Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen don't worsen illness or cause death in hospitalized COVID-19 patients, a new study involving more than 72,000 people in the United Kingdom suggests.
In the observational study, published late last week in The Lancet Rheumatology, a team led by researchers from the University of Edinburgh enrolled 72,179 COVID-19 patients from 255 UK healthcare centers who had death data available from Jan 17 to Aug 10, 2020. Of those patients, 4,211 (5.8%) had a record of taking NSAIDs in the 14 days before hospitalization.
The authors called it the largest ongoing prospective study of its kind and did not consider aspirin an NSAID for their analysis.
Roughly one third of the 4,211 coronavirus patients who had used NSAIDs before hospitalization (30.4%) died, compared with 31.3% of 67,968 patients who had not taken the drugs.
There were no significant differences in COVID-19 severity between the groups, and after adjusting for variables that could have explained any differences, NSAIDs were not linked to higher in-hospital death rates (match odds ratio [OR], 0.95; 95% confidence interval [CI], 0.84 to 1.07); need for critical care (OR, 1.01; 95% CI, 0.87 to 1.17), invasive ventilation (OR, 0.96; 95% CI, 0.80 to 1.17), noninvasive ventilation (OR, 1.12; 95% CI, 0.96 to 1.32), or supplemental oxygen (OR, 1.00; 95% CI, 0.89 to 1.12); or acute kidney injury (OR, 1.08; 95% CI, 0.92 to 1.26).
The use of NSAIDs did not increase death rates in patients with rheumatological disease (matched OR, 0.90; 95% CI, 0.68 to 1.19). Nor were there any significant differences in death rates by type of NSAID used, with ibuprofen being the most common, followed by diclofenac, ketorolac, naproxen, oxicams, and COX-2 inhibitors.
No recommended changes in use
The authors noted that early in the pandemic some experts suspected that NSAIDs, important opioid alternatives, worsened COVID-19 illness. NSAIDs are over-the-counter drugs commonly used for pain relief, often by patients with conditions such as rheumatoid arthritis, gout, and osteoarthritis.
"We now have clear evidence that NSAIDs are safe to use in patients with COVID-19, which should provide reassurance to both clinicians and patients that they can continue to be used in the same way as before the pandemic began," lead study author Ewen Harrison, MBChB, PhD, said in a Lancet press release.
Because the study didn't capture whether patients continued to use NSAIDs in the hospital, the researchers said that they couldn't recommend for or against their use after hospitalization. They also found no evidence that use of NSAIDs benefit COVID-19 patients.
The authors called for future research on whether NSAIDs reduce inflammation in patients with COVID-19 and, depending on the findings, on the cellular mechanisms behind those effects.
"Finally, including groups that compare NSAIDs with alternative analgesics should be considered to provide evidence for clinicians and patients on the risks associated with alternative medications," they wrote. "In conclusion, policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity."
Findings back WHO, FDA, EMA statements
In a commentary in the same journal, Danish researchers Kristian Kragholm, MD, PhD, of Aalborg University Hospital; Christian Torp-Pedersen, MD, of Nordsjaellands Hospital; and Emil Fosbol, MD, PhD, of Rigshospitalet, noted that it was unclear whether possible harmful effects of NSAIDs were masked by stopping NSAIDs during hospitalization, taking lower dosages, or treatment duration.
But they said that the study findings back current clinical statements from the World Health Organization, US Food and Drug Administration, and the European Medicines Agency on the lack of harm from NSAID use in COVID-19 patients.
"The current study complements several previous observational studies, of which most have supported the lack of association between NSAID use and COVID-19 severity," Kragholm, Torp-Pedersen, and Fosbol wrote. "Ultimately, based on current knowledge, clinicians should not refrain from or discontinue NSAIDs in patients with COVID-19 if NSAID treatment is indicated."