Hydroxychloroquine In Patients Research Articles

Skin and ophthalmic complications of chloroquine and hydroxychloroquine in patients with rheumatoid arthritis and systemic lupus erythematous

ABSTRACT Immunosuppressive agents are routinely used to control autoimmunity. However, some adverse events are correlated to their clinical applications. The aim of this study was to study the clinical findings and ocular and cutaneous side effects of chloroquine (CQ) and hydroxychloroquine (HCQ), as current immunomodulators, in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This descriptive study was performed on 360 individuals referred to the Rheumatology clinic during 2003–2020. Demographic characteristics and other information were collected from patients with RA and SLE. Skin and ocular complications were evaluated in patients who were on treatment with CQ and HCQ. Study populations consisted of 199 subjects with RA and 161 cases with SLE. The frequencies of skin and ocular complications in all patients treated with CQ and HCQ were 32 (17.65%) and 94 (51.9%), respectively. The prevalence of skin complications in patients with RA and SLE was 20 (10.05%) and 22 (13.66%), respectively. The frequencies of ocular complications in patients with RA and SLE were, respectively, 58 (29.4%) and 36 (22.5%). Multiple logistic regression analysis revealed that ophthalmic complications of CQ and HCQ in all patients were dependent on the effects of the duration of drug uses, disease duration, and cumulative doses (p < 0.05), unlike skin complications. Disease types had no effect on ocular complications. Based on these findings, treatment with CQ and HCQ participates in some skin and ocular complications in patients with RA and SLE which are largely associated with the duration of disease and treatment.

Efficacy and Safety of Hydroxychloroquine in Patients with IgA Nephropathy: A Meta-Analysis.

The purpose of this study was to determine efficacy and safety of hydroxychloroquine (HCQ) for patients with IgA nephropathy (IgAN). PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure and VIP database up to February 2023 were searched for associated studies comparing HCQ with any other nonHCQ for treating IgAN. The effects of proteinuria, a 50% decrease in proteinuria, estimated glomerular filtration rate (eGFR) and adverse events in patients with IgAN were examined in a meta-analysis. Data were extracted and pooled using RevMan 5.3. Three randomized controlled trials (RCTs), two retrospective and two prospective studies (675 patients) that matched our inclusion criteria were identified. Compared with a control group, HCQ significantly reduced proteinuria (mean difference (MD): -0.26, 95% confidence interval (CI): -0.44 to -0.08, p < 0.01). Patients receiving HCQ plus renin-angiotensin system inhibitors (RASSi) had a better efficacy in proteinuria alleviation and a 50% decrease in proteinuria compared with control groups (MD: -0.38, 95% CI: -0.50 to -0.25, p < 0.001 and relative risk (RR) = 3.31, 95% CI: 1.73 to 6.36, p < 0.001). No appreciable variations were observed in eGFR between HCQ groups and control groups in treating patients with IgAN (MD: -2.00, 95% CI: -4.36 to 0.36, p = 0.10). Moreover, no serious adverse events were observed during HCQ treatment. Our results indicate HCQ is an efficient, secure treatment for IgAN.

Hydroxychloroquine use is associated with reduced mortality risk in older adults with rheumatoid arthritis.

There is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE). In a retrospective cohort of Medicare beneficiaries aged ≥ 65years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users. The study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832-1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45-0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58-0.78). HCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points • Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. • We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use.

Safe Introduction of Hydroxychloroquine Focusing on Early Intolerance Due to Adverse Drug Reactions in Patients with Systemic Lupus Erythematosus.

Objective This study explored the predictors of hydroxychloroquine intolerance and propose appropriate methods to initiate hydroxychloroquine in patients with systemic lupus erythematosus. Methods This retrospective study registered consecutive patients who were diagnosed with systemic lupus erythematosus and started treatment with hydroxychloroquine between 2015 and 2021. Any adverse events that required dose reduction or cessation of hydroxychloroquine, indicating intolerance to the drug, were recorded for up to 26 weeks after initiation of hydroxychloroquine. Results A total of 130 patients were included. Hydroxychloroquine intolerance due to adverse drug reactions was observed in 28 patients (21.5%), including gastrointestinal symptoms in 15 (11.5%) and cutaneous reactions in 7 (5.4%). Furthermore, the intolerance was observed more frequently in the maintenance group (patients treated daily with <20 mg prednisolone) than in the induction group (7.1% vs. 25.5%, p=0.04), and none of the patients in the induction group developed cutaneous reactions. The initial dose of hydroxychloroquine per ideal body weight was associated with hydroxychloroquine intolerance in a dose-dependent manner. Multivariable analyses revealed that the hydroxychloroquine dose per ideal body weight and higher levels of C4 predicted hydroxychloroquine intolerance. In particular, C4 levels were positively correlated with cutaneous reactions, whereas the dose of prednisolone was negatively correlated with gastrointestinal reactions. Conclusion Low-dose hydroxychloroquine may be optimal for induction in patients with systemic lupus erythematosus who have high C4 levels or are taking low doses of steroids.

Chloroquine and Hydroxychloroquine in the Treatment of Dry Eye Disease.

The role of chloroquine (CQ) and hydroxychloroquine (HCQ) in the management of dry eye disease is still unclear. This systematic review and meta-analysis investigates the efficacy and feasibility of CQ and HCQ in patients with dry eye disease. In February 2023, PubMed, Embase, Google Scholar, and Web of Science were accessed. Data from 462 patients (mean age 54.4 ± 2.8 years) were collected. Compared to baseline, the tear breakup time (p < 0.0001) and Schirmer I test (p < 0.0001) were significantly increased, and the Ocular Surface Disease Index (OSDI, p < 0.0001) and corneal staining (p < 0.0001) were significantly decreased at the last follow-up in the CQ/HCQ group. At the last follow-up, the OSDI was significantly lower in the CQ/HCQ group compared to the control group (p < 0.0001). Corneal staining was significantly greater in the control group compared to the CQ/HCQ group (p < 0.0001). The Schirmer I test showed no significant difference between the groups (p = 0.2). Altogether, CQ and HCQ improved the symptoms and signs of dry eye disease.

A phase 2 basket trial of ulixertinib (BVD-523) in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies harboring MAPK pathway mutations (BVD-523-HCQ).

TPS4174 Background: RAS-induced signaling through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway plays an important role in the pathogenesis of many solid tumors. Ulixertinib (BVD-523) is a first-in-class and best-in-class small molecule inhibitor of ERK 1/2 that is currently being investigated in multiple cancer clinical trials, both as a single agent and as part of combination therapy. Preclinical studies have demonstrated that inhibition of the RAS/MAPK/ERK signaling cascade leads to upregulation of autophagy, a catabolic pathway that includes the lysosomal degradation of proteins to support cellular metabolism during times of cellular stress. Given cancer cells’ increased reliance on autophagy to enhance their survival in this context, this study seeks to evaluate the combination of ulixertinib with hydroxychloroquine, an antimalarial drug known to suppress autophagy, in patients with advanced gastrointestinal malignancies harboring mutations in genes involved in MAPK signaling. Methods: This is an open-label, multicenter, phase II basket study of ulixertinib in combination with hydroxychloroquine in patients with advanced GI malignancies harboring mutations in one of the following MAPK signaling-associated genes: KRAS, NRAS, HRAS, BRAF (non-V600), MEK1/2, or ERK1/2. The completed Phase 1 dose-escalation trial (NCT04145297) established the recommended Phase 2 dose which will be the doses used in this study; ulixertinib 450mg PO BID combined with hydroxychloroquine 600mg PO BID, both drugs administered daily in 28-day cycles, with tumor assessments after every 2 cycles. The trial has five baskets based on primary disease: cholangiocarcinoma, pancreatic adenocarcinoma, colorectal adenocarcinoma, esophageal adenocarcinoma, and gastric adenocarcinoma. A Simon two-stage design will be employed within each of the 5 disease-specific baskets noted above, with the first stage of enrollment consisting of n=13 patients/ basket. To be considered evaluable, a patient must complete at least one cycle of therapy and receive at least 75% of the prescribed dose during that first cycle. If ≥ 4 patients in a specific basket achieve a response (complete or partial), that basket will then open to Stage 2 with enrollment of an additional 30 patients. Primary study endpoints will include safety/toxicity as well as ORR by RECIST 1.1. The secondary endpoint for efficacy is progression-free survival. Exploratory endpoints include pharmacokinetics of both ulixertinib and hydroxychloroquine, as well as predictive biomarkers from blood and tumor tissue-based samples. At the time of abstract submission, 26 of the planned 65 patients in Stage 1 had been enrolled. Clinical trial information: NCT05221320 .

Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P=0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Clinical and immunological effects of hydroxychloroquine in patients with active rheumatoid arthritis despite antirheumatic treatment.

To investigate the efficacy and safety of hydroxychloroquine (HCQ) in patients with rheumatoid arthritis (RA). Patients with active RA, despite conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), were recruited. HCQ was administered for 24 weeks, in addition to prior treatment. The primary end-point was the proportion of patients achieving American College of Rheumatology (ACR) 20 at Week 24, compared to that of a propensity score-matched historical control group. Sixty patients were enrolled and administered HCQ. We also identified 276 patients as candidates for the historical control group. Propensity score matching yielded 46 patients in each group. The proportion of patients achieving ACR20 at Week 24 was significantly higher in the HCQ group than in the control group (54.4% vs. 28.3%, P = .007). The proportion of patients achieving ACR50 and ACR70 at Week 24 were also higher in the HCQ group than in the control group (ACR50, 30.4% vs. 4.3%, P = .006; ACR70, 17.4% vs. 0%, P = .005). Neither HCQ retinopathy nor any new safety signal was observed during the study. The addition of HCQ to csDMARDs was effective, with no new safety signal in patients with RA.

Phase 1/2 study of devimistat in combination with hydroxychloroquine (HCQ) in patients with relapsed or refractory (R/R) clear cell sarcoma (CCS).

TPS11595 Background: CCS of the soft tissues is a rare and aggressive subtype of sarcoma that often starts in the tendons of the arms or legs. It is molecularly characterized by t(12;22)(q13;q12) translocation, resulting in EWSR1-ATF1 or EWSR1-CREB1 gene fusion. Despite reports of occasional responses to systemic therapies, currently available therapies have shown limited efficacy in advanced CCS. Therefore, there is a significant unmet medical need for more active agents in CCS. Devimistat is a stable intermediate of a lipoate analog that inhibits pyruvate dehydrogenase and α-ketoglutarate dehydrogenase enzymes of the tricarboxylic acid (TCA) cycle preferentially within the mitochondria of cancer cells. Devimistat induces autophagy in cancer cells. In a metastatic mouse model of CCS, treatment with devimistat in combination with chloroquine significantly suppressed tumor growth (Egawa et al, 2018). Based on this data, we hypothesized that inhibition of autophagy with HCQ may sensitize cancer cells to devimistat with increased efficacy and acceptable toxicity. Given its expected synergy, we have initiated a single-arm phase I/II prospective, multicenter, open-label, non-randomized study to evaluate maximally tolerated dose (MTD), safety, and efficacy of devimistat in combination with HCQ in patients with R/R CCS. Methods: In the phase 1 portion of the study, patients with R/R CCS and other fusion-positive R/R sarcomas will be enrolled and a standard 3+3 design will be followed to evaluate toxicity, MTD, and recommended phase 2 dose. There will be two patient groups based on weight, and dose escalation will be conducted separately for each group. Starting dose of HCQ will be 5mg/kg PO BID for patients &lt; 45 kg and 200 mg PO BID for patients ≥45 kg on days 1 through 5 of every 28 days. The first dose of HCQ each day will be followed 2 hours later by 1,000 mg/m2 devimistat (for patients &lt; 45 kg) and 2,000 mg/m2 of devimistat (for patients ≥ 45 kg) administered over 2 hours. A maximum of 36 patients will be enrolled for the phase I portion, 18 for each patient group. In the phase 2 portion of the study, only relapsed or refractory CCS patients will be enrolled, and the response rate will be determined using RECIST 1.1. In phase 2, pharmacokinetics, duration of response, clinical benefit rate, progression-free survival, overall survival, safety, and patient-reported outcomes will also be assessed. This portion of the study will utilize Simon’s admissible two-stage design with 29 patients. This study started enrolling participants in November 2021 and has dosed six patients to date. The first two dose-escalation cohorts for patients ≥45 kg have been completed without DLT and the third dose level will be opening shortly. Clinical trial information: NCT04593758.

