The ARIKAYCE Academy
The ARIKAYCE Academy is an online resource center that provides access to insightful commentary, featuring experts in MAC lung disease. With The ARIKAYCE Academy, you can watch videos at your convenience and download materials for later reading.
Explore in-depth information about the management of MAC lung disease, including insights from experts in the field
This content was created by Insmed. Experts have been compensated for their time.
See experts review data and share insights
See experts review data and share insights
INDICATION
LIMITED POPULATION: ARIKAYCE® (amikacin liposome inhalation suspension) is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.1
This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Limitation of Use: ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.1
* See the full Prescribing Information for ARIKAYCE for information about Limited Population.
PLEASE SEE IMPORTANT SAFETY INFORMATION IN THIS PRESENTATION AND FULL PRESCRIBING INFORMATION, INCLUDING BOXED WARNING, AVAILABLE AT ARIKAYCEHCP.COM.
My name is Dr Juzar Ali. I’m professor of medicine in the section of pulmonary critical care at the LSU School of Medicine in New Orleans, and the director of the NTM Bronchiectasis Program Clinic at University Medical Center. I’m participating in this program as a paid speaker of Insmed.
MAC lung disease is a complex medical problem with multiple manifestations. It does affect the structure and function of the lung along with the infection. The treatment is multifaceted and complex, as well as long-term. Because of that, engagement of the patient and their caregivers in their care is important. I feel very strongly that counseling the patient right from the start is crucial. If we take the patient with us and explain to them the disease process, the complications of not treating, the advantages of treatment, and then what to expect as our outcome, and also be aware of the challenges during the treatment, this becomes part of the counseling that must be done.
The first goal of counseling is to establish a platform from which we start our discussion about what the disease is, and what are its ramifications and manifestations that the patients see. The way I explain to the patient is that the treatment for MAC lung disease is partly based on antibiotic treatment, partly based on treatment of its underlying disease process, and partly based on addressing other comorbidities that may affect the treatment.
Shared decision-making is something that we are doing in the management of MAC lung disease.
Engagement of the patient, engagement of their caregivers, engagement of their family is as important as just taking some pills. And most importantly, this is a long-term treatment which requires you to navigate your healthcare at various levels outside the scope of a clinic visit. So this treatment plan does not start with a clinic visit and does not end with a clinic visit. It continues, almost sometimes on a 24/7 basis. And therefore, communication between patients, caregivers, providers is a constant state of dynamic flux that must be established and must be recognized. Because of that, shared decision-making is critical.
Generally our follow-up of our patients with MAC lung disease is at least every 3 months. That follow-up is a clinic follow-up. My program also does a lot of interval follow-ups through telephonic contacts with the patient. This depends upon what part and what phase of their treatment they are in. Those that have just started, we may be in touch with them almost on a weekly basis, keeping in mind that they’re always free to call us because communication is the key, and that has to be encouraged and kept in mind.
Some key topics I cover with my patients are setting expectations of guideline-recommended treatment, including the expected duration of therapy. The 2020 NTM guidelines recommend this being 12 months of treatment after initial culture conversion. Acknowledging that initial multidrug therapy may not work, and we will reevaluate at 6 months.
After diagnosing my patient with MAC lung disease and starting them on the guideline-based therapy with oral antibiotics, I stress sputum surveillance and sputum checking. At the end of 6 months of that therapy, if they still remain culture-positive, I add ARIKAYCE to that treatment plan according to the 2020 guidelines.
Initially, adding any treatment to a list of medication that the patients are taking is understandably met with a little degree of disappointment and resistance. But if one explains to them the goal of adding this treatment and how it is different to the present treatment that they are taking, their appreciation and their understanding of this improves.
They know that there is an alternative going forward, and most importantly, they feel that all is not lost and there is hope.
What I do is to explain to them that taking ARIKAYCE inhalational treatment is part of the overall MAC lung disease treatment.
