IL-5 Inhibitors for Treatment of Asthma

Transcript:

Stanley Goldstein, MD: Let’s discuss the other biologics now. We’ve discussed omalizumab. What about the anti-IL-5, anti-eosinophilic? Can you pick up and discuss mepolizumab and benralizumab?

Shahzad Mustafa, MD: Yes, I can take that. There are 3 FDA-approved biologics that are anti-IL-5 or what you would say anti-eosinophilic, mepolizumab, reslizumab, and benralizumab. They have similarities, but benralizumab’s mechanism of action being a little different than reslizumab and mepolizumab. But, at the end of the day, these are anti-IL-5 agents that are aimed at decreasing eosinophils and eosinophilic inflammation. There are subtleties in delivery, whereas reslizumab is an IV infusion, the others are subcutaneous injection, whether it’s at 4 weeks or 8 weights. There are subtleties, but that’s the general principal for all 3 of these as allergists and pulmonologists use them regularly. 

When you’re considering them, and Stan touched upon this very nicely, these patients are not binary. There’s tremendous overlap in these individuals. You may have individuals with elevated IgE and elevated eosinophils, which is not uncommon, and I’m sure we all see that in our clinical practice. With individuals with elevated eosinophils, which depending on the specific drug, the studies looked at 150 eosinophils in the blood count, peripherally up to 300, 400, but the bottom line is individuals with elevated eosinophils may benefit from these agents. Here, the best predictor of response is the eosinophil count. The higher the eosinophil level, the more likely the individual is to respond to the medication. By response, I mean most of these studies which now date back several years and there’s been multiple landmark studies on all of these agents, is that primary outcome is generally decreasing steroid-requiring exacerbations. In all-comers, if you look at a big Cochrane review, the general rule of thumb is that you’re going to hopefully decrease steroid-requiring exacerbations by about 50% with these patients, and if that happens, it’s considered a success.

Of course, we would like to improve symptoms, we’ve talked about quality of life, we’d like to improve lung function, and those are secondary outcomes that we hope to see with these agents as well. But the primary goal remains decreasing steroid-requiring exacerbations, keeping these guys out of the urgent care, EDs, certainly the hospital. That’s the biomarker that we’re using for these anti-IL-5 agents, is eosinophils. But, again, Stan touched upon it very nicely, and I think it’s very important that we are working in a Th2-high space, and all of these biologics fall in that space. These are not individual options. There’s a lot of overlap, and I think that’s where the clinician comes in in trying to make a good judgment. Even though we’re not great at predicting the future, making a good judgment of which one of these biologics would be best for this patient. This is an important decision, as Dr. Mosnaim said, it could have huge impact and huge improvement if we get it right.

Stanley Goldstein, MD: Thanks for that discussion. Let’s say we have a patient who has high eosinophils, and we’re thinking about an anti-IL-5 agent, is there any specific way that you could determine which one you would use? How do you think about that and how do you have the patient involved in that conversation, and how do you have the referring physician involved in that conversation?

Shahzad Mustafa, MD: This is the buzzword into what we should all be doing right now, is shared decision-making. As physicians, we know the science, we know studies, and we present that information to our patients and their families and then we come to a decision together that may be best for them. Every individual brings different perspectives, different backgrounds to the discussion, so it’s hard for us to just deliver information. These agents should be similarly efficacious, so it comes down to dosing— an IV infusion versus a self-injectable, whether you can do it at a doctor’s office, or at home, whether mepolizumab is dosed every 4 weeks versus benralizumab which can be eventually dosed every 8 weeks.

Comorbidity is an important one, too. Some of these medications are now, we’re certainly looking at all of them in other conditions that are not all FDA approved yet, but there is some data for a different one of these agents in different conditions; for example, mepolizumab has good data in Churg-Strauss or EGPA. You want to be thinking about what other conditions can be improved while we take care of the patient’s asthma, because as we talked about earlier, so many of these patients have comorbidities. 

I present the data to the patient, to their family, and we discuss through it with the type of dosing, where they want dosing, what their comfort level is. The safety profile, which we’ll talk about, these are generally very well tolerated medications. They do have subtle differences, so we work through that as well, but it really should be a collaborative effort between the clinician and the patient because very rarely is one obviously better than the other, at least in my opinion. I’d love to hear you guys weigh in, too. But there are options and how you wade through that I think is important with shared decision-making.

Transcript Edited for Clarity