Long-term Use Of Hydroxychloroquine Research Articles

Cardiac manifestations in patients with systemic lupus erythematosus and rheumatoid arthritis: Relation to long-term use of hydroxychloroquine

Aim of the workto investigate and record cardiac side effects of long-term use of hydroxychloroquine (HCQ) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Patients and methodsThis study included 25 patients with RA and 25 with SLE. The study population was either in remission or demonstrated low disease activity, as assessed by the SLE disease activity index 2000 (SLEDAI-2 K) for SLE patients and the disease activity score 28 (DAS28) for RA patients. All patients had been receiving HCQ for at least two years. They did not exhibit any symptoms of coronavirus disease-2019 (COVID-19) and received COVID-19 vaccination. Cardiac adverse events were assessed through electrocardiogram (ECG) and echocardiography (ECHO) examinations. Results94 % (n = 47) were females and 6 % (n = 3) were males. The age of the subjects ranged from 20 to 60 years, with a mean age of 41.6 ± 11.2 years. Out of the 50 ECGs assessed, 84 % (n = 42) exhibited no abnormalities. Additionally, all ECGs showed QTc within the normal range. Only 2 RA patients had heart failure characterized by reduced ejection fraction (EF). There was no significant association between the cumulative dosage of HCQ administered in SLE patients and the ECG abnormalities (p = 0.76), QTc (p = 0.228) or EF (p = 0.96). Moreover, there was no significant association between the cumulative dosage of HCQ administered in RA patients and the ECG abnormalities (p = 0.479), QTc (p = 0.85) or EF (p = 0.69). ConclusionThis study affirms the cardiac tolerability of HCQ in the sustained therapeutic management of SLA and RA patients.

Hydroxychloroquine-induced Retinal Toxicity.

Long-term use of hydroxychloroquine can cause retinopathy, which may result in severe and progressive visual loss. In the past decade, hydroxychloroquine use has markedly increased and modern retinal imaging techniques have enabled the detection of early, pre-symptomatic disease. As a consequence, the prevalence of retinal toxicity in long-term hydroxychloroquine users is known to be higher than was previously estimated. The pathophysiology of the retinopathy is incompletely characterised, although significant advances have been made in understanding the disease from clinical imaging studies. Hydroxychloroquine retinopathy elicits sufficient public health concern to justify the implementation of retinopathy screening programs for patients at risk. Here, we describe the historical background of hydroxychloroquine retinopathy and summarize its current understanding. We review the utility and limitations of each of the mainstream diagnostic tests used to detect hydroxychloroquine retinopathy. The key considerations towards a consensus on the definition of hydroxychloroquine retinopathy are outlined in the context of what is known of the natural history of the disease. We compare the current screening recommendations for hydroxychloroquine retinopathy, identifying where additional evidence is required, and the management of proven cases of toxicity. Finally, we highlight the areas for further investigation, which may further reduce the risk of visual loss in hydroxychloroquine users.

An Electronic Dashboard to Improve Dosing of Hydroxychloroquine Within the Veterans Health Care System: Time Series Analysis.

Hydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided. We developed and piloted an electronic health record-based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ. Patients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021. At the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (-0.06; 95% CI -0.08 to -0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (-0.06; 95% CI -0.08 to -0.05). The use of an electronic health record-based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ.

Hydroxychloroquine on the Pulmonary Vascular Diseases in Interstitial Lung Disease: Immunologic Effects, and Virus Interplay.

To investigate the effects of hydroxychloroquine (HCQ) drug use on the risk of pulmonary vascular disease (PVD) in an interstitial lung disease cohort (ILD cohort, ILD+ virus infection), we retrospectively enrolled the ILD cohort with HCQ (HCQ users, N = 4703) and the ILD cohort without HCQ (non-HCQ users, N = 4703) by time-dependence after propensity score matching. Cox models were used to analyze the risk of PVD. We calculated the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for PVD after adjusting for sex, age, comorbidities, index date and immunosuppressants, such as steroids, etc. Compared with the HCQ nonusers, in HCQ users, the aHRs (95% CIs) for PVD were (2.24 (1.42, 3.54)), and the women’s aHRs for PVD were (2.54, (1.49, 4.35)). The aHRs based on the days of HCQ use for PVD of 28–30 days, 31–120 days, and >120 days were (1.27 (0.81, 1.99)), (3.00 (1.81, 4.87)) and (3.83 (2.46, 5.97)), respectively. The medium or long-term use of HCQ or young women receiving HCQ were associated with a higher aHR for PVD in the ILD cohort. These findings indicated interplay of the primary immunologic effect of ILD, comorbidities, women, age and virus in the HCQ users.