It would be important to state that not all times we are successful and not all patients are receptive to what I have just outlined. There are times when a patient is totally against starting the treatment, not realizing the importance of it. In those cases, my practice pattern is that I give them the option. I give them all the information, I give them all the brochures that are appropriate and available, and then I have a telephonic communication with them a week or 2 later, whereby they may ask me some additional questions. And I usually find that either on their subsequent visit or on their subsequent phone call, they are more receptive to starting the treatment.
And then lastly, in my practice, I have established what I call as my ARIKAYCE dashboard. And that dashboard is actually the list of the patients that are currently on ARIKAYCE. And I have a team member that communicates with them regularly as to how they are doing with that treatment and they have access to that team member. Now, all of these are very practice-specific things, and I’m by no way saying that this is the only way to go, but this is one pattern of how a multidisciplinary, multilevel team effort is required and is helpful for implementing the start, continuation, and the maintenance of treatment.
I share with them the data of the CONVERT trial by showing there were 2 arms, one who took the ARIKAYCE, along with the oral drugs, and one group that did not. Of the group that took the ARIKAYCE along with the oral drugs, 3 times of the people who took that converted to culture-negativity at the 6-month period. Going forward, if they continued their treatment for 12 months, 7 times of those people converted and remained culture-negative. Further, after treatment was completed, only those patients that were on ARIKAYCE originally remained culture-negative. This data goes a long way in assuring the patient that there is information to start the ARIKAYCE treatment.1
The primary endpoint was culture conversion by Month 6. This was defined as 3 consecutive negative sputum cultures, the first of which had to be achieved by Month 4. The primary endpoint of culture conversion by Month 6 was achieved by more than 3 times as many patients on ARIKAYCE plus multidrug therapy arm. That is 65 out of the 224, 29%, compared with patients on multidrug therapy alone, and they were 10 out of 112, which came to 8.9%.1
Two of the key secondary endpoints were change from baseline in the 6-minute walk test and the change from baseline on the St George Respiratory Questionnaire. By Month 6, the change from baseline in 6-minute walk test to distance and the St George Respiratory question score did not demonstrate any clinical benefit.1
Another secondary endpoint was culture conversion 12 months after initial conversion and 3 months off treatment. The exploratory endpoint was culture conversion, assessed 12 months off treatment. Patients were assessed on whether they maintained culture conversion for 12 months, or whether they continue to maintain culture conversion for an additional 3 months off treatment, after receiving ARIKAYCE plus multidrug therapy.1
The secondary endpoint of maintaining culture conversion was achieved by approximately 7 times as many patients receiving ARIKAYCE plus multidrug therapy compared with patients receiving multidrug therapy alone. 18.3% of patients receiving ARIKAYCE plus multidrug therapy maintained culture conversion 12 months after their first culture conversion compared to 2.7 of the patients on multidrug therapy alone.1
Furthermore, 16.1% of patients receiving ARIKAYCE plus multidrug therapy continue to maintain culture conversion 3 months off treatment compared to no patients on multidrug therapy alone.1
I pay a lot of attention and a lot of significance to explaining the safety data on ARIKAYCE. I inform my patients of some serious, as well as common, adverse events associated with ARIKAYCE so that they are prepared. I let them know that ARIKAYCE has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of their underlying pulmonary disease that have led to hospitalizations in some cases.1 I also share some other serious adverse reactions such as anaphylaxis and hypersensitivity reactions, ototoxicity, nephrotoxicity, neuromuscular blockade, and embryo-fetal toxicity. I also tell them about the most common adverse events in patients who received ARIKAYCE plus standard therapy were dysphonia, cough, bronchospasm, hemoptysis, musculoskeletal pain, upper airway irritation, ototoxicity, fatigue and asthenia, exacerbation of underlying pulmonary disease, diarrhea, nausea, and headache.1 When discussing these adverse events with my patients, I use patient-friendly language so that it is clear to them.
My colleagues and I conducted a telephone survey of our patients who were taking ARIKAYCE. This was a retrospective telephone survey of 26 patients who were prescribed ARIKAYCE that was conducted during the 2-month period at 2 academic medical centers in the United States.2
The purpose of this survey was to get a real-world, real-time information from the ground level, from the patients themselves, as to how they were feeling after they had started the treatment and what they were doing, or we were helping them to do, to mitigate some of the adverse reactions that they may be having pertinent to the use of ARIKAYCE.2
We use measures that address local symptoms, which include use of cough drops, use of frequent gargling, cleaning their mouth after the use of the inhaler.2
It is important to note that each patient does respond to treatment differently and the same intervention may not work for everyone. In my opinion, it’s important to inform patients about potential side effects early on and reassure them that we will manage them together.
I counsel my patients on the use of ARIKAYCE by making them understand that ARIKAYCE is to be administered through the nebulizer that they have been given. This nebulizer is very specific to the use of ARIKAYCE. This treatment cannot be mixed with any other inhalation treatment that they may be doing or any other mechanism of airway clearance that they may be using. They are told that they should be comfortable with the nebulizer apparatus and with the use of it according to their daily routine. I go over with them that sometimes some patients find it better to take it in the evening or sometimes some patients take it at a different part of the day, but it has to be taken once a day. I also suggest that if they have any problems with the use of the nebulizer, the way of taking it, or any other questions about that, my team and the patient support program is there to guide them.
In summary, key educational and counseling points during management with ARIKAYCE include review details of administration, including dosing and frequency, and prepare patients on the need for frequent follow-up, provide education on potential side effects, and explain mitigation strategies, and to continue prescribed treatment, continue to monitor for culture status, and emphasize and educate patients on the importance of continuing treatment even after culture conversion has occurred. The 2020 NTM guidelines recommend this being 12 months of treatment after initial culture conversion.
IMPORTANT SAFETY INFORMATION AND BOXED WARNING
WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS
ARIKAYCE (amikacin liposome inhalation suspension) has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.
Hypersensitivity Pneumonitis has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate.
Hemoptysis has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (18.4%) compared to patients treated with a background regimen alone (13.4%). If hemoptysis occurs, manage patients as medically appropriate.
Bronchospasm has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (28.7%) compared to patients treated with a background regimen alone (10.7%). If bronchospasm occurs during the use of ARIKAYCE, treat patients as medically appropriate.
Exacerbations of underlying pulmonary disease have been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease (COPD), infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (15.2%) compared to patients treated with background regimen alone (9.8%). If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat patients as medically appropriate.
Anaphylaxis and Hypersensitivity Reactions: Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures.
Ototoxicity has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE plus background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (8.1% in ARIKAYCE plus background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background regimen vs 2.7% in the background regimen alone arm). Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage patients as medically appropriate, including potentially discontinuing ARIKAYCE.
Nephrotoxicity was observed during the clinical trials of ARIKAYCE in patients with MAC lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE.
Neuromuscular Blockade: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions. Closely monitor patients with known or suspected neuromuscular disorders, such as myasthenia gravis. If neuromuscular blockade occurs, it may be reversed by the administration of calcium salts but mechanical respiratory assistance may be necessary.
Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use ARIKAYCE during pregnancy, or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus.
Contraindications: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside.
Most Common Adverse Reactions: The most common adverse reactions in Trial 1 at an incidence ≥5% for patients using ARIKAYCE plus background regimen compared to patients treated with background regimen alone were dysphonia (48% vs 2%), cough (40% vs 17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%), musculoskeletal pain (18% vs 9%), upper airway irritation (18% vs 2%), ototoxicity (17% vs 10%), fatigue and asthenia (16% vs 10%), exacerbation of underlying pulmonary disease (15% vs 10%), diarrhea (13% vs 5%), nausea (12% vs 4%), headache (10% vs 5%), pneumonia (9% vs 9%), pyrexia (8% vs 5%), decreased weight (7% vs 1%), vomiting (7% vs 4%), rash (6% vs 1%), change in sputum (6% vs 1%), and chest discomfort (5% vs 3%).
Drug Interactions: Avoid concomitant use of ARIKAYCE with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity. Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol.
Overdosage: Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute toxicity should be treated with immediate withdrawal of ARIKAYCE, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing amikacin from the body. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment.
INDICATION
LIMITED POPULATION: ARIKAYCE® (amikacin liposome inhalation suspension) is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.1
This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Limitation of Use: ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.1
PLEASE SEE FULL PRESCRIBING INFORMATION AT ARIKAYCEHCP.COM.
INDICATION
LIMITED POPULATION: ARIKAYCE® (amikacin liposome inhalation suspension) is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.1
This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Limitation of Use: ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.1
* See the full Prescribing Information for ARIKAYCE for information about Limited Population.
PLEASE SEE IMPORTANT SAFETY INFORMATION IN THIS PRESENTATION AND FULL PRESCRIBING INFORMATION, INCLUDING BOXED WARNING, AVAILABLE AT ARIKAYCEHCP.COM.
My name is Dr Juzar Ali. I’m professor of medicine in the section of pulmonary critical care at the LSU School of Medicine in New Orleans, and the director of the NTM Bronchiectasis Program Clinic at University Medical Center. I’m participating in this program as a paid speaker of Insmed.
MAC lung disease is a complex medical problem with multiple manifestations. It does affect the structure and function of the lung along with the infection. The treatment is multifaceted and complex, as well as long-term. Because of that, engagement of the patient and their caregivers in their care is important. I feel very strongly that counseling the patient right from the start is crucial. If we take the patient with us and explain to them the disease process, the complications of not treating, the advantages of treatment, and then what to expect as our outcome, and also be aware of the challenges during the treatment, this becomes part of the counseling that must be done.
The first goal of counseling is to establish a platform from which we start our discussion about what the disease is, and what are its ramifications and manifestations that the patients see. The way I explain to the patient is that the treatment for MAC lung disease is partly based on antibiotic treatment, partly based on treatment of its underlying disease process, and partly based on addressing other comorbidities that may affect the treatment.
Shared decision-making is something that we are doing in the management of MAC lung disease.
Engagement of the patient, engagement of their caregivers, engagement of their family is as important as just taking some pills. And most importantly, this is a long-term treatment which requires you to navigate your healthcare at various levels outside the scope of a clinic visit. So this treatment plan does not start with a clinic visit and does not end with a clinic visit. It continues, almost sometimes on a 24/7 basis. And therefore, communication between patients, caregivers, providers is a constant state of dynamic flux that must be established and must be recognized. Because of that, shared decision-making is critical.
Generally our follow-up of our patients with MAC lung disease is at least every 3 months. That follow-up is a clinic follow-up. My program also does a lot of interval follow-ups through telephonic contacts with the patient. This depends upon what part and what phase of their treatment they are in. Those that have just started, we may be in touch with them almost on a weekly basis, keeping in mind that they’re always free to call us because communication is the key, and that has to be encouraged and kept in mind.
Some key topics I cover with my patients are setting expectations of guideline-recommended treatment, including the expected duration of therapy. The 2020 NTM guidelines recommend this being 12 months of treatment after initial culture conversion. Acknowledging that initial multidrug therapy may not work, and we will reevaluate at 6 months.
After diagnosing my patient with MAC lung disease and starting them on the guideline-based therapy with oral antibiotics, I stress sputum surveillance and sputum checking. At the end of 6 months of that therapy, if they still remain culture-positive, I add ARIKAYCE to that treatment plan according to the 2020 guidelines.
Initially, adding any treatment to a list of medication that the patients are taking is understandably met with a little degree of disappointment and resistance. But if one explains to them the goal of adding this treatment and how it is different to the present treatment that they are taking, their appreciation and their understanding of this improves.
They know that there is an alternative going forward, and most importantly, they feel that all is not lost and there is hope.
What I do is to explain to them that taking ARIKAYCE inhalational treatment is part of the overall MAC lung disease treatment.
It would be important to state that not all times we are successful and not all patients are receptive to what I have just outlined. There are times when a patient is totally against starting the treatment, not realizing the importance of it. In those cases, my practice pattern is that I give them the option. I give them all the information, I give them all the brochures that are appropriate and available, and then I have a telephonic communication with them a week or 2 later, whereby they may ask me some additional questions. And I usually find that either on their subsequent visit or on their subsequent phone call, they are more receptive to starting the treatment.
And then lastly, in my practice, I have established what I call as my ARIKAYCE dashboard. And that dashboard is actually the list of the patients that are currently on ARIKAYCE. And I have a team member that communicates with them regularly as to how they are doing with that treatment and they have access to that team member. Now, all of these are very practice-specific things, and I’m by no way saying that this is the only way to go, but this is one pattern of how a multidisciplinary, multilevel team effort is required and is helpful for implementing the start, continuation, and the maintenance of treatment.
I share with them the data of the CONVERT trial by showing there were 2 arms, one who took the ARIKAYCE, along with the oral drugs, and one group that did not. Of the group that took the ARIKAYCE along with the oral drugs, 3 times of the people who took that converted to culture-negativity at the 6-month period. Going forward, if they continued their treatment for 12 months, 7 times of those people converted and remained culture-negative. Further, after treatment was completed, only those patients that were on ARIKAYCE originally remained culture-negative. This data goes a long way in assuring the patient that there is information to start the ARIKAYCE treatment.1
The primary endpoint was culture conversion by Month 6. This was defined as 3 consecutive negative sputum cultures, the first of which had to be achieved by Month 4. The primary endpoint of culture conversion by Month 6 was achieved by more than 3 times as many patients on ARIKAYCE plus multidrug therapy arm. That is 65 out of the 224, 29%, compared with patients on multidrug therapy alone, and they were 10 out of 112, which came to 8.9%.1
Two of the key secondary endpoints were change from baseline in the 6-minute walk test and the change from baseline on the St George Respiratory Questionnaire. By Month 6, the change from baseline in 6-minute walk test to distance and the St George Respiratory question score did not demonstrate any clinical benefit.1
Another secondary endpoint was culture conversion 12 months after initial conversion and 3 months off treatment. The exploratory endpoint was culture conversion, assessed 12 months off treatment. Patients were assessed on whether they maintained culture conversion for 12 months, or whether they continue to maintain culture conversion for an additional 3 months off treatment, after receiving ARIKAYCE plus multidrug therapy.1
The secondary endpoint of maintaining culture conversion was achieved by approximately 7 times as many patients receiving ARIKAYCE plus multidrug therapy compared with patients receiving multidrug therapy alone. 18.3% of patients receiving ARIKAYCE plus multidrug therapy maintained culture conversion 12 months after their first culture conversion compared to 2.7 of the patients on multidrug therapy alone.1
Furthermore, 16.1% of patients receiving ARIKAYCE plus multidrug therapy continue to maintain culture conversion 3 months off treatment compared to no patients on multidrug therapy alone.1
I pay a lot of attention and a lot of significance to explaining the safety data on ARIKAYCE. I inform my patients of some serious, as well as common, adverse events associated with ARIKAYCE so that they are prepared. I let them know that ARIKAYCE has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of their underlying pulmonary disease that have led to hospitalizations in some cases.1 I also share some other serious adverse reactions such as anaphylaxis and hypersensitivity reactions, ototoxicity, nephrotoxicity, neuromuscular blockade, and embryo-fetal toxicity. I also tell them about the most common adverse events in patients who received ARIKAYCE plus standard therapy were dysphonia, cough, bronchospasm, hemoptysis, musculoskeletal pain, upper airway irritation, ototoxicity, fatigue and asthenia, exacerbation of underlying pulmonary disease, diarrhea, nausea, and headache.1 When discussing these adverse events with my patients, I use patient-friendly language so that it is clear to them.
My colleagues and I conducted a telephone survey of our patients who were taking ARIKAYCE. This was a retrospective telephone survey of 26 patients who were prescribed ARIKAYCE that was conducted during the 2-month period at 2 academic medical centers in the United States.2
The purpose of this survey was to get a real-world, real-time information from the ground level, from the patients themselves, as to how they were feeling after they had started the treatment and what they were doing, or we were helping them to do, to mitigate some of the adverse reactions that they may be having pertinent to the use of ARIKAYCE.2
We use measures that address local symptoms, which include use of cough drops, use of frequent gargling, cleaning their mouth after the use of the inhaler.2
It is important to note that each patient does respond to treatment differently and the same intervention may not work for everyone. In my opinion, it’s important to inform patients about potential side effects early on and reassure them that we will manage them together.
