特考韦瑞治疗刚果民主共和国I分支猴痘病毒感染

Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo.

作者信息

Ali Rosine, Alonga Jules, Biampata Jean-Luc, Kombozi Basika Michael, Maljkovic Berry Irina, Bisento Nella, Blum Emily, Bonnett Tyler, Cone Katherine, Crozier Ian, Davey Richard, Dilu Ali, Dodd Lori E, Gulati Iman, Hruby Dennis, Ibanda Augustin, Isse Francis, Kasareka Sylva Sivasingana, Kayembe Gaby, Kojan Richard, Luzolo Esaie Kindombe, Lane H Clifford, Lawanga Leader, Liesenborghs Laurens, Shosongo Lunghe Claude, Lula Yves, Lusakibanza Mariano, Lutete Gaston Tona, Mbala-Kingebeni Placide, Miranda Alejandra, Mukadi-Bamuleka Daniel, Mukendi Gael, Lupola Patrick Mutombo, Muyembe-Tamfum Jean-Jacques, Ndungunu Robin, Nganga Bruce, Ntamabyaliro Nsengi, Nussenblatt Veronique, Omulepu Imoite, Omalokoho Onosomba John, Proschan Michael, Rubenstein Kevin, Saknite Inga, Schechner Adam, Shaw-Saliba Kathryn, Sivahera Billy, Smolskis Mary, Tillman Amy, Tkaczyk Eric, Tshimanga Celestin, Tshiani Mbaya Olivier, Tshomba Antoine, Yemba Unda Tshomba Freddy, Vallee David, Vogel Susan, Weyers Shera

机构信息

Institut Nationale de Recherche Biomédicale, Kinshasa, Democratic Republic of Congo.

Kole General Hospital, Kole, Democratic Republic of Congo.

出版信息

N Engl J Med. 2025 Apr 17;392(15):1484-1496. doi: 10.1056/NEJMoa2412439.

DOI:10.1056/NEJMoa2412439

PMID:40239067

Abstract

BACKGROUND

Tecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking.

METHODS

We conducted a double-blind, randomized, placebo-controlled trial of tecovirimat in patients with mpox in the Democratic Republic of Congo (DRC). Patients with at least one mpox skin lesion and positive polymerase-chain-reaction results for clade I MPXV were assigned in a 1:1 ratio to receive tecovirimat or placebo. All patients received supportive care. The primary end point was resolution of mpox lesions, measured in number of days after randomization. Safety was also assessed.

RESULTS

From October 7, 2022, through July 9, 2024, a total of 597 patients underwent randomization - 295 to receive tecovirimat and 302 to receive placebo. The median time from randomization to lesion resolution was 7 days with tecovirimat and 8 days with placebo; the competing-risks hazard ratio for lesion resolution was 1.13 (95% confidence interval [CI], 0.97 to 1.31; P = 0.14). Results were similar whether patients began the trial regimen within 7 days after the reported onset of symptoms (competing-risks hazard ratio, 1.16; 95% CI, 0.98 to 1.37) or more than 7 days after onset (competing-risks hazard ratio, 1.00; 95% CI, 0.71 to 1.40). Overall mortality was 1.7%, which was lower than the case fatality rate of 4.6% reported in the DRC in 2023. At 14 days, the percentages of patients who had blood, lesion, and oropharyngeal samples negative for MPXV by PCR were similar in the two groups. Adverse events occurred in 72.9% of the patients in the tecovirimat group and 70.5% of those in the placebo group, and serious adverse events were reported in 5.1% and 5.0%, respectively.

CONCLUSIONS

Tecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV. No safety concerns were identified. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM007 ClinicalTrials.gov number, NCT05559099.).

摘要

背景

基于动物疗效研究和健康人体安全性评估结果，特考韦瑞玛在欧洲和美国可用于治疗猴痘（原称猴天花）。缺乏关于猴痘患者安全性和疗效的随机对照试验证据。

方法

我们在刚果民主共和国对猴痘患者进行了一项特考韦瑞玛的双盲、随机、安慰剂对照试验。至少有一处猴痘皮肤病变且I型猴痘病毒聚合酶链反应结果呈阳性的患者按1:1比例分配接受特考韦瑞玛或安慰剂治疗。所有患者均接受支持性治疗。主要终点是猴痘病变的消退情况，以随机分组后的天数衡量。同时也评估了安全性。

结果

从2022年10月7日至2024年7月9日，共有597例患者接受随机分组，其中295例接受特考韦瑞玛治疗，302例接受安慰剂治疗。接受特考韦瑞玛治疗的患者从随机分组到病变消退的中位时间为7天，接受安慰剂治疗的为8天；病变消退的竞争风险风险比为1.13（95%置信区间[CI]，0.97至1.31；P = 0.14）。无论患者在报告症状出现后7天内开始试验方案（竞争风险风险比，1.16；95%CI，0.98至1.37）还是在症状出现后7天以上开始（竞争风险风险比，1.00；95%CI，0.71至1.40），结果相似。总体死亡率为1.7%，低于刚果民主共和国2023年报告的4.6%的病死率。在第14天，两组中通过聚合酶链反应检测猴痘病毒血液、病变和口咽样本呈阴性的患者百分比相似。特考韦瑞玛组72.9%的患者和安慰剂组70.5%的患者发生了不良事件，严重不良事件报告率分别为5.1%和5.0%。