Nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex - disease burden, unmet needs, and advances in treatment developments

Abstract

Introduction: Nontuberculous mycobacterial (NTM) lung disease (LD) is the most common clinical manifestation of NTM infection and is a growing health concern. Up to 85% of NTM-LD cases are caused by Mycobacterium avium complex (MAC). Increased awareness of NTM-LD caused by MAC is needed as patients with this disease experience substantial burden and unmet treatment needs. Areas covered: This review provides clinicians and regulatory and healthcare decision makers an overview of the clinical, economic, and humanistic burden of NTM-LD and the unmet treatment needs faced by patients and clinicians. The review focuses on NTM-LD caused by MAC. A summary of the 2020 NTM guidelines specifically for MAC-LD and an overview of novel treatment options, including amikacin liposome inhalation suspension (ALIS) as the first approved therapy for refractory MAC-LD, and investigational drugs in testing phase are provided. Expert opinion: Key advancements in NTM-LD management include recent updates to clinical practice guidelines, approval of ALIS for the treatment of refractory MAC-LD, and ongoing clinical trials of investigational treatments. Yet opportunities still exist to improve patient outcomes, including development of better screening tools, such as reliable and responsive biomarkers to help identify high-risk patients, and addressing unmet treatment needs.

Nano-delivery to the lung - by inhalation or other routes and why nano when micro is largely sufficient?

“…Upon inhalation, the liposomes reach the lungs where they can enter alveolar macrophages where the MAC bacteria live whereas free amikacin has a limited ability to cross the membranes of mammalian cells, reducing its ability to achieve sufficient anti-mycobacterial levels inside the infected cells. The liposomal formulation of amikacin has shown better in vitro and in vivo efficiency in the delivery of the drug into macrophages, airways, and lung tissue compared to its non-liposomal counterpart [85][86][87].…”

Contemporary Concise Review 2021: COVID‐19 and other respiratory infections

“…Recent epidemiology studies have revealed a rising incidence of non-tuberculous Mycobacterium pulmonary disease (NTM-PD) both regionally and globally, with a higher prevalence in Asian countries than the Western world. 76 The presence of comorbidities is a poor prognostic factor leading to a higher hospitalization and mortality rate. 77 The latest treatment guideline endorses the use of amikacin liposome inhalation suspension (ALIS) in refractory Mycobacterium avium complex (MAC)-PD, which is defined as remaining sputum culture-positive after 6 months of guideline-based therapy (GBT).…”

“…Recent epidemiology studies have revealed a rising incidence of non‐tuberculous Mycobacterium pulmonary disease (NTM‐PD) both regionally and globally, with a higher prevalence in Asian countries than the Western world. 76 The presence of comorbidities is a poor prognostic factor leading to a higher hospitalization and mortality rate. 77 …”

Impact of initiation of amikacin liposome inhalation suspension on hospitalizations and other healthcare resource utilization measures: a retrospective cohort study in real-world settings

“…A recent meta-analysis of 14 studies from Asia, Europe, and North America estimated the 5-year all-cause mortality for MAC-LD was 27% [ 14 ]. Failure to respond to treatment is common, and approximately 20–40% of MAC-LD cases are refractory to treatment [ 15 – 18 ]. Refractory MAC-LD is associated with increased healthcare resource utilization (HCRU) [ 19 ] and a reported 2-year mortality of 45% [ 20 ].…”