I counsel my patients on the use of ARIKAYCE by making them understand that ARIKAYCE is to be administered through the nebulizer that they have been given. This nebulizer is very specific to the use of ARIKAYCE. This treatment cannot be mixed with any other inhalation treatment that they may be doing or any other mechanism of airway clearance that they may be using. They are told that they should be comfortable with the nebulizer apparatus and with the use of it according to their daily routine. I go over with them that sometimes some patients find it better to take it in the evening or sometimes some patients take it at a different part of the day, but it has to be taken once a day. I also suggest that if they have any problems with the use of the nebulizer, the way of taking it, or any other questions about that, my team and the patient support program is there to guide them.
In summary, key educational and counseling points during management with ARIKAYCE include review details of administration, including dosing and frequency, and prepare patients on the need for frequent follow-up, provide education on potential side effects, and explain mitigation strategies, and to continue prescribed treatment, continue to monitor for culture status, and emphasize and educate patients on the importance of continuing treatment even after culture conversion has occurred. The 2020 NTM guidelines recommend this being 12 months of treatment after initial culture conversion.
IMPORTANT SAFETY INFORMATION AND BOXED WARNING
WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS
ARIKAYCE (amikacin liposome inhalation suspension) has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.
Hypersensitivity Pneumonitis has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate.
Hemoptysis has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (18.4%) compared to patients treated with a background regimen alone (13.4%). If hemoptysis occurs, manage patients as medically appropriate.
Bronchospasm has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (28.7%) compared to patients treated with a background regimen alone (10.7%). If bronchospasm occurs during the use of ARIKAYCE, treat patients as medically appropriate.
Exacerbations of underlying pulmonary disease have been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease (COPD), infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (15.2%) compared to patients treated with background regimen alone (9.8%). If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat patients as medically appropriate.
Anaphylaxis and Hypersensitivity Reactions: Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures.
Ototoxicity has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE plus background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (8.1% in ARIKAYCE plus background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background regimen vs 2.7% in the background regimen alone arm). Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage patients as medically appropriate, including potentially discontinuing ARIKAYCE.
Nephrotoxicity was observed during the clinical trials of ARIKAYCE in patients with MAC lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE.
Neuromuscular Blockade: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions. Closely monitor patients with known or suspected neuromuscular disorders, such as myasthenia gravis. If neuromuscular blockade occurs, it may be reversed by the administration of calcium salts but mechanical respiratory assistance may be necessary.
Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use ARIKAYCE during pregnancy, or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus.
Contraindications: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside.
Most Common Adverse Reactions: The most common adverse reactions in Trial 1 at an incidence ≥5% for patients using ARIKAYCE plus background regimen compared to patients treated with background regimen alone were dysphonia (48% vs 2%), cough (40% vs 17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%), musculoskeletal pain (18% vs 9%), upper airway irritation (18% vs 2%), ototoxicity (17% vs 10%), fatigue and asthenia (16% vs 10%), exacerbation of underlying pulmonary disease (15% vs 10%), diarrhea (13% vs 5%), nausea (12% vs 4%), headache (10% vs 5%), pneumonia (9% vs 9%), pyrexia (8% vs 5%), decreased weight (7% vs 1%), vomiting (7% vs 4%), rash (6% vs 1%), change in sputum (6% vs 1%), and chest discomfort (5% vs 3%).
Drug Interactions: Avoid concomitant use of ARIKAYCE with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity. Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol.
Overdosage: Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute toxicity should be treated with immediate withdrawal of ARIKAYCE, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing amikacin from the body. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment.
