Casirivimab/imdevimab tied to better outcomes than bamlanivimab/etesevimab in COVID-19 outpatients infected by Gamma variant

Treatment with casirivimab/imdevimab combination therapy appears to be associated with a reduced risk of hospitalization or death compared with bamlanivimab/etesevimab in outpatients with COVID-19 infected by the Gamma variant, according to a study presented at ECCMID 2021.

“New monoclonal antibodies (mAbs) like bamlanivimab/etesevimab and casirivimab/imdevimab are possible treatments for COVID-19, … [and] has been released in the market and authorized for clinical use in some European countries and in the US,” said lead author Dr Marco Falcone from the Department of Clinical and Experimental Medicine at the University of Pisa, Pisa, Italy.

“[In addition,] several preclinical studies showed that these antibodies are able to interfere with the viral entry of the virus, and that they are also potentially active against several variants of the virus,” he added.

The researchers conducted a prospective, observational study involving 214 outpatients with COVID-19 at two hospitals in Italy (University Hospital of Pisa and San Donato Hospital, Arezzo). Patients received either bamlanivimab/etesevimab (n=91) or casirivimab/imdevimab combination (n=123) within 10 days from symptom onset. Real-time RT-PCR testing of nasopharyngeal swabs was performed on days 0, 7, 14, and 21 to identify variants of concern (VOC), such as the Alpha (B.1.1.7) and Gamma (P.1) variants. All patients were reported to be at high risk of COVID-19 progression according to the FDA/AIFA recommendations. Patients were followed up until 21 days from mAbs infusion. [ECCMID 2021, abstract 4716]

Overall, 53 and 52 patients were infected by the Alpha variant in the bamlanivimab/etesevimab and casirivimab/imdevimab groups, respectively, while 20 and 23 patients had the Gamma variant, respectively. “Alpha variants were more prevalent in Italy, and the Gamma variants were less common but [it] accounted for about 20 percent of our cases,” Falcone said.

Among patients infected by the Gamma variant, significantly more patients on bamlanivimab/etesevimab had a composite of hospitalization or death within 30 days than those on casirivimab/imdevimab (55.5 percent vs 17.4 percent; p=0.013).

Patients infected by the Gamma variant treated with bamlanivimab/etesevimab also demonstrated a significantly longer time to virological cure than those treated with casirivimab/imdevimab (median 17 vs 14; p=0.04).

In addition, the researchers found that infection with the Gamma variant (hazard ratio [HR], 9.84; p<0.001) and time from symptom onset to mAbs infusion (HR, 1.36; p=0.003) were independently associated with an increased risk of hospitalization or death within 30 days. “[These drugs should be delivered] as soon as possible, … “and not to delay the infusion [as] these drugs are very active in the early phase of infection,” Falcone noted.

On the other hand, casirivimab/imdevimab was found to be a protective factor in this case, Falcone said. “This is probably related to the efficacy that we found with this combination against the Gamma variant that was quite common in our guard,” he added.

Among patients infected with the Alpha variant, there was no difference in the composite outcome of hospitalization or death between the bamlanivimab/etesevimab and casirivimab/imdevimab treatment groups (5.7 percent vs 4.3 percent), showing that “both mAbs combination had a very good efficacy in preventing progression to severe disease,” said Falcone.

“[In conclusion,] among patients infected by the Gamma variant, … treatment with bamlanivimab/etesevimab was associated with a higher risk of hospitalization or death compared with patients who received casirivimab/imdevimab, … [and] should be avoided because of a high risk of failure,” said Falcone.

“It is very important … [to identify the] variant of the virus that infected the patients because the knowledge of the variant may allow a more appropriate use and a better choice of the best mAbs combination,” he added.