Nonhospitalized, unvaccinated adult patients (≥ 18 years-old) who had mild-to-moderate, laboratory-confirmed coronavirus disease 2019 (Covid-19) that presented with early onset signs and symptoms (≤ 5 days) and had at least one risk factor for severe Covid-19.
Participants had at least one of the following risk factors: age > 60 years, active cancer, chronic kidney disease, chronic obstructive pulmonary disease, body mass index (BMI) ≥ 30 kg/m2, serious heart conditions, and diabetes mellitus.
Adults who received severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination with an anticipated need for hospitalization for Covid-19 within the next 48 hours, severe renal dysfunction, pregnancy or planning to become pregnant, severe neutropenia (absolute neutrophil count <500/mcL), and thrombocytopenia (platelet count <100,000/mcL).
Intervention (n = 716): Molnupiravir 800 mg orally twice daily for 5 days.
Comparison (n = 717): Identical placebo taken orally twice daily for 5 days.
Outcome: The primary efficacy outcome was the rate of hospitalization or death through day 29, while the primary safety outcome was the incidence of adverse events. All actively enrolled participants underwent a 7-month follow-up visit.
The primary efficacy endpoint of all-cause hospitalization or death through day 29 was statistically significant, but with wide confidence intervals. The authors did not report the p-value. The outcomes of the individual components of the composite primary endpoint were not reported, so it is unclear whether all-cause hospitalization or death had driven the overall results.
The MOVe-Out trial was a phase 3, double-blind, placebo-controlled study, which utilized a mITT to analyze the results. The study compared molnupiravir 800 mg orally twice daily for five days to placebo in nonhospitalized adults, who were unvaccinated with mild-to-moderate, laboratory-confirmed SARS-CoV-2 infection that presented with early onset signs and symptoms (≤ 5 days) and had at least one risk factor for severe Covid-19. The trial found an absolute risk reduction of 3.6% and a 30.4% relative risk reduction of hospitalization and death at 29 days in patients who received molnupiravir compared to placebo. Molnupiravir was well-tolerated, with minimal adverse events. Molnupiravir is not recommended in children, patients who are pregnant or planning to become pregnant, severely impaired renal dysfunction, neutropenic, or thrombocytopenic. The relative risk reduction of 30.4% for molnupiravir demonstrated less efficacy compared to other preferred therapies such as nirmatrelvir/ritonavir and remdesivir. Therefore, molnupiravir should only be used if patients cannot receive nirmatrelvir/ritonavir or remdesivir.
The MOVe-Out trial studied whether molnupiravir (LagevrioTM), a medication that targets viruses, was helpful in preventing hospitalization or death from Covid-19. The patients in the trial were not hospitalized, not vaccinated against the virus that causes Covid-19, had signs or symptoms of Covid-19 within five days, and could develop severe Covid-19, which could lead to hospitalization or death. The study found that molnupiravir reduced hospitalization or death by 30% and had few side effects. However, because other medications have been shown to better than molnupiravir in preventing hospitalization or death from Covid-19, your healthcare provider should only prescribe molnupiravir if it is not possible for you to receive these other medications.
A Tribute to Dr. Noelle K. de Leon In Memoriam
We are saddened to report that Dr. Noelle de Leon passed away on Nov. 25, 2022 at the tender age of 40, after a brief but fierce battle with Stage 4 biliary intrahepatic cholangiocarcinoma. We would like to recognize Dr. de Leon’s longstanding contributions to the Evidence-Based Practice (EBP) section of the Journal of Contemporary Pharmacy Practice (JCPhP), where she used her expertise to help develop the critical appraisal skills of her co-authors and acted as Ad Hoc Section Editor when requested. Dr. de Leon published a total of 9 articles in the Journal, including 7 articles for the EBP section during her time in this role since 2015, the last of which appears in this issue of the Journal.
Dr. de Leon was a clinical pharmacist specializing in cardiovascular critical care and anticoagulation management at UC San Francisco Medical Center and an Assistant Clinical Professor at the UC San Francisco School of Pharmacy, where she mentored countless residents over the years. Dr. de Leon obtained her PharmD from the University of Southern California and went on to complete a PGY1 residency focused on critical care at Community Regional Medical Center, and a PGY2 Cardiology residency at Western University of Health Sciences/VA Greater Los Angeles Healthcare System. Even though she was on medical leave, she was nominated for and won the UCSF Pharmacist of the Year. She was described as someone who “brings energy, professionalism, intellect, systems-level thinking, teaching ability, and clinical expertise to the team.”
Dr. Cynthia Jackevicius, Associate Editor of the Journal who oversees the EBP Section, Noelle’s PGY2 Residency Program Director, and Professor at Western University of Health Sciences, said: “Anyone who had the good fortune of meeting Noelle discovered that she was truly a special person – she had a unique combination of kindness and humor, intellect, determination, and professionalism that made her loved and respected by all she met. It was readily apparent that she was a natural teacher and leader right from the time of her residency. I am truly grateful to have been able to work with Noelle during her residency, and for the last 7 years (up until her diagnosis 4 months ago) on the EBP Section critical appraisals for the Journal. On top of her remarkable professional role, Noelle was also a devoted mother and wife, and dear friend to so many of us.”
Dr. Genene Salman, Associate Professor at Marshall B. Ketchum University College of Pharmacy said: “I was fortunate to work with Noelle as a co-author for three EBP reviews for the Journal of Contemporary Pharmacy Practice starting in February 2017. She mentored and guided me, my colleagues, and students on how to critically analyze clinical trials. Noelle was conscientious, thoughtful, and eloquent. She truly cared about her work. Noelle was approachable and humble, always welcoming questions and feedback. She had a positive impact in so many lives and the profession of pharmacy. We miss her dearly.”
Former JCPhP Editor-in-Chief Dr. Anandi V. Law added: “Noelle was one of our postdocs and I remember her as a kind and intelligent individual. I was fortunate to be able to work with her and Cynthia on the EBP part of the Journal. It is a loss for the profession, and we will miss her. We all join in conveying our sympathies to her husband and daughters.”
Our thoughts go out to her family, friends and colleagues. If you would like to learn more about Noelle and her journey, please see the GoFundMe page that her husband (Dr. Michael Tse, also a pharmacist) started at the end of October. Donations will go towards an educational fund for her two young daughters.
As her husband, Dr. Tse, wrote: “This was always Noelle's priority since she did not have these resources growing up. She had to navigate a lot of her own education and despite it all, she still succeeded. She didn't want our girls to have go to through the same struggles as herself hence this fund will lead them in the right direction.”
Citation: Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med 2022;386(6):509–520. doi:10.1056/NEJMoa2116044.
About the Editor
Cynthia Jackevicius, BScPhm, PharmD, MSc, BCPS, BCCP, FCSHP, FAHA, FCCP, FCCS, FACC, a professor of pharmacy practice at Western University of Health Sciences, is the evidence-based practice section editor. Dr. Jackevicius teaches evidence-based practice skills to health care professionals. She advocates for the adoption of an evidence-based practice, incorporating the best available evidence, patients’ values and preferences, and clinicians’ expertise into clinical decision-making. She has no conflicts of interest to report.