/administración & dosificación , Síndrome de QT Prolongado/inducido químicamente , Anciano , Síndrome de Sjögren/tratamiento farmacológico , Quimioterapia Combinada , Levofloxacino/uso terapéutico , Levofloxacino/administración & dosificación , Levofloxacino/efectos adversos , Adulto , SARS-CoV-2 , COVID-19

RESUMEN

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.

Asunto(s)

Antirreumáticos , Enfermedades Cardiovasculares , Hidroxicloroquina , Lupus Eritematoso Sistémico , Humanos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Infarto del Miocardio/epidemiología , Infarto del Miocardio/inducido químicamente , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Estudios de Cohortes , Francia/epidemiología , Tromboembolia/epidemiología , Tromboembolia/prevención & control , Factores de Riesgo , Anciano

RESUMEN

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.

Asunto(s)

Antirreumáticos , Artritis Reumatoide , Bases de Datos Factuales , Hidroxicloroquina , Osteoporosis , Humanos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/diagnóstico , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Estudios Retrospectivos , Osteoporosis/epidemiología , Osteoporosis/inducido químicamente , Osteoporosis/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Antirreumáticos/efectos adversos , Taiwán/epidemiología , Factores de Riesgo , Adulto , Anciano , Medición de Riesgo , Densidad Ósea/efectos de los fármacos , Resultado del Tratamiento , Factores de Tiempo , Factores Protectores

Asunto(s)

Antirreumáticos , Hidroxicloroquina , Lupus Eritematoso Sistémico , Enfermedades de la Retina , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Humanos , Enfermedades de la Retina/inducido químicamente , Lupus Eritematoso Sistémico/tratamiento farmacológico , Antirreumáticos/efectos adversos

RESUMEN

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.

Asunto(s)

COVID-19 , Mortalidad Hospitalaria , Síndrome de QT Prolongado , Humanos , Masculino , Femenino , COVID-19/mortalidad , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/complicaciones , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/epidemiología , Síndrome de QT Prolongado/mortalidad , Síndrome de QT Prolongado/fisiopatología , Prevalencia , Factores de Riesgo , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Electrocardiografía , Hospitalización , Medición de Riesgo , Anciano de 80 o más Años , Frecuencia Cardíaca

RESUMEN

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.

Asunto(s)

Fóvea Central , Hidroxicloroquina , Lupus Eritematoso Sistémico , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Fóvea Central/patología , Femenino , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Tomografía de Coherencia Óptica , Adulto , Agudeza Visual

Asunto(s)

Cloroquina , Hidroxicloroquina , Enfermedades de la Retina , Tomografía de Coherencia Óptica , Humanos , Hidroxicloroquina/efectos adversos , Cloroquina/efectos adversos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Hungría , Antirreumáticos/efectos adversos , Electrorretinografía , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/diagnóstico , Degeneración Macular/inducido químicamente , Guías de Práctica Clínica como Asunto

RESUMEN

Background and Objectives: The coronavirus disease of 2019 (COVID-19) pandemic has posed a serious threat to humanity and is considered a global health emergency. Antimalarial drugs (ADs) have been used in the treatment of immuno-inflammatory arthritis (IIA) and coronavirus infection (COVID-19). The aim of this review is to analyze the current knowledge about the immunomodulatory and antiviral mechanisms of action, characteristics of use, and side effects of antimalarial drugs. Material and Methods: A literature search was carried out using PubMed, MEDLINE, SCOPUS, and Google Scholar databases. The inclusion criteria were the results of randomized and cohort studies, meta-analyses, systematic reviews, and original full-text manuscripts in the English language containing statistically confirmed conclusions. The exclusion criteria were summary reports, newspaper articles, and personal messages. Qualitative methods were used for theoretical knowledge on antimalarial drug usage in AIRDs and SARS-CoV-2 such as a summarization of the literature and a comparison of the treatment methods. Results: The ADs were considered a "candidate" for the therapy of a new coronavirus infection due to mechanisms of antiviral activity, such as interactions with endocytic pathways, the prevention of glycosylation of the ACE2 receptors, blocking sialic acid receptors, and reducing the manifestations of cytokine storms. The majority of clinical trials suggest no role of antimalarial drugs in COVID-19 treatment or prevention. These circumstances do not allow for their use in the treatment and prevention of COVID-19. Conclusions: The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for COVID-19. Furthermore, the need for high doses in the treatment of viral infections increases the likelihood of gastrointestinal side effects, the prolongation of QT, and retinopathy. Large randomized clinical trials (RCTs) have refuted the fact that there is a positive effect on the course and results of COVID-19.

Asunto(s)

Antimaláricos , Tratamiento Farmacológico de COVID-19 , Enfermedades Reumáticas , SARS-CoV-2 , Humanos , Antimaláricos/uso terapéutico , Antimaláricos/efectos adversos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/complicaciones , COVID-19 , Antivirales/uso terapéutico , Antivirales/efectos adversos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos

RESUMEN

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.

