Rheumatology Drugs Under Study for COVID-19

Patients with chronic autoimmune inflammatory disorders, such as rheumatoid arthritis, are at a higher risk of infections than the general population. While infections in this patient population can lead to organ failure and death, the risk of flares and disease relapse can be far more serious, say researchers writing in a review published in Autoimmunity Reviews.

The COVID-19 pandemic raises a few questions for patients. Since most biologics used to treat autoimmune diseases can increase the risk of infections, rheumatology patients are asking their doctors if they should taper their medications or stop taking them altogether during the COVID-19 pandemic. Physicians say no.

"The use of synthetic and biologic disease-modifying drugs is associated with a potential further increase in the incidence of serious infections, but the poor control of RA disease activity is an even greater infectious risk factor," Ennio Giulio Favalli, et al. wrote in the journal on March 20. "Rheumatoid arthritis patients should be encouraged to continue their treatment even during COVID-19 outbreak. In our opinion, this strategy is reasonable as it aims to prevent disease flares that can contributes to increase patient burden, disability, poor quality of life, and healthcare use."

In rheumatoid arthritis, the presence of comorbidities, such as diabetes mellitus, cardiovascular diseases, renal failure, interstitial lung disease, and chronic obstructive pulmonary disease (COPD), can heighten the risk of infection from any cause. But then, immunosuppressive therapies are associated with an increased risk of infections. The combination of the two sources of infection can complicate care even further.

If patients opt to discontinue their treatments, physicians may recommend corticosteroids as a bridging therapy, but corticosteroids are associated with severe infections and a high risk of comorbidities which increases the risk of both bacterial and viral infections. A 2012 retrospective study by Widdifield et al. published in Arthritis Care and Research, reported an increased risk of herpes zoster infections of 8.54 cases per 1,000 patient years in patients treated with corticosteroids.

Favalli et al. also highlight rheumatoid arthritis treatments under study as a treatment for COVID-19, but in particular, for patients with severe cases of COVID-19 that are associated with interstitial pneumonia with alveolar damage so severe, that it can lead to severe acute respiratory distress syndrome (ARDS) or death. For the most severe of COVID-19 cases, ideally, treatment should control the cytokine storm which can include increased numbers of interleukin-1β, IL-2, IL-6, IL-7, IL-8, tumor necrosis factor-α (TNF) and chemokines.

Potential treatments for COVID-19 that require study, include:

• Anti-malarials chloroquine and hydroxychloroquine. These drugs have been used to treat COVID-19 patients in other countries. In the U.S., it's been embraced as a treatment option in specific cases despite the lack of clinical trials testing.

• IL-6 inhibitors, such as tocilizumab or sarilumab, may be a promising treatment alternative for critical cases of interstitial pneumonia complicated by Cytokines Release Syndrome.

• Baricitinib works by interfering with viral penetration into the cell by blocking NAK-mediated endocytosis. Research shows that it is associated with an increased risk of herpes zoster infections.

• A retrospective, longitudinal, population-based study on csDMARDs for rheumatoid arthritis found that csDMARDs, without corticosteroids, could decrease the risk of a mild viral infection to a small degree.

REFERENCE

Ennio Giulio Favalli, Francesca Ingegnoli, Orazio De Lucia, Gilberto Cincinelli, Rolando Cimaz, Roberto Caporali. "COVID-19 Infection and Rheumatoid Arthritis: Faraway, So Close!"Autoimmunity Reviews. Online ahead of print March 20, 2020.