Study: Immune-suppressed not at higher risk of poor COVID outcomes

A large US study finds that hospitalized COVID-19 patients taking medications that suppress the immune system, including cancer patients, are not at overall higher risk for dying of their infection or requiring invasive mechanical ventilation than those not taking these drugs.

Early in the pandemic, immunosuppressed patients were thought to be at elevated risk of poor COVID-19 outcomes. Some damage to the lungs and other organs in severe infections are believed to result from overactivation of the immune system, and by summer 2020, physicians were treating severe COVID-19 with immunosuppressive drugs such as dexamethasone, the researchers noted.

Only rituximab tied to death, ventilation

In the retrospective study, published this week in The Lancet Rheumatology, a team led by Johns Hopkins University researchers analyzed the electronic health records of 222,575 adults hospitalized at 42 health systems for treatment of COVID-19 from Jan 1, 2020, to Jun 11, 2021.

Of those patients, 16,494 (7%) had been taking immunosuppressive medications long term for conditions such as rheumatologic disease (33%), solid organ transplant (26%), and cancer (22%). Average patient age was 59 years, half were men, and their most common underlying illnesses were diabetes (23%), pulmonary disease (17%), and kidney disease (13%).

In a propensity score–matched cohort made up of 12,841 immunosuppressed and 29,386 non-immunosuppressed patients, immunosuppression was tied to a reduced risk of invasive mechanical ventilation (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.83 to 0.96). In addition, there was no link between long-term immunosuppressive therapy and risk of in-hospital death.

Of the 303 drugs in 15 medication classes included in the study, none were associated with elevated risk of invasive mechanical ventilation or death except for the monoclonal antibody preparation rituximab for rheumatologic disease (HR, 1.72; 95% CI, 1.10 to 2.69) and cancer (HR, 2.57; 95% CI, 1.86 to 3.56).

The analysis also found a link between JAK inhibitors—a relatively new class of immunosuppressive drug used to treat inflammatory conditions such as arthritis and inflammatory bowel disease—and a 58% lower risk of COVID-19 in-hospital death.

In general, results were consistent across subgroup analyses that included race or sex, and across sensitivity analyses that varied exposure, covariate, and outcome definitions.

Most patients can continue taking immunosuppressants

The authors said that patients taking immunosuppressive drugs can safely continue, but that those on rituximab should talk with their physician about their options.

"At a minimum, people who take rituximab should continue to protect themselves from developing COVID-19," lead author Kayte Andersen, MSc, a doctoral candidate, said in a Johns Hopkins University press release. "It also makes it all the more important that people around those taking rituximab get vaccinated."

In a related commentary, David Liew, MBBS, PhD, of the University of Melbourne and Philip Robinson, MBBS, PhD, of the University of Queensland School of Clinical Medicine, both in Australia, said that patients taking rituximab can either continue taking it and use post-exposure prophylaxis (prevention) with monoclonal antibodies or new small-molecule antiviral treatments or pre-exposure prophylaxis with long-acting monoclonal antibodies.

Alternatively, Liew and Robinson said, physicians might prescribe other therapies, which they acknowledged is difficult in the treatment of some indications for which rituximab is first-line therapy.

"The detriment from choosing an inferior option…will need to be balanced against potentially improved outcomes with COVID-19," they wrote. "This equation will vary with new SARS-CoV-2 variants, changing epidemiology, and between individual patients; currently, such a complex decision lacks data to inform it."

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