Safety of Short-Term Treatments with Oral Chloroquine and Hydroxychloroquine in Patients with and without COVID-19: A Systematic Review.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have recently become the focus of global attention as possible treatments for Coronavirus Disease 2019 (COVID-19). The current systematic review aims to assess their safety in short treatments (≤14 days), whether used alone or in combination with other drugs. Following the PRISMA and SWiM recommendations, a search was conducted using four health databases for all relevant English-, Chinese-, and Spanish-language studies from inception through 30 July 2021. Patients treated for any condition and with any comparator were included. The outcomes of interest were early drug adverse effects and their frequency. A total of 254 articles met the inclusion criteria, including case and case-control reports as well as cross-sectional, cohort, and randomised studies. The results were summarised either qualitatively in table or narrative form or, when possible (99 studies), quantitatively in terms of adverse event frequencies. Quality evaluation was conducted using the CARE, STROBE, and JADAD tools. This systematic review showed that safety depended on drug indication. In COVID-19 patients, cardiac adverse effects, such as corrected QT interval prolongation, were relatively frequent (0–27.3% and up to 33% if combined with azithromycin), though the risk of torsade de pointes was low. Compared to non-COVID-19 patients, COVID-19 patients experienced a higher frequency of cardiac adverse effects regardless of the regimen used. Dermatological adverse effects affected 0–10% of patients with autoimmune diseases and COVID-19. A broad spectrum of neuropsychiatric adverse effects affected patients treated with CQ for malaria with variable frequencies and some cases were reported in COVID-19 patients. Gastrointestinal adverse effects occurred regardless of drug indication affecting 0–50% of patients. In conclusion, CQ and HCQ are two safe drugs widely used in the treatment of malaria and autoimmune diseases. However, recent findings on their cardiac and neuropsychiatric adverse effects should be considered if these drugs were to be proposed as antivirals again.

Relationship between index of cardio-electrophysiological balance and hydroxychloroquine in patients with COVID-19

Hydroxychloroquine (HCQ) treatment is frequently prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitorization is recommended because HCQ causes QT interval prolongation. The index of cardioelectrophysiological balance (iCEB), calculated as the ratio of QT interval / QRS duration. In recent years, iCEB has been described as an important marker for dysrhthmias. Decreased or increased iCEB is related with lethal ventricular arrhythmias. In our research, we purposed to investigate the relationship between iCEB and HCQ in patients with COVID-19. 200 patients (males, 84; females, 116; 60.4 ± 13.8 years) with PCR positive and chest tomography findings compatible with COVID-19 pneumonia were registered in the research. Demographic, clinical, and laboratory data for all patients were collected. ECG was recorded from all patients on admission to COVID-19 clinic, in oral treatment with HCQ (200 mg, twice daily) for at least 5 days. iCEB (QT/QRS) was calculated from the 12-lead electrocardiogram.The mean age of the patients was 60.4 ± 13.8 years. Compared to admission ECG, ECG on day 5 showed significant increases in heart rate, QT interval, corrected QT (QTc) interval, and iCEB. Our results suggested that iCEB is related with HCQ treatment in patients with COVID-19. Previous studies stated that high iCEB is related with torsade de Pointes (TdP), ventricular tachycardia.

Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial.

