沙特国民警卫队卫生事务部Yaseen M. Arabi团队研究了干扰素β-1b和洛匹那韦-利托那韦治疗中东呼吸综合征的疗效。2020年10月7日，该研究发表在《新英格兰医学杂志》上。

重组干扰素β-1b和洛匹那韦-利托那韦联合治疗是否可降低中东呼吸综合征（MERS）住院患者的死亡率尚不清楚。

研究组在沙特阿拉伯的9个地区进行了一项随机、自适应、双盲、安慰剂对照试验，招募了95例经实验室确诊的MERS成年住院患者，将其随机分组，其中43例接受重组干扰素β-1b加洛匹那韦-利托那韦治疗（干预组），52例患者接受安慰剂治疗。主要结局为90天全因死亡率。

第90天，干预组中共有12例患者（28％）死亡，安慰剂组中有23例（44％）。对主要结局分析得出的风险差异为-19个百分点。在预先指定的亚组分析中，症状发作后7天内进行治疗，与安慰剂相比，可有效降低90天死亡率，但在7天后再治疗则无显著差异。干预组中有4例患者（9％）发生严重不良事件，安慰剂组中有10例（19％）。

总之，重组干扰素β-1b联合洛匹那韦-利托那韦治疗MERS住院患者，与安慰剂相比，可显著降低死亡率。当症状发作后7天内开始治疗效果最好。

附：英文原文

Title: Interferon Beta-1b and Lopinavir–Ritonavir for Middle East Respiratory Syndrome | NEJM

Author: Yaseen M. Arabi, M.D.,, Ayed Y. Asiri, M.D.,, Abdullah M. Assiri, M.D.,, Hanan H. Balkhy, M.D.,, Ali Al Bshabshe, M.D.,, Majed Al Jeraisy, Pharm.D.,, Yasser Mandourah, M.D.,, Mohamed H.A. Azzam, M.D.,, Abdulhadi M. Bin Eshaq, M.D.,, Sameera Al Johani, M.B., B.S.,, Shmeylan Al Harbi, Pharm.D., B.C.P.S,, Hani A.A. Jokhdar, M.B., Ch.B., Ph.D.,, Ahmad M. Deeb, R.N., M.S.N.,, Ziad A. Memish, M.D.,, Jesna Jose, M.Sc.,, Sameeh Ghazal, M.D.,, Sarah Al Faraj, M.D.,, Ghaleb A. Al Mekhlafi, M.D.,, Nisreen M. Sherbeeni, M.D.,, Fatehi E. Elzein, M.D.,, Fahad Al-Hameed, M.D.,, Asim Al Saedi, M.D.,, Naif K. Alharbi, Ph.D.,, Robert A. Fowler, M.D.C.M.,, Frederick G. Hayden, M.D.,, Abdulaziz Al-Dawood, M.D.,, Mohamed Abdelzaher, M.D.,, Wail Bajhmom, M.B., B.S., Ph.D.,, Badriah M. AlMutairi, R.N.,, Mohamed A. Hussein, M.S.C.S., M.S.P.H., Ph.D.,, and Adel Alothman, M.D.

Issue&Volume: 2020-10-07

Abstract:

Background

Whether combined treatment with recombinant interferon beta-1b and lopinavir–ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear.

Methods

We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir–ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results.

Results

A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of 19 percentage points (upper boundary of the 97.5% confidence interval [CI], 3; one-sided P=0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group.

Conclusions

A combination of recombinant interferon beta-1b and lopinavir–ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset.

DOI: 10.1056/NEJMoa2015294

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2015294