This webinar was recorded on September 19, 2023
Despite optimal use of inhaled and oral therapies, some people still have uncontrolled asthma. How can Biologics improve control?
Speaker:
Vikram Tejwani, MD
Assistant Professor of Medicine
Cleveland Clinic Lerner College of Medicine (CCLCM)
Case Western Reserve University (CWRU) School of Medicine
Respiratory Institute, Cleveland Clinic
Dr. Tejwani is a physician in the asthma and COPD centers at Cleveland Clinic, where he joined after completion of a pulmonary and Critical Care Fellowship at Johns Hopkins University. Dr. Tejwani is an active scientific investigator in both asthma and COPD and an assistant professor at the Cleveland Clinic Lerner Center College of Medicine. He is passionate about patient education and translating nuanced evidence and data into actionable recommendations and has enjoyed partnering with Allergy & Asthma Network on numerous patient-centered and academic endeavors.
CE is not available for this webinar.
Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.
De De: Hello everyone, thank you for joining us today. I’m De De Gardner. Welcome to this afternoon’s webinar. We are in for a real treat with Vick Tejwani as our presenter. We have a few housekeeping items before we start today. First, all participants will be on mute for the webinar. We will record today’s webinar and posted on our website within a few days. You can find all of our recorded webinars on our website at allergyasthmanetwork.org. You will find our recorded webinars and any upcoming webinars at the bottom of the page. This 11 are will be one hour, including time for questions. We will take questions at the end of the webinar. You can put your questions at the Q&A at any time. The question and answer box is at the bottom of your screen. We have someone monitoring the chat if you have any questions or need help. We’ll get to as many questions as we can before we conclude today’s webinar. We do not offer education credits for this webinar but we offer a certificate of attendance. A few days after the webinar you will receive an email with the supplemental documents and a link to download the certificate of attendance. We will try to add the link to the certificate in the chat box. Let’s get started. Today’s topic is Biologics–Biologics: Turning the Tide on Severe Asthma. Despite optimal use of inhaled therapy, some people have uncontrolled asthma, how can Biologics improve control? The mission of the network is to end the needless death and suffering due to allergies, asthma or related conditions throughout reach, advocacy and research. Today it is my pleasure to introduce our speaker Dr. Vick Tejwani. He is a physician and the asthma and COPD centers at the Cleveland clinic after completing a fellowship at Johns Hopkins University. He is an active scientific investigator of both asthma and COPD and an assistant professor at the Cleveland clinic Lerner College of medicine. He is passionate about transferring Nuance data into active recommendations, and has enjoyed partnering with the asthma network on academic endeavors. We want to thank him for making this webinar possible today. I will turn it over to you Dr. Vick Tejwani. I am not hearing you.
Dr. Tejwani: Sorry, I was having issues with the mute button. Thank you for organizing this. I am excited about the topic, as I’m sure many of our attendees are. It has been a wonderful — well — it is a good time to be in asthma position a lot has been changing the last several years. To some degree we have a good problem which is when to deploy therapies for refractory cases, and which therapy to deploy. These are better problems than were present a decade ago when it was really just systemic or otherwise — just systemic steroids. Thank you for supporting this. In brief, for today, I would like to go over three main criteria regarding Biologics in asthma. One is a review of the burden of severe asthma and some data to parse out how prevalent that actually is. Two, which will be the main focus of the talk is consideration and initiation of biologic therapies. Three, although as I have alluded to, in many on the call no, we have — know, we have come a long way, there are still limitations with initiating and discontinuing biologic therapy. We will try to touch upon those and where things may be going on ahead. To begin with, there is varied definitions of severe asthma. But, in brief, it is asthma that requires high dose inhaled critical steroids or oral corticosteroids or uncontrolled despite this. This is different from difficult to treat asthma and there is a nice image that was in the most recent guideline from last year in 2022 which is, this is based on a single study which was published in 2015. I will note for our audience in America is that these — this data is from the Netherlands and so it is a different population, a little more homogenous in terms of ethnic variability’s and social economics. These numbers will not translate exactly the globe. I do think the highlight among your asthma populations you have a number of those, 25%, that require high intensity treatment. Then a number of those that, despite that high intensity treatment, don’t have great symptom control. This is the difficult to treat asthma definition. Then you have a very small minority of these patients, post estimates in America suggest this number is actually 5% to 10% different than the 3.7% demonstrated in the Netherlands study. Despite the treatment, and importantly, good adherence and inhaler technique, they still have four symptom control. This is the population that Biologics are geared to address. It is the 5% to 10% of severe individuals that Biologics are geared towards. We will hammer home three take-home points. I want to start with ensuring that you actually have the accurate diagnosis of asthma and guideline-based therapy. Before we do come back to this, I enjoy the study. Which, most studies that go over asthma say that asthma is responsible for this many days of work missed or school missed or this many dollars to the health care system. But this study looked at was if you took at all the individuals with asthma that are uncontrolled, probably in the 25% range, and you got them well-controlled, how much money would that translate into. It is a huge amount.
