Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform

Rentsch, Christopher T; DeVito, Nicholas J; MacKenna, Brian; Morton, Caroline E; Bhaskaran, Krishnan; Brown, Jeremy; Schultze, Anna; Hulme, William; Croker, Richard; Walker, Alex J; Williamson, Elizabeth; Bates, Chris; Bacon, Seb; Mehrkar, Amir; Curtis, Helen J; Evans, David; Wing, Kevin; Inglesby, Peter; Mathur, Rohini; Drysdale, Henry; Wong, Angel; McDonald, Helen I; Cockburn, Jonathan; Forbes, Harriet; Parry, John; Hester, Frank; Harper, Sam; Smeeth, Liam; Douglas, Ian; Dixon, William G; Evans, Stephen; Tomlinson, Laurie

doi:10.1016/s2665-9913(20)30378-7

Cited by 60 publications

(53 citation statements)

References 26 publications

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“…Hydroxychloroquine did not prevent illness compatible with COVID-19 when used as postexposure prophylaxis within 4 days after exposure [82]. As a further proof of the lack of efficacy of prophylactic use of hydroxychloroquine, a very recent observational population-based cohort study showed no evidence of a difference in COVID-19 mortality among people who received this drug for treatment of rheumatological disease before the COVID-19 outbreak in United Kingdom [83]. The RECOVERY trial found that, among 4716 patients hospitalised with COVID-19, hydroxychloroquine did not reduce 28-day mortality when compared to usual standard of care.…”

Section: Chloroquine and Hydroxychloroquinementioning

confidence: 97%

A recurrent question from a primary care physician: How should I treat my COVID-19 patients at home? An update

Suter¹,

Perico²,

Cortinovis³

et al. 2020

Clin Med Invest

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1099 patients with laboratory-confirmed COVID-19 [5], at the time of admission to hospital, the most common symptoms were cough (67.8%), fever (43%), and fatigue (38.1%), and less frequently myalgia/ arthralgia (14.9%), a sore throat (13.9%) and headache (13.6), while nausea or vomiting (5.0%) and diarrhoea (3.8%) were uncommon. Similar clinical characteristics are also encountered in European and US COVID-19 patients in the early phase of the infection. Given the rising global death toll associated with the pandemic, in the past few months we have witnessed a race to find drugs/biologic treatments to save the lives of hospitalised, severely ill patients, as well as to develop vaccines [6,7]. To this end, randomised clinical trials are underway, including the SOLIDARITY trial launched on 20 th March by WHO which is characterised by its simplicity, to test experimental drug candidates or repurposed medicines. Therapeutic approaches to the early, mild phase of COVID-19 are also being debated, and here, too, there is an emphasis on the need for randomised clinical trials. However, there are times, like the present, when the focus is mainly on containing the epidemic and providing relief to hospitals dealing with unprecedented demands being made on their workforce in caring for COVID-19 patients. At this time, it is crucial to provide recommendations to primary care physicians, especially those practicing in resource-poor settings, on treating patients in the early phase of COVID-19 with initial mild symptoms at home. These measures may apply to conditions beyond the in-depth pathophysiology of the illness. This is an update of our recommendations that focuses on a combination of two drug classes that target the most common symptoms and prophylactic therapy and oxygen therapy, when needed [8]. These are based on the pharmacological rationale and the available clinical evidence of efficacy in COVID-19 patients, including results of published randomized clinical trials, for each of our recommended class of drugs. Recommended treatments should start immediately when COVID-19 early symptoms appear without waiting results of a nasopharyngeal swab, if any. Anti-inflammatory drugs Myalgias, arthralgias and fever are common symptoms of a mild COVID-19 infection that highlight an inflammatory process. Thus, the rationale for the use of anti-inflammatory agents is to limit host inflammatory responses to the viral infection. Suter F (2020) A recurrent question from a primary care physician: How should I treat my COVID-19 patients at home? An update Volume 5: 2-9

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Section: Chloroquine and Hydroxychloroquinementioning

confidence: 97%

A recurrent question from a primary care physician: How should I treat my COVID-19 patients at home? An update