During the first year of the COVID-19 pandemic, unauthorized drugs were widely used. Ivermectin and hydroxychloroquine are drugs that inhibit viral replication in vitro and that have been used in several medical centers. This clinical trial analyzes their efficacy in hospitalized patients with moderate COVID-19. Methods: This a controlled, clinical, randomized, double-blind trial that included hospitalized patients with COVID-19-induced pneumonia, without severe respiratory failure. Patients were randomized to one of three groups: Group 1—hydroxychloroquine, 400 mg every 12 h on the first day and, subsequently, 200 mg every 12 h for 4 days; Group 2—ivermectin, 12 mg or 18 mg, according to patient weight; and Group 3—placebo. At inclusion, blood samples for arterial blood gases and biochemical markers were obtained. The primary outcome was established as the length of stay due to patient improvement and the rate of respiratory deterioration or death. Results: During the month of August 2020, the admission of patients requiring hospitalization mostly encompassed cases with severe respiratory failure, so we ended the recruitment process and analyzed the data that was available at the time. One hundred and six (106) patients with an average age of 53 yrs (±16.9) were included, with a greater proportion of males (n = 66, 62.2%). Seventy-two percent (72%) (n = 76) had an associated comorbidity. Ninety percent (90%) of patients were discharged due to improvement (n = 96). The average duration of hospitalization was 6 days (IQR, 3–10). No difference in hospitalization duration was found between the treatment groups (Group1: 7 vs. Group 2: 6 vs. Group 3: 5, p = 0.43) nor in respiratory deterioration or death (Group 1: 18% vs. Group 2: 22.2% vs. Group 3: 24.3%, p = 0.83). Conclusions: In non-critical hospitalized patients with COVID-19 pneumonia, neither ivermectin nor hydroxychloroquine decreases the number of in-hospital days, respiratory deterioration, or deaths.

Phase I study of hydroxychloroquine plus binimetinib in patients with metastatic pancreatic cancer (the HOPE trial).

TPS634 Background: Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a dearth of effective therapeutic options. Over 90% of PDAC harbor activating mutations in the KRAS oncoprotein, which in turn leads to activation of downstream effector proteins in the the RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signaling cascade serving to promote tumor cell survival, growth and metastasis. Unfortunately, single agent treatment with MAPK-inhibitors have had limited therapeutic efficacy in patients with PDAC owing to development of various tumor-cell intrinsic resistance mechanisms, including upregulation of autophagy. Hydroxychloroquine is an antimalarial drug that functions to inhibit autophagy by inhibiting acidification of lysosomes. Previously published preclinical data suggest combination therapy with binimetinib, a MEK 1/2 inhibitor, and hydroxychloroquine leads to enhanced killing of PDAC cells in vitro and in vivo. Methods: This is a single arm, single center phase I trial of binimetinib plus hydroxychloroquine in patients with metastatic pancreatic cancer harboring a KRAS mutation. All patients will receive binimetinib at a fixed dose of 45mg PO twice daily (14-day cycles) while hydroxychloroquine will be dosed at 400mg PO twice daily (14-day cycles) and dose escalated using a Bayesian optimal interval design with a target toxicity rate of 0.3. Key eligibility criteria include histologically confirmed metastatic pancreatic adenocarcinoma, prior treatment with at least one line of systemic therapy and a documented KRAS mutation. An estimated 24 patients will be enrolled in the first phase of this study and up to 15 patients in the dose expansion cohort. The primary endpoint of this study is to determine the maximum tolerated dose (MTD) of hydroxychloroquine when combined with a fixed dose of binimetinib. Key secondary endpoints include safety and toxicity profile, response rate, progression free survival (PFS) and overall survival (OS). This study is ongoing and has enrolled 10 patients at the time of submission. Clinical trial information: NCT04132505.

Changes in QTc interval after hydroxychloroquine therapy in patients with COVID-19 infection: a large, retrospective, multicentre cohort study

ObjectiveTo evaluate the extent of hydroxychloroquine-induced corrected QT (QTc) prolongation and its relation to COVID-19 infection severity and incidence of polymorphic ventricular arrhythmias and sudden arrhythmic deaths.DesignA large-scale cohort study...