This is not hearing asthma, this is just — curing asthma this is just controlling it, either through inhaler therapy or biologic therapy. What this graph shows is that it would be approximately $15 billion per year in direct cost that would be reduced. And if you count missed days of work, missed days of schools which would be indirect costs related to this, it would be another $30 billion per year. They projected this out over the next 20 years. It’s nearly a trillion dollars in aggregate or a than a trillion, when you consider direct and indirect cost over the next 20 years. That could be achieved just from getting that 20% or so of individuals of uncontrolled asthma, control. This is purely quantifying it from a financial perspective. It does not account for — this is a metric of quality of life years, or they do not have adequate quality of life. It is a huge amount. 700,000 of quality of life years per year that are lost essentially to poor asthma control. So, I say this just to underscore what a huge — this is just within the U.S. — what a huge burden, certainly severe asthma poses, but also lack of asthma control, some of which can be achieved with better inhaler use and better inhaler prescription can result in. This is to underscore the emphasis on asthma control is critical and will reduce health care costs and improve patient’s quality of life. This is just saying that although that number is the smaller amount of overall individuals with asthma, they have this disproportionate system — symptom burden on the quality of light — life and health care utilization. Back to our first take-home point. From a practical perspective, many patients are referred to in clinic and sometimes for asthma control, sometimes purely with the query of, I think this individual may need biologic therapy. For the majority of these patients if you go and go through the to ensure to make sure they are on the appropriate therapy per guidelines, you go over symptoms, counseling them on their disease, making an action plan, do inhaler education to make sure they are using the right way. Inhalers are not very intuitive. Sometimes due to insurance coverage patients have to switch from inhaler to inhaler. For all of these reasons, you can avoid Biologics in many patients with this part of it. This needs to be on the back of our minds to ensure that we have the right diagnosis, two we have controlled anything we can, this might include exposures, allergens in the house, some of these are nonmodifiable. It is just dust or humidity outside, or smoke from fires as we have recently experienced. Then, ensure that they are using the inhalers correctly and understand that it can be complex, particularly with smart therapy, which inhaler you use on a regular basis, which one you use when you get into trouble. Spending time on all of this pays dividends for asthma control and often you can avoid needing Biologics. The other thing about asthma is it is not a disease that occurs in isolation.
Many similar conditions will present in a similar fashion. Anytime you are uptight treating someone’s asthma regimen without getting relief, you think is this really asthma I am dealing with? For something mimicking it? This is a great figure showing that all of these comorbidities mimic asthma. You may be treating the wrong thing. They are associated with worse asthma control. Individuals with higher BMIs have severe asthma. Depression and anxiety are associated with worse asthma control, sleep apnea. Want to make sure these comorbid ease are addressed. For me, as in asthma specialist it is hard to tackle these all independently so I think it is important that there might be an EMT you work with closely. I think prescribing a PPI or antihistamine to start treatment is wonderful but maybe a gastroenterologist where the reflux gets more refractory where they need and ended — endoscopy to closer assess it. It’s fills this network caring for the asthma patient. Undoubtedly many of your patients will experience these and this is the reason it is harder to control. I have come across this fairly often. There is a figure I show my patients often to exemplify that reflux can come up. I joke with my patients that I never anticipated caring about the stomach and esophagus as a lung doctor but it interplay is so much that you can’t isolate the asthma loan without thinking about these things. It before we move on to discussing Biologics, I want to emphasize that before you get to that point you want to make sure that foundation Lee, you think you have — foundational he you think you have — foundationally, you have your patients on the therapy, and they’re using the inhalers the right way. And also their actual physical use of it to make sure it is getting delivered. Two it is this more global assessment of the individual and comorbidities particularly those we showed in the last slide that trickle on with asthma, and can either mimic or worsen asthma. You will find that when you do that, those patients that seemed “severe”, move into the difficult to treat category or they are able to get control. And requires an intense amount of therapy and Biologics. Once you have achieved that, you will have patients that despite all of this, either the comorbidities will be present or they are well-controlled, or it is just there asthma that is driving it. Then you get to the part, where this individual truly has severe asthma, with exacerbations.
