@article{Harris_V-2024_184456,
title = {Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC): a randomised controlled trial},
author = {Harris, V. and Holmes, J. and Gbinigie-Thompson, O. and Rahman, N. and Richards, D. and Hayward, G. and Dorward, J. and Lowe, D. and Standing, J. and Breuer, J. and Khoo, S. and Petrou, S. and Hood, K. and Ahmed, H. and Carson-Stevens, A. and Nguyen-Van-Tam, J. and Patel, M. and Saville, B. and Francis, N. and Thomas, N. and Evans, P. and Dobson, M. and Png, M. and Lown, M. and van Hecke, O. and Jani, B. and Hart, N. and Butler, D. and Cureton, L. and Patil, M. and Andersson, M. and Coates, M. and Bateman, C. and Davies, J. and Raymundo-Wood, I. and Ustianowski, A. and Yu, L. and Hobbs, F. and Little, P. and Butler, C. and Moftah, A. and Goodman, A. and Halifax, R. and Turnbull, C. and Sundaralingam, A. and Agyeman, A. and Shah, D. and Brown, J. and Thalasselis, C. and Woodall, M. and Yongblah, F. and Howell, A. and Patel, K. and Hussain, I. and Penfold, R. and Hutchinson, S. and Poonian, S. and Imlach, M. and Popoola, O. and Irving, G. and Pora, A. and Jacobsen, N. and Prasad, V. and Kennard, J. and Prasad, R. and Khan, U. and Razzaq, O. and Knox, K. and Richardson, S. and Krasucki, C. and Royal, S. and Law, T. and Safa, A. and Lee, R. and Sehdev, S. and Lester, N. and Sevenoaks, T. and Lewis, D. and Sheikh, A. and Lunn, J. and Short, V. and Mackintosh, C. and Singh Sidhu, B. and Mathukia, M. and Singh, I. and Moore, P. and Soni, Y. and Morton, S. and Wilson, P. and Murphy, D. and Wingfield, D. and Nally, R. and Wong, M. and Ndukauba, C. and Wooding, N. and Ogundapo, O. and Woods, S. and Okeke, H. and Yong, J. and Ahmed, T. and Allcock, D. and Atherton, G. and Beltran-Martinez, A. and Benedict, O. and Bird, N. and Brennan, L. and Burns, G. and Butler, M. and Butler, D. and Carson-Stevens, A. and Cheng, Z. and Danson, R. and de Kare-Silver, N. and Dhasmana, D. and Dickson, J. and Engamba, S. and Fisher, S. and Fox, R. and Frost, E. and Gaunt, R. and Ghosh, S. and Gilkar, I. and Goodman, A. and Granier, S. and Packham, A. and Dowsell, S. and Gulati, R. and Patel, A.},
month = {sep},
year = {2024},
abstract = {Background: No randomised controlled trials have yet reported on the effectiveness of molnupiravir on longer term outcomes for COVID-19. The PANORAMIC trial found molnupiravir reduced time to recovery in acute COVID-19 over 28 days. We aimed to report the effect of molnupiravir treatment for COVID-19 on wellbeing, severe and persistent symptoms, new infections, health care and social service use, medication use, and time off work at 3 months and 6 months post-randomisation. Methods: This study is a follow-up to the main analysis, which was based on the first 28 days of follow-up and has been previously reported. For this multicentre, primary care, open-label, multi-arm, prospective randomised controlled trial conducted in the UK, participants were eligible if aged at least 50 years, or at least 18 years with a comorbidity, and unwell 5 days or less with confirmed COVID-19 in the community. Participants were randomly assigned to the usual care group or molnupiravir group plus usual care (800 mg twice a day for 5 days), which was stratified by age (&lt;50 years or ≥50 years) and vaccination status (at least one dose: yes or no). The primary outcome was hospitalisation or death (or both) at 28 days; all longer term outcomes were considered to be secondary outcomes and included self-reported ratings of wellness (on a scale of 0–10), experiencing any symptom (fever, cough, shortness of breath, fatigue, muscle ache, nausea and vomiting, diarrhoea, loss of smell or taste, headache, dizziness, abdominal pain, and generally feeling unwell) rated as severe (moderately bad or major problem) or persistent, any health and social care use, health-related quality of life (measured by the EQ-5D-5L), time off work or school, new infections, and hospitalisation. Findings: Between Dec 8, 2021, and April 27, 2022, 25 783 participants were randomly assigned to the molnupiravir plus usual care group (n=12 821) or usual care group (n=12 962). Long-term follow-up data were available for 23 008 (89·2%) of 25 784 participants with 11 778 (91·9%) of 12 821 participants in the molnupiravir plus usual care group and 11 230 (86·6%) of 12 963 in the usual care group. 22 806 (99·1%) of 23 008 had at least one previous dose of a SARS-CoV-2 vaccine. Any severe (3 months: adjusted risk difference –1·6% [–2·6% to –0·6%]; probability superiority [p(sup)]&gt;0·99; number needed to treat [NNT] 62·5; 6 months: –1·9% [–2·9% to –0·9%]; p(sup)&gt;0·99, NNT 52·6) or persistent symptoms (3 months: adjusted risk difference –2·1% [–2·9% to –1·5%]; p(sup)&gt;0·99; NNT 47·6; 6 months: –2·5% [–3·3% to –1·6%]; p(sup)&gt;0·99; NNT 40) were reduced in severity, and health-related quality of life (measured by the EQ-5D-5L) improved in the molnupiravir plus usual care group at 3 months and 6 months (3 months: adjusted mean difference 1·08 [0·65 to 1·53]; p(sup)&gt;0·99; 6 months: 1·09 [0·63 to 1·55]; p(sup)&gt;0·99). Ratings of wellness (3 months: adjusted mean difference 0·15 (0·11 to 0·19); p(sup)&gt;0·99; 6 months: 0·12 (0·07 to 0·16); p(sup)&gt;0·99), experiencing any more severe symptom (3 months; adjusted risk difference –1·6% [–2·6% to –0·6%]; p(sup)=0·99; 6 months: –1·9% [–2·9% to –0·9%]; p(sup)&gt;0·99), and health-care use (3 months: adjusted risk difference –1·4% [–2·3% to –0·4%]; p(sup)&gt;0·99; NNT 71·4; 6 months: –0·5% [–1·5% to 0·4%]; p(sup)&gt;0·99; NNT 200) had high probabilities of superiority with molnupiravir treatment. There were significant differences in persistence of any symptom (910 [8·9%] of 10 190 vs 1027 [11%] of 9332, NNT 67) at 6 months, and reported time off work at 3 months (2017 [17·9%] of 11 274 vs 2385 [22·4%] of 10 628) and 6 months (460 [4·4%] of 10 562 vs 527 [5·4%] of 9846; NNT 100). There were no differences in hospitalisations at long-term follow-up. Interpretation: In a vaccinated population, people treated with molnupiravir for acute COVID-19 felt better, experienced fewer and less severe COVID-19 associated symptoms, accessed health care less often, and took less time off work at 6 months. However, the absolute differences in this open-label design are small with high numbers needed to treat.},
journal = {The Lancet Infectious Diseases},
publisher = {Elsevier},
url = {http://dx.doi.org/10.1016/S1473-3099(24)00431-6},
}