Оценка эффективности мефлохина в отношении инфекции, вызванной SARS-CoV-2 в клинических и экспериментальных условиях

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 ± 0.18 lg PFU/g, which was lower (p &lt; 0.05) than in the control group (3.5 ± 0.21 lg PFU/g) and ribavirin group (5.2 ± 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (р &lt; 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (р &lt; 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (р &gt; 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.

Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study.

BackgroundCoronavirus disease (COVID-19) is an infectious disease due to SARS-COV-2. Patients with risk factors are vulnerable to severe morbidity and mortality. Favipiravir (FPV) and hydroxychloroquine (HCQ) are considered possible COVID-19 treatments.ObjectiveTo investigate the effectiveness and safety of FPV compared to HCQ in patients with COVID-19 as the standard of care approved by the national protocol there.MethodsThis is a retrospective cohort study on patients with COVID-19 who were administered either FPV or HCQ at King Faisal Medical Complex, Taif, Saudi Arabia, from June 2020 to August 2020.ResultsIn total, 508 patients were included in the analysis. Patients were categorized into three groups by medication. Patients enrolled in this study were 244 (55.8%) on FPV, 193 (44.2%) on HCQ and 71 (13.81%) on neither medication. Patients who received FPV had higher age and greater comorbidity. Most of the patients were discharged on day 14 (n = 303, 59.6%), 26 (36.6%) in neither med, 154 (63.1%) in FPV and 123 (63.7%) in HCQ groups with significant difference between groups (P < 0.0001). Mortality rate was 8.2% (n = 20) in FPV and 7.3% (n = 14) in HCQ groups with significant difference between groups (P = 0.048). Regarding drug safety, 19.7% of patients treated with FPV vs 7.8% HCQ have adverse effects with significant difference between groups (P < 0.0001). Most of the side effects were increase ALT and AST. Meanwhile, prolonged Q-T interval was reported only in the HCQ group (2.6%). From Cox regression modeling, only mechanical ventilation due to Covid 19 was predictive for mortality (HR: 16.598, 95% CI: 7.095–38.828, P < 0.0001). Meanwhile, there was no significant difference in the prediction of discharge of FPV (vs HCQ) (HR: 0.933, 95% CI: 0.729–1.195, P = 0.5843), predictors of mortality were HCQ (vs FPV) (HR: 2.3, 95% CI: 0.994–5.487, P = 0.0518). Kaplan–Meier survival curves showed improved survival time and discharged time among patients in the HCQ versus FPV group with an insignificant difference between them (P = 0.85, P = 0.06, respectively).ConclusionThe present study concluded that FPV and HCQ showed comparable efficacy in decrease mortality and oxygen requirements. FPV likely has a more favorable safety profile regarding cardiac toxicity. A randomized clinical trial with large patient numbers is recommended to confirm the effectiveness of these drugs in COVID-19 patients.

Effect of azithromycin and hydroxychloroquine in patients hospitalized with COVID-19: Network meta-analysis of randomized controlled trials.

Chloroquine or its derivative hydroxychloroquine (HCQ) combined with or without azithromycin (AZ) have been widely investigated in observational studies as a treatment option for coronavirus 2019 (COVID‐19) infection. The network meta‐analysis aims to summarize evidence from randomized controlled trials (RCTs) to determine if AZ or HCQ is associated with improved clinical outcomes. PubMed and Embase were searched from inception to March 7, 2021. We included published RCTs that investigated the efficacy of AZ, HCQ, or its combination among hospitalized patients with COVID‐19 infection. The outcomes of interest were all‐cause mortality and the use of mechanical ventilation. The pooled odds ratio was calculated using a random‐effect model. A total of 10 RCTs were analyzed. Participant's mean age ranged from 40.4 to 66.5 years. There was no significant effect on mortality associated with AZ plus HCQ (odds ratio [OR] = 0.562 [95% confidence interval {CI}: 0.168–1.887]), AZ alone (OR = 0.965 [95% CI: 0.865–1.077]), or HCQ alone (OR = 1.122 [95% CI: 0.995–1.266]; p = 0.06). Similarly, based on pooled effect sizes derived from direct and indirect evidence, none of the treatments had a significant benefit in decreasing the use of mechanical ventilation. No heterogeneity was identified (Cochran's Q = 1.68; p = 0.95; τ 2 = 0; I 2 = 0% [95% CI: 0%–0%]). Evidence from RCTs suggests that AZ with or without HCQ was not associated with a significant effect on the mortality or mechanical ventilation rates in hospitalized patients with COVID‐19. More research is needed to explore therapeutics agents that can effectively reduce the mortality or severity of COVID‐19.