Basically all of the studies were Biologics were done on individuals that had at least two exacerbations over the last 12 months. This is really more so for the exacerbate her — exacerbater phenotype. I’m thinking about Biologics I need to sort out which one may be the best. For these individuals — I guess all of these are important, but you will get a CBC with differential which will get you a AEC count. With individuals with severe asthma that are on oral corticosteroids steroids. It can be difficult to get a full count off of steroids. Steroids will increase your neutrophils, while suppressing your account. You will see the asthma patient and you’ll think wow, their account was almost zero or almost 10, or .01 if you’re looking at it per thousand. It turns out that every time it was checked, they were showing up to an urgent care and getting the just tried steroids at home before they came there. That is what that Asterix is denoting. That when you’re looking at their accounts you’re clarifying if they were on systemic steroids or not. The threshold for most Biologics is 150 to 300. The other measure of D2 immunity is nitric oxide. It is just and exhaled breath in and you are exhaling the nitric Arson back — nitric oxide. This can be suppressed by systemic steroids but it can be suppressed by inhaled corticosteroids, since it is an airway measurement. In other uses, it is used to see if individuals are having a response to inhaled corticosteroids. Keep that in mind. If it is low just know what inhalers they took that morning before the testing was done. Then importantly, IgE testing should be performed, for your more classically allergic asthma individuals. Additionally, historically we have had to have done skin testing for Allergan testing but now that can actually be done via blood. There are different panels based on where you are. If they find something that they are clearly positive to and is avoidable, it is possible you may be able to address that trigger without progressing all the way to Biologics. Typically you will have — to ensure there are not COPD comorbidities, for individuals who have a smoking history. Asthma loan — alone can reduce your FEV1. An activation history to make sure they would benefit from biologic. We have talked about corticosteroids –comorbidities. There are other comorbidities, that I don’t typically address as often including food allergies, which have their own indications were Biologics.
What I deal with is the one airway hypothesis that was going on in the nose and sinuses in terms of allergies is going on in the airways. If they have upper airway cough syndrome or symptoms, that is a comorbidities that you want to assure his address before moving onto Biologics. It’s important to know if there — they are nasal polyps. There are three specific Biologics that will be hateful in — helpful in that environment. We will show those three again in the slide. I will show various iterations of this slide. I’m sure all of you have seen something like this or some other version. This is the result of decades worth of both bench transitional and clinical investigative work. Essentially it is to show that this is the inside of the airway when we get exposed to cigarette smoke, pollutants, viruses, fungi. It activates something on the others of our airways called Alarmin, one of them being TSLP, which causes these downstream effects with T2 cytokines an activates B cells which is our immunoglobulin. So we will look at this again. I don’t think it is critical — it is important to have an understanding. But from a purely practical perspective it is not important to have all of the steps committed to memory. But all downstream leads to the syndrome we all recognize as asthma. As a brief tangent, this is from a paper, a clinical guideline we put on earlier this year for measuring nitric oxide. One of the importantances it is part of a team to phenotype. We are looking for that over 25 parts per billion cutpoint. So this is another version of that slide and right now there are six FDA approved agents for the treatment of severe asthma. Then MEPOLIZUMAB interleukin five. Dupilumab four IL-4. And — which is upstream, that is the one that hopefully is most beneficial for individuals who don’t have a T2 phenotype. The other things I want to highlight on this figure which are distinct from the last one is another alarmin. We will talk about the date on this. Just to highlight that, we are focusing our talk today on asthma but this can lead to other allergic type of conditions that have their own indications for Biologics which we are not discussing today. So once you have determined this individual truly has severe asthma. I have done optimized their inhaler regimen to the best I can, I have done their Allergan testing, gone over there exposure history. We have avoided everything that was possible to review and I have addressed to their comorbidities. I am very rarely starting a patient on biologic. It takes to visits, sometimes three, to make sure we have checked off the boxes before we commit them to the therapy.
Once you have determined that, you beside which biologic to use. Thre’s limited — there is limited data to guide this. Your truly allergic individual with elevated IgE. Maybe they had allergies as a child. That would be an individual, that would be