An assessment of 1300 hospitalized patients in New York shows the rheumatic drug is neither beneficial nor harmful to reducing mortality from coronavirus.
The promise of hydroxychloroquine for the care of patients with coronavirus 2019 (COVID-19) may be exaggerated. So may be its limitations.
Hydroxychloroquine was not associated with neither greatly lowered nor increased risk of intubation or death among hospitalized patients with COVID-19, according to new findings from a 1300-plus clinical trial conducted with patients treated in New York City.
The results, presented by a team of Columbia University Irving Medical Center and New York-Presbyterian Hospital clinicians, show the much-debated aminoquinoline therapy given Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) in late March requires more randomized, controlled trial data to understand its true benefit for COVID-19.
Investigators, led by Neil W. Schluger, MD, of the Division of Pulmonary, Allergy, and Cricitcal Care Medicine at Columbia, sought to examine the association between hydroxychloroquine and respiratory failure in hospitalized patients with COVID-19. As they noted, the therapy has been linked to more potent antiviral properties—as well as a stronger safety profile and benefit for resting oxygen saturation—than its fellow agent chloroquine.
That said, the original report supporting hydroxychloroquine as a COVID-19 therapy was a 26-patient, open-label, single-group trial that assessed a 200 mg dose 3 times daily over 10 days. The findings were difficult to interpret because 6 patients were excluded from analysis due to clinical worsening or loss to follow-up.
As such, the large-scale assessment in New York-based patients was considered necessary for appraisal of the drug.
“We hypothesized that hydroxychloroquine use would be associated with a lower risk of a composite end point of intubation or death in analyses that were adjusted for major predictors of respiratory failure and weighted according to propensity scores assessing the probability of hydroxychloroquine use,” Schluger and colleagues wrote.
The team assessed data from consecutive patients hospitalized with COVID-19, excluding those who were intubated , died, or discharged within 24 hours of presenting to the emergency department (ED). Outcomes in patients who received hydroxychloroquine were compared to those who did not using a multivariable, inverse probability-weighting Cox model.
In 1376 eligible patients observed between March 7 and April 8—a median 22.5 days of follow-up per patient—811 (58.9%) received hydroxychloroquine 600 mg twice on day 1, then 400 mg daily for a median 5 days. Nearly half (45.8%) were treated within 24 hours of presenting to the ED; almost all (85.9%) were treated within 48 hours.
On average, hydroxychloroquine-treated patients were more severely ill at baseline than those who did not receive the drug (median ratio, partial pressure of arterial oxygen to the fraction of inspired oxygen, 223 vs 360).
A total of 346 patients (25.1%) had a primary endpoint even: 180 were intubated; 66 subsequently died; 166 died without intubation. Intubation or death occurred in 32.3% of patients treated with hydroxychloroquine, and 14.9% of patients not treated with the therapy.
Though crude analysis shows the hazard ratio (HR) for intubation or death with hydroxychloroquine versus without in hospitalized patients with COVID-19 is 2.37 (95% CI, 1.84-3.02), investigators noted the multivariable (HR, 1.00; 95% CI, 0.76-1.32) and inverse probability-weighting (HR, 1.04; 95% CI, 0.82-1.32) scores show the primary endpoint was not as pronounced in the therapy.
Indeed, adjustment for confounders including race, age, ethnic group, body mass index (BMI), diabetes, underlying kidney or chronic lung disease, or hypertension—among other influential factors of intubation or death—show hydroxychloroquine does not increase the severity of hospitalized COVID-19 progression.
That said, it also did not lower patient risk of death or intubation, neither. Schluger and colleagues noted clinical guidance at their facility has been since updated to remove suggestion that patients with COVID-19 be treated with hydroxychloroquine. Though their findings do not evidence a ruling on either use or non-use of the drug, they also do not support its present use beyond further assessment of its efficacy.
In other words, they concluded the best use of hydroxychloroquine going forward is in randomized, controlled trials understanding its benefit for patients with COVID-19.
“The study results should not be taken to rule out either benefit or harm of hydroxychloroquine treatment, given the observational design and the 95% confidence interval, but the results do not support the use of hydroxychloroquine at present, outside randomized clinical trials testing its efficacy,” they wrote.
The study, “Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19,” was published online in The New England Journal of Medicine.