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Mycobacterium avium complex pulmonary disease patients with limited treatment options

2024; European Respiratory Society; Volume: 10; Issue: 1 Linguagem: Inglês

10.1183/23120541.00610-2023

2312-0541

Stefano Aliberti, Francesco Blasi, Pierre–Régis Burgel, Andrea Calcagno, Andreas Fløe, Dorothy Grogono, Apostolos Papavasileiou, Eva Polverino, Concepción Prados, Gernot Rohde, Helmut J.F. Salzer, Adrián Sánchez‐Montalvá, Michal Shteinberg, Eva Van Braeckel, Jakko van Ingen, Nicolas Véziris, Dirk Wagner, Michael R. Loebinger,

Tuberculosis Research and Epidemiology

Over the past decades, the prevalence and incidence of non-tuberculous mycobacteria pulmonary disease (NTM-PD) have increased worldwide, with Mycobacterium avium complex being the most common causative agents [1–5]. The 2020 ATS/ERS/ESCMID/IDSA guidelines recommended a treatment regimen with at least three drugs, including a macrolide, in patients with a nodular-bronchiectatic, macrolide-susceptible Mycobacterium avium complex pulmonary disease (MAC-PD) [6]. For patients with cavitary or advanced/severe bronchiectatic disease, guidelines suggest the addition of parenteral amikacin into the initial regimen [6]. Once treatment is initiated, up to 40% of NTM-PD patients might experience an unsuccessful outcome [7, 8]. For the first time, the 2020 ATS/ERS/ESCMID/IDSA guidelines identified patients with a "refractory" MAC-PD as those with a positive sputum culture after six months of guideline-based therapy (GBT) [6]. In refractory MAC-PD, a recommendation was made in the guidelines to add Amikacin Liposome Inhalation Suspension (ALIS) to the treatment regimen [6]. This recommendation was based on the CONVERT study, demonstrating an improved culture conversion rate in refractory MAC-PD [6, 9]. Based on those results, the US Food and Drug Administration (FDA) approved ARIKAYCE, a proprietary ALIS formulation by Insmed, Inc., Bridgewater, NJ, USA, for "treatment-refractory MAC lung disease" [10]. The European Medicines Agency (EMA) went further, licensing ARIKAYCE to treat NTM lung infections "caused by MAC in adults with limited treatment options who do not have cystic fibrosis" [11]. However, the term "limited treatment options" (LTOs) might sound ambiguous, and no clinical study, expert consensus or guidelines exist to clarify the meaning of limited treatment options. The experts convened on such ambiguity in their preliminary discussion and decided to possibly contribute to shedding light on the issue term. With regards to the reimbursement of Arikayce, the product is generally covered by health insurers in the US and is fully reimbursed by the National Health Insurance of Japan. In Europe, the product is fully reimbursed in the UK, France, Ireland, Belgium, The Netherlands, and Finland. In Germany, Denmark, and Greece it is generally funded for individual patients. Footnotes This manuscript has recently been accepted for publication in the ERJ Open Research . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article. Conflict of interest: Andreas Fløe reports participation on advisory board for Insmed Inc., outside the submitted work. Conflict of interest: Pierre Regis Burgel reports grants or contracts from GSK and Vertex, outside the submitted work; consulting fees from Astra-Zeneca, Chiesi, GSK, Insmed, MSD, Pfizer, Vertex, Viatris, and Zambon, outside the submitted work. Conflict of interest: Andrea Calcagno reports receiving support for the present manuscript from Insmed. Consulting fees from Insmed, outside the submitted work; Speakers honoraria from Insmed, outside the submitted work. Conflict of interest: Eva Polveri reports support for the present manuscript from Lena Group. Grants or contracts from Grifols, outside the submitted; consulting fees from Insmed, Chiesi, Zambon, and Electromed, outside the submitted work; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Insmed, Chiesi, Zambon, Teva, Boeringer, Glaxo, and Electromed, outside the submitted work; Payment for expert testimony from Chiesi, outside the submitted work; Support for attending meetings and/or travel from Insmed, Teva, Glaxo, and Chiesi, outside the submitted work; Participation on a Data Safety Monitoring Board or Advisory Board for Insmed, Electromed, and Chiesi, outside the submitted work. Conflict of interest: Gernot Rohdereports personal fees from Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis and Pfizer for consultancy during advisory board meetings, outside the submitted work; personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer and Vertex for lectures including service on speakers bureaus, outside the submitted work. Conflict of interest: Helmut J.F. Salzer reports receiving support for the present manuscript from Insmed. Honoraria for lectures from Insmed, GSK, Gilead, and Chiesi, outside the submitted work. Conflict of interest: Adrián Sánchez-Montalvá reports receiving support for the present manuscript from Insmed. Consulting fees from Insmed, outside the submitted work. Conflict of