Beneficial Effect Of Hydroxychloroquine Research Articles

Hydroxychloroquine increased cholesterol transfer to high-density lipoprotein in systemic lupus erythematosus: A possible mechanism for the reversal of atherosclerosis in the disease.

The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking. To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE. Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An in vitro transfer of four lipids (14C-Phospolipid, 3H-Cholesteryl ester, 3H-Triglyceride, and 14C-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants. Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference (p > .05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 ± 14.04 vs 49.79 ± 8.0mg/dL; p < .05) but lower than CONTROL (58.37 ± 14.04 vs 68.58 ± 9.99mg/dL; p < .05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 ± 16.43 vs 167.11 ± 30.18mg/dL; p < .05, 75.05 ± 22.52 vs 96.05 ± 25.63mg/dL; p < .05) and CONTROL (148.16 ± 16.43 vs 174.11 ± 23.70mg/dL; p < .05, 75.05 ± 22.52 vs 88.53 ± 20.24mg/dL; p < .05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups (p = .002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 ± 1.05% vs. 4.44 ± 1.05%; p < .05). The latter was significantly decreased compared to CONTROL (5.40 ± 1.05% vs. 5.99 ± 1.71%; p < .05).The percentages of transfer of triacylglycerol (4.93 ± 0.69% vs. 4.50 ± 0.69% vs. 5.14 ± 1.01%; p = .054), esterified cholesterol (5.24 ± 0.70% vs. 4.96 ± 0.89% vs. 5.69 ± 1.27%; p = .079), and phospholipid (15.67 ± 1.03% vs. 15.34 ± 1.44% vs. 16.47 ± 1.89%; p = .066) were similar among groups. The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE.

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering.

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

AB0341 SLE PREGNANCIES AT HIGH RISK FOR PRE-ECLAMPSIA BENEFIT MOST FROM COMBINATION OF LOW DOSE ASPIRIN AND HYDROXYCHLOROQUINE

Background:Women with SLE face a high risk of preeclampsia (PE). Low dose Aspirin (LDA) is known to protect against PE in non-autoimmune patients and is recommended for SLE patients1. Besides, a beneficial effect of hydroxychloroquine (HCQ) on the occurrence of PE has recently been discussed2.Objectives:To investigate the influence of LDA and HCQ on the occurrence of PE in SLE patients.Methods:Pregnancies of women with SLE from an outpatient pregnancy clinic were prospectively evaluated. Clinical characteristics, medication use and pregnancy outcomes were analysed. Association of LDA use (latest from gestational week 16 on) and HCQ use (from 1st trimester on) with PE were analysed using a multiple logistic regression model (adjustment for age, BMI, hypertension, disease activity in 1st trimester, lupus nephritis, nulliparity, history of PE and high-risk aPL profile3).Results:We enrolled 190 lupus pregnancies (148 women, 1995-2019). Additional risk factors for PE were present in 83.7%: 55.8% showed a high-risk profile (HRP) for PE according to ACOG4 (history of PE, hypertension, lupus nephritis or aPL), another 27.9% had at least one moderate risk factor (nulliparous, BMI&gt;30 or age&gt;35) (see table 1).Each 20.5% of pregnancies received HCQ only or LDA only, while 22.6% were prescribed both drugs. 36.3% took neither HCQ nor LDA. Women with HRP were more likely to take LDA alone or in combination with HCQ (28.3% and 35.8%, respectively).PE occurred in 13.2% of pregnancies (7.7% in HCQ only, 15.4% in LDA only, 14.0% in HCQ and LDA, 14.5% in no HCQ or LDA). Most pregnancies affected by PE carried a HRP (88.0%).Use of LDA was significantly associated with a lower risk for PE [aOR 0.21 (95%-CI 0.05-0.99), p&lt;0.05]. HCQ use also had a moderating effect on the incidence of PE, but this effect did not reach significance [aOR 0.47 (95%-CI 0.15-1.52), p=0.21]. If only pregnancies with HRP were considered, the effect size increased for HCQ (LDA [aOR 0.18 (95%-CI 0.04-0.96), p&lt;0.05], HCQ [aOR 0.28 (95%-CI 0.07-1.14), p=0.075]).Conclusion:In this prospective real-life cohort, timely LDA medication was associated with a lower risk of PE in SLE pregnancies. In a multiple regression model taking LDA and HCQ into account, the favourable effect on the occurrence of PE was partially explained by HCQ. In particular, SLE patients at high risk for PE seem to benefit from HCQ during pregnancy. Future research may reveal mechanisms by which HCQ might lower the incidence of PE.

