Conv. Plasma
Nigella Sativa

All HCQ studies
Meta analysis
study COVID-19 treatment researchHCQHCQ (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

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

Lane et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30276-9
Aug 2020  
  Source   PDF   All Studies   Meta AnalysisMeta
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
Retrospective study of RA patients using HCQ vs. sulfasalazine (another DMARD). HCQ treatment showed no increased risk in the short term (up to 30 days) among patients with RA. Long term use was associated with excess cardiovascular mortality.
Addition of AZ increased the risk of cardiovascular mortality with combined use up to 30 days. This is several times longer than typical COVID-19 use. This result also comes from just 2 of the 14 databases, with the negative result from just one database (VA) and much lower statistically insignificant difference in mortality from the other database (Clinformatics).
Confounding by indication. Patients conditions vary, the severity of a patient's RA or other conditions was not taken into account. Results varied widely across different databases, and different subsets of databases were used in different analyses. Baseline risk of serious adverse events unknown. Health care database analysis subject to misclassification errors.
Lane et al., 21 Aug 2020, peer-reviewed, 62 authors.
This PaperHCQAll
Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study
Jennifer C E Lane, MSc James Weaver, Kristin Kostka, PhD Talita Duarte-Salles, Maria Tereza F Abrahao, Heba Alghoul, Osaid Alser, Thamir M Alshammari, Patricia Biedermann, Juan M Banda, Edward Burn, Paula Casajust, PhD Mitchell M Conover, Aedin C Culhane, MD Alexander Davydov, Scott L Duvall, MD, O Zhuk MD Dmitry Dymshyts, MSc Sergio Fernandez-Bertolin, Kristina Fišter, PhD Jill Hardin, Laura Hester, Prof George Hripcsak, Benjamin Skov Kaas-Hansen, Seamus Kent, Sajan Khosla, PhD Spyros Kolovos, Christophe G Lambert, Prof Johan Van Der Lei, Kristine E Lynch, PhD Rupa Makadia, Andrea V Margulis, Michael E Matheny, Paras Mehta, Daniel R Morales, Henry Morgan-Stewart, Mees Mosseveld, Danielle Newby, PhD Fredrik Nyberg, Anna Ostropolets, Rae Woong Park, Albert Prats-Uribe, Gowtham A Rao, Christian Reich, Jenna Reps, Peter Rijnbeek, Selva Muthu Kumaran Sathappan, Martijn Schuemie, Sarah Seager, Anthony G Sena, Azza Shoaibi, Matthew Spotnitz, Marc A Suchard, Carmen O Torre, David Vizcaya, Haini Wen, Marcel De Wilde, Junqing Xie, Seng Chan You, Lin Zhang, Oleg Zhuk, Dr Patrick Ryan, Daniel Prieto-Alhambra
The Lancet Rheumatology, doi:10.1016/s2665-9913(20)30276-9
Background Hydroxychloroquine, 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. Methods In 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. Findings The 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. Selfcontrolled 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]). Interpretation Hydroxychloroquine 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.
Austin, Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples, Stat Med
Borba, Val, Sampaio, Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial, JAMA Netw Open
Chatre, Roubille, Vernhet, Jorgensen, Pers, Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature, Drug Saf
Chen, Lin, Lan, Hydroxychloroquine reduces risk of incident diabetes mellitus in lupus patients in a dose-dependent manner: a population-based cohort study, Rheumatology
Chorin, Dai, Shulman, The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin, Nat Med
Colson, Rolain, Lagier, Brouqui, Raoult, Chloroquine and hydroxychloroquine as available weapons to fight COVID-19, Int J Antimicrob Agents
Costello, David, Jani, Impact of adverse events associated with medications in the treatment and prevention of rheumatoid arthritis, Clin Ther
Dersimonian, Laird, Meta-analysis in clinical trials, Control Clin Trials
Devaux, Rolain, Colson, Raoult, New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19?, Int J Antimicrob Agents
Gautret, Lagier, Parola, Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Guo, Cai, Chai, Liang, Bai et al., The cardiotoxicity of macrolides: a systematic review, Pharmazie
Hofschneider, Winter, Lemmel, Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis, Rheumatol Int
Lu, Yuan, Li, Cardiac risks associated with antibiotics: azithromycin and levofloxacin, Expert Opin Drug Saf
Luo, Hu Q Guirong, Wu, Wu, Xu, Data mining and safety analysis of drugs for novel coronavirus pneumonia treatment based on FAERS: chloroquine phosphate, Herald Med
Mercuro, Yen, Shim, Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19), JAMA Cardiol, doi:10.1001/jamacardio.2020.1834
Ray, Murray, Hall, Arbogast, Stein, Azithromycin and the risk of cardiovascular death, N Engl J Med
Recovery, Statement from the Chief Investigators of the Randomised Evaluation of COVid-19 thERapY (RECOVERY) Trial on hydroxychloroquine
Roden, Harrington, Poppas, Russo, Considerations for drug interactions on QTC in exploratory COVID-19 (coronavirus disease 2019) treatment, Circulation
Savarino, Boelaert, Cassone, Majori, Cauda, Effects of chloroquine on viral infections: an old drug against today's diseases?, Lancet Infect Dis
Schuemie, Hripcsak, Ryan, Madigan, Suchard, Robust empirical calibration of p-values using observational data, Stat Med
Schuemie, Ryan, Dumouchel, Suchard, Madigan, Interpreting observational studies: why empirical calibration is needed to correct p-values, Stat Med
Sepriano, Kerschbaumer, Smolen, Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis, Ann Rheum Dis
Shinjo, Bonfá, Wojdyla, Antimalarial treatment may have a time-dependent effect on lupus survival: data from a multinational Latin American inception cohort, Arthritis Rheum
Simpson, Madigan, Zorych, Schuemie, Ryan et al., Multiple self-controlled case series for large-scale longitudinal observational databases, Biometrics
Suchard, Schuemie, Krumholz, Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis, Lancet
Suchard, Simpson, Zorych, Ryan, Madigan, Massive parallelization of serial inference algorithms for a complex generalized linear model, ACM Trans Model Comput Simul
Tian, Schuemie, Suchard, Evaluating large-scale propensity score performance through real-world and synthetic data experiments, Int J Epidemiol
Tselios, Deeb, Gladman, Harvey, Urowitz, Antimalarial-induced cardiomyopathy: a systematic review of the literature, Lupus
Vigerust, Shepherd, Virus glycosylation: role in virulence and immune interactions, Trends Microbiol
Voss, Boyce, Ryan, Van Der Lei, Rijnbeek et al., Accuracy of an automated knowledge base for identifying drug adverse reactions, J Biomed Inform
Wallace, Gudsoorkar, Weisman, Venuturupalli, New insights into mechanisms of therapeutic effects of antimalarial agents in SLE, Nat Rev Rheumatol
Wang, Cao, Zhang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wasko, Hubert, Lingala, Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis, JAMA
Who, Solidarity" clinical trial for COVID-19 treatments update on hydroxychloroquine
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop