Severe COVID-19 rare in tixagevimab/cilgavimab-treated SARDs patients

Breakthrough COVID-19 is not uncommon following pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab among patients with systemic autoimmune rheumatic diseases (SARDs), reports a recent study. However, most of the infections in this high-risk population are not severe.

In addition, disease-modifying antirheumatic drug (DMARD) type, including CD20 inhibitors, appear to have no significant effect on the risk of breakthrough COVID-19.

“As of July 2023, there is no PrEP against SARS-CoV-2 for severely immunocompromised patients such as patients with SARDs using CD20 inhibitors or other potent immunosuppressive agents,” the researchers said. “Our findings highlight the high clinical need for PrEP to prevent COVID-19 among particularly vulnerable patients.”

In this retrospective cohort study, a total of 444 patients with SARDs (mean age 62.0 years, 78.2 percent female) who received tixagevimab/cilgavimab between 2 January 2022 and 16 November 2022 met the inclusion criteria. The research team identified the risk factors associated with breakthrough COVID-19 using multivariable Cox regression models adjusted for baseline factors.

Of the patients, 83 (18.7 percent) had breakthrough COVID-19 (incidence rate, 31.5 per 1,000 person-months, 95 percent confidence interval [CI], 24.70‒38.24), seven (1.6 percent) were hospitalized, and one (0.2 percent) died. [J Rheumatol 2024;51:305-312]

An inverse association was observed between older age and breakthrough COVID-19 (adjusted hazard ratio [aHR], 0.86 per 10 years, 95 percent CI, 0.75‒0.99). In addition, patients with higher baseline spike antibody levels were less likely to have a SARS-CoV-2 infection (aHR, 0.42, 95 percent CI, 0.18‒0.99 for spike antibody levels >200 vs <0.4 units).

“We found a lower risk for breakthrough infection among older patients, which may in part be a result of behavioural differences such as more shielding practices, smaller social contacts, or differences in COVID-19 testing practices,” according to the researchers.

“In addition, higher baseline spike antibodies were protective against breakthrough COVID-19, highlighting the additional protection afforded by prior immunity from vaccination,” they noted.

Delaying treatment

A previous study showed that temporary interruption of immunosuppression (eg, holding methotrexate or mycophenolate mofetil) or a delay in CD20 inhibitor treatment to administer vaccines could be a good complementary strategy in patients taking these drugs. [Arthritis Rheumatol 2023;75:E1-16]

“Alternatively, the spike antibody may be a surrogate for overall immune system function, including cellular immunity that may have prevented symptomatic COVID-19,” the researchers said.

Notably, the risk of breakthrough COVID-19 (aHR, 1.05, 95 percent CI, 0.44‒2.49) was comparable between users of CD20 inhibitors and those on conventional synthetic (cs)DMARD.

“We did not find disease- or treatment-specific factors associated with breakthrough COVID-19,” the researchers said.

“[T]hough patients using CD20 inhibitors have been reported to be at an increased risk of breakthrough infection and severe COVID-19, those who received tixagevimab/cilgavimab had a similar risk of breakthrough COVID-19 as those using csDMARDs alone,” they added. [Nat Rev Rheumatol 2022;18:191-204; ACR Open Rheumatol 2022;4:238-246; Lancet Rheumatol 2021;3:e419-426]