Hydroxychloroquine and COVID-19: Lack of Efficacy and the Social Construction of Plausibility.

Severe acute respiratory syndrome coronavirus 2 SARS- Cov2 has taken the world by surprise. Among the first promising repurposing agents proposed for treatment and prophylaxis, 2 antimalarial agents came into limelight: chloroquine and its less toxic derivative, hydroxychloroquine (HCQ). Intense research and public debates have followed. As HCQ is still used and studied, future research may bring novel evidence, modifying the state-of-the-art. Despite the lack of a single randomized control trial (RCT) with positive results, there are currently (as for the search on 30th of August 2020) more than 250 RCT registered on ClinicalTrials.gov with HCQ in COVID patients, and more than 150 of them are "still recruiting" or "not yet recruiting" patients. Our study combines a therapeutic evaluation of RCT data with a sociological analysis of related controversies, examining scientific and public arena discourses. Although any hope of a positive effect was brought exclusively by some and not all of the observational studies, none of the 7 RCT published until now have found any benefit. From a sociological perspective, the HCQ controversy is a useful case study for understanding the construction of plausibility in a cultural context polarized into competing versions of reality, with different epistemologies and ideologies. The results of the first RCTs have been published, and they are disappointing; beneficial effects of HCQ could not be proven either for negative conversion on polymerase chain reactions of COVID patients or for postexposure prophylaxis. The question to be asked is: how many studies do we need until HCQ is abandoned? Argumentative time work, appealing to temporal properties of HCQ including its historical use, accumulation of evidence, alternative therapeutic scenarios, and sensationalist tempo for rhetorical purpose, plays a significant role in its continuing legitimation.

Covid-19: Hydroxychloroquine does not benefit hospitalised patients, UK trial finds.

Hydroxychloroquine does not reduce the risk of dying or improve other outcomes in hospitalised patients treated for covid-19, preliminary results from the UK RECOVERY trial have shown. Announcing the results, Martin Landray, the study’s deputy chief investigator, said, “We have concluded that there is no beneficial effect of hydroxychloroquine in patients hospitalised with covid-19. We have therefore decided to stop enrolling participants to the hydroxychloroquine arm with immediate effect.” The data show the death rate at 28 days in covid-19 patients taking hydroxychloroquine is 25.7% compared with 23.5% in patients provided with only usual hospital care (hazard ratio 1.11 (95% confidence interval 0.98-1.26); P=0.10). So far 1542 patients in the trial have been randomised to hydroxychloroquine and 3132 patients randomised to usual care alone. There was also no evidence that hydroxychloroquine impacted on length of …

Recovery of renal function in patients with lupus nephritis and reduced renal function: the beneficial effect of hydroxychloroquine.

Reduced renal function is associated with worse renal outcome in patients with lupus nephritis (LN). However, there is insufficient knowledge regarding renal function recovery in patients with LN with reduced baseline renal function. Therefore, the present study aimed to investigate renal function recovery and related factors in patients with reduced baseline renal function. The present retrospective longitudinal cohort study included patients with LN and reduced renal function. Reduced renal function was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. Recovery of renal function was determined by an eGFR of >60 mL/min/1.73 m2 at six months after baseline, and factors associated with it were evaluated using logistic regression analysis. We included 90 patients with LN, with a mean eGFR value of 37.2 ± 13.9 mL/min/1.73 m2. Forty-six (51.1%) patients recovered their renal function after six months. On multivariate analysis, hydroxychloroquine use (odds ratio (OR) = 3.891, 95% confidence interval (CI) 1.196-12.653, p = 0.024), prolonged LN (OR = 0.926, 95% CI 0.874-0.981, p = 0.009) and high-grade tubular atrophy (OR = 0.451, 95% CI 0.208-0.829, p = 0.013) were associated with renal function recovery. During follow up, 25 patients were on end-stage renal disease (ESRD). Kaplan-Meier analysis revealed that renal function recovery after six months and lower probability of ESRD are associated. In patients with LN and reduced renal function, renal function recovery at six months was associated with use of hydroxychloroquine and inversely related to longer duration of LN and higher grade of tubular atrophy.