Development and Validation of the Quantification Method for Hydroxychloroquine in Volumetric Absorptive Microsampling (VAMS) Using High-Performance Liquid Chromatography-Photodiode Array.

Hydroxychloroquine is an antimalarial drug used for systemic lupus erythematosus, rheumatoid arthritis, and malaria treatment. However, hydroxychloroquine has several side effects such as ocular toxicity, neurotoxicity, gastrointestinal disorder, and also severe toxicity such as cardiotoxicity. Therefore, therapeutic drug monitoring of high dose or long-term use of hydroxychloroquine is needed. This study aims to obtain an optimum and validated analysis and preparation method for hydroxychloroquine in volumetric absorptive microsampling (VAMS) using the high-performance liquid chromatography–photodiode array detector based on the Food and Drug Administration guidelines (2018). Hydroxychloroquine quantification was performed using HPLC-PDA with Waters Sunfire™ C18 (5 µm; 250 × 4,6 mm) column. Mobile phase consists of acetonitrile-diethylamine 1% (65 : 35, v/v) (isocratic elution) and delivered at a flow rate of 0.8 mL/min throughout the 12 minutes run. Sample in VAMS is extracted by liquid-liquid extraction with ammonia 1% and n-hexane-ethyl acetate (50 : 50 v/v) as a extraction solvent. This method has successfully qualified the Food and Drug Administration (2018) parameters, with 2 ng/mL of LLOQ, range of calibration curve 2–6500 ng/mL, and coefficient of correlation 0.9993–0.9997.

Hydroxychloroquine dose tapering or discontinuation in cutaneous lupus erythematosus after remission: A retrospective multicenter cohort study of 56 patients

Hydroxychloroquine dose tapering or discontinuation in cutaneous lupus erythematosus after remission: A retrospective multicenter cohort study of 56 patients

Evaluation of hydroxychloroquine induced retinal toxicity in systemic lupus erythematosus patients

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder, which affects the major organs in the human body. Pathophysiology of SLE is unknown. It mainly affects the joints, and restricts their movement. Hydroxychloroquine (HCQ) an anti-malarial drug is used as the first line of drugs used to treat SLE. The major adverse effect of this drug is irreversible retinopathy. The aim of the study was to evaluate the incidence and prevalence of retinopathy in patients with long-term usage of hydroxychloroquine (for more than 1 year).Methods: In patients with SLE, we recorded a review on HCQ induced toxicity among those taking it for longer period (>1 year). All the patients were above 18 years of age. A total data of 210 patients suffering from SLE and taking HCQ for more than one year was collected. Patients were categorized according to gender and dose pattern. Out of 210 patients, 0 patients were found to be retinal toxic induced by HCQ.Results: Suitable statistical tools were used and data was analysed which showed the incidence and prevalence of HCQ induced toxicity. With the results of our study we can understand that incidence and prevalence rates were very low among the subjects.Conclusions: HCQ is said to reduce the risk of disease remission, improves survival, minimizes the risks of vital organ damage, reduces the frequency of flares and has a protective effect on cardiovascular health. HCQ medication is usually well tolerated. But irreversible retinopathy is the major effect on long term use of HCQ. The present study concludes that in the nominal daily dose of 200mg did not reveal any signs of retinal toxicity in 100% of the population tested within 5 years of HCQ treatment suggesting that the toxicity is rare and can be prevented by reducing the dose of the drug.

The impact of hydroxychloroquine and azithromycin on the corrected qt interval in patients with the novel Coronavirus disease 2019.

