Chronic Medications to Maintain Lung Health Clinical Care Guidelines

These guidelines were developed by consensus based on expert opinion and a medical literature review to provide evidence-based recommendations for chronic medication use for lung health maintenance.

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Chronic Medications for Maintenance of Lung Health in CF Patients Ages 6 and Older: Executive Summary

Mogayzel PJ Jr, Naureckas ET, Robinson KA, Mueller G, Hadjiliadis D, Hoag JB, Lubsch L, Hazle L, Sabadosa K, Marshall B; Pulmonary Clinical Practice Guidelines Committee. Cystic Fibrosis Pulmonary Guidelines: Chronic Medications for Maintenance of Lung Health. Am J Respir Crit Care Med. 2013 Apr;187(7):680-9.

The treatment of cystic fibrosis has continued to evolve and become more complex with the development of a wide variety of medication options to improve and maintain lung health. At the same time, these therapies place a significant burden on patients with CF and their families, and their optimal use remains open to discussion.

To aid care providers in the use of these medications, the Cystic Fibrosis Foundation established the Pulmonary Clinical Practice Guidelines Committee to evaluate therapies and provide recommendations for their use to treating providers. In 2007, the committee developed guidelines based on the existing evidence for each medication and for specific patient populations.

The 2007 chronic medications guideline was updated in 2013. Studies of new medications approved for use in the U.S. after the publication of the 2007 guideline and additional data published on existing therapies were reviewed by a panel of experts. The guideline includes recommendations for aerosol therapy (bronchodilators, antibiotics, and mucoactive agents), oral antibiotics, anti-inflammatory drugs, and cystic fibrosis transmembrane conductance regulator (CFTR) modulators.

Since the publication of the guideline in 2013, additional CFTR modulators have been approved by the U.S. Food and Drug Administration (FDA). Important questions regarding how to best use these medications, long-term risks versus benefits, and other issues remain to be answered. The consensus guideline is intended to synthesize the available data to offer recommendations to providers on management strategies targeting their individual patients.

Methodology

A multidisciplinary committee of 17 members reviewed the 2007 guidelines and developed a series of questions related to chronic drug therapies for CF. An evidence-based review was commissioned from Johns Hopkins University, with systematic reviews completed for each question. New reviews were conducted for each question, as some questions were new or revised, new medications and indications had been developed, and full systematic reviews were not completed for all questions during the development of the 2007 guidelines.

The review was limited to parallel, or cross-over, randomized controlled trials (RCTs). Members of the committee disclosed any potential conflicts of interest. If any perceived conflict was identified, members did not participate in any discussions or decisions on recommendations regarding that therapy.

Subcommittees were created to review the evidence summaries and draft recommendations for presentation to the entire committee. Final recommendations were graded using the U.S. Preventive Services Task Force (USPSTF) scheme, which encompasses an estimate of the magnitude of net benefit and certainty of net benefit. Find additional information about the U.S. Preventive Services Task Force (USPSTF) grading definitions

Primary Recommendations

Bronchodilators

Recommendations Evaluation of the Evidence
1. B2 agonists: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I
2. Anticholinergics: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I

Inhaled Antibiotics

Recommendations Evaluation of the Evidence
4. Tobramycin: Mild lung disease — Recommend use Certainty of moderate benefit is moderate
Recommendation: B
5. Tobramycin: Moderate to severe lung disease — Strongly recommend use Certainty of substantial benefit is high
Recommendation: A
6. Aztreonam: Mild lung disease — Recommend use Certainty of moderate benefit is moderate
Recommendation: B
6. Aztreonam: Moderate to severe lung disease — Strongly recommend use Certainty of substantial benefit is high
Recommendation: A
7. Other inhaled antibiotics: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I

Oral Antibiotics

Recommendations Evaluation of the Evidence
8. Anti-Staphylococcus aureus agents for chronic use: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I
9. Anti-Staphylococcus aureus agents for prophylactic use: Recommend against use Certainty of benefit is moderate and benefit is negative
Recommendation: D
10. Anti-Pseudomonas aeruginosa agent: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I

Mucolytics

Recommendations Evaluation of the Evidence
11. Dornase alfa: Mild lung disease — Recommend use Certainty of moderate benefit is moderate
Recommendation: B
12. Dornase alfa: Moderate to severe lung disease — Strongly recommend use Certainty of substantial benefit is high
Recommendation: A
13. Hypertonic saline: All lung disease regardless of severity — Recommend use Certainty of moderate benefit is moderate
Recommendation: B

