From the Desk of the Executive Medical Director: We waited 12 years for this?

December 30, 2019

This December, a draft of the Expert Panel Report 4 (EPR 4) from the National Asthma Education and Prevention Program (NAEPP) was posted for public comment. The deadline to submit your comments is Jan. 6.

Since the publication in 2007 of the EPR 3 from the NAEPP of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, there has been a flood of new data on asthma management. EPR 3 quickly became the bible of the diagnosis and management of asthma in the United States. Numerous new therapies have been approved for our patients suffering with this condition.

In the meantime, there have been yearly updates to the Global Initiative for Asthma (GINA), which have kept up with the continued changes in our understanding of how best to manage the condition and where new approved therapies should be used in the care of the asthma patient. This annually-updated document has been filling our unmet need for asthma guidelines but is not always geared to the United States.

I have been eagerly waiting EPR 4. I was really excited until I delved into the 373-page document. To say I was underwhelmed would be putting it mildly. First, it is not a complete guideline. It is a Grading of Recommendations Assessment, Development and Evaluation (GRADE) paper, which addresses only selected topics in asthma management. If you are not familiar with GRADE, it was introduced in 2004 to evaluate evidence in the medical literature used in clinical guidelines.

In a way, it is grading the clinical guideline recommendations by rating the quality of evidence for that recommendation from very low to high. Most medical societies are moving to the GRADE system. The Joint Task Force on Practice Parameters, funded by the College and the American Academy of Allergy, Asthma and Immunology, has moved toward that system, and we will see more and more of these types of “guidelines.” It sounds like the GRADE system makes sense, but I feel that in many cases it may not be very beneficial to the practicing clinician. I believe this to be the case with the new EPR 4 report.

The report examined these different areas of interest in asthma management:

  1. Exhaled Nitric Oxide
  2. Allergen Reduction
  3. Inhaled Corticosteroids
  4. Long-Acting Muscarinic Antagonists (LAMA)
  5. Immunotherapy
  6. Bronchial Thermoplasty

The first thing I noticed was that the report’s list of topics did not include biologics in asthma. I would guess that most practicing allergists would be interested in this subject over most of the others being evaluated by the GRADE system. In the panel’s notes on their stepwise approach in the management of asthma in individuals ages 12 and older, they state, “The evidence-based reviews that informed the GRADE methodology employed in this report did not include studies that examined the role of anti-IgE or more recently FDA-approved biologics. Thus, this report does not contain specific recommendations for the use of biologics in asthma in Steps 5 and 6.” Next, we are referred to the recently released GRADE guideline on severe asthma of the European Respiratory Society/ American Thoracic Society (ERS/ATS). Now, these are highly respected pulmonary medical organizations, but there was minimal input from the allergy community when I looked at their author list. The ERS/ATS guideline will definitely not have the clout of one from the NHLBI.

In the topic of inhaled corticosteroid use, the EPR 4 gives the option of using inhaled corticosteroids with a short acting beta agonist as needed for concomitant therapy in patients 12 years and older with mild persistent asthma. Also, they give a strong recommendation in the same age group for inhaled corticosteroids combined with the long acting beta agonist formoterol for both control and quick relief in those with moderate to severe persistent asthma. Both of these recommendations make sense from the clinical data, but they are off-label at this time. Hopefully we will see approval of the changes by the FDA in the near future, as many of us are concerned about the legal aspects of off-label use, even when another government agency recommends it.

The EPR 4 on immunotherapy gave conditional approval to subcutaneous immunotherapy as an adjuvant treatment in allergic asthma, which we as allergists know is an important modality for that condition. For reasons I don’t understand, they recommended against the use of sublingual immunotherapy (SLIT) tablets. This does not seem to follow the evidence, as dust mite SLIT tablets are approved in many European countries for allergic asthma based on double-blind placebo-controlled studies.

I have just touched on a few of my concerns with EPR 4 in this column. Please download a copy to review and submit your comments by Jan. 6. There is no doubt that all the physicians, allied health professionals, and staff should be congratulated for their hard work in putting this report together. I just wish it were more complete, objective and user-friendly for the allergist caring for asthma patients. I guess I will wait another 12 years.