Baricitinib, ivermectin, favipiravir rank high among COVID-19 oral antivirals

Baricitinib, ivermectin, and favipiravir stood out in terms of efficacy in a network meta-analysis evaluating various novel oral antivirals for the treatment of COVID-19.

“[B]aricitinib has reduced in-hospital mortality in hospitalized COVID-19 patients, with moderate certainty of evidence. Ivermectin appeared to be a [better] option than placebo in improving recovery time, while favipiravir was associated with SpO₂ [improvement],” said the researchers.

The investigators used data from 36 randomized controlled trials for the network meta-analysis. In these studies, a total of 33,555 hospitalized COVID-19 patients were randomized to receive one of seven oral antivirals against COVID-19: baricitinib, chloroquine, favipiravir, hydroxychloroquine (HCQ), HCQ plus azithromycin (HCQ + AZT), ivermectin, and lopinavir/ritonavir. [Clin Epidemiol 2023:15:1041-1053]

In-hospital mortality

With regard to the primary outcome, treatment with baricitinib resulted in a statistically significant improvement in in-hospital mortality as opposed to placebo (odds ratio [OR], 0.57, 95 percent confidence interval [CI], 0.36–0.92). This translates to a 43-percent reduction in the odds of experiencing in-hospital mortality compared with patients receiving placebo treatment. The ORs for the other antivirals ranged between 0.76 and 0.94.

These findings are supported by the ranking in the surface for each outcome under the cumulative ranking curve (SUCRA) probability plot, wherein baricitinib ranked the highest (SUCRA value, 0.889) followed by HCQ + AZT (SUCRA value, 0.638). The least effective therapies were ivermectin and placebo (SUCRA values, 0.351 and 0.228, respectively).

“[A] higher probability of SUCRA in each simulation indicates a higher probability of being the optimal treatment regimen,” the researchers explained. “[As such, the SUCRA plot data imply that] baricitinib is the only treatment that is significantly superior in reducing in-hospital mortality.”

The findings align with evidence showing that baricitinib treatment led to a significant reduction in the risk of death in hospitalized COVID-19 patients. [Lancet 2022;400:359-368; Lancet Respir Med 2021;9:1407-1418; J Infect 2020;81:318-356]

“Baricitinib prevents SARS-CoV-2 from entering and infecting alveolar lung cells. This mechanism may help reduce cytokine bursts in COVID-19 because the JAK-STAT signalling pathway is crucial for its development,” the researchers explained. [Arthritis Res Ther 2019;21:183; Lancet 2020;395:e30-e31; Cell 2021;184:460-475.e21]

Recovery time, SpO₂ improvement

Ivermectin, a macrocyclic lactone antiparasitic agent, ranked first in improving recovery time of hospitalized COVID-19 patients compared with placebo (mean difference, -1.36, 95 percent CI, -2.32 to -0.39). This was also evident in the SUCRA plot (SUCRA value, 0.758); HCQ ranked second (SUCRA value, 0.632), followed by baricitinib (SUCRA value, 0.576).

Regarding SpO₂ improvement, favipiravir showed better efficacy than ivermectin (OR, 1.7, 95 percent CI, 0.09–3.45). The favipiravir group demonstrated an average increase of 1.77 units in SpO₂ improvement compared with the ivermectin group. In the SUCRA plot, favipiravir took the lead (SUCRA value, 0.736) while ivermectin ranked last (SUCRA value, 0.046).

More practical treatment option

Oral antivirals are important tools in the COVID-19 treatment armamentarium, as these are more practical and patient-friendly especially for nonhospitalized individuals with COVID-19, the researchers noted.

“Our findings may be useful in the selection of novel oral antivirals for optimal treatment of hospitalized COVID-19 patients … We anticipate that these findings will contribute to shared decision-making between patients and their clinicians,” they said.

The researchers added that these preliminary observations may be used to guide clinical practice until more data are made available. The findings also underscore the importance of public health measures to address infectious waves caused by novel COVID-19 variants and subsequently kickstart the development of new oral antiviral agents that could better counter emerging variants.