Treatment with CD20 inhibitors for immune-mediated diseases is associated with an increased mortality risk among patients with COVID-19 compared with the general population with COVID-19, according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021.

Although immune-mediated diseases do not appear to increase the risk for severe COVID-19, treatment of these disorders with CD20 inhibitors may be associated with increased COVID-19 mortality risk.

The objective of the current study was to determine the outcomes of COVID-19 among patients who received anti-CD20 therapy compared with the general population.

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Using a large health care system database, patients with COVID-19 with immune-mediated diseases who received treatment with anti-CD20 therapy were identified and matched 5:1 with the general population with COVID-19 by age, sex, and index date of a positive polymerase chain reaction (PCR) test. Cox regression analysis was used to compare the risk for hospitalization, mechanical ventilation, and death.

The study sample included 114 patients (mean age, 55±15 years; 70% women) with immune-mediated diseases who received anti-CD20 therapy within 1 year prior to index date of PCR-confirmed COVID-19, between January 2020 and January 2021. The matched comparator group included 559 patients (mean age, 54±15 years; 70% women).

Rheumatic disease and neurologic conditions were the most common reasons for CD20 inhibitor use (52% and 42%, respectively).

Use of CD20 inhibitors was less than 1 year in 33 patients (29%), 1 to 3 years in 51 patients (45%), and greater than 3 years in 30 patients (26%). Of these, 48 patients (42%) received a dose of a CD20 inhibitor within 3 months before COVID-19 onset.

Treatment with CD20 inhibitors was associated with a 2-fold increased mortality risk (adjusted hazard ratio, 2.16; 95% CI, 1.03-4.54) in patients with COVID-19 vs the comparator participants (11% vs 4%, respectively). However, no differences were noted regarding the risks for hospitalization (31% vs 22%, respectively) and mechanical ventilation (5% vs 5%, respectively).

Mortality risk was higher for patients receiving short-term anti-CD20 therapy (<1 year) than the comparator participants (9% vs 3%; unadjusted hazard ratio, 2.82; 95% CI, 1.34-5.96), but the difference was not statistically significant in the adjusted model (adjusted hazard ratio, 2.33; 95% CI, 0.92-5.91). 

Among long-term CD20 inhibitor users, the mortality was numerically higher among the patient than the comparator group (15% vs 6%, respectively), but the difference was not statistically significant in the unadjusted (unadjusted hazard ratio, 2.92; 95% CI, 0.95-8.99) and adjusted (adjusted hazard ratio, 2.41; 95% CI, 0.66-8.87) models.

“Patients who used CD20 inhibitors for immune-mediated diseases prior to COVID-19 infection had higher mortality than matched comparators. These results highlight the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing COVID-19 pandemic,” the researchers concluded.

I often hear patients asking, “Why am I taking this medication?”  Whether it is a medication prescribed by a primary care physician, specialist, or emergency medicine provider, this question needs to be answered and understood by all patients. Prescription labels for medications taken as-needed typically include the indication for use, but prescriptions for chronic illnesses typically do not. This information is especially important when patients are on multiple medications. The issue comes down to health literacy.

Studies have shown that more than 75% of patients lack understanding about prescription label instructions, and some patients stop taking medications if they don’t know what it is prescribed for.1 This lack of information is a source of frustration for patients, their caretakers/families, and their providers. Many older patients in my practice ask me about their medications. After explaining the indication for each medication, I write the reason for the prescription on the bottle with a marker if they have their medicine with them or I indicate the information on their paperwork. The simple act of writing down the purpose for the medication helps patients understand why the agent is important to their heath and serves as a reminder over time.  

Misunderstanding the “why” may affect patient’s willingness to take needed medications. Medication nonadherence affects quality of life and leads to more than $100 billion in avoidable hospitalizations.2 Not knowing the “why” can lead to chronic illness exacerbations causing multiple office/emergency department visits or hospitalizations as well as increased time spent by office staff and/or pharmacy staff to address patient questions. To help reduce this burden, the Institute of Medicine encourages the standardization of prescription use instructions given that the medication label is a key source of information for patients.3 This practice can save time, confusion, and money for patients, families, providers, pharmacists, hospitals, and insurance companies.

Nurse practitioners (NP) can lead this transformation in their practice. Awareness that patients need information on the purpose of their medications is necessary for change to begin. After discussing this need with patients, colleagues, and support staff, the indication for use of each medication can be written on prescriptions for all patients. This act will serve as a reminder of the “why” and will help patients take control of their health care.

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Karen A. Bocchicchio MSN, FNP-C, APN-C, is a practicing clinician as well as lead clinician at a Penn Medicine primary care office in New Jersey. She is a clinical nursing adjunct for nurse practitioner students at Rowan University. She is also pursuing her DNP at Rutgers University.


1. Davis TC, Federman AD, Bass PF 3rd, et al. Improving patient understanding of prescription drug label instructions. J Gen Intern Med. 2009;24(1):57-62. doi:10.1007/s11606-008-0833-4

2. Cutler DM, Everett W. Thinking outside the pillbox–medication adherence as a priority for health care reform. N Engl J Med. 2010;362(17):1553-1555. doi:10.1056/NEJMp1002305

3. Institute of Medicine. Standardizing Medication Labels: Confusing Patients Less: Workshop Summary. The National Academies Press; 2008.


Patel N, D’Silva K, Hsu T, et al. Association of CD20 inhibitor use with severe COVID-19 outcomes. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 0085. 

This article originally appeared on Rheumatology Advisor