当前位置:科学网首页 > 小柯机器人 >详情
玻璃体注射faricimab治疗糖尿病性黄斑水肿疗效显著且安全持久
作者:小柯机器人 发布时间:2022/1/30 23:09:43

美国休斯顿卫理公会医院Charles C Wykoff团队研究了玻璃体腔内注射faricimab治疗糖尿病性黄斑水肿的疗效、持久性和安全性。2022年1月24日出版的《柳叶刀》杂志发表了这项成果。

为了减轻糖尿病性黄斑水肿的治疗负担并优化患者预后,研究组介绍了两项faricimab 3期临床试验的1年结果,faricimab是一种新型血管生成素-2和血管内皮生长因子-A双特异性抗体。

研究组在全球353个地点进行了两项随机、双盲、非劣效性试验,招募患有糖尿病性黄斑水肿中心导致视力丧失的成年人,将其按1:1:1随机分配,分别接受每8周玻璃体腔内注射faricimab 6.0 mg,个体化治疗间隔(PTI)注射faricimab 6.0 mg,或每8周注射2.0 mg阿柏西普,直至第100周。

根据主动给药就诊时的疾病活动情况,延长、维持或缩短PTI给药间隔(每4周至每16周)。主要终点是1年时最佳矫正视力的平均变化,48周、52周和56周的平均值。疗效分析包括意向治疗人群(非劣效边缘为糖尿病视网膜病变早期治疗研究组评估[ETDRS]改善4个字母);安全性分析包括至少接受一剂研究治疗的患者。

研究组共对3247名患者进行了资格筛查,其中第一项试验1532名,第二项试验1715名。经排除后,2018年9月5日至2019年9月19日的试验共940名患者入组,2018年10月9日至2019年9月20日的试验共951名患者入组。

这1891名患者进行随机分组后,每8周faricimab组中第一项试验315人,第二项试验317人;faricimab PTI组中分别为313人和319人,阿柏西普组中分别为312人和315人。

第一项试验中每8周faricimab组的ETDRS改善10.7字母,阿柏西普组改善10.9字母;第二项试验中两组分别改善11.8字母和10.3字母。两项试验中faricimab PTI组的ETDRS分别改善11.6字母和10.8字母。

两项试验中每8周faricimab组的眼部不良事件发生率分别为31%和43%,faricimab PTI组分别为34%和37%,阿柏西普组分别为33%和36%,各组间的不良事件发生率相差不大。

研究结果表明,每16周可调剂量的faricimab可显著改善视力和解剖结构,表明faricimab有可能延长糖尿病黄斑水肿患者的治疗持续时间。

附:英文原文

Title: Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials

Author: Charles C Wykoff, Francis Abreu, Anthony P Adamis, Karen Basu, David A Eichenbaum, Zdenka Haskova, Hugh Lin, Anat Loewenstein, Shaun Mohan, Ian A Pearce, Taiji Sakamoto, Patricio G Schlottmann, David Silverman, Jennifer K Sun, John A Wells, Jeffrey R Willis, Ramin Tadayoni, Thomas Aaberg, Ashkan Abbey, Elmira Abdulaeva, Santiago Abengoechea, Prema Abraham, Thomas Ach, Serrhel Adams, Alfredo Adan Civera, Sean Adrean, Hansjurgen Agostini, Suhail Alam, Arturo Alezzandrini, Virgil Alfaro, Daniel Aliseda, Arghavan Almony, Pedro Amat, Payam Amini, Andrew Antoszyk, Luis Arias, Riaz Asaria, Marcos Avila, Carl C Awh, Joaquin Bafalluy, Carl Baker, Francesco Bandello, Mark Barakat, Karen Barraza, Gyorgy Bator, Caroline Baumal, Rubens Belfort Jr, Chris Bergstrom, George Bertolucci, Thomas Bochow, Matthias Bolz, Emilia Borcz, Arnaldo Bordon, David Boyer, Galina Bratko, Michael Brent, Jamin Brown, David M Brown, Maria Budzinskaya, Sylvia Buffet, Stuart Burgess, Ben Burton, Miguel Busquets, Francisco Cabrera, Carlo Cagini, Jorge Calzada, Peter Campochiaro, John Carlson, Alessandro Castellarin, Carlos Cava, Voraporn Chaikitmongkol, Clement Chan, Emmanuel Chang, Jonathan Chang, Andrew Chang, Steve Charles, Nauman Chaudhry, Caroline Chee, Judy Chen, Fred Chen, Shih-Jen Chen, Richard Cheong-Leen, Allen Chiang, Mark Chittum, David Chow, Brian Connolly, Pierre Loic Cornut, Karl Csaky, Carl Danzig, Arup Das, Vesselin Daskalov, Carmen Desco, Amr Dessouki, John Dickinson, Brian Do, Michael Dollin, Pravin Dugel, Jaroslava Dusova, David Eichenbaum, Bora Eldem, Robert Engstrom, Jan Ernest, Joan Josep Escobar, Simona Esposti, Nicole Eter, Naomi Falk, Andrej Farkas, Leonard Feiner, Nicolas Feltgen, Carlos Fernandez, Alvaro Fernandez Vega, Philip Ferrone, Joao Figueira, Marta Figueroa, .Oliver Findl, Howard Fine, Jorge Fortun, Gregory M Fox, Scott Foxman, Carsten Framme, Samantha Fraser-Bell, Arthur Fu, Akira Fukutomi, Nicholas Fung, Federico Furno Sola, Roberto Gallego-Pinazo, Renata Garcia, Alfredo Garcia-Layana, Maciej Gawecki, Sheen George

Issue&Volume: 2022-01-24

Abstract:

Background

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.

Methods

YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).

Findings

3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference 0·2 ETDRS letters [2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).

Interpretation

Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.

DOI: 10.1016/S0140-6736(22)00018-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00018-6/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
官方网址:http://www.thelancet.com/
投稿链接:http://ees.elsevier.com/thelancet