SP0087 Systemic Lupus Erythematosus and the Antiphospholipid Syndrome

By definition, the antiphospholipid syndrome (APS) is present when a patient has persistently positive serological tests for antiphospholipid antibodies (aPL) and there is a history of at least one thrombotic...

Beneficial effect of hydroxychloroquine on cutaneous lupus erythematosus in a Japanese girl

Beneficial effect of hydroxychloroquine on cutaneous lupus erythematosus in a Japanese girl

Therapeutic potential of hydroxychloroquine on serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) in rheumatoid arthritis patients

ObjectiveTo assess the serum B-cell activating factor belonging to the tumor necrosis factor family (BAFF) level in rheumatoid arthritis (RA) patients in view of different treatment regimens received and evaluate its relation with disease activity. Patients and methodsNinety female RA patients were included. Sixty were on disease modifying anti-rheumatic drugs (DMARDs); 34 on hydroxychloroquine (HCQ) plus methotrexate (MTX), 26 on leflunomide (LFN) plus MTX and 30 newly diagnosed cases not yet on any treatment. Thirty age and gender matched healthy subjects served as controls. Full history taking, clinical examination and relevant laboratory investigations were performed. Disease activity score, in 28 joints (DAS-28), was calculated. ResultsSerum BAFF level was significantly higher in patients (1.82±0.91ng/ml) compared to control (0.71±0.33ng/ml; p<0.001). There was a significantly lower BAFF and disease activity in patients receiving DMARDs (1.55±0.73ng/ml and 3.08±0.73) compared to new cases (2.36±1.02ng/ml and 3.46±0.82) (p<0.001 and p=0.036, respectively). Those receiving HCQ+MTX had a lower BAFF level (1.29±0.51ng/ml) compared to those receiving LFN+MTX (1.94±0.85ng/ml; p=0.002). The BAFF level significantly correlated with the presence of anti-CCP antibodies, DAS28 and MTX dose in all RA patients (r=0.24, p=0.02; r=0.504, p<0.001; r=0.51, p<0.001, respectively). Only DAS28 and MTX dose would highly influence the BAFF level (p=0.015 and p=0.001, respectively). ConclusionElevated level of BAFF in RA has been confirmed with a notable relation to disease activity making it a promising marker. The beneficial effect of hydroxychloroquine in dampening BAFF level throws light on the importance of considering it in combination among the newly developed biologics that also target B-cells.

Have some beneficial effects of hydroxychloroquine been overestimated? Potential biases in observational studies of drug effects: Comment on the article by Pons‐Estel et al

Have some beneficial effects of hydroxychloroquine been overestimated? Potential biases in observational studies of drug effects: Comment on the article by Pons‐Estel et al

Disease-modifying antirheumatic drugs, including methotrexate, sulfasalazine, gold, antimalarials, and D-penicillamine.

Rheumatoid arthritis is a progressive inflammatory disease with evidence of early cartilage damage. Consequently, there is a trend toward earlier use of disease-modifying antirheumatic drugs. This review focuses on recent data on methotrexate, sulfasalazine, gold, hydroxychloroquine, D-penicillamine, and combination therapy. Methotrexate is focused on most, reflecting the increasing popularity of this agent; studies continue to show its good clinical efficacy. Combination therapy studies have been disappointing and are still marred by short duration and low power. Sulfasalazine has a fairly rapid onset of clinical effects and modulates immune function. Gold is still the subject of new studies, with evidence that clinical experience leads to improved patient efficacy. The beneficial effect of hydroxychloroquine in mild rheumatoid arthritis has been confirmed, and information on D-penicillamine suggests an effect on oxygen radical scavenging. Clinical studies are still required to ascertain the relative efficacy of these drugs, and potential long-term adverse effects remain a source of concern.