Tixagevimab copackaged with cilgavimab (Evusheld) is a safe and effective preexposure prophylaxis (PrEP) in patients undergoing B-cell-depleting therapies who have poor immune response to COVID-19 vaccination and are at high risk for serious COVID-19 illness, a small, single-site study suggests.
Evusheld, the only COVID-19 PrEP option available, has Emergency Use Authorization (EUA) from the Food and Drug Administration for treatment of immunocompromised patients who may not respond sufficiently to COVID-19 vaccination and patients who’ve had a severe adverse reaction to COVID-19 vaccination.
“We report the largest real-world experience of Evusheld in this population, and our findings are encouraging,” lead study author Cassandra Calabrese, DO, rheumatologist and infectious disease specialist at Cleveland Clinic, said in an interview.
“Of 412 patients who received Evusheld, 12 [2.9%] developed breakthrough COVID-19, with 11 having mild courses and 1 who required hospitalization but recovered,” she added.
“Our data suggest that Evusheld PrEP, in combination with aggressive outpatient treatment of COVID-19, is likely effective in lowering risk of severe COVID in this vulnerable group.
“Practitioners who care for patients with immune-mediated inflammatory diseases should triage high-risk patients for Evusheld as well as rapid diagnosis and aggressive outpatient therapy if infected,” Dr. Calabrese advised.
For the study, Dr. Calabrese and colleagues at Cleveland Clinic searched the health care system pharmacy records for patients with immune‐mediated inflammatory diseases (IMIDs) or inborn errors of humoral immunity (IEI) who met the criteria to receive Evusheld. The researchers included patients on B-cell-depleting therapies or with humoral IEI who had received at least one dose of Evusheld and were later diagnosed with COVID-19, and they excluded those treated with B-cell-depleting therapies for cancer.
EVUSHELD was well tolerated
After extracting data on COVID-19 infection, vaccination status, and outcomes, they found that, between Jan. 18 and May 28, 2022, 412 patients with IMIDs or humoral IEI received Evusheld. No deaths occurred among these patients and, overall, they tolerated the medication well.
All 12 patients who experienced breakthrough COVID-19 infection were treated with B-cell-depleting therapies. Among the 12 patients:
- Six patients developed infection 13-84 (median 19) days after receiving 150 mg/150 mg tixagevimab/cilgavimab.
- Six patients developed infection 19-72 (median of 38.5) days after either a single dose of 300 mg/300 mg or a second dose of 150 mg/150 mg.
- Eleven patients had mild illness and recovered at home; one patient was hospitalized and treated with high-flow oxygen. All cases had been vaccinated against COVID-19 (five received two vaccinations, six received three, and one received four).
- One possible serious adverse event involved a patient with COVID-19 and immune-mediated thrombocytopenia (ITP) who was hospitalized soon after receiving Evusheld with ITP flare that resolved with intravenous immunoglobulin.
Dr. Calabrese acknowledged limitations to the study, including few patients, lack of a comparator group, and the study period falling during the Omicron wave.
“Also, nine of the breakthrough cases received additional COVID-19 therapy (oral antiviral or monoclonal antibody), which falls within standard of care for this high-risk group but prevents ascribing effectiveness to individual components of the regimen,” she added.
“Evusheld is authorized for PrEP against COVID-19 in patients at high risk for severe COVID due to suboptimal vaccine responses. This includes patients receiving B-cell-depleting drugs like rituximab, and patients with inborn errors of humoral immunity,” Dr. Calabrese explained.
“It is well known that this group of patients is at very high risk for severe COVID and death, even when fully vaccinated, and it has become clear that more strategies are needed to protect this vulnerable group, including use of Evusheld as well as aggressive treatment if infected,” she added.