INDICATION
LIMITED POPULATION: ARIKAYCE® (amikacin liposome inhalation suspension) is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.1
This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
Limitation of Use: ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.1
PLEASE SEE FULL PRESCRIBING INFORMATION AT ARIKAYCEHCP.COM.
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Review expert commentary on topics related to the management of MAC lung disease
Julie Philley, MD, Pulmonary and Critical Care Medicine Expert
What is the significance of the 6-month mark while treating with multidrug therapy? In this article, Dr Julie Philley reviews steps for what's next when patients do not experience culture conversion.
Frequent monitoring is vital for successful long-term patient management.1 The 6-month evaluation uncovers whether or not a patient is responding to initial treatment early in the disease course,1 and patients are considered to have refractory MAC lung disease if they do not culture convert after 6 months.2 The lack of culture conversion by 6 months may be predictive of treatment failure at 12 months.3 This challenge is important to address because there is a risk of greater decline in lung function4,5 and worse outcomes in patients who are not responding to standard therapy.6 I check sputums monthly, and if culture conversion is not achieved by 6 months, many of my patients require additional treatment. The next step in my management strategy is to expand the therapeutic regimen based on the 2020 ATS/ERS/ESCMID/IDSA NTM Treatment Guidelines. Timely initiation of therapy after 6 months of failure to convert is essential to creating an optimal treatment journey.1
Watch experts discuss how they counsel patients through the 6-month treatment milestone >
Watch experts discuss how they counsel patients through the 6-month treatment milestone >
ATS, American Thoracic Society; ERS, European Respiratory Society; ESCMID, European Society of Clinical Microbiology and Infectious Diseases; IDSA, Infectious Diseases Society of America; MAC, Mycobacterium avium complex; NTM, nontuberculous mycobacteria.
Dr Philley was compensated for her time in creating this material.
References: 1. Daley CL, Iaccarino JM Jr, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline. Clin Infect Dis. 2020;71(4):e1-e36. doi:10.1093/cid/ciaa241 2. ARIKAYCE. Prescribing information. Insmed Incorporated; October 2020 3. Moon SM, Jhun BW, Daley CL, Koh W-J. Unresolved issues in treatment outcome definitions for nontuberculous mycobacterial pulmonary disease. Eur Respir J. 2019;53(5):1801636. doi:10.1183/13993003.01636-2018 4. Park HY, Jeong B-H, Chon HR, Jeon K, Daley CL, Koh W-J. Lung function decline according to clinical course in nontuberculous mycobacterial lung disease. Chest. 2016;150(6):1222-1232. doi:10.1016/j.chest.2016.06.005 5. Huang C-T, Tsai Y-J, Wu H-D, et al. Impact of non-tuberculous mycobacteria on pulmonary function decline in chronic obstructive pulmonary disease. Int J Tuberc Lung Dis. 2012;16(4):539-545. doi:10.5588/ijtld.11.0412 6. O’Connell ML, Birkenkamp KE, Kleiner DE, Folio LR, Holland SM, Olivier KN. Lung manifestations in an autopsy-based series of pulmonary or disseminated nontuberculous mycobacterial disease. Chest. 2012;141(5):1203-1209. doi:10.1378/chest.11-0425
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Pamela McShane, MD, Pulmonary and Critical Care Medicine Expert
Now that you've made the decision to add ARIKAYCE, what should you expect? This article by Dr Pamela McShane summarizes goals and recommendations for management, as well as endpoints and safety results from the CONVERT study.
Culture conversion is an important goal of therapy for my patients with MAC lung disease because it is an objective measure of the status of the infection.1 Taking into consideration the individual patient’s presentation, I believe it makes sense to adjust treatment after Month 6 in patients whose cultures have not converted. Some patients with refractory MAC lung disease may have limited treatment options; however, there is an effective treatment that has been shown to improve their odds of achieving culture conversion by Month 12 and beyond.2
At the 6‐month critical time point, the 2020 ATS/ERS/ESCMID/IDSA NTM Treatment Guidelines strongly recommend adding ARIKAYCE® (amikacin liposome inhalation suspension),3 which has demonstrated efficacy in patients with refractory MAC lung disease.2
The clinical data supporting ARIKAYCE comes from the Phase 3 CONVERT (INS 212) study.