Asunto(s)

Aborto Habitual , Hidroxicloroquina , Sistema de Registros , Humanos , Femenino , Embarazo , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , Adulto , Aborto Habitual/epidemiología , Francia/epidemiología , Estudios Prospectivos , Resultado del Embarazo , Adulto Joven , Persona de Mediana Edad , Adolescente

RESUMEN

During the COVID-19 pandemic, several drugs were repositioned and combined to quickly find a way to mitigate the effects of the infection. However, the adverse effects of these combinations on the gastrointestinal tract are unknown. We aimed investigate whether Hydroxychloroquine (HD), Azithromycin (AZ), and Ivermectin (IV) used in combination for the treatment of COVID-19, can lead to the development of gastrointestinal disorders. This is a systematic review and network meta-analysis conducted using Stata and Revman software, respectively. The protocol was registered with PROSPERO (CRD42023372802). A search of clinical trials in Cochrane Library databases, Embase, Web of Science, Lilacs, PubMed, Scopus and Clinicaltrials.gov conducted on November 26, 2023. The eligibility of the studies was assessed based on PICO criteria, including trials that compared different treatments and control group. The analysis of the quality of the evidence was carried out according to the GRADE. Six trials involving 1,686 COVID-19 patients were included. No trials on the association of HD or AZ with IV met the inclusion criteria, only studies on the association between HD and AZ were included. Nausea, vomiting, diarrhea, abdominal pain and increased transaminases were related. The symptoms of vomiting and nausea were evaluated through a network meta-analysis, while the symptom of abdominal pain was evaluated through a meta-analysis. No significant associations with these symptoms were observed for HD, AZ, or their combination, compared to control. Low heterogeneity and absence of inconsistency in indirect and direct comparisons were noted. Limitations included small sample sizes, varied drug dosages, and potential publication bias during the pandemic peak. This review unveils that there are no associations between gastrointestinal adverse effects and the combined treatment of HD with AZ in the management of COVID-19, as compared to either the use of a control group or the administration of the drugs individually, on the other hand, highlighting the very low or low certainty of evidence for the evaluated outcomes. To accurately conclude the absence of side effects, further high-quality randomized studies are needed.

Asunto(s)

Azitromicina , Tratamiento Farmacológico de COVID-19 , Quimioterapia Combinada , Enfermedades Gastrointestinales , Hidroxicloroquina , Metaanálisis en Red , SARS-CoV-2 , Azitromicina/uso terapéutico , Azitromicina/efectos adversos , Humanos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/epidemiología , COVID-19 , Ivermectina/uso terapéutico , Ivermectina/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/efectos adversos , Antivirales/uso terapéutico , Antivirales/efectos adversos

RESUMEN

ABSTRACT: Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean corrected QT (QTc) interval and odds ratio of prolonged QTc interval in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc (10.29 ms,  P  = 0.458) among HCQ users compared to non-HCQ users in patients with RA. There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc compared to non-HCQ users (odds ratio 1.57, 95% CI, 1.19, 2.08). The results of this study suggest that clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring for patients on HCQ for the treatment of systemic autoimmune rheumatic diseases.

Asunto(s)

Antirreumáticos , Arritmias Cardíacas , Enfermedades Autoinmunes , Cloroquina , Muerte Súbita Cardíaca , Hidroxicloroquina , Enfermedades Reumáticas , Hidroxicloroquina/efectos adversos , Humanos , Antirreumáticos/efectos adversos , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/fisiopatología , Cloroquina/efectos adversos , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/mortalidad , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/epidemiología , Enfermedades Autoinmunes/inducido químicamente , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/mortalidad , Enfermedades Autoinmunes/tratamiento farmacológico , Medición de Riesgo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Factores de Riesgo , Cardiotoxicidad , Anciano , Frecuencia Cardíaca/efectos de los fármacos , Adulto Joven , Resultado del Tratamiento , Potenciales de Acción/efectos de los fármacos , Adolescente , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/mortalidad

RESUMEN

Background and Objective: Hydroxychloroquine sulfate (HCQ) is a lysosomotropic agent administered in systemic lupus erythematosus and rheumatoid arthritis that has fewer toxic effects than chloroquine. However, HCQ may still be responsible for retinal toxicity. In this study, we observed structural changes in the retinas of experimental rats after prolonged exposure to HCQ. Matherials and Methods: We investigated several aspects regarding retinal changes, at both the histopathological and ultrastructural levels. We used 96 male albino Wistar rats distributed into four equal groups (n = 24 per group): the first three groups were treated with different doses of HCQ (50, 100, and 200 mg/kg HCQ, injected intraperitoneally in a single dose daily), and the last group (the control group, n = 24) was treated with saline solution administered in the same way (0.4 mL of saline solution). The treated groups received HCQ daily for 4 months, and every month, six animals from each group were sacrificed to assess retinal changes. The eyes were examined via optical (OM) and electronic microscopy (EM). Statistical analysis was deployed, and results regarding retinal morpho-photometry were acquired. Results: We observed structural retinal changes in both high and low doses of HCQ; while high doses determined a significant thinning of the retina, lower doses caused retinal thickening. Morphological retinal changes upon exposure to HCQ are believed to be caused by accumulated HCQ in lysosomes found in retinal ganglion cells and in the inner nuclear and photoreceptor cell layers. Such changes were most evident in the group receiving HCQ intraperitoneally in doses of 100 mg/kg for a longer period (4 months). Conclusions: The present study highlights histopathological and ultrastructural retinal changes induced by chronic HCQ administration, which were strongly connected to the dosage and period of exposure.

