Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE) : a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial

被引:0
|
作者
Allen, Jeffrey A. [1 ]
Lin, Jie [2 ]
Basta, Ivana [3 ]
Dysgaard, Tina [4 ]
Eggers, Christian [5 ]
Guptill, Jeffrey [6 ,7 ]
Gwathmey, Kelly G. [8 ]
Hewamadduma, Channa [9 ,10 ]
Hofman, Erik [6 ]
Hussain, Yessar M. [11 ]
Kuwabara, Satoshi [12 ]
Le Masson, Gwendal [13 ]
Leypoldt, Frank [14 ,15 ]
Chang, Ting [16 ]
Lipowska, Marta [17 ,18 ]
Lowe, Murray [6 ]
Lauria, Giuseppe [19 ]
Querol, Luis [20 ,21 ]
Simu, Mihaela-Adriana [22 ]
Suresh, Niraja [23 ]
Tse, Anissa [6 ]
Ulrichts, Peter [6 ]
Van Hoorick, Benjamin [6 ]
Yamasaki, Ryo [24 ,25 ]
Lewis, Richard A. [26 ]
van Doorn, Pieter A. [27 ]
机构
[1] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA
[2] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai, Peoples R China
[3] Univ Belgrade, Univ Clin Ctr Serbia, Fac Med, Neurol Clin, Belgrade, Serbia
[4] Univ Copenhagen, Dept Neurol, Copenhagen, Denmark
[5] Johannes Kepler Univ Linz, Kepler Univ Hosp, Dept Neurol, Linz, Austria
[6] Argenx, Ghent, Belgium
[7] Duke Univ, Sch Med, Durham, NC USA
[8] Virginia Commonwealth Univ, Dept Neurol, Richmond, VA USA
[9] Univ Sheffield, Sheffield Inst Translat Neurosci SITRAN, Sheffield, England
[10] Sheffield Teaching Hosp NHS Fdn Trust, Sheffield, England
[11] Austin Neuromuscular Ctr, Austin, TX USA
[12] Chiba Univ, Grad Sch Med, Dept Neurol, Chiba, Japan
[13] Univ Hosp Bordeaux, AOC Natl Reference Ctr Neuromuscular Disorders, ALS Ctr, Dept Neurol,CHU Bordeaux,NerveMuscle Unit, Bordeaux, France
[14] Christian Albrecht Univ Kiel, Inst Clin Chem, Dept Neurol, Kiel, Germany
[15] Univ Med Ctr Schleswig Holstein, Kiel, Germany
[16] Fourth Mil Med Univ, Tangdu Hosp, Dept Neurol, Xian, Peoples R China
[17] Med Univ Warsaw, Dept Neurol, Warsaw, Poland
[18] European Reference Network Rare Neuromuscular Dis, Paris, France
[19] IRCCS Fdn Ist Neurol Carlo Besta, Milan, Italy
[20] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
[21] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
[22] Victor Babes Univ Med & Pharm, Dept Neurol, Timisoara, Romania
[23] Univ S Florida, Dept Neurol, Tampa, FL USA
[24] Kyushu Univ Hosp, Dept Neurol, Fukuoka, Japan
[25] Kyushu Univ, Neurol Inst, Grad Sch Med Sci, Dept Neurol, Fukuoka, Japan
[26] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA USA
[27] Erasmus MC, Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands
来源
LANCET NEUROLOGY | 2024年 / 23卷 / 10期
关键词
NERVE SOCIETY GUIDELINE; MANAGEMENT; CIDP; IVIG;
D O I
暂无
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system that can lead to severe disability from muscle weakness and sensory disturbances. Around a third of patients do not respond to currently available treatments, and many patients with a partial response have residual neurological impairment, highlighting the need for effective alternatives. Efgartigimod alfa, a human IgG1 antibody Fc fragment, has demonstrated efficacy and safety in patients with generalised myasthenia gravis. We evaluated the safety, tolerability, and efficacy of subcutaneous efgartigimod PH20 in adults with CIDP.<br /> Methods ADHERE, a multistage, double-blind, placebo-controlled trial, enrolled participants with CIDP from 146 clinical sites from Asia-Pacific, Europe, and North America. Participants with evidence of clinically meaningful deterioration entered an open-label phase of weekly 1000 mg subcutaneous efgartigimod PH20 for no longer than 12 weeks (stage A). Those with confirmed evidence of clinical improvement (ECI; treatment responders) entered a randomised-withdrawal phase of 1000 mg subcutaneous efgartigimod PH20 weekly treatment versus placebo for a maximum of 48 weeks (stage B). Participants were randomised (1:1) through interactive response technology and stratified by their adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score change during stage A and their most recent CIDP medication within 6 months before screening. Investigators, the clinical research organisation, and participants were masked to the treatment. The primary endpoint in stage A, evaluated in the stage A safety population, was confirmed ECI (>= 1 points aINCAT decrease, >= 4 points [centile metric] Inflammatory Raschbuilt Overall Disability Scale increase, or >= 8 kPa grip strength increase after four injections and two consecutive visits). The primary endpoint in stage B, evaluated in the modified intention-to-treat population, was the risk of relapse (time to first aINCAT increase of >= 1 points). ADHERE is registered with ClinicalTrials.gov (NCT04281472) and EudraCT (2019-003076-39) and is completed.<br /> Findings Between April 15, 2020, and May 11, 2023, 629 participants were screened; 322 (114 female, 208 male) entered stage A, of whom 214 (66%, 95% CI 61<middle dot>0-71<middle dot>6) had confirmed ECI. In stage B, 221 participants were randomised (79 female, 142 male; 111 to subcutaneous efgartigimod PH20, 110 to placebo). Subcutaneous efgartigimod PH20 significantly reduced the risk of relapse versus placebo (hazard ratio 0<middle dot>39 [95% CI 0<middle dot>25-0<middle dot>61]; p<0<middle dot>0001). 31 (27<middle dot>9% [19<middle dot>6-36<middle dot>3]) participants given subcutaneous efgartigimod PH20 had a relapse versus 59 (53<middle dot>6% [44<middle dot>3-63<middle dot>0]) given placebo. In stage A, treatment-emergent adverse events (TEAEs) occurred in 204 (63%) participants and serious TEAEs in 21 (7%). In stage B, TEAEs occurred in 71 (64%) participants on subcutaneous efgartigimod PH20 and 62 (56%) participants on placebo, and serious TEAEs in six (5%) on subcutaneous efgartigimod PH20 and six (5%) on placebo. Three deaths occurred: two in stage A (one non-related and one unlikely related to treatment) and one in stage B (placebo group).<br /> Interpretation ADHERE showed the efficacy of subcutaneous efgartigimod PH20 in reducing the risk of relapse versus placebo in people with CIDP who responded to treatment. Further studies are needed to provide data on the longer-term effects of efgartigimod alfa and how it compares with currently available treatment options.
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页码:1013 / 1024
页数:12
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