Amikacin Liposome Inhalation Suspension for Refractory Mycobacterium avium Complex Lung Disease Sustainability and Durability of Culture Conversion and Safety of Long-term Exposure

被引：34

作者：

Griffith, David E. ^{[1
,15
]}

Thomson, Rachel ^{[3
]}

Flume, Patrick A. ^{[5
,6
]}

Aksamit, Timothy R. ^{[7
]}

Field, Stephen K. ^{[8
]}

Addrizzo-Harris, Doreen J. ^{[9
]}

Morimoto, Kozo ^{[10
]}

Hoefsloot, Wouter ^{[11
]}

Mange, Kevin C. ^{[13
]}

Yuen, Dayton W. ^{[13
]}

Ciesielska, Monika ^{[13
]}

Wallace, Richard J., Jr. ^{[2
]}

van Ingen, Jakko ^{[12
]}

Brown-Elliott, Barbara A. ^{[2
]}

Coulter, Chris ^{[4
]}

Winthrop, Kevin L. ^{[14
]}

机构：

[1] Univ Texas Tyler, Hlth Sci Ctr, Pulm Infect Dis Sect, Tyler, TX 75799 USA

[2] Univ Texas Tyler, Hlth Sci Ctr, Dept Microbiol, Tyler, TX 75799 USA

[3] Univ Queensland, Gallipoli Med Res Inst, Brisbane, Qld, Australia

[4] Univ Queensland, Queensland Mycobacterium Reference Lab, Pathol Queensland, Brisbane, Qld, Australia

[5] Med Univ South Carolina, Dept Med, Charleston, SC 29425 USA

[6] Med Univ South Carolina, Dept Pediat, Charleston, SC 29425 USA

[7] Mayo Clin, Pulm Dis & Crit Care Med, Rochester, MN USA

[8] Univ Calgary, Cumming Sch Med, Dept Med, Div Respirol & TB Serv, Calgary, AB, Canada

[9] NYU, Grossman Sch Med, Div Pulm Crit Care & Sleep Med, New York, NY USA

[10] Japan AntiTB Assoc, Fukujuji Hosp, Div Clin Res, Tokyo, Japan

[11] Radboud Univ Nijmegen, Med Ctr Dekkerswald, Dept Pulm Dis, Nijmegen, Netherlands

[12] Radboud Univ Nijmegen, Dept Med Microbiol, Med Ctr, Nijmegen, Netherlands

[13] Insmed Inc, Bridgewater, MA USA

[14] Oregon Hlth & Sci Univ, Sch Med, Div Infect Dis, Portland, OR 97201 USA

[15] Natl Jewish Hlth, Dept Med, Div Mycobacterial & Resp Infect, Denver, CO 80206 USA

来源：

CHEST | 2021年 / 160卷 / 03期

关键词：

ALIS; culture conversion; durability; Mycobacterium avium complex; nontuberculous mycobacteria; THERAPY; DIAGNOSIS;

D O I：

10.1016/j.chest.2021.03.070

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

BACKGROUND: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001). RESEARCH QUESTION: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion? STUDY DESIGN AND METHODS: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/ 112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P 1/4 .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment. INTERPRETATION: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion.

引用

页码：831 / 842

页数：12

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