With the coronavirus disease 2019 (COVID-19) continuing to spread all over the world, although there is no specific treatment until now, hydroxychloroquine and azithromycin have been reported to be effective in recent studies. Although long-term use of hydroxychloroquine and azithromycin has been reported to cause QT prolongation and malign arrhythmia, there is not enough data about the effect of short-term use on arrhythmia. Therefore, this study aims to assess the effect of hydroxychloroquine alone and hydroxychloroquine + azithromycin on corrected QT (QTc). A baseline electrocardiogram and on-treatment baseline electrocardiogram were retrospectively collected in COVID-19 patients who received hydroxychloroquine and/or azithromycin. The QTc interval was calculated, and the baseline and peak QTc intervals were compared. In addition, the peak QTc intervals of monotherapy and combination therapy were compared. Of the 155 patients included, 102 (65.8%) patients were using hydroxychloroquine, and 53 (34.2%) patients were using hydroxychloroquine + azithromycin combination. The use of both hydroxychloroquine alone and hydroxychloroquine + azithromycin combined therapy significantly prolonged the QTc, and the QTc interval was significantly longer in patients receiving combination therapy. QTc prolongation caused early termination in both groups, 5 (4.9%) patients in the monotherapy group and 6 (11.3%) patients in the combination therapy group. In this study, patients who received hydroxychloroquine for the treatment of COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc.

Evaluation of corneal safety in systemic lupus erythematosus patients undergoing long-term hydroxychloroquine treatment

Purpose The aim of this study was to examine the effects of long-term use of hydroxychloroquine (HQ) on the pachymetric, aberrometric, and densitometric values of the cornea and corneal endothelium in lupus patients. Method Twenty-two eyes (study group) of 22 patients using HQ for treatment of lupus and 25 eyes (control group) of 25 healthy individuals were included in this prospective study. A specular microscopy was used to measure corneal endothelial cell density (ECD), percentage of hexagonal cells (HEX%), coefficient of variation of the cell size (CV). Then, a Pentacam® HR corneal tomography system was used to measure central corneal thickness (CCT), corneal aberrometry values in 6-mm pupil diameters and corneal densitometry values in 6-mm corneal zones (0–2 mm and 2–6 mm). Results While ECD was significantly lower in the study group than in the control group (p = 0.034), CCT was significantly higher in the study group (p = 0.032). The higher-order aberrations values and the anterior corneal densitometry values in the 0–2 mm and 2–6 mm corneal zones in the study group were found to be significantly higher than the control group (p = 0.021, p = 0.007 and p = 0.013). Conclusion Prolonged use of HQ may cause some changes in the cornea. In the follow-up of these cases, detailed examination of the cornea as well as the macula may be important for the protection of corneal health.

The effect of long-term hydroxychloroquine use on the corneal endothelium in patients with systemic lupus erythematosus.

To evaluate the effect of long-term effects of hydroxychloroquine (HCQ) use on the corneal endothelium in patients with systemic lupus erythematosus (SLE). The study included 30 eyes of 15 patients who used HCQ for at least five years and were followed up in the rheumatology clinic for SLE and 29 eyes of 15 patients newly diagnosed with SLE who had not taken any medication. All patients underwent complete ophthalmologic examinations, central corneal thickness measurements, endothelial cell counts and endothelial morphological examinations by specular microscopy. The mean age was 41.25 ± 6.89years in group 1 and 41.81 ± 5.78years in group 2 (p = 0.737). The mean corneal endothelial cell density was 2662 ± 184cells/mm2 in group 1 and 2649 ± 315cells/mm2 in group 2 (p = 0.843). The percentage of cell hexagonality was 46.6 ± 11.8% in group 1 and 48.7 ± 13.8% in group 2 (p = 0.625). A difference was noted in endothelial cell variation in both groups, at 36.7 ± 6.9% in group 1 and 39.9 ± 6.2% in group 2 (p = 0.057) but not statistically significant. No difference was observed between the two groups in terms of central corneal thickness. The duration of HCQ use was negatively correlated with hexagonality (r = -0.564, p = 0.001) CONCLUSION: Long-term use of HCQ in SLE patients had no negative effect on endothelial cell density and cell variation, but a negative correlation existed between the duration of HCQ usage and hexagonality.