Anti-Inflammatory

Recommendations Evaluation of the Evidence
14. Inhaled corticosteroids: Recommend against use for patients without asthma or allergic bronchopulmonary aspergillosis (ABPA) Certainty of no benefit is high
Recommendation: D
15. Oral corticosteroids: Recommend against use for patients without asthma or ABPA

Certainty of harm is high

Recommendation: D

16. Ibuprofen: Patients under 18 years old with FEV1 >60% — Recommend use (physicians should obtain and target peak plasma concentration between 50-100 μg/ml) Certainty of moderate benefit is moderate
Recommendation: B
17. Ibuprofen: Patients over 18 years old — Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I
18. Azithromycin: Patients with chronic P. aeruginosa infection — Recommend use (patients should be screened for nontuberculous mycobacterium before initiation and at 6- or 12-month intervals and withheld in the presence of active nontuberculous mycobacterium infection) Certainty of moderate benefit is high
Recommendation: B
19. Azithromycin: Patients not chronically infected with P. aeruginosa — Recommend use Certainty of small benefit is moderate
Recommendation: C
20. Leukotriene modifiers: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I
21. N-acetyl cysteine: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit
Recommendation: I
22. Inhaled glutathione: Evidence insufficient to recommend for or against chronic use Certainty of benefit is low and cannot estimate magnitude of benefit.
Recommendation: I

CFTR Modulators

Recommendations Evaluation of the Evidence
23. Ivacaftor: Patients with at least one copy of the G551 CFTR mutation — Strongly recommend use Certainty of substantial benefit is high
Recommendation: A

Unanswered Questions

Since publication of the 2013 guidelines, the use of CFTR-modulating agents has greatly increased. Ivacaftor is now approved for use in patients as young as 2 years of age with non-G551D gating mutations (G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) and the R117H mutation. Ivacaftor/lumacaftor has been approved for patients greater than 6 years of age who are homozygous for the F508del mutation. Other CFTR modulators are in clinical development. The most appropriate use of these medications remains unanswered.

  • What is the optimal sequence of inhaled therapies?
  • What are the long-term benefits/risks of chronic therapies?
  • How is the relative effectiveness of chronic therapies best determined?
  • Are there important drug-to-drug interactions that may impact efficacy?
  • What is the benefit/risk of chronic therapies in patients younger than age 6 and when should they be initiated? This question is addressed in the Preschool Guidelines.
  • How will CFTR modulators impact the use of other chronic medications?
  • What is the impact of the burden of therapy on self-management?
  • What is the optimal inhaled antibiotic regimen?

Further Reading

  • Elborn JS, Vataire AL, Fukushima A, Aballea S, Khemiri A, Moore C, Medic G, Hemels ME. Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis. Clin Ther. 2016 Oct;38(10):2204-2226. doi: 10.1016/j.clinthera.2016.08.014. Epub 2016 Sep 29.
  • Ahmed MI, Mukherjee S. Treatment for chronic methicillin-sensitive Staphylococcus aureus pulmonary infection in people with cystic fibrosis. Cochrane Database Syst Rev. 2016 Mar 22;3:CD011581. doi: 10.1002/14651858.CD011581.pub2.
  • Borowitz D, Lubarsky B, Wilschanski M, Munck A, Gelfond D, Bodewes F, Schwarzenberg SJ. Nutritional Status Improved in Cystic Fibrosis Patients with the G551D Mutation After Treatment with Ivacaftor. Dig Dis Sci. 2016 Jan;61(1):198-207. doi: 10.1007/s10620-015-3834-2. Epub 2015 Aug 7.
  • Nichols DP, Happoldt CL, Bratcher PE, Caceres SM, Chmiel JF, Malcolm KC, Saavedra MT, Saiman L, Taylor-Cousar JL, Nick JA. Impact of azithromycin on the clinical and antimicrobial effectiveness of tobramycin in the treatment of cystic fibrosis. J Cyst Fibros. 2017 May;16(3):358-366. doi: 10.1016/j.jcf.2016.12.003. Epub 2016 Dec 24.
  • Quittner A, Suthoff E, Rendas-Baum R, Bayliss MS, Sermet-Gaudelus I, Castiglione B, Vera-Llonch M. Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial. Health Qual Life Outcomes. 2015 Jul 2;13:93. doi: 10.1186/s12955-015-0293-6.

This executive summary was prepared by:

Michelle Prickett, MD, (Northwestern) and Edward T. Naureckas, MD, (The University of Chicago Medicine)

The guidelines were published in April 2013, they were reviewed in April 2019 and it was determined that no update is needed at this time.

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