Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And joining me today is Dr. Miranda Curtiss. She's a pulmonologist and an allergist at UAB Medicine, and she's here today to highlight biologics and monoclonal antibodies for the treatment of severe asthma.

Melanie Cole, MS: Dr. Curtiss, thank you so much for joining us today. I'd like you to jump right in and tell us about the UAB Asthma Clinic and how it offers options for patients whose severe asthma is not well controlled, including biologics and monoclonal antibodies, and we'll get into those in more details, but give us a little overview of the clinic.

Dr Miranda Curtiss: Well, we have a clinic that focuses on severe asthma patients. So, these are patients who need to be treated with the high-dose inhaled steroid and at least two other controllers. So for most patients, that's an inhaled steroid and a long-acting beta-agonist in the same inhaler and either an additional medication in the same inhaler, which is the long-acting muscarinic antagonist or patients who are on the ICS LABA and also taking Singulair. So, those are the criteria that we're looking for to define patients who have severe asthma, so people who are on either of those regimens and still having asthma flares where they need at least two oral steroid courses in a year or have one severe admission or severe exacerbation requiring admission. So, this kind of defines the patient population we're looking at where we would consider treating with biologics.

So once patients are in our clinic, we also look at comorbidities that can be either affecting how the patients perceive their asthma symptoms and causing them to have a lot of symptoms that can be from another problem that's not only their asthma and try to address those problems. So, this is making sure we're not missing sleep apnea, making sure that the sinus inflammation and sinusitis isn't contributing to some of their asthma symptoms. For most of our patients though, we really are looking at people who have severe asthma and then, we move on to phenotyping their asthma. We mainly can do this with looking at the peripheral blood eosinophil counts, looking at their fractional exhaled nitric oxide, which is a fairly quick, kind of point-of-care test that we can run in clinic. Looking for the patients who have developed either fixed obstruction or sort of a progressive loss of lung function over time. And then, also just characterizing whether they are patients who are atopic or not. We screen for alpha-1 antitrypsin deficiency in our patients just to make sure that we've ruled that out. And then, we move on to using biologics for our patients.

So, most of the patients that we see are probably going to be candidates for several different biologic agents. These are most helpful for patients whose eosinophil count is above 150, and they actually have to meet their criteria to qualify for several of these agents. From that point, we then integrate our pheno results in the presence of atopy and make an assessment as far as whether we want to use the dupilumab, which is going to block IL4 and IL13 signaling, or if we want to choose one of the agents that blocks either IL5 cytokine or IL5 receptor. So in general, patients who have a high pheno and have an eosinophil count of greater than 150 are more likely to initially benefit from Dupixent. And so, that's how we're making our initial choice as far as which of those two agents to use.

There's another agent that's also approved for patients who are atopic with an IgE level of greater than 30 and the presence of a perennial allergen sensitization. Those patients could be treated with Xolair. So, that's a different agent that we could look at, and then for the patients who have any level of eosinophil count. So even an eosinophil count of less than 150, a different agent that we could use is an antibody to the cytokine TSLP, which is tezepelumab. So, we have several choices. And so, this is where we start to use the fractional exhaled nitric oxide and the presence of other comorbidities to help guide us as far as which treatments we use. So, patients who have nasal polyps in their sinuses, several of these agents are also approved to treat that. There are some patients who have an extremely high eosinophil count and then also have asthma. And in those cases, we try to confirm if that eosinophil count is greater than 1500 over more than a 30-day window. Then, that pushes us more strongly to rule out EGPA and rule out malignancy in those patients. And then, the highest dose of mepolizumab, the 300-milligram dose, would be approved for that group. Patients who have chronic hives get a lot of benefit from treatment with omalizumab and that can help also control their asthma.

So, this is sort of how we're, thinking about what is the agent we use. We like to give patients about a six-month trial or so to get a good idea of whether the medication's working or not. And if doesn't seem to be working, then we look at switching to a different agent. So, this is kind of how we're approaching the initial assessment about which agent to use, and then how do we decide when it's time to switch versus do we just keep going with the same agent. People who have a really good response, we keep them with the same monoclonal antibody. And they just can stay on that as long as they're continuing to have good control with it.

Melanie Cole, MS: What a comprehensive overview that was, Dr. Curtiss. And thank you so much for telling us how you're making those decisions between these biologics and the specific considerations for patients with other medical comorbidities as you said. Now, tell us a little bit about cost and insurance coverage as this is relatively new. Speak about how that is worked.

