Clinical trial safety profile

Adverse reactions in ≥5% of ARIKAYCE-treated MAC patients (n=223) and more frequent than standard therapy alone (n=112) in the CONVERT trial1

Table shows adverse events greater than or equal to 5 percent with ARIKAYCE + standard therapy were more frequent than standard therapy alone.
Scroll to see full chart. ➝
Table shows adverse events greater than or equal to 5 percent with ARIKAYCE + standard therapy were more frequent than standard therapy alone.
Adverse reaction ARIKAYCE + standard therapy (n=223) n (%) Standard therapy alone (n=112) n (%)
Dysphonia a 106 (48) 2 (2)
Cough b 88 (40) 19 (17)
Bronchospasm c 64 (29) 12 (11)
Hemoptysis 41 (18) 15 (13)
Musculoskeletal pain d 40 (18) 10 (9)
Upper airway irritation e 39 (18) 2 (2)
Ototoxicity f 38 (17) 11 (10)
Fatigue and asthenia 36 (16) 11 (10)
Exacerbation of underlying pulmonary disease g 34 (15) 11 (10)
Diarrhea 28 (13) 5 (5)
Nausea 26 (12) 4 (4)
Headache 22 (10) 5 (5)
Pneumoniah 20 (9) 10 (9)
Pyrexia 17 (8) 5 (5)
Weight decreased 16 (7) 1 (1)
Vomiting i 15 (7) 4 (4)
Rash j 14 (6) 1 (1)
Change in sputum k 13 (6) 1 (1)
Chest discomfort 12 (5) 3 (3)

Additional adverse reactions in <5% of patients1

Selected adverse reactions that occurred in <5% of patients and at a higher frequency in ARIKAYCE-treated patients in the CONVERT trial included:

  • Anxietyl (5% vs 0%)
  • Oral fungal infectionm (4% vs 2%)
  • Bronchitis (4% vs 3%)
  • Dysgeusia (3% vs 0%)
  • Hypersensitivity pneumonitisn (3% vs 0%)
  • Dry mouth (3% vs 0%)
  • Epistaxis (3% vs 1%)
  • Respiratory failureo (3% vs 2%)
  • Pneumothoraxp (2% vs 1%)
  • Exercise tolerance decreased (1% vs 0%)
  • Balance disorder (1% vs 0%)
  • Neuromuscular disorderq (1% vs 0%)

TEAEs over time

TEAEs reported in ≥10% of patients receiving ARIKAYCE + standard therapy or standard therapy alone2

Discontinuations due to  treatment-emergent adverse events for ARIKAYCE + standard therapy primarily occurred early in the trial and declined over time. Discontinuations due to  treatment-emergent adverse events for ARIKAYCE + standard therapy primarily occurred early in the trial and declined over time.

Adapted with permission of the American Thoracic Society. Copyright © 2021 American Thoracic Society. All rights reserved. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society. Readers are encouraged to read the entire article for the correct context at https://www.atsjournals.org/doi/pdf/10.1164/rccm.201807-1318OC. The authors, editors, and The American Thoracic Society are not responsible for errors or omissions in adaptations.

Data indicate the month at which the events were first reported after initiation of therapy.2

Incidence of TEAEs Month 1 to Month 6

  • Patients who reported TEAEs and serious TEAEs in the CONVERT trial were 98.2% and 19.7% for ARIKAYCE + standard therapy vs 91.1% and 16.1% for standard therapy alone, respectively1,2

Discontinuations due to TEAEs primarily occurred early in the trial and declined over time.3

No new safety signals detected4

In the open-label safety extension study of the CONVERT trial, the safety and tolerability of ARIKAYCE + standard therapy remained consistent.

No new safety signals detected with up to 20 months of total ARIKAYCE exposure.

Respiratory AEs following ARIKAYCE initiation were common. Nephrotoxicity-related AEs and measured hearing decline were infrequent over the 12-month treatment phase in the extension study.

INS-312 was a 12-month open-label extension of the CONVERT trial that assessed the long-term safety and tolerability of once-daily ARIKAYCE + standard therapy. Eligible patients who completed both Month 6 and Month 8/EOT visits could consent to enroll directly in INS-312, in which case the Month 8/EOT visit served as the INS-312 baseline. All patients were treated with ARIKAYCE in INS-312. The frequency of TEAEs, TEAEs leading to study withdrawal, serious TEAEs, TEAEs of special interest, and clinically significant abnormalities in laboratory results and vital signs constituted the primary endpoint.4

Discussing the following strategies with patients may help with certain adverse events

Treatment plan1

Bronchodilator use

Additional management strategies from a survey recommend5

Lozenges

Soothing fluid intake

Survey limitations and disclosures5

  • This information is not included in the ARIKAYCE full Prescribing Information
  • The data are from a telephone survey of 26 patients prescribed ARIKAYCE conducted during a 2-month period at 2 academic medical centers in the United States
  • Writing assistance was provided to the authors through funding from Insmed Incorporated. Insmed was not involved with the conceptualization, development, conduct, or analyses of the survey

Survey management strategies for select respiratory adverse events5

Graph of management strategies and select respiratory adverse events such as increased coughing, dysphonia, dyspnea, and increased sputum.
| Management strategy | Increased coughing | Dysphonia | Dyspnea | Increased sputum | |------------------------------------------------------------------------------------------------------------------|--------------------|-----------|---------|------------------| | Bronchodilator use | * | | * | | | Changing ARIKAYCE administration to evening | * | * | | | | Brief interruptions of ARIKAYCE | * | * | * | | | Antitussive agents | * | * | | | | Lozenges | * | * | | | | Warm water or glycerin gargle postdosing | * | * | | | | Soothing fluid intake | * | * | | | | Limiting physical activity | | | * | | | Increased supplemental oxygen, if already administering | | | * | | | Airway clearance (eg, specific breathing techniques, chest percussion, and positive expiratory pressure therapy) | | | | * |

Customize management strategies to individual patients according to their specific needs

Use your clinical judgment when evaluating which strategy to use, including temporarily interrupting or discontinuing ARIKAYCE treatment, if necessary. Educating both patients and their extended care team may aid in early recognition and management of respiratory AEs, which could help contribute to a successful treatment outcome.5,6

Footnotes

aIncludes aphonia and dysphonia.

bIncludes cough, productive cough, and upper airway cough syndrome.

cIncludes asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, and wheezing.

dIncludes back pain, arthralgia, myalgia, pain/body aches, muscle spasm, and musculoskeletal pain.

eIncludes oropharyngeal pain, oropharyngeal discomfort, throat irritation, pharyngeal erythema, upper airway inflammation, pharyngeal edema, vocal cord inflammation, laryngeal pain, laryngeal erythema, and laryngitis.

fIncludes deafness, deafness neurosensory, deafness unilateral, dizziness, hypoacusis, presyncope, tinnitus, vertigo, and balance disorders.

gIncludes COPD, infective exacerbation of COPD, and infective exacerbation of bronchiectasis.

hIncludes atypical pneumonia, empyema, infection pleural effusion, lower respiratory tract infection, lung infection, lung infection pseudomonas, pneumonia, pneumonia aspiration, pneumonia pseudomonas, pseudomonas infection, and respiratory tract infection.

iIncludes vomiting and post-tussive vomiting.

jIncludes rash, rash maculo-papular, drug eruption, and urticaria.

kIncludes increased sputum, sputum purulent, and sputum discolored.

Footnotes

lIncludes anxiety and anxiety disorder.

mIncludes oral candidiasis and oral fungal infection.

nIncludes allergic alveolitis, interstitial lung disease, and pneumonitis.

oIncludes acute respiratory failure and respiratory failure.

pIncludes pneumothorax, pneumothorax spontaneous, and pneumomediastinum.

qIncludes muscle weakness and neuropathy peripheral.

AE=adverse event; EOT=end of treatment; NTM=nontuberculous mycobacteria; TEAE=treatment-emergent adverse event.

References:
1. ARIKAYCE [package insert]. Bridgewater, NJ: Insmed Incorporated; 2020. 2. Griffith DE, Eagle G, Thomson R, et al; 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. 3. Data on file. Insmed Incorporated. Bridgewater, NJ. 4. Winthrop KL, Flume PA, Thomson R, et al; INS-312 Study Group. Amikacin liposome inhalation suspension for MAC lung disease: a 12-month open-label extension study [published online ahead of print December 16, 2020]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.202008-925OC. 5. Swenson C, Lapinel NC, Ali J. Clinical management of respiratory adverse events associated with amikacin liposome inhalation suspension: results from a patient survey. Open Forum Infect Dis. 2020:7(4). doi:10.1093/ofid/ofaa079. 6. Daley CL, Iaccarino JM, 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.
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