tetano
Editor, Senior Moderator
J Infect
. 2024 Nov 7:106339.
doi: 10.1016/j.jinf.2024.106339. Online ahead of print. Real-world effectiveness and safety of simnotrelvir/ritonavir for COVID-19: A nationwide, multicenter, prospective, observational cohort study in China
Bing Han[SUP] 1 [/SUP], Chunling Du[SUP] 2 [/SUP], Min Deng[SUP] 3 [/SUP], Renhong Tang[SUP] 4 [/SUP], Jianping Dong[SUP] 5 [/SUP], Xu Song[SUP] 6 [/SUP], Yunfeng Qiao[SUP] 7 [/SUP], Zheng Ni[SUP] 8 [/SUP], WenJie Yang[SUP] 9 [/SUP], Jiankun Yang[SUP] 10 [/SUP], Tianxin Xiang[SUP] 11 [/SUP], Yan Huang[SUP] 12 [/SUP], Yu Zhong[SUP] 13 [/SUP], Zhongfa Zhang[SUP] 14 [/SUP], Lisheng Yang[SUP] 15 [/SUP], Jikang Yang[SUP] 16 [/SUP], Huaying Wang[SUP] 17 [/SUP], Lanbing Zheng[SUP] 18 [/SUP], Libing Ma[SUP] 19 [/SUP], Zhinan Shou[SUP] 20 [/SUP], Ran Cao[SUP] 21 [/SUP], Huajing Ma[SUP] 22 [/SUP], Gang He[SUP] 23 [/SUP], Jing Yuan[SUP] 24 [/SUP], Chongjie Pang[SUP] 25 [/SUP], Jing Xu[SUP] 26 [/SUP], Jing Huang[SUP] 27 [/SUP], Xiaomei Yuan[SUP] 28 [/SUP], Yunfeng Wu[SUP] 29 [/SUP], Yong Xiong[SUP] 30 [/SUP], Xiangjie Zhang[SUP] 31 [/SUP], Hongying Liu[SUP] 32 [/SUP], Binfeng Gao[SUP] 33 [/SUP], Huan Chen[SUP] 34 [/SUP], Tengfei Ma[SUP] 35 [/SUP], Shuangsuo Dang[SUP] 36 [/SUP], Qingyu Zhang[SUP] 37 [/SUP], Rui Yuan[SUP] 38 [/SUP], Yunqing Wei[SUP] 39 [/SUP], Tongbai Xu[SUP] 40 [/SUP], Zhulian Deng[SUP] 41 [/SUP], Yan Gong[SUP] 42 [/SUP], Jianfen Gao[SUP] 43 [/SUP], Rongmeng Jiang[SUP] 44 [/SUP]
Affiliations
Background: Simnotrelvir 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 the time to the resolution of symptoms in adult COVID-19 patients. However, real-world data on effectiveness of simnotrelvir/ritonavir against SARS-CoV-2 during XBB omicron variant surges are still limited.
Study design and methods: This was a nationwide, multicenter, prospective, observational real-world study at 42 sites in China. Adult patients with mild to moderate COVID-19 and at disease onset were eligible for participation. Patients were grouped in S/R group (treated with S/R) and control group (not receiving oral antivirals for COVID-19). The primary endpoint was the COVID-19-related hospitalization or all-cause mortality within 28 days. Secondary endpoints included the time from confirmed SARS-CoV-2 infection to negative conversion, and the time to resolution of COVID-19 symptoms. Besides, serious adverse events (SAE), adverse drug reactions (ADR) and combined medication were reported. Propensity Score-Matched (PSM) analysis (1:1) was performed for adjustment for baseline variables. Hazard ratios (HR) and adjusted risk ratios (aRR) were estimated using the Cox and Modified poisson regression, respectively.
Results: Between June 6, 2023 and December 27, 2023, 3522 patients were enrolled. S/R was associated with a reduced incidence of COVID-19-related hospitalization (6/1896 [0.3%] vs. 43/1408 [3.1%]; HR: 0.110, 95% confidence interval [CI]: 0.043 to 0.283, p<0.001 vs control), consistently with the results after PSM (4/1381 [0.3%] in S/R vs. 40/1381 patients [2.9%]; aRR: 0.12; 95% CI: 0.05, 0.29; P<0.001). No deaths occurred in both S/R and control groups. Matched Patients over 65 and patients with risk factors who received S/R achieved significantly reduced risk of COVID-19 related hospitalization (aRR: 0.032; 95% CI: 0.004, 0.268; aRR: 0.034; 95% CI: 0.005, 0.252, respectively; all P<0.001). Furthermore, S/R shortened the median time to viral clearance by 1 day (6.0 vs 7.0 days; 95% CI: -2.0 to -1.0; P<0.001) and reduced the median time to symptom resolution by 2 days (8.0 days vs 10.0 days; 95% CI: -2.0 to -1.0; P<0.001). Besides, the proportion of patients in the S/R group using combined medication was significantly lower than that in the control group (30.2% vs 49.4%). Subgroup analysis showed potential protective effect of S/R in the elderly and patients with more than 1 risk factor.
Conclusion: In real world, S/R significantly reduced the incidence of COVID-19-related hospitalization, demonstrated favorable safety profiles, and less use of combined medication.
Keywords: COVID-19; COVID-19 related hospitalization; SARS-CoV-2; real world study; simnotrelvir.
