ArticleThe Lancet. Rheumatology2021
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.
Article in The Lancet. Rheumatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 4 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Exploring the long-term hydroxychloroquine's effects on COVID-19 outcomes in patients with autoimmune diseases: a systematic review and meta-analysis.European journal of clinical pharmacology · 2026Pooled it
- Usefulness of linked data for infectious disease events: a systematic review.Epidemiology and infection · 2023Pooled it
- Pooled it
- Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.PloS one · 2022Pooled it
- Cost-effectiveness of hydroxychloroquine retinopathy screening: the current guideline versus no screening and reduced regimens.The European journal of health economics : HEPAC : health economics in prevention and care · 2025Article
- Evaluation of the effects of pre-exposure treatment with hydroxychloroquine on the risk of COVID-19 infection and on the efficacy of anti-COVID-19 vaccination during lupus or Gougerot-Sjögren's disease: Prepcov multicentre trial.Lupus science & medicine · 2025Article
- Effectiveness of Drug Repurposing and Natural Products Against SARS-CoV-2: A Comprehensive Review.Clinical pharmacology : advances and applications · 2024Review
- Considerations for Pharmacologic Management of Rheumatoid Arthritis in the COVID-19 Era: a Narrative Review.Current rheumatology reports · 2023Review
- Article
- Comparison of Risk Factors During First and Second Wave of COVID-19 in Patients with Autoimmune Rheumatic Diseases (AIRD): Results from KRACC Subset.Mediterranean journal of rheumatology · 2023Article
- The Intersection of COVID-19 and Rheumatoid Arthritis: Shared Mechanisms, Treatment Challenges, and Potential Therapeutic Approaches.Aging and disease · 2023Review
- Occurrence and outcome of COVID-19 in AIRD patients on concomitant treatment with Tofacitinib- results from KRA COVID COHORT (KRACC) subset.BMC rheumatology · 2023Article
- Pediatric Systemic Lupus Erythematous in COVID-19 Era.Viruses · 2023Review
- Article
- COVID-19 Infection in Rheumatic Patients on Chronic Antimalarial Drugs: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2022Review
- The challenges of data in future pandemics.Epidemics · 2022Review
- Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis.medRxiv : the preprint server for health sciences · 2022Article
- The relationship between hydroxychloroquine plasma concentration and COVID-19 outcomes in rheumatoid arthritis patients in Saudi Arabia.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort.The Journal of international medical research · 2022Article
- COVID-19-A Trigger Factor for Severe Immune-Mediated Thrombocytopenia in Active Rheumatoid Arthritis.Life (Basel, Switzerland) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundHydroxychloroquine has been shown to inhibit entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but clinical studies found no evidence of reduced mortality when treating patients with COVID-19. We aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease.
methodsWe did a prespecified observational, population-based cohort study using national primary care data and linked death registrations in the OpenSAFELY platform, which covers approximately 40% of the general population in England, UK. We included all adults aged 18 years and older registered with a general practice for 1 year or more on March 1, 2020. We used Cox regression to estimate the association between ongoing routine hydroxychloroquine use before the COVID-19 outbreak in England (considered as March 1, 2020) compared with non-users of hydroxychloroquine and risk of COVID-19 mortality among people with rheumatoid arthritis or systemic lupus erythematosus. Model adjustment was informed by a directed acyclic graph.
findingsBetween Sept 1, 2019, and March 1, 2020, of 194 637 people with rheumatoid arthritis or systemic lupus erythematosus, 30 569 (15·7%) received two or more prescriptions of hydroxychloroquine. Between March 1 and July 13, 2020, there were 547 COVID-19 deaths, 70 among hydroxychloroquine users. Estimated standardised cumulative COVID-19 mortality was 0·23% (95% CI 0·18 to 0·29) among users and 0·22% (0·20 to 0·25) among non-users; an absolute difference of 0·008% (-0·051 to 0·066). After accounting for age, sex, ethnicity, use of other immunosuppressive drugs, and geographical region, no association with COVID-19 mortality was observed (HR 1·03, 95% CI 0·80 to 1·33). We found no evidence of interactions with age or other immunosuppressive drugs. Quantitative bias analyses indicated that our observed associations were robust to missing information for additional biologic treatments for rheumatological disease. We observed similar associations with the negative control outcome of non-COVID-19 mortality.
interpretationWe found no evidence of a difference in COVID-19 mortality among people who received hydroxychloroquine for treatment of rheumatological disease before the COVID-19 outbreak in England. Therefore, completion of randomised trials investigating pre-exposure prophylactic use of hydroxychloroquine for prevention of severe outcomes from COVID-19 are warranted.
fundingMedical Research Council.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.