Suter¹,

Perico²,

Cortinovis³

et al. 2020

Clin Med Invest

View full text Add to dashboard Cite

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“…There are also conflicting results on whether patients taking hydroxychloroquine for the treatment of their rheumatic diseases are more likely to be infected with SARS-CoV-2. 80 , 81 A population-based cohort study including 30 569 patients with rheumatoid arthritis or systemic lupus erythematosus identified from a UK national primary care database (OpenSAFELY) 82 showed no difference in COVID-19-related mortality amongst hydroxychloroquine users versus non-users (HR 1·03, 95% CI 0·80 to 1·33). 82 Overall, the data do not support use of hydroxychloroquine in the context of COVID-19.…”

Section: Antirheumatic Drugs For the Management Of Covid-19mentioning

confidence: 99%

The role of antirheumatics in patients with COVID-19

Nissen

Sciascia

Andrade

et al. 2021

The Lancet Rheumatology

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The COVID-19 pandemic has resulted in more than 2 million deaths globally. Two interconnected stages of disease are generally recognised; an initial viral stage and a subsequent immune response phase with the clinical characteristics of hyperinflammation associated with acute respiratory distress syndrome. Therefore, many immune modulators and immunosuppressive drugs, which are widely used in rheumatological practice, have been proposed as treatments for patients with moderate or severe COVID-19. In this Review, we provide an overview of what is currently known about the efficacy and safety of antirheumatic therapies for the treatment of patients with COVID-19. Dexamethasone has been shown to reduce COVID-19 related mortality, interleukin-6 inhibitors to reduce risk of cardiovascular or respiratory organ support, and baricitinib to reduce time to recovery in hospitalised patients requiring oxygen support. Further studies are needed to identify whether there is any role for glucocorticoids in patients with less severe COVID-19. Although evidence on the use of other antirheumatic drugs has suggested some benefits, results from adequately powered clinical trials are urgently needed. The heterogeneity in dosing and the absence of uniform inclusion criteria and defined stage of disease studied in many clinical trials have affected the conclusions and comparability of trial results. However, after the success of dexamethasone in proving the anti-inflammatory hypothesis, the next 12 months will undoubtedly bring further clarity about the clinical utility and optimal dose and timing of other anti-rheumatic drugs in the management of COVID-19.

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“…In contrast to these larger ‘positive’ reports, and other smaller reports of benefit, there have been several other observational studies which have not shown benefit in patients receiving hydroxychloroquine for rheumatological conditions, including another database analysis of 159 patients taking hydroxychloroquine compared with historical controls [ 58 ]. A publication reporting a large retrospective observational study using the OpenSAFELY platform, which comprises 40% of health records in the UK, and 30,569 patients with rheumatological conditions who had received ≥2 prescriptions of hydroxychloroquine in the previous 6 months found no difference in the COVID-19 mortality of hydroxychloroquine users [ 59 ]. These studies suffer variably from uncertain drug exposure, confounding by indication and underlying disease severity, as patients with milder rheumatological illness are normally started on drugs such as hydroxychloroquine and graduate to other medications with more severe illness.…”

Section: Antiviral Activitymentioning

confidence: 99%

Does hydroxychloroquine still have any role in the COVID-19 pandemic?

Schilling

White

2021

Expert Opinion on Pharmacotherapy

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Introduction:The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic. Areas covered: Here, the authors discuss the history of hydroxychloroquine and chloroquine, the in vitro data which led to their widespread repurposing and adoption in COVID-19 and their complex pharmacokinetics. The evidence for the use of these drugs is assessed through in vivo animal experiments and the wealth of conflicting data and interpretations published during COVID-19, including the more informative results from randomized controlled trials (RCTs). The safety aspects of these drugs, in particular cardiotoxicity, are then reviewed. Expert opinion: The evidence from clinical trials in COVID-19 supports the well-established safety record of the 4-aminoquinolines at currently recommended dosage. In hospitalized patients with severe COVID-19 RCTs show clearly that the 4-aminoquinolines are not beneficial. The only treatments with proven benefit at this stage of infection are immunomodulators (dexamethasone, IL-6 receptor antagonists). No antiviral drugs have proven life-saving in late-stage COVID-19.

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Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform

Cited by 60 publications

References 26 publications

A recurrent question from a primary care physician: How should I treat my COVID-19 patients at home? An update

A recurrent question from a primary care physician: How should I treat my COVID-19 patients at home? An update

The role of antirheumatics in patients with COVID-19

Does hydroxychloroquine still have any role in the COVID-19 pandemic?

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