Exercise Caution Amid the COVID-19 Pandemic

New information on the severe acute respiratory syndrome coronavirus (sars-cov-2), which causes the coronavirus disease 2019 (COVID- 19), continues to emerge daily.

As health care providers navigate the most severe global pandemic in more than a century, concerns arise among those who care for some of our most vulnerable populations. One such population is patients with rheumatologic conditions who take immunosuppressant medications. Patients with conditions such as ankylosing spondylitis (AS), lupus, psoriatic arthritis (PSA), rheumatoid arthritis (RA), and scleroderma may have a higher risk of contracting SARS-CoV-2, regardless of whether they are prescribed immunosuppressants.¹

Patients on disease-modifying antirheumatic drugs (DMARDs) are at higher risk of infections, including SARS-CoV-2, as well as secondary infections and poor outcomes. Initial mortality reports from the SARS-CoV-2 pandemic have also been higher for this population.² The risks of infection for patients on DMARDs (biologics and other immunosuppressive agents) are well described in the literature. A study by Quartuccio et al using administrative data from 5596 patients with AS, PSA, or RA identified a relationship between the recent initiation of a biologic and hospitalization for an infection.¹ The most common types of infection identified were upper and lower respiratory tract infections. This is particularly important considering that SARS-CoV-2 is a virus of the lower respiratory tract.

Furthermore, patients on DMARDs may overlook their initial infection state. Patients who are immunosuppressed may present with different symptoms than their immunocompetent counterparts. For example, because of decreased ability to mount an immune response, this population may not present with a fever when infected with SARS-CoV-2.

The PSOLAR study (NCT00508547) reported the incidence rate of serious infection for patients undergoing treatment with tumor necrosis factor inhibitors (TNFIs; adalimumab, etanercept, infliximab), ustekinumab, methotrexate, and other DMARDs, such as cyclosporine.³ Serious infection incidence was numerically higher with TNFIs than with other biologics, but these differences were not statistically significant. To date, no confirmative data are available to support relative infection risks among different biologic DMARDs.

The PSOLAR study also reported that diabetes, history of infection, older age, and a level 4 or 5 Physician’s Global Assessment were statistically significant factors for increased risk for serious infection. Importantly, the additional risk factors listed above could increase infection risk even further.

TNFIs have been on the market for 2 decades and are known to increase the risk of infection of SARSCoV- 2.1 Other biologics used in rheumatology, such as B-cell modulators, IL-6 inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, Janus kinase inhibitors, and T-cell modulators, are also immunosuppressive and increase infection risk. The American College of Rheumatology 2015 guidelines for RA recommended the use of combination DMARDs over TNFIs and abatacept over TNFIs if a patient had a history of previous serious infections.⁴

General recommendations remain that first, an individual should choose strategies to minimize the risk of infection, by receiving an annual influenza vaccination, for example, and practicing self-hygiene. If a patient on a biologic or other immunosuppressive agent becomes ill, they should discontinue the medication until resolution of the infection. If a patient was prescribed an antibiotic, antifungal, or antiviral agent to treat an acute infection, the individual should remain off the immunocompromising biologics until they finish their course of the prescribed regimen and the infection resolves before reinitiating biologics.

At this time during the SARS-CoV-2 outbreak, CDC recommendations for patients on immunosuppressive medications do not differ greatly from those for the general population. Patients are advised to avoid contact with people who are sick; to not touch the eyes, mouth, or nose with unwashed hands; to wash hands with soap and water often for at least 20 seconds; and to use alcohol-based hand sanitizer when not near soap and water. All immunocompromised patients should also inform their provider of any travel destinations if they become ill after having traveled abroad or locally and of any acute infection or injury, which could lead to further infection. Patients should also evaluate their health condition prior to each injection of a biologic agent, during which practitioners assess for general wellness, fever symptoms, significant cuts and injuries, and sores. Finally, remind patients frequently of the importance of routine immunizations such as the influenza vaccine and to receive only inactivated vaccines. Patients with planned surgical procedures should discontinue biologic agents for the appropriate period determined by their providers prior to the procedure.

