Moderate, high rheumatic disease activity linked to higher risk for COVID-related death
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Moderate and high disease activity, as well as the use of immunosuppressants, were associated with a higher risk for COVID-related death in patients with rheumatic diseases, according to data in the Annals of the Rheumatic Diseases.
The researchers noted that, although the use of most disease-modifying antirheumatic drugs were not linked to higher risk of death from COVID-19, there were “notable exceptions” with rituximab and sulfasalazine.
“As in the general population, older age, male sex, cardiovascular and chronic lung disease were associated with COVID-19 related death,” Pedro M. Machado, MD, of University College London and Northwick Park Hospital, told Healio Rheumatology. “Some rheumatic disease-specific factors were also associated with COVID-19 related-death. Specifically, moderate or high disease activity was associated with 2-fold increased risk of death. Reassuringly, most medications used by people with rheumatic diseases were not associated with higher death.”
To examine which factors are associated with death related to COVID-19 among patients with rheumatic diseases, Strangfeld and colleagues analyzed data from the COVID-19 Global Rheumatology Alliance, a physician-reported, observational registry. Established March 24, 2020, the registry includes international data on patients with COVID-19 and a preexisting rheumatic disease. As of July 1, 2020, it contained information on 3,830 patients.
Focusing on the period from March 24, 2020, and July 1, 2020, the researchers analyzed patients’ age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications — all used as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. The primary outcome was death related to COVID-19. In all, the registry included 3,729 patients with complete death, age, sex and DMARD therapy information. Among those patients, 390 died.
The most common rheumatic diseases among the included patients were rheumatoid arthritis, with 37.4%, connective tissue diseases other than systemic lupus erythematosus, at 14.3%, SLE, at 10.5%, psoriatic arthritis, with 11.8%, and other spondyloarthritis, at 11.6%.
According to the researchers, independent factors associated with COVID-19-related death were age — being 66 to 75 years (OR = 3; 95% CI, 2.13-4.22) and being older than 75 years (OR = 6.18; 95% CI, 4.47-8.53), both compared with being 65 years or younger — male sex (OR = 1.46; 95% CI, 1.11-1.91), hypertension combined with cardiovascular disease (OR = 1.89; 95% CI, 1.31-2.73), chronic lung disease (OR = 1.68; 95% CI, 1.26-2.25) and a prednisolone-equivalent dosage more than 10 mg per day compared with no glucocorticoid intake (OR = 1.69; 95% CI, 1.18-2.41).
In addition, moderate and high disease activity, compared with remission and low disease activity, was associated with higher odds of death related to COVID-19 (OR = 1.87; 1.27-2.77). Treatment with rituximab (Rituxan; Genentech, Biogen) (OR = 4.04; 95% CI, 2.32-7.03), sulfasalazine (OR = 3.6; 95% CI, 1.66-7.78), immunosuppressants — azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus — (OR = 2.22; 95% CI, 1.43-3.46), and not receiving any DMARDs (OR = 2.11; 95% CI, 1.48-3.01) were also associated with higher odds of death, compared with methotrexate monotherapy.
“Overall, this article highlights that the risk of dying from COVID-19 varies according to people’s underlying disease activity and what medicine they are taking,” Machado said. “It is important for people with a rheumatic disease to continue to control their disease activity with anti-rheumatic medication, but preferably without increasing the dose of any glucocorticoids, if possible.”
Perspective
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The impacts of COVID-19 on rheumatology patients are profound. In this study, researchers reviewed data from the Global Rheumatology Alliance among patients with rheumatic illnesses with presumed or confirmed COVID-19 with the primary outcome being death.
Country-specific differences in death included highest ratio of death in UK and Italy with lower numbers reported in U.S. Factors associated with death include aged >65 years, male gender, chronic lung disease with hypertension, high or moderate disease activity and prednisone more than 10 mg/day.
Current or former smoking was only associated with death in RA group. Medications conferring special risks included rituximab as well as sulfasalazine. In stratified analysis, association between death and sulfasalazine use was not statistically significant except in ever-smokers where there was a threefold higher OR.
This finding is surprising given the dogma that sulfasalazine has low immunosuppressive effects, however, it maybe hypothesized that sulfasalazine is commonly used in patients with multiple comorbidities, such as renal failure/chronic lung disease where methotrexate use is rather difficult. Besides sulfasalazine, rituximab, given its B-cell depletion effects leading to decreased viral-mediated immunity, stands out in COVID-19-related deaths. Also, patients with higher disease activity tend have poorer outcomes when dealing with COVID-19, thereby necessitating the goal of steroid-free remission.
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