Dr Miranda Curtiss: So, we have several pharmacists who are working with us. Because these medications, many of them can be either given in a medical setting. We usually use an infusion center or they can be administered at home. Some of them initially were only available for use in an infusion center or a medical clinic. So, omalizumab is a good example, where that was the only option. And especially for patients who need to travel from a distance to come to get their shot, that was really challenging.

What happened during the pandemic was that more of the biologics transitioned over to being available for home use. So, the first available for home use was mepolizumab. And then, after that, now, really almost all of them can be administered either in a medical setting or at home. So, that's one of the first questions, where is most convenient for patients to get their treatment? So, some people have a serious phobia of needles. And if it's possible for us to help them get the medication in the infusion center, we definitely try to do that. But, when a medication is given in a medical setting, insurance covers that through something called a medical benefit. And so, that's different from the way they decide, whether to cover an injection at home. That goes through a process called the pharmacy benefit and different insurers will cover one way or the other in different ways. And so, this is why we have several pharmacists that help us. Because when we're making an assessment about starting someone on a medication, our pharmacists will actually check if the insurance would agree to cover the medication, and then they also check as what the copay would be. And if the copay is too high, then we next look at some of the options that the pharmaceutical companies give, which are through copay programs. If patients can be signed up for those programs, then we sign them up, and then we see what the cost will be after that. And so, we have to do this both for pharmacy side and if home administration isn't going to be an option, then we look at this also on the medical side. So, we actually have a pharmacist who's working on each of those questions for us.

And then, we also have a clinic coordinator who helps well. Because all of the medications that we're talking about have to get dispensed through a specialty pharmacy. And so, these are usually pharmacies that will mail the medication directly to the patient. And so, they all have to have prior authorizations that are done. And then, we go through this process of making sure that if there's an insurance change, that we kind of reassess what the cost is going to be. If the copay card needs to be renewed, those usually are good for a year, so we renew those, you know, help with the patients to make sure we get that reprocessed.

And so in addition to that, if we've looked at all of these things and still the copay is going to be really difficult for the patient, then we look at patient assistance programs that the drug companies offer to the patient to help patients who couldn't otherwise afford the medications be able to get the medications. And so, there's a process to apply for those. And this is again where our nurse coordinators and our pharmacists work directly with the patients to get all the information they need to find out if they could go through the patient assistance programs.

So, it's a major process to try to address the cost. But for the patients who really need these medications, they can really profoundly affect how their asthma is. You know, we've had patients who've had really frequent severe flares who have a really good response to the medication. So, it can be really important to the patient to be able to get on the medication and then also to make sure that they can afford to continue to be on the medication over time.

Melanie Cole, MS: For other providers, that is a very multidisciplinary approach with many aspects. And you really are looking at this so closely and taking such good care of your patients. As we get ready to wrap up, tell us a little bit about followup and outcomes and how you're monitoring for treatment response. Anything you'd like other providers to know about monoclonal antibodies and biologics for severe asthma at the UAB Asthma Clinic?

Dr Miranda Curtiss: Our goal is that our patients reach the point that they still need to use their inhaled controller medications. So, they can't go on a biologic and then stop using their inhaled or oral medications. They still will need to continue those. The goal with the biologics is that by using the biologics and using their controllers, that if they happen to be around some sort of trigger, either smoke or getting an upper respiratory tract infection, that they don't have a flare that's so severe that they need any treatment other than to just use their rescue inhaler more frequently.

So, our goal is that our patients have less frequent exacerbations and less severe exacerbations by using the biologics. So, the goal is that we see them at least every three months when they're uncontrolled. And then if they have a really good response to the biologic and have good control, we still see them about every six months. Part of this is just to make sure that we keep up with all of the PAs and the copay programs and everything that's involved with continuing to be on the biologics.

And the other is just to make sure that there hasn't been something that changed, where they were well controlled and then they stopped being well controlled. And in that case, then we'll repeat the whole process and look again at what's going on now. Now, is there a problem with sleep apnea or sinus disease, or something that maybe wasn't a problem before that's causing these symptoms? Or is it really just that the asthma is not controlled anymore and we have to change to a different biologic?

Melanie Cole, MS: So much great information and advancements in your field of medicine. Really an exciting time. Thank you so much, Dr. Curtiss, for joining us today. And for more information, you can visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. I'm Melanie Cole. Thanks so much for joining us today.