Rituximab Increases Risk of Severe COVID-19 in Patients with Rheumatic Disease

Patients with inflammatory rheumatic and musculoskeletal diseases on rituximab therapy may have a greater risk for severe COVID-19, according to a study.

“In particular, rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases, especially if they have other comorbidities that render them particularly at risk of severe COVID-19 outcomes,” the researchers wrote in their conclusion.

They examined data from the French RMD COVID-19 cohort, which consisted of patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases who had confirmed or highly suspected COVID-19, spanning April 15, 2020, and Nov. 20, 2020. Patients were stratified and compared by whether or not they received rituximab. The main outcome was COVID-19 severity; severe disease was defined as requiring intensive care unit (ICU) admission or death. Additional outcomes included analyzing deaths and duration of hospital stay. Adjustment for confounding factors took into consideration age, sex, arterial hypertension, diabetes, smoking status, body mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease (rheumatoid arthritis vs others).

Final analysis included 1,090 patients, of whom 63 were receiving rituximab and 1,027 were not. The mean age was 55.2 years (standard deviation, 16.4 years), and two-thirds of the cohort was female (n=734). Overall, 137 patients developed severe COVID-19, and 89 patients died.

In adjusted analyses, the rituximab group was more likely to have severe disease (effect size, 3.26; 95% confidence interval [CI], 1.66–6.40; P=0.0006) and have a significantly longer duration of hospital stay (effect size, 0.62; 95% CI, 0.46–0.85; P=0.0024). A much larger proportion of patients died in the rituximab group than the no rituximab group (n=13 [21%] vs n=76 [7%]); however, the rituximab group did not have a significantly increased adjusted risk of death (effect size, 1.32; 95% CI, 0.55­–3.19; P=0.53).

The study appeared in The Lancet Rheumatology.

Rituximab Data: More Questions Than Answers?

An accompanying editorial stated, “These data are very relevant to our daily clinical practice, but raise many questions.”

Maxime Dougados, MD, author of the editorial, wrote that it makes sense to discontinue rituximab if patients are in remission, or offer a different therapy, as other therapies do not appear to pose the same COVID-19-associated risks as rituximab. However, questions arise in patients with systemic autoimmune diseases that are only controlled by rituximab. One solution may be to give these patients rituximab without pre-administering corticosteroids, which have been shown to increase severe COVID-19 risk.

“Moreover, it has been shown that this pre-administration was useful in avoiding anaphylactic reactions to the infusion, especially during the first cycle of rituximab treatment, but less useful during the following cycles,” Dr. Dougados explained. “Another possibility is to consider reducing the dose of rituximab either by increasing the interval between infusions or by reducing the dose of each infusion.”