NSAID use does not predispose OA patients to COVID-19 infection

Patients with osteoarthritis (OA) can safely continue taking their nonsteroidal anti-inflammatory drugs (NSAIDs), which have been shown to have a null effect on the risk of contracting COVID-19 or all-cause mortality, as reported in a study.

The study involved a large UK cohort of 13,202 patients with OA with a current prescription for an NSAID and 12,457 individuals with a current prescription for comparator drugs (co‐codamol or co‐dydramol), the incidence rates of suspected or confirmed COVID‐19 were 15.4 and 19.9 per 1,000 person‐years, respectively. [Arthritis Rheum 2021;73:731-739]

All-cause mortality also occurred with less frequency in the NSAID than the comparator group (incidence rate, 14.0 vs 34.6 per 1,000 person‐years).

Multivariable Cox proportional hazards regression model confirmed that compared with co-codamol (eg, paracetamol and codeine) or co-dydramol (eg, paracetamol and dihydrocodeine), NSAIDs conferred a risk increase for neither COVID‐19 (adjusted hazard ratio [aHR], 0.82, 95 percent confidence interval [CI], 0.62–1.10) nor all-cause mortality (aHR, 0.97, 95 percent CI 0.75–1.27).

Results in the propensity score-matched cohort of 8,595 NSAID users and 8,595 patients exposed to the comparator drugs followed the same pattern (aHR for COVID-19, 0.79, 95 percent CI, 0.57–1.11; aHR for all-cause mortality, 0.85, 95 percent CI, 0.61–1.20).

“These results … suggest that in the absence of acute illness, NSAIDs can be safely prescribed during the ongoing pandemic,” according to a team of UK-based researchers.

In the unmatched cohort, NSAID users were younger (mean age, 65.4 vs 71.7 years) and more likely to be men (37.8 percent vs 33.4 percent) compared with patients taking the comparator drugs. There was no difference in the number of current smokers and body mass index, although the NSAID group had a lower prevalence of comorbidities, including cardiovascular disease, diabetes, respiratory disease, and cancers.

The researchers pointed out that the null association between NSAID use and the risk of COVID‐19 or mortality was consistent in subgroups defined by age and sex.

Concerns about the use of NSAIDs and susceptibility to COVID‐19 at the outset of the pandemic have been predicated on the fact that SARS-CoV‐2 enters host cells via the angiotensin-converting enzyme 2 (ACE2) receptor—an enzyme whose expression is said to increase with NSAID use, they explained.

“However, our findings do not support [such] conjecture. Indeed, [this is in line with] previous studies investigating the impact of ibuprofen on the severity of COVID‐19 in South Korea and Denmark,” they said.

In those studies, NSAIDs contributed no additional risk of morbidity or mortality. Also, they identified no clear differences in outcomes across age or sex, although the study from Denmark may not have been sufficiently powered to identify these as potential effect modifiers. [Clin Infect Dis 2020;doi:10.1093/cid/ciaa1056; PLoS Med 2020;17:e1003308]

These findings are reassuring, “because older patients are at a substantially higher risk of developing COVID‐19 and have a poorer prognosis, [and] given the high prevalence of NSAID use in this age group,” according to the researchers. [Nature 2020;584:430-436; Open Heart 2017;4:e000550]

Nevertheless, the data have to be validated in other cohorts, as the analysis was restricted to patients with pre-existing OA to reduce the risk of confounding by indication and immortal time bias, they said.

“Further research into the impact of NSAIDs [by type and dose] on the expression of the ACE2 receptor and consequent susceptibility to SARS–CoV‐2 in relevant human cell types is also urgently required,” they added.