Asunto(s)

Hidroxicloroquina , Ratas Wistar , Retina , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/farmacología , Hidroxicloroquina/efectos adversos , Animales , Ratas , Retina/efectos de los fármacos , Retina/ultraestructura , Retina/patología , Masculino , Antirreumáticos/uso terapéutico , Antirreumáticos/farmacología

RESUMEN

PURPOSE: To assess the quality of hydroxychloroquine (HCQ)-induced retinopathy screening at a Canadian tertiary center, we concentrate on risk factor documentation within the electronic health record, in accordance with the 2016 AAO guidelines. METHODS: We performed a retrospective quality assessment study based on chart review of patients who underwent screening for HCQ-induced retinopathy at the Centre Hospitalier de l'Université de Montréal (CHUM) from 2016 to 2019. We evaluated four key risk factors for HCQ-induced retinopathy: daily dose, duration of use, renal disease, and tamoxifen use, using a three-tier grading system (ideal, adequate, inadequate) for documentation assessment. Pareto and root cause analyses were conducted to identify potential improvement solutions. RESULTS: Documentation quality varied in our study: daily dosage was 33% ideal, 31% appropriate, and 36% inappropriate. Duration of use documentation was 75% ideal, 2% adequate, and 24% inadequate. Renal disease documentation was only 6% ideal, with 62% adequate and 32% of charts lacking any past medical history. Among women's charts, tamoxifen use wasn't documented at all, with 65% adequately documenting medication lists. Pareto analysis indicated that improving renal disease and tamoxifen documentation could reduce 64% of non-ideal records, and enhancing daily dose documentation could decrease this by up to 90%. CONCLUSION: Accurate documentation of key risk factors is critical for HCQ-induced retinopathy screening, impacting both exam initiation and frequency. Our study identifies potential improvements in the screening process at the hospital, referring physician, and ophthalmologist levels. Implementing integrated pathways could enhance patient experience and screening effectiveness.

Asunto(s)

Antirreumáticos , Hospitales de Enseñanza , Hidroxicloroquina , Enfermedades de la Retina , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/administración & dosificación , Estudios Retrospectivos , Femenino , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Masculino , Persona de Mediana Edad , Antirreumáticos/efectos adversos , Antirreumáticos/administración & dosificación , Canadá , Anciano , Factores de Riesgo , Tamizaje Masivo/métodos , Adulto

RESUMEN

Ocular damage in systemic lupus erythematosus (SLE) may cause insidious visual impairment, but its clinical features and the risk of hydroxychloroquine (HCQ)-related complications are still controversial. We performed a meta-analysis to evaluate ocular damage in SLE, the correlation between eye and systemic involvement, and the ocular side effects of treatment. The database PubMed, Embase, and Ovid were used for literature from reception to July, 2023, and the calculation was carried out with R. About 48,693 patients from 66 studies were included. The results indicated that ocular damage in SLE was insidious, appearing in 28 % of patients with no complaints. The most common symptoms and manifestations were dry eye (30 %) and keratoconjunctivitis sicca (26 %). Retinopathy was detected in 10 % of patients and was related to antiphospholipid antibodies (25 % versus 8 %). The proportion of retinopathy also significantly increased in patients with lupus nephropathy or neuropsychiatric systemic lupus erythematosus (risk ratio of 2.29 and 1.95, respectively). HCQ was used in 82 % of patients, of which 4 % suffered from ocular toxicity. HCQ-related retinopathy was dose-dependent. Dosage below 5 mg/kg/d was relatively effective and safe for long-term use, while routine examination was recommended.

Asunto(s)

Antirreumáticos , Hidroxicloroquina , Lupus Eritematoso Sistémico , Humanos , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Factores de Riesgo , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Oftalmopatías/inducido químicamente , Oftalmopatías/etiología

RESUMEN

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.

Asunto(s)

Tratamiento Farmacológico de COVID-19 , COVID-19 , Hidroxicloroquina , Salud Pública , SARS-CoV-2 , Humanos , Hidroxicloroquina/uso terapéutico , Hidroxicloroquina/efectos adversos , COVID-19/epidemiología , Pandemias , Salud Global , Comunicación , Medios de Comunicación Sociales