Real-world effectiveness and safety of simnotrelvir/ritonavir for COVID-19: A nationwide, multicenter, prospective, observational cohort study in China

• DOI: 10.1016/j.jinf.2024.106339
• Publication Date: 2024-11-07T17:04:15Z
• Authors: Bing Han; Chunling Du; Min Deng; Renhong Tang; Jianping Dong; Xu Song; Yunfeng Qiao; Zheng Ni; WenJie Yang; Jiankun Yang; Tianxin Xiang; Yan Huang; Yu Zhong; Zhongfa Zhang; Lisheng Yang; Jikang Yang; Jinghua Wang; Lanbing Zheng; Libing Ma; Zhinan Shou; Ran Cao; Jinghua Ma; Gang He; Jing Yuan; Chongjie Pang; Jing Xu; Jing Huang; Xiaomei Yuan; Yunfeng Wu; Yong Xiong; Xiangjie Zhang; Hongying Liu; Binfeng Gao; Huan Chen; Tengfei Ma; Shuangsuo Dang; Qingyu Zhang; Rui Yuan; Yunqing Wei; Tongbai Xu; Zhulian Deng; Yan Gong; Jianfen Gao; Rongmeng Jiang
• Keywords: Ritonavir; Clinical endpoint; Lopinavir

Highlights•First large-scale real-world study of oral antivirals in treating COVID-19 China.•S/R reduces the risk related hospitalization, especially elderly.•During XBB circulation, S/R shows faster symptom resolution and viral clearance.SummaryBackgroundSimnotrelvir has demonstrated potent anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a Phase II/III study, Simnotrelvir plus ritonavir (S/R, co-packaged) shortened time to symptoms adult patients. However, data on effectiveness simnotrelvir/ritonavir SARS-CoV-2 during omicron variant surges are still limited.Study design methodsThis was nationwide, multicenter, prospective, observational at 42 sites China. Adult patients with mild moderate disease onset were eligible for participation. Patients grouped group (treated S/R) control (not receiving COVID-19). The primary endpoint COVID-19-related hospitalization or all-cause mortality within 28 days. Secondary endpoints included from confirmed infection negative conversion, symptoms. Besides, serious adverse events (SAE), drug reactions (ADR) combined medication reported. Propensity Score-Matched (PSM) analysis (1:1) performed adjustment baseline variables. Hazard ratios (HR) adjusted (aRR) estimated using Cox Modified poisson regression, respectively.ResultsBetween June 6, 2023 December 27, 2023, 3522 enrolled. associated reduced incidence (6/1896 [0.3%] vs. 43/1408 [3.1%]; HR: 0.110, 95% confidence interval [CI]: 0.043 0.283, p<0.001 vs control), consistently results after PSM (4/1381 40/1381 [2.9%]; aRR: 0.12; CI: 0.05, 0.29; P<0.001). No deaths occurred both groups. Matched over 65 factors who received achieved significantly (aRR: 0.032; 0.004, 0.268; 0.034; 0.005, 0.252, respectively; all Furthermore, median clearance by 1 day (6.0 7.0 days; -2.0 -1.0; P<0.001) days (8.0 10.0 proportion lower than that (30.2% 49.4%). Subgroup showed potential protective effect elderly more factor.ConclusionIn real world, favorable safety profiles, less use medication.