Long-term benefits with molnupiravir modest at best in COVID-19 treatment

The antiviral molnupiravir confers continued but modest benefits in terms of reducing COVID-19–related symptoms up to 6 months after the index infection in a vaccinated population, according to a secondary analysis of the PANORAMIC trial.

Long-term follow-up data from 23,008 participants (89.2 percent of the trial population, mean age 57.2 years, 58.4 percent female, 94.7 percent White, 99.1 percent had received at least one dose of vaccination) showed that “cough, shortness of breath, fatigue, muscle aches, and being generally unwell were less prevalent in the molnupiravir plus usual care group at 3 months and 6 months,” the investigators reported.

Relative to those who had received usual care alone, fewer participants who had undergone a 5-day course of molnupiravir in addition to usual care reported experiencing any symptoms that were rated as severe (3 months: 16.9 percent vs 18.3 percent, number needed to treat [NNT]=62.5; 6 months: 16.5 percent vs 18.3 percent, NNT=52.6) or any persistent symptoms (3 months: 8.9 percent vs 11.0 percent, NNT=47.6; 6 months: 8.5 percent vs 11.0 percent, NNT=40). [Lancet Infect Dis 2024;doi:10.1016/S1473-3099(24)00431-6]

Participant rating of wellness was higher in the molnupiravir plus usual care group than in the usual care alone group, with an adjusted mean difference of 0.15 at 3 months and 0.12 at 6 months. The same was true for health-related quality of life, with an adjusted mean difference in the EQ-5D-5L score of 1.08 at 3 months and 1.09 at 6 months.

Additionally, participants in the molnupiravir plus usual care group were less likely to use any healthcare or social service at 3 months (14.1 percent vs 15.5 percent; NNT=71.4) and at 6 months (8.9 percent vs 9.2 percent; NNT=200), as well as to have taken time off work or study at 3 months (17.9 percent vs 22.4 percent; NNT=18.9) and at 6 months (4.4 percent vs 5.4 percent; NNT=90.9).

Very few participants were hospitalized due to COVID-19 during the long-term follow-up, with no significant between-group difference in either COVID-19-related or all-cause hospitalizations at 3 and 6 months.

“Participant rating of wellness, any symptom rated moderately bad or worse, any persistent symptom, and health or social care use, and time off work were all statistically superior in the molnupiravir plus usual care group at 3 months and 6 months but with small absolute effects,” the investigators said.

“This study was a secondary long-term analysis, and although we did not correct for multiplicity, the number of statistically superior outcomes make chance a very unlikely explanation of the results,” they continued, noting however that small absolute differences that are statistically significant may not necessarily be clinically meaningful.

In a news release, lead investigator Dr Victoria Harris from the Nuffield Department of Primary Care Health Sciences in Oxford, England, pointed to the fact that the NNTs were high. This means that “a large number of patients would need to be treated with molnupiravir to see one additional beneficial outcome compared to usual care.”

“For instance, only one person would have less severe symptoms from a total of 53 people who took molnupiravir, and only one person would have used fewer NHS services from a total of 71 people who took molnupiravir. Given the small additional number of participants who benefited from taking molnupiravir, compared to those who did not take the drug, long-term health benefits will need to be weighed up against costs and any unwanted effects,” Harris stated.

In the UK, molnupiravir costs about GBP 500 per course. As such, providing all COVID-19 patients with the drug would have substantial financial implications for the NHS. Harris and colleagues believe that their data could help relevant stakeholders make decisions about the long-term treatment of COVID-19.