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Q:

3/29/2019
I have a 32 year-old man with severe NSAID-exacerbated respiratory disease, nasal polyps, sinusitis (Sampter's Triad), whose asthma and nasal polyps are relatively unresponsive to nasal steroids, polypectomies, high dose ICS/LABA and montelukast. He's needing more frequent oral prednisone. I'm considering the following:
1) Adding Zileuton CR 600 - 2 tabs BID
2) Adding biological
3) ASA denensitization at a center skilled in this procedure

My questions are as follows:
(1) Which biologic would you prefer in such a case - do you feel dupilimab has any advantage over mepolizumab or vice versa? Would you use omalizumab, benralizumab, mepolizumab, dupilumab?
(2) Do you believe dietary changes might be helpful?
(3) Would you stop the montelukast when starting the zileuton or stay on montelukast as well as zileuton?
(4) Would you consider aspirin desensitization in addition to starting a biological or wait to see response on biological?

A:

I asked Andrew White, MD, FAAAAI, to comment on your question. Here is his reply:

(1) Which biologic would you prefer in such a case - do you feel dupilimab has any advantage over mepolizumab or vice versa? Would you use omalizumab, benralizumab, mepolizumab, dupilumab?

None of these medications have FDA approval for treatment of polyposis. Omalizumab, mepolizumab and dupilumab all have data, none of them specifically for AERD. There are no head to head studies, thus it is impossible with such limited clinical experience and data to recommend one treatment above another.

(2) Do you believe dietary changes might be helpful?

Schneider TR et al demonstrated the effectiveness of a rigorous dietary intervention (high omega 3, low omega 6) and showed benefit. This should be offered as an option for all AERD patients.

Schneider TR, Johns CB, Palumbo ML, Murphy KC, Cahill KN, Laidlaw TM. Dietary Fatty Acid Modification for the Treatment of Aspirin-Exacerbated Respiratory Disease: A Prospective Pilot Trial. J Allergy Clin Immunol Pract. 2018 May - Jun;6(3):825-831. doi: 10.1016/j.jaip.2017.10.011. Epub 2017 Nov 10.

(3) Would you stop the montelukast when starting the zileuton or stay on montelukast as well as zileuton?

Montelukast acts by blocking the CysLT1 receptor. Zileuton acts by inhibiting 5 lipoxygenase. These actions act separately and although there is surely some redundancy, there is probably a role to use them both together. My practice is to add zileuton to montelukast when montelukast has clearly been beneficial but further treatment necessary. If zileuton effective, then I would try to withdraw the montelukast to see if it is necessary. I am not aware of any data to support this approach. I suspect practice patterns vary on this point.

(4) Would you consider aspirin desensitization in addition to starting a biological or wait to see response on biological?

I would recommend doing one intervention at a time. If you start multiple treatments simultaneously you will not know what is effective. There are pros/cons to each decision and best to use shared decision making in your discussion you’re your patient. Aspirin is a very inexpensive treatment when compared with many of the other options you bring up. We need more data to help guide decision making at the point you are at.

I hope this information is of help to you and your patient.

Regards,
Eric Macy, MD, MS, FAAAAI

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