Rheumatoid Arthritis Increases Risk of Death From COVID-19

Research indicates rheumatoid arthritis (RA) is a risk factor for more severe outcomes, including death, from COVID-19, according to a study published in ACR Open Rheumatology.¹ The study also revealed that a gout diagnosis did not increase these chances despite poorer outcomes being associated with high serum levels of interleukin 6 (IL-6), IL-8, tumor necrosis factor α (TNF‐α), and cardiometabolic comorbidities, all of which patients with gout are more likely to have.

“Data on COVID‐19 outcomes for people with the two most common inflammatory arthropathies, gout and RA, are scarce,” stated investigators. “Gout is caused by an exuberant autoinflammatory interleukin 1β–driven innate immune system response to monosodium urate crystals. Theoretically, this has the potential to lead to an increased immune response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)…RA is a T‐cell and B‐cell–mediated autoimmune disease that primarily affects the joints but also includes systemic manifestations. Like gout, RA is an independent risk factor for cardiovascular disease.”

Using a multivariable‐adjusted analysis of UK Biobank, investigators set out to determine if patients with RA or gout had a higher chance of contracting COVID-19 and subsequent COVID-19-related death. The study identified 2118 case patients, 457 of which died and 1602 survived. Gout was determined by either self-reported symptoms or hospital-diagnosis. In total 13,105 patients in the gout-case control cohort had the condition and 460,024 patients were controls. RA was also determined by self-reported symptoms and hospital-recorded RA diagnosis. The RA cohort had 5409 patients with RA and 467,730 controls. There were 59 patients that were diagnosed after July 26, 2020 who were removed due to unknown outcomes.

Both the RA and gout cohorts had 3 data sets to ascertain association with COVID-19 outcomes. Data set A tested for general association between RA and gout and COVID-19 diagnosis and used the 2118 case patients along with 471,021 controls. Data set B analyzed the percentage of people with gout and RA who had been diagnosed with COVID-19 and died and compared it with those who survived. Data set C was used to determine the death related to COVID-19 in the population-based UK Biobank cohort, which included 457 people who died and 472,682 others who survived.

With adjustments for age, sex, ethnicity, BMI, smoking status and Townsend deprivation index, gout and RA were associated with a 1.5‐fold (95% confidence interval [CI] 1.2–1.8) and 2.2‐fold (95% CI 1.7–2.9) increased risk of COVID‐19 diagnosis, respectively. However, after an additional 15 comorbidities were evaluated, gout was no longer connected with a COVID-19 diagnosis. RA continued to have an association with COVID-19 (odds ratio [OR] 1.3; 95% CI 1.0–1.8). Death related to COVID-19 for patients with a COVID-19 diagnosis (data set B) was not associated with gout or RA. In the data set C, gout was associated with a 1.7-fold increase in COVID-19-related death in model 1, but not in model 2. RA was linked with an increased risk of death in both models, independent of comorbidities and other risk factors (OR 1.9; 95% CI 1.2–3.0).

Limitations of the study included the population from which the information was derived, which consisted of mostly middle-aged White Europeans from the United Kingdom, thus limiting generalizability. Further, outcomes may have been influenced as treatments had evolved, as the patient information was extrapolated between March and August 2020. Prescription information was only available until August 2019, so it may not accurately reflect the patient’s current medication. This means that disease‐modifying antirheumatic drugs (DMARDs) and the effect of disease activity in the RA cohort could not be assessed. Additionally, only patients aged 49-86 years were included in the study, which could have skewed the data as this demographic is known to have a higher fatality ratio. Lastly, ascertainment of gout was validated, but RA cases were not.

“In summary, we found evidence for an effect of RA on the risk of death from COVID‐19, independent of included comorbidities and known risk factors,” concluded investigators. “This needs to be further explored in large data sets in which a range of other factors can be investigated (eg, RA therapies).”

Reference:

Topless RK, Phipps-Green A, Leask M, et al. Gout, Rheumatoid Arthritis, and the Risk of Death Related to Coronavirus Disease 2019: An Analysis of the UK Biobank [published online ahead of print, 2021 Apr 15]. ACR Open Rheumatol. 2021;10.1002/acr2.11252. doi:10.1002/acr2.11252