In the backdrop of the pandemic, panic has led many people to seek chloroquine or hydroxychloroquine to either treat their infection or use as prophylaxis against COVID- 19.⁵ Hydroxychloroquine is a DMARD that serves as the cornerstone of pharmacotherapy for patients with multiple rheumatologic conditions, including lupus and RA. The World Health Organization is in the midst of exploring the potential role of chloroquine and hydroxychloroquine in the management of COVID-19. In the meantime, federal and state authorities have enacted mandates, such as New York State Executive Order 202.10, to preclude dispensation of these medications for other than their FDA-approved indications, unless the patient is enrolled in a bona fide study.⁶ Large community pharmacy chains, such as CVS Health, Express Scripts, and Walgreens, have also set policies to halt hoarding of chloroquine and hydroxychloroquine.⁷ These mandates are an effort to reduce drug shortages for those who require these medications chronically for an established rheumatologic disorder.6 Pharmacists have become an important gatekeeper in this regard, as even health care clinicians have been noted to hoard these medications for themselves, their family members, or their friends.⁸

Pharmacists play a key role in educating the public and controlling distribution of medications. It is imperative that health care providers and patients are aware that DMARD use may lead to immunosuppression that could increase infection risk during this unprecedented public health crisis. Critically, they should also realize the potential for afebrile presentation of infection, the importance of holding biologics if an infection is present, and the need to seek health care promptly. Furthermore, the general population must understand the risks imposed on patients with rheumatologic disorders if their maintenance medications are depleted.

Amelia L. Persico, PharmD, MBA, is a PGY-2 pain and palliative care pharmacy resident, and Sooyeon Kwon, PharmD, PhD, is a clinical pharmacy specialist for rheumatology, both at Albany Stratton VA Medical Center in Albany, New York.Jeffrey Fudin, PharmD, DAIPM, FCCP, FASHP, FFSMB, is CEO and founder of Remitigate LLC and the owner and managing editor of paindr. com. He is also an adjunct associate professor at Western New England University College of Pharmacy and Health Sciences in Springfield, Massachusetts, an adjunct associate professor of pharmacy practice and pain management at Albany College of Pharmacy and Health Sciences in Albany, New York, and the director of the PGY-2 pain residency at Albany Stratton VA Medical Center.

REFERENCES

• Quartuccio L, Zabotti A, Del Zotto S, Zanier L, De Vita S, Valent F. Risk of serious infection among patients receiving biologics for chronic inflammatory diseases: usefulness of administrative data. JAMA Advanced Research. 2019;15:87- 93. doi: 10.1016/j.jare.2018.09.003.
• Yang Y, Peng F, Wang R, et al. The deadly coronaviruses: the 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China [published online March 3, 2020]. JAMA Autoimmun. doi: 10.1016/j.jaut.2020.102434.
• Ritchlin CT, Stahle M, Poulin Y, et al. Serious infections in patients with self-reported psoriatic arthritis from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) treated with biologics. BMC Rheumatol. 2019;3:52. doi: 10.1186/s41927- 019-0094-3.
• Singh JA, Saag KG, Bridge SL Jr, et al; American College of Rheumatology. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2016;68(1):1-25. doi: 10.1002/acr.22783.
• World Health Organization. COVID-1 informal consultation on the potential role of chloroquine in the clinical management of COVID19 Infection. who.int/blueprint/ priority-diseases/key-action/RD-Blueprint-expert-group-on- CQ-call-Mar-13-2020.pdf?ua=1. Published March 13, 2020. Accessed March 26, 2020.
• No. 202.10: continuing temporary suspension and modification of laws relating to the disaster emergency. New York State website. governor.ny.gov/news/no-20210-continuing-temporary- suspension-and-modification-laws-relating-disaster-emergency. Published March 23, 2020. Accessed March 26, 2020.
• Humer C, Mishra M. Pharmacies set policies to stop U.S. hoarding of potential coronavirus treatments. Reuters website. reuters.com/article/us-health-coronavirus-cvs-health/pharmacies- set-policies-to-stop-u-s-hoarding-of-potential-coronavirus- treatments-idUSKBN21C2CQ. Published March 25, 2020. Accessed March 26, 2020.
• Rowland C. As Trump touts an unproven coronavirus treatment, supplies evaporate for patients who need those drugs. Washington Post. March 23, 2020. washingtonpost.com/ business/2020/03/20/hospitals-doctors-are-wiping-out-supplies- an-unproven-coronavirus-treatment/. Accessed March 26, 2020.