Cardiovascular Safety of Hydroxychloroquine in US Veterans With Rheumatoid Arthritis.

Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.

Hydroxychloroquine serum concentration in coronavirus disease 2019 (COVID-19) patients: a retrospective study

Algeria has adopted a therapeutic protocol using hydroxychloroquine (HCQ) as a first-line treatment for patients with coronavirus disease 2019 (COVID-19). The administration of HCQ must be accompanied by appropriate cardiac and therapeutic pharmacological monitoring to avoid side effects and toxicity. This work is a retrospective descriptive study aiming to estimate the HCQ levels of COVID-19 patients. HCQ concentrations in blood samples from COVID-19 patients were determined using high performance liquid chromatography with diode array detector (HPLC-DAD) after liquid-liquid extraction of plasma. The coefficient of determination (r 2) of this method was 0.9999. The limits of quantification and detection were 0.05 mg/L and 0.02 mg/L, respectively, with coefficients of variance less than 6%. Patient monitoring was performed following recommendations for the therapeutic pharmacological monitoring of HCQ in patients treated for SARS-CoV-2 (COVID-19) infection validated by the coordinated action (AC43) of the National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Therapeutic Pharmacological Monitoring and Personalization of Treatments (STP-PT) group. A total of 267 blood samples from 240 patients were analyzed, 49% for males and 51% for females. More than a third of the patients were 60–80 years old. The majority (68%) of the HCQ concentrations were between 0.1 and 1 mg/L. Additionally, more than 20% were between 0.05 and 0.1 mg/L, while only 7.5% were less than 0.05mg/L and 1.5% were greater than 1 mg/L. In summary, patients with COVID-19 showed a good tolerance to HCQ in the majority of cases. Key Points HCQ was proposed to be a promised treatement for COVID-19. A reverse phase HPLC-DAD method was validated for HCQ concentration determination in plasma. Patients hospitalized for COVID-19 were monitored according to the guideline established by the French National Team AC43 of the ANRS and the STP-PT group. Patients showed a very good tolerance to HCQ with no observed cases of toxicity.

Open-label randomized control trial of hydroxychloroquine in patients with moderate to severe coronavirus disease 2019 infection

BackgroundAt onset of coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) was repurposed for treatment of patients based on reports that it had in vitro activity. The aim of this study was to find out if HCQ reduces number of days of hospitalization when given to patients with moderate to severe COVID-19 infections who require hospitalized care. MethodsThis was an open-label randomized control trial of HCQ administered 400 mg twice on day 1, then 400 mg once daily from day 2 to day 5 in patients with moderate to severe COVID-19 infection. Assessment was not blinded. Standard of care was given to both arms.Primary outcome was number of days of hospitalization till discharge or death. ResultOne hundred ten patients (55 in each arm) were included. Mean age was 58 years. Baseline characteristics were well matched. There was no difference in the primary outcome (13.67 vs 13.89; p = 0.98). Number of deaths were more in HCQ arm (RR: 1.81; 95% CI: 1.13–2.93; p = 0.03). There was no difference in number of days on oxygen or normalization of oxygen saturation, number who needed ventilator, days to ventilator requirement and days on ventilator. Twenty-nine patients in control arm received remdesivir. When adjusted analysis was done after removal of these patients, there was no difference in primary or secondary outcomes. Number of deaths in adjusted analysis were not significant (RR: 1.28; 95% CI: 0.87–1.88; p = 0.37). ConclusionHCQ does not change the number of days of hospitalization when compared with control.