On Aug. 24, 2020, the combination of hydroxychloroquine and azithromycin has been linked to significant cardiovascular risks, including mortality, in the largest safety study ever performed comparing hydroxychloroquine treatment to hydroxychloroquine and azithromycin treatment for rheumatoid arthritis patients. Hydroxychloroquine is commonly used to treat rheumatoid arthritis, while azithromycin is a frequently-prescribed antibiotic to treat infections such as pneumonia, chest and sinus infections, etc. This network study, led by the Observational Health Data Sciences and Informatics (OHDSI) community, was published in Lancet Rheumatology.

In patients with rheumatoid arthritis, hydroxychloroquine treatment in the short term (30 days) was found to not carry excess risk of complications associated with its use, but hydroxychloroquine treatment in the long term had a 65% relative increase in cardiovascular-related mortality, compared to sulfasalazine, a similar rheumatoid arthritis drug.

It was first released on MedRxiv and has already made significant impacts in the healthcare community. On April 23, the European Medicines Agency (EMA) cited the study in a warning about the risk of serious side effects with chloroquine and hydroxychloroquine. In July, the EMA again highlighted the study, among other efforts within the OHDSI community, in its eighth revision of The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Guide on Methodological Standards in Pharmacoepidemiology.

Hydroxychloroquine and azithromycin together had a cardiovascular mortality risk that was more than twice (2.19) as high as the comparative treatment even in the short term based on findings from more than 320,000 users of that combination therapy. This treatment also produced a 15-20% increased rate of angina/chest pain and heart failure.

Hydroxychloroquine, a drug commonly used in the treatment of malaria and lupus in addition to rheumatoid arthritis, gained early attention during the pandemic as a potential COVID-19 treatment.

This is the first published study to be generated from the OHDSI COVID Study-a-thon, a global effort in March to set the foundation for OHDSI efforts to design and execute network observational studies around characterisation, patient-level prediction and population-level effect estimation to inform decision-making around the global pandemic.

The OHDSI community examined more than 950,000 hydroxychloroquine users through de-identified electronic health records and administrative claims data over a 20-year period. Records were collected from 14 different databases spanning six nations (Germany, Japan, Netherlands, Spain, United Kingdom, United States) and then mapped to the OMOP Common Data Model to generate this large-scale analysis.