Tocilizumab augments response to remdesivir, dexamethasone in ICU patients with COVID-19
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NASHVILLE, Tenn. — Combination therapy with remdesivir and dexamethasone plus tocilizumab yielded reductions in inflammatory markers and mortality and more discharges for patients with COVID-19 hospitalized in the ICU, researchers reported.
However, the addition of baricitinib (Olumiant, Lilly) adversely impacted treatment responsiveness to remdesivir (Veklury, Gilead) and dexamethasone, whereas the addition of tocilizumab (Actemra, Genentech) augmented responsiveness, according to data presented at the CHEST Annual Meeting.
“In our study, we ultimately found that critically ill COVID-19 patients treated with mainstay therapy of remdesivir and dexamethasone along with supplementation with baricitinib vs. tocilizumab had worse clinical outcomes — specifically, increased mortality and decreased discharges to home. Further, mainstay therapy was found to be augmented by tocilizumab,” Stephanie N. Williams, MD, PGY3 resident physician at Florida State University/Sarasota Memorial Healthcare System, told Healio. “These findings shed light on the question of superiority of one immunotherapy agent over the other and [the] need for further investigation into this.”
Williams and colleagues assessed the impact of supplementation of remdesivir and dexamethasone in combination with tocilizumab or baricitinib initiated within 48 hours of index hospitalization for COVID-19 on inflammatory markers and discharge.
The researchers analyzed electronic medical record data and treatment responsiveness, based on levels of C-reactive protein, ferritin, lactate dehydrogenase and D-dimer collected from assays within the first 24 hours of hospitalization and then between 25 and 72 hours of initiating remdesivir and dexamethasone with and without tocilizumab or baricitinib.
“Early during the COVID-19 pandemic, there was so much unknown about the optimal management of SARS-CoV-2 infection in rapidly deteriorating patients. This study was prompted largely by this desire to learn more, specifically in relation to the immunomodulatory role of management,” Williams told Healio.
The study included 459 patients with COVID-19 admitted to the ICU and treated with remdesivir and dexamethasone from March 2020 through January 2022. Of these patients, 326 (mean age, 67 years; standard deviation [SD], 57-77) were treated with the combination drugs alone, 85 (mean age, 62; SD, 48-68) were supplemented with baricitinib and 41 (mean age, 61 years; SD, 51-69) were supplemented with tocilizumab. Patients were statistically similar in sex (65% men), race (76% white) and BMI (32 kg/m2). Also, 70% had hypertension, 59% obesity, 38% diabetes, 36% anemia, 29% coagulopathy, 22% COPD and 17% renal failure.
Researchers found that initial C-reactive protein levels within the first 24 hours of hospitalization were reduced 25 to 72 hours after receiving treatment, including by –3.4 mg/dL in the remdesivir/dexamethasone group, by –4.3 mg/dL in the baricitinib group and by –7.2 mg/d in the tocilizumab group (P = .014).
For ferritin, researchers found that initial levels increased by 7 U/L in the remdesivir/dexamethasone group and declined by –94 U/L for those supplemented with baricitinib and by –29 U/L for those supplemented with tocilizumab.
Lactate dehydrogenase levels within 24 hours of hospitalization decreased 25 to 72 hours later by –3 U/L for the remdesivir/dexamethasone group, increased 85 U/L for the baricitinib group and decreased –33 U/L for the tocilizumab group.
Researchers also observed that D-dimer remained unchanged for the remdesivir/dexamethasone group, increased by 0.88 µg/mL for those also taking baricitinib and decreased –0.01 µg/mL for those also taking tocilizumab.
Researchers concluded that remdesivir/dexamethasone plus tocilizumab showed the largest reduction of inflammatory markers.
Those receiving remdesivir/dexamethasone plus tocilizumab had the lowest percentage of hospital mortality at 43% (P > .017), followed by remdesivir/dexamethasone at 51% and remdesivir/dexamethasone plus baricitinib at 71% (P = .0019).
In terms of discharge to home, remdesivir/dexamethasone plus tocilizumab also showed the highest percentage at 43% (P = .0038), whereas remdesivir/dexamethasone followed again at 24% and remdesivir/dexamethasone plus baricitinib had the lowest percentage at 18%.
“Our findings speak further to the need for more data to investigate and compare outcomes of different immunomodulatory therapies in an attempt to determine potential superiority of a particular agent, and thereby guide future management,” Williams told Healio.
Looking ahead, Williams said it will be important to look at larger study cohorts. In addition, “there remains a need to refine early longitudinal biomarker tracking to identify patient-centric COVID-19 treatment responsiveness to COVID-19-directed treatments,” she said.