Baltimore, MD—Patients taking immunosuppressive medications generally don’t have a higher risk of dying from COVID-19 or having to use a ventilator to breathe than patients hospitalized with the infection who are not immunosuppressed.

Johns Hopkins Bloomberg School of Public Health researchers reached that conclusion in a large, nationwide study of COVID-19 cases. Results published in The Lancet Rheumatology were based on analysis of electronic health–record data on adults hospitalized with COVID-19 from January 2020 to June 2021. Included were 222,575 patients, 7% of whom had been on immunosuppressive medications prior to hospitalization.

“In general, people taking immunosuppressive medications may be reassured that they can safely continue to do so during this pandemic," explained study lead author Kayte Andersen, MSc, a doctoral candidate in the Bloomberg School's Department of Epidemiology.

“These findings are encouraging and important, given how commonly these medications are used,” added G. Caleb Alexander, MD, professor of epidemiology at the Bloomberg School.

Of note is that among 303 drugs examined in the study, only one, rituximab, a monoclonal antibody preparation that targets antibody-producing B cells, was found to be associated with a substantially increased risk of death compared with medically similar hospitalized COVID-19 patients.

Researchers analyzed data on 153 cancer patients taking rituximab and 100 patients taking rituximab for a rheumatologic condition. Taking sex, age, medical conditions, and other factors into account, the study determined that the risk of death for the cancer patients taking rituximab was more than double and the risk for patients with a rheumatologic condition was nearly three-quarters higher compared with medically similar people in the study.

“Given the finding, patients taking rituximab should discuss their options with their doctor,” Dr. Andersen recommended. “At a minimum, people who take rituximab should continue to protect themselves from developing COVID-19. It also makes it all the more important that people around those taking rituximab get vaccinated.”

Data for the retrospective cohort study came from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health–record repository of hospitalized patients with confirmed or suspected COVID-19 in the United States, between January 1, 2020, and June 11, 2021, within 42 health systems. Researchers looked at immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines.

Patients whose cases were analyzed had a mean age of 59 years and were evenly divided by sex. Their most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). Among the 16,494 on long-term immunosuppression, the most common conditions were rheumatological disease (33%), solid-organ transplant (26%), or cancer (22%).

The authors report that, in the propensity score–matched cohort including 12,841 immunosuppressed patients and 29,386 nonimmunosuppressed patients, immunosuppression actually was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83-0·96) and no overall association between long-term immunosuppression and the risk of in-hospital death was identified.

“None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation,” the researchers advise. “Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10-2·69) and for cancer (2·57, 1·86-3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions.”

The study team concludes that, among the cohort, except with rituximab, no increased risk of mechanical ventilation or in-hospital death was found for the rheumatological, antineoplastic, or antimetabolite therapies considered.

On the other hand, the researchers raise the possibility that Janus kinase (JAK) inhibitors, which are used to treat arthritis, inflammatory bowel disease, and other inflammatory conditions, might be linked to significantly lower risk, 58%, of COVID-19-related in-hospital death. JAK inhibitors such as baricitinib have recently been used to treat severe COVID-19.

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