- Open‐label, multicenter, randomized trial that included 336 patients with refractory MAC lung disease2,4 (224 patients received ARIKAYCE plus standard therapy and 112 patients received standard therapy alone)2
- Primary endpoint: proportion of patients who culture converted by Month 62
- ARIKAYCE plus standard therapy (n=65 [29.0%]) compared with standard therapy alone (n=10 [8.9%]) (P<0.0001)
- Secondary endpoints2
- Change in 6MWT and SGRQ scores at Month 6
- ARIKAYCE did not demonstrate clinical benefit
- Remained culture‐negative for 12 months of treatment
- 18.3% of patients who received ARIKAYCE plus standard therapy compared with 2.7% of patients who received standard therapy alone (P<0.0001)
- Remained culture‐negative for 12 months of treatment and 3 months off treatment (ITT population)
- 16.1% of patients who received ARIKAYCE plus standard therapy compared with 0% of patients who received standard therapy alone
- Change in 6MWT and SGRQ scores at Month 6
- Safety
- The most common adverse reactions were respiratory in nature and mild to moderate in severity5
- Dysphonia, cough, bronchospasm, and hemoptysis were the most common adverse reactions reported in patients who received ARIKAYCE plus standard therapy2
The data from the CONVERT study suggest that ARIKAYCE helps achieve and maintain culture conversion rates, with a greater number of patients remaining culture‐negative for 12 months. More than half of patients who achieved culture conversion with ARIKAYCE maintained conversion for 3 months off therapy, whereas no patients receiving standard therapy alone maintained culture conversion for the same amount of time. In the CONVERT study, standard therapy alone was not shown to help patients with refractory MAC lung disease stay culture-negative. ARIKAYCE has been shown to help patients achieve sustained culture conversion that lasts months after discontinuation of therapy.2 With these data in mind, I feel confident when adding ARIKAYCE to my patients’ treatment regimens.
6MWT, 6‐minute walk test; ATS, American Thoracic Society; ERS, European Respiratory Society; ESCMID, European Society of Clinical Microbiology and Infectious Diseases; IDSA, Infectious Diseases Society of America; ITT, intent‐to‐treat; MAC, Mycobacterium avium complex; NTM, nontuberculous mycobacteria; SGRQ, St George’s Respiratory Questionnaire.
Dr McShane was compensated for her time in creating this material.
References: 1. Griffith DE, Adjemian J, Brown‐Elliott BA, et al. Semiquantitative Culture Analysis During Therapy for Mycobacterium avium Complex Lung Disease. Am J Respir Crit Care Med. 2015;192(6):754‐760. doi:10.1164/rccm.201503‐0444OC 2. ARIKAYCE Prescribing information. Insmed Incorporated; October 2020 3. Daley CL, Iaccarino JM Jr, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline. Clin Infect Dis. 2020;71(4):e1‐e36. doi:10.1093/cid/ciaa241 4. Griffith DE, Eagle G, Thomson R, et al; for the CONVERT Study Group. Amikacin liposome inhalation suspension for refractory Mycobacterium avium complex lung disease: sustainability and durability of culture conversion and safety of long‐term exposure. Chest. 2021;160(3):831‐842. doi:10.1016/j.chest.2021.03.070 5. Griffith DE, Eagle G, Thomson R, et al; for the CONVERT Study Group. Amikacin liposome inhalation suspension for treatment‐refractory lung disease caused by Mycobacterium avium complex (CONVERT): a prospective, open‐label, randomized study. Am J Respir Crit Care Med. 2018;198(12):1559‐1569. doi:10.1164/rccm.201807‐1318OC
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Nicole Lapinel, MD
Patient counseling is critical at diagnosis and throughout the treatment journey. In this advertorial, Dr Nicole Lapinel shares her approach to counseling patients with MAC lung disease.
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This convenient piece provides guidelines for managing MAC lung disease and adding ARIKAYCE in a handy, at-a-glance format.
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