O20 A case series of paediatric primary Sjögren’s syndrome: differential diagnoses and multidisciplinary management

O20 A case series of paediatric primary Sjögren’s syndrome: differential diagnoses and multidisciplinary management

Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study.

SummaryBackgroundHydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis.MethodsIn this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I2 value was less than 0·4.FindingsThe study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Self-controlled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12–2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22–3·95]), chest pain or angina (1·15 [1·05–1·26]), and heart failure (1·22 [1·02–1·45]).InterpretationHydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit–risk trade-off when counselling those on hydroxychloroquine treatment.FundingNational Institute for Health Research (NIHR) Oxford Biomedical Research Centre, NIHR Senior Research Fellowship programme, US National Institutes of Health, US Department of Veterans Affairs, Janssen Research and Development, IQVIA, Korea Health Industry Development Institute through the Ministry of Health and Welfare Republic of Korea, Versus Arthritis, UK Medical Research Council Doctoral Training Partnership, Foundation Alfonso Martin Escudero, Innovation Fund Denmark, Novo Nordisk Foundation, Singapore Ministry of Health's National Medical Research Council Open Fund Large Collaborative Grant, VINCI, Innovative Medicines Initiative 2 Joint Undertaking, EU's Horizon 2020 research and innovation programme, and European Federation of Pharmaceutical Industries and Associations.

Long-term hydroxychloroquine therapy improves the quality of sleep in patients with primary Sjögren's syndrome: a real-world study.

Patients with primary Sjögren's syndrome (pSS) often suffer from sleep disturbance. Studies suggest it may be related to symptoms, including xerostomia and dry eyes. Clinical studies have confirmed that hydroxychloroquine (HCQ) has a definite effect on pSS, but there is no clear report about its effect on sleep disorders in pSS patients. A total of 383 pSS patients were enrolled and followed up. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of the patients, and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) scale was used to evaluate the quality of life (QoL) of patients. The European League assessed the patient's condition against Rheumatism Sjögren's syndrome patients reported index (ESSPRI). According to PSQI, patients were divided into two groups: good sleep group (GSG) and poor sleep group (PSG). The risk factors of sleep disorder are analyzed by univariate and multivariate analysis. The patients were further divided into HCQ-administered group and non-administered group, and the differences of baseline characteristics and outcome in follow-up between the two groups were compared. There were 208 patients with PSG (54.3%) and 175 patients with GSG (45.7%). Further, there is no statistical difference between the two groups in baseline data. Also, there were 112 cases (53.8%) and 118 cases (67.4%) taking HCQ in the two groups, respectively, P=0.007. Univariate and multivariate analysis showed that long-term use of HCQ, menopause, and income were related to sleep quality. The patients were divided into the HCQ-administered group (n=230) and non-administered group (n=153) according to whether they took HCQ. One hundred eighteen patients (51.3%) in the HCQ-administered group had a good sleep, and 58 patients in the non- administered group had a good sleep (37.9%), P<0.05. At followup, the PSQI of the two groups were 7.3±2.1 vs. 8.1±2.4, respectively, P<0.05 and the ESSPRI were 4.9±1.1 vs. 5.4±1.3, P<0.05. The QoL of the two groups of patients was statistically different in all four dimensions, P<0.05. Long-term use of HCQ can reduce the risk of sleep disturbance in patients with primary Sjögren's syndrome.

SAT0169 HYDROXYCHLOROQUINE PRESCRIPTION PATTERNS IN EUROPE - THE EUROPEAN SURVEY FOR LUPUS PATIENTS (ESLP)

Background:Long-term use of hydroxychloroquine (HCQ) is very common in patients with lupus erythematosus. It has been associated with wide-ranging benefits and it is generally well tolerated1. However, long-term use (i.e. &gt; 5 years) and high-dose HCQ (i.e. &gt; 5 mg/kg/day) are both considered to be risk factors for developing HCQ retinopathy2.Advances in our understanding of HCQ retinopathy has led to changes in the recommendations for HCQ dosing and retinopathy screening1-3. The latest EULAR guidelines for the management of systemic lupus erythematosus (SLE)4recommend a maximum HCQ dose of 5 mg/kg/day and ophthalmological screening at baseline and annually after 5 years of HCQ treatment.Objectives:To assess whether recent EULAR guidelines regarding HCQ dosing and retinopathy screening are affecting prescription patterns and screening frequencies in Europe.Methods:Patients in Europe were given the opportunity to complete the online European Survey for Lupus Patients (ESLP) initiated by LUPUS EUROPE. The survey was promoted on social media from the 26thof June – 11thof July 2019. The survey consisted of 29 questions. Each participant was asked, among other things, to report their body weight (kg), daily HCQ dose and if they have received baseline screening and/or regular eye examinations.Results:The online survey was completed by 2938 lupus patients from 36 countries. The majority were female (86.5%) and diagnosed with SLE (85.7%). The daily HCQ dose (mg/kg) was available from 1678 patients (57.1%). The median ± IQR HCQ dose was 4.3 ± 2.5 mg/kg/day with a median treatment duration of 7 years (IQR: 3 – 14).The recommended daily HCQ dose of 5 mg/kg was exceeded by 618 patients (36.8%). Low HCQ dose (≤ 4 mg/kg) was reported by 769 patients (45.8%). In addition, 284 out of 1786 patients (15.9%) reported they skipped HCQ once a week or more often. Nevertheless, only 8.7% of patients reported that they were more likely to skip HCQ than other medication. Patients from Belgium, Israel, France and Portugal reported the highest HCQ dosages. In contrast, patients from Spain reported the lowest HCQ dosages (Figure 1).Figure 1.HCQ dose (mg/kg/day) reported by patients (• median HCQ dose). PRT: Portugal, POL: Poland, NLD: Netherlands, ITA: Italy, ISR: Israel, GRC: Greece, FRA: France, FIN: Finland, ESP: Spain, DEU: Germany, CHE: Switzerland, BEL: Belgium.Moreover, 935 out of 1137 patients diagnosed in the past 10 years (82.2%) reported that they have received an ophthalmological screening at baseline. Lastly, 1167 patients reported long-term use of HCQ (i.e. ≥ 5 years). Only about 64% of them (n=748) reported that they receive regular eye examinations (i.e. at least once every year).Conclusion:Studies have suggested that prescription patterns in the USA and UK were already affected by guidelines regarding HCQ dosing1. We show large inter- and intra-country variations of HCQ dosing in Europe. Additionally, most centers fail to follow recent recommendations4regarding annual screening of retinopathy in case of long-term HCQ use.More research is needed to assess the clinical efficacy of low-dose HCQ and to confirm whether proper screening modalities are being employed as recommended by recent guidelines2-4.

Initial data from the COVID-19 Global Rheumatology Alliance provider registries.

Milena Gianfrancesco and colleagues1Gianfrancesco MA Hyrich KL Gossec L et al.Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.Lancet Rheumatol. 2020; (published online April 16.)https://doi.org/10.1016/S2665-9913(20)30095-3Summary Full Text Full Text PDF Scopus (162) Google Scholar underlined the potential use of disease-modifying drugs, such as hydroxychloroquine, for coronavirus disease 2019 (COVID-19) treatment, but I was struck by the absence of information about long-term hydroxychloroquine treatment among the reported patients.1Gianfrancesco MA Hyrich KL Gossec L et al.Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.Lancet Rheumatol. 2020; (published online April 16.)https://doi.org/10.1016/S2665-9913(20)30095-3Summary Full Text Full Text PDF Scopus (162) Google Scholar Antimalarial drugs have raised hopes and fierce debate among scientific and public communities worldwide, rapidly creating a political dimension.2Flinders M Coronavirus and the politics of crisis fatigue. The Conversation.http://theconversation.com/coronavirus-and-the-politics-of-crisis-fatigue-134702Date: March 25, 2020Date accessed: April 20, 2020Google Scholar Use of such drugs is a concern for both clinicians and the general population on different levels. It is unknown whether patients with inflammatory rheumatic disease under treatment are more at risk for infection or serious disease due to severe acute respiratory syndrome coronavirus 2 than the general population. The aim of the COVID-19 Global Rheumatology Alliance provider registries is to determine such features. Beyond this primary objective, description and understanding of the determinants of COVID-19 in patients taking immunomodulatory or immunosuppressive drugs (such as hydroxychloroquine and IL-6 receptor antagonists) might help with understanding the disease pathophysiology to prevent the appearance or decrease the severity of COVID-19 pneumonia or neurological events. It is critical to indicate in further reports the occurrence of clinically significant disease in patients treated with hydroxychloroquine, as this drug could be useful in preventing severe disease or minimising the viral excretion period. On April 6, a letter in the Annals of the Rheumatic Diseases stated that “hydroxychloroquine use might be an explanation for no report on systemic lupus erythematosus patients with COVID-19”,3Joob B Wiwanitkit V SLE, hydroxychloroquine and no SLE patients with covid-19: a comment.Ann Rheum Dis. 2020; (published online April 15.)DOI:10.1136/annrheumdis-2020-217506Crossref PubMed Scopus (20) Google Scholar showing the confidence clinicians might place in incomplete data. I declare no competing interests. Initial data from the COVID-19 Global Rheumatology Alliance provider registries – Authors' replyWe agree that information regarding long-term use of hydroxychloroquine and coronavirus disease 2019 (COVID-19) outcomes is needed. When reporting a case to the COVID-19 Global Rheumatology Alliance registry, providers are asked to report on various medications taken before the patient had COVID-19. Although specific details on individual medications might not have been included in our Comment,1 we report the percentage of cases on a number of immunomodulatory and immunosuppressive drugs, including antimalarials, on a weekly basis to our website , Twitter account , and mailing list, so these data are widely accessible and regularly updated. Full-Text PDF Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registriesIndividuals with inflammatory rheumatic disease require special consideration with regard to coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many of these individuals are considered at-risk for serious infections due to their immunocompromised state resulting from their underlying immune conditions and use of targeted immune-modulating therapies such as biologics.1–4 However, some disease-modifying drugs commonly used to treat rheumatic diseases, such as hydroxychloroquine, are being investigated as potential therapies for COVID-19. Full-Text PDF

Initial data from the COVID-19 Global Rheumatology Alliance provider registries - Authors' reply.

We agree that information regarding long-term use of hydroxychloroquine and coronavirus disease 2019 (COVID-19) outcomes is needed. When reporting a case to the COVID-19 Global Rheumatology Alliance registry, providers are asked to report on various medications taken before the patient had COVID-19. Although specific details on individual medications might not have been included in our Comment,1 we report the percentage of cases on a number of immunomodulatory and immunosuppressive drugs, including antimalarials, on a weekly basis to our website, Twitter account, and mailing list, so these data are widely accessible and regularly updated.

Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.

Author(s): Gianfrancesco, Milena A; Hyrich, Kimme L; Gossec, Laure; Strangfeld, Anja; Carmona, Loreto; Mateus, Elsa F; Sufka, Paul; Grainger, Rebecca; Wallace, Zachary; Bhana, Suleman; Sirotich, Emily; Liew, Jean; Hausmann, Jonathan S; Costello, Wendy; Robinson, Philip; Machado, Pedro M; Yazdany, Jinoos; COVID-19 Global Rheumatology Alliance Steering Committee

Long-term use of hydroxychloroquine reduces antiphospholipid antibodies levels in patients with primary antiphospholipid syndrome.

Hydroxychloroquine (HCQ) was suggested to play a role in lowering antiphospholipid antibody titers and preventing thrombotic recurrences in patients with systemic lupus erythematosus, but few data are available in patients with primary antiphospholipid syndrome (PAPS). In this retrospective, propensity score-matched cohort study, we evaluated the impact of HCQ on aPL titers and the incidence of thrombotic events in 57 exposed patients compared to 57 not exposed patients. These were matched for sex/type of disease onset/follow-up duration, age at the beginning of the follow-up ±10years and initial date of the follow-up ±5years. At baseline, no significant differences in demographical, clinical and serological features were observed between the two groups except for positive anti-extractable nuclear antigen antibodies (21% in HCQ exposed vs 0% in HCQ not exposed, P=0.001). Both the levels of IgG anti-cardiolipin and IgG/IgM anti-β2-glycoprotein I (anti-β2GPI) were significantly reduced at end of follow-up compared to the baseline in HCQ-exposed patients, while there were no differences in the other group. Moreover, anti-β2GPI IgG titers were significantly decreased when the end of follow-up was compared between the two groups (P<0.002). Among patients with a history of thrombosis, the annual incidence of recurrence was 1.16% in HCQ exposed and 1.71% in not exposed patients, with a significant reduction in the incidence of arterial events (0 vs 1.14%). This study shows a strong reduction in aPL titers together with an apparent decrease in the incidence of arterial thrombosis recurrence in PAPS patients treated with HCQ.

Restrictive Cardiomyopathy Associated With Long-Term Use of Hydroxychloroquine for Systemic Lupus Erythematosus

Hydroxychloroquine (HQ) is commonly prescribed for autoimmune diseases such as systemic lupus erythematosus. We report a case of a 75-year-old female presenting with de novo decompensated heart failure and restrictive cardiomyopathy (left ventricular ejection fraction: 40%-45%) after treatment with HQ for more than 11 years. Hydroxychloroquine was discontinued, and follow-up echocardiogram 57 days after discontinuation showed normalization of her left ventricular ejection fraction. A score of 7 on the Naranjo Adverse Drug Reaction Probability Scale indicates that HQ is a probable cause of this patient’s cardiomyopathy. An adverse drug effect due to HQ should be considered in treated patients who present with restrictive cardiomyopathy. Discontinuation may allow for partial or complete reversal of the cardiomyopathy.

Analysis of Inner and Outer Retinal Thickness in Patients Using Hydroxychloroquine Prior to Development of Retinopathy.

Retinopathy is a known risk of long-term use of hydroxychloroquine sulfate. However, whether the inner as well as outer retina are involved before retinopathy develops and whether changes in the retina might signal impending toxic effects during screening remain unknown. To determine the degree of inner and outer retinal involvement in short- and long-term use of hydroxychloroquine before the development of retinopathy. This retrospective medical record review of spectral-domain optical coherence tomography (SD-OCT) findings was performed at an academic medical center. Thirty-two patients without retinopathy and with high-quality SD-OCT images were studied. Twenty-seven patients were age matched (49-65 years old) for comparison of retinal layers among patients who used the drug less than 5 years (n = 12) or longer than 15 years (n = 15) at the initial visit. Populations were also defined (without age limitation) for comparison of change during 25 to 52 months of follow-up among patients with initial use of less than 5 years (n = 7) or longer than 15 years (n = 8). Data were collected from 2010 to 2015. Measurements of inner and outer retinal thickness in SD-OCT images using commercial software and a Stanford pixel-by-pixel segmentation software that also provided topographic maps of thickness dimensions and change. Thirty-two patients (5 men and 27 women) were included in the analysis. Measurements of inner retinal thickness between short- and long-term hydroxychloroquine users (n = 27) in different retinal regions, and during a median 39 months of follow-up (n = 15), showed no statistically significant differences or change. Similarly, no significant differences or changes were identified in outer retinal thickness except for the final visit of 1 patient who developed focal parafoveal thinning, a toxic effect of hydroxychloroquine use. Cirrus ganglion cell analysis measurements were inaccurate in the presence of outer retinal damage. The inner retina appears not to be involved in hydroxychloroquine-induced retinopathy to any clinically relevant degree within the limitations of our sample size. No clinically apparent warning of outer retinal damage was seen in the SD-OCT images of long-term hydroxychloroquine users until the actual appearance of focal retinopathy. Early detection of hydroxychloroquine-induced retinopathy is known to prevent visual acuity loss and serious progression after the therapy is stopped, and these data suggest that screening should seek distinct new areas of retinopathy (shown by topographic thickness maps) rather than long-term progressive thinning.