oral-nirmatrelvir-for-high-risk-nonhospitalized-adults-with-covid-19 2022-02-17T18:02:06.562Z f48a5fc4-8228-47ec-ba84-e6c8e22ded59 mas_evidence_types:Randomised%20controlled%20trials Primary research RCT (n=2246) found treatment of symptomatic Covid-19 with nirmatrelvir + ritonavir reduced risk of progression to severe Covid-19 vs placebo (incidence 0.77% with 0 deaths vs.7.01% with 7 deaths placebo group;relative risk reduction 89.1%; p<0.001) without evident safety concerns <p>According to an editorial, this is the first small-molecule antiviral agent designed specifically to inhibit SARS-CoV-2.2; the active component, nirmatrelvir, is an inhibitor of the SARS-CoV-2 3-chymotrypsin&ndash;like cysteine protease enzyme, one of two essential proteases encoded by the virus. It notes that although the results are clear, it is worth considering the difference between absolute and relative risk reduction, pointing out relative risk reductions were large and similar across most subgroups, but those at lower risk had a very small absolute benefit. In addition, this trial was performed between mid-July and early December 2021 when the delta variant was most likely responsible for the majority of infections and it is not yet know how nirmatrelvir plus ritonavir will perform as new variants, such as omicron, emerge. Furthermore, resistance to the new agent has not yet been seen, but just as newer variants have evolved to be less susceptible to immune control (including control by monoclonal antibodies), it suggests likelihood that resistance to a single agent such as nirmatrelvir will become an issue and discusses how best to use this drug, particularly as supplies are currently constrained and likely to remain so for some time. It alludes to the findings of study to help in that decision as absolute benefit will accrue primarily to patients at highest risk for disease progression, particularly those with multiple and serious coexisting conditions and those unable to mount sufficient immune responses. It also notes that the timing of nirmatrelvir therapy is probably critical as well, as is the case for other antiviral agents, such as remdesivir. It highlights that it will be very important to assess patients individually, since ritonavir interferes with the metabolism of many therapeutic agents, from antiseizure to immunosuppressive to anticoagulant medications.</p> https://www.medicinesresources.nhs.uk/oral-nirmatrelvir-for-high-risk-nonhospitalized-adults-with-covid-19.html <p><a href="https://www.nejm.org/doi/full/10.1056/NEJMe2202160">Editorial</a></p> https://www.nejm.org/doi/full/10.1056/NEJMoa2118542 2022-02-16T00:00:00Z 2022-02-17T16:25:29.21Z