interest: Michal Shteinberg reports receiving support for the present manuscript from Insmed. Grants or contracts from GSK, Trumed, and Novartis, outside the submitted work; consulting fees from GSK, Boehringer Ingelheim, Kamada, and Zambon, outside the submitted work; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Insmed, Boehringer Ingelheim, GSK, Astra Zeneca, Teva, Novartis, Kamada, and Sanofi, outside the submitted work; Support for attending meetings and/or travel from Novartis, Actelion, Boehringer Ingelheim, GSK, and Rafa, outside the submitted work; Participation on a Data Safety Monitoring Board or Advisory Board for Bonus Therapeutics, Israel, outside the submitted work; Leadership or fiduciary role in other board, society, committee or advocacy group for EMBARC management, Israel Pulmonology Society board, and Israel society for TB and mycobacterial diseases, outside the submitted work; Receipt of equipment, materials, drugs, medical writing, gifts or other services from Trudell medical intnl: Receipt of supply to clinical trial, outside the submitted work; Other financial or non-financial interests: Associate Editor- Am J Resp Crit Care Med, Direct stipend, outside the submitted work. Conflict of interest: Eva Van Braeckel reports support for the present manuscript from Publi Creations SAM – Lenagroup. Grants or contracts from Insmed, outside the submitted work; Consulting fees from Insmed, outside the submitted work; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Insmed, outside the submitted work; Chair of Belgian Respiratory Society working group on respiratory infections, unpaid, outside the submitted work. Conflict of interest: Jakko van Ingen reports grants or contracts from MannKind and AN2, outside the submitted work; Patents planned, issued or pending: Inhaled tigecycline for M. abscessus treatment, outside the submitted work. Conflict of interest: Nicolas Veziris reports receiving support for the present manuscript from Insmed. Grants or contracts from BIOVERSYS, outside the submitted work; consulting fees from INSMED, and BECTON DICKINSON, outside the submitted work; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Insmed, outside the submitted work; Payment for expert testimony from Insmed, outside the submitted work; Support for attending meetings and/or travel from Insmed, outside the submitted work; Other financial or non-financial interests: Involved in the Respiri-NTM consortium with Janssen, outside the submitted work. Conflict of interest: Dirk Wagner reports support for the present manuscript from PUBLI CREATIONS SAM via an unrestricted grant by Insmed Inc. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biomerieux, outside the submitted work; Participation on a Data Safety Monitoring Board or Advisory Board for Pfizer, outside the submitted work; Participation in clinical trials for Insmed, outside the submitted work. Conflict of interest: Stefano Aliberti reports grants or contracts from INSMED Incorporated, CHIESI, Fisher & Paykel, and GSK, outside the submitted work; Royalties or licences from McGRAW HILL, outside the submitted work; consulting fees from INSMED Incorporated, INSMED Italy, INSMED Ireland Ltd, ZAMBON Spa, AstraZeneca UK Limited, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione internazionale MENARINI, Moderna, Chiesi, MSD Italia S.r.l., BRAHMS, Physioassist SAS, and GlaxoSmithKline Spa, outside the submitted work; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline Spa, Thermofisher Scientific, INSMED Italy, INSMED Ireland Ltd, Zambon, and Fondazione Internazionale Menarini, outside the submitted work; Participation on a Data Safety Monitoring Board or Advisory Board for INSMED Incorporated, INSMED Italy, AstraZeneca UK Limited, and MSD Italia S.r.l, outside the submitted work. Conflict of interest: Francesco Blasi reports grants or contracts from ASTRAZENECA, CHIESI, GLAXOSMITHKLINE, and INSMED, outside the submitted work; consulting fees from GLAXOSMITHKLINE, MENARINI, and OM PHARMA, outside the submitted work; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from ASTRAZENECA, CHIESI, GLAXOSMITHKLINE, GRIFOLS, INSMED, MENARINI, NOVARTIS, OMPHARMA, PFIZER, SANOFI, VERTEX, VIATRIS, and ZAMBON, outside the submitted work. Conflict of interest: Apostolos Papavasileiou reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Insmed, outside the submitted work. Conflict of interest: Michael Loebinger reports consulting fees from Armata, 30 T, Astra Zeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2, Savara, Boehringer Ingelheim, and Mannkind, outside the submitted work; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Insmed, outside the submitted work; Leadership or fiduciary role in other board, society, committee or advocacy group: Chair of ERS resp infection group, outside the submitted work. Conflict of interest: Dorothy Grogono reports consulting fees from Insmed, outside the submitted work; Support received from Insmed for attending consensus meeting. Conflict of interest: The remaining authors have nothing to disclose.