. 2024 Nov 7:106339.
doi: 10.1016/j.jinf.2024.106339. Online ahead of print. Real-world effectiveness and safety of simnotrelvir/ritonavir for COVID-19: A nationwide, multicenter, prospective, observational cohort study in China
Bing Han[SUP] 1 [/SUP], Chunling Du[SUP] 2 [/SUP], Min Deng[SUP] 3 [/SUP], Renhong Tang[SUP] 4 [/SUP], Jianping Dong[SUP] 5 [/SUP], Xu Song[SUP] 6 [/SUP], Yunfeng Qiao[SUP] 7 [/SUP], Zheng Ni[SUP] 8 [/SUP], WenJie Yang[SUP] 9 [/SUP], Jiankun Yang[SUP] 10 [/SUP], Tianxin Xiang[SUP] 11 [/SUP], Yan Huang[SUP] 12 [/SUP], Yu Zhong[SUP] 13 [/SUP], Zhongfa Zhang[SUP] 14 [/SUP], Lisheng Yang[SUP] 15 [/SUP], Jikang Yang[SUP] 16 [/SUP], Huaying Wang[SUP] 17 [/SUP], Lanbing Zheng[SUP] 18 [/SUP], Libing Ma[SUP] 19 [/SUP], Zhinan Shou[SUP] 20 [/SUP], Ran Cao[SUP] 21 [/SUP], Huajing Ma[SUP] 22 [/SUP], Gang He[SUP] 23 [/SUP], Jing Yuan[SUP] 24 [/SUP], Chongjie Pang[SUP] 25 [/SUP], Jing Xu[SUP] 26 [/SUP], Jing Huang[SUP] 27 [/SUP], Xiaomei Yuan[SUP] 28 [/SUP], Yunfeng Wu[SUP] 29 [/SUP], Yong Xiong[SUP] 30 [/SUP], Xiangjie Zhang[SUP] 31 [/SUP], Hongying Liu[SUP] 32 [/SUP], Binfeng Gao[SUP] 33 [/SUP], Huan Chen[SUP] 34 [/SUP], Tengfei Ma[SUP] 35 [/SUP], Shuangsuo Dang[SUP] 36 [/SUP], Qingyu Zhang[SUP] 37 [/SUP], Rui Yuan[SUP] 38 [/SUP], Yunqing Wei[SUP] 39 [/SUP], Tongbai Xu[SUP] 40 [/SUP], Zhulian Deng[SUP] 41 [/SUP], Yan Gong[SUP] 42 [/SUP], Jianfen Gao[SUP] 43 [/SUP], Rongmeng Jiang[SUP] 44 [/SUP]
Affiliations
- PMID: 39521253
- DOI: 10.1016/j.jinf.2024.106339
Background: Simnotrelvir 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 the time to the resolution of symptoms in adult COVID-19 patients. However, real-world data on effectiveness of simnotrelvir/ritonavir against SARS-CoV-2 during XBB omicron variant surges are still limited.
Study design and methods: This was a nationwide, multicenter, prospective, observational real-world study at 42 sites in China. Adult patients with mild to moderate COVID-19 and at disease onset were eligible for participation. Patients were grouped in S/R group (treated with S/R) and control group (not receiving oral antivirals for COVID-19). The primary endpoint was the COVID-19-related hospitalization or all-cause mortality within 28 days. Secondary endpoints included the time from confirmed SARS-CoV-2 infection to negative conversion, and the time to resolution of COVID-19 symptoms. Besides, serious adverse events (SAE), adverse drug reactions (ADR) and combined medication were reported. Propensity Score-Matched (PSM) analysis (1:1) was performed for adjustment for baseline variables. Hazard ratios (HR) and adjusted risk ratios (aRR) were estimated using the Cox and Modified poisson regression, respectively.
Results: Between June 6, 2023 and December 27, 2023, 3522 patients were enrolled. S/R was associated with a reduced incidence of COVID-19-related hospitalization (6/1896 [0.3%] vs. 43/1408 [3.1%]; HR: 0.110, 95% confidence interval [CI]: 0.043 to 0.283, p<0.001 vs control), consistently with the results after PSM (4/1381 [0.3%] in S/R vs. 40/1381 patients [2.9%]; aRR: 0.12; 95% CI: 0.05, 0.29; P<0.001). No deaths occurred in both S/R and control groups. Matched Patients over 65 and patients with risk factors who received S/R achieved significantly reduced risk of COVID-19 related hospitalization (aRR: 0.032; 95% CI: 0.004, 0.268; aRR: 0.034; 95% CI: 0.005, 0.252, respectively; all P<0.001). Furthermore, S/R shortened the median time to viral clearance by 1 day (6.0 vs 7.0 days; 95% CI: -2.0 to -1.0; P<0.001) and reduced the median time to symptom resolution by 2 days (8.0 days vs 10.0 days; 95% CI: -2.0 to -1.0; P<0.001). Besides, the proportion of patients in the S/R group using combined medication was significantly lower than that in the control group (30.2% vs 49.4%). Subgroup analysis showed potential protective effect of S/R in the elderly and patients with more than 1 risk factor.
Conclusion: In real world, S/R significantly reduced the incidence of COVID-19-related hospitalization, demonstrated favorable safety profiles, and less use of combined medication.
Keywords: COVID-19; COVID-19 related hospitalization; SARS-CoV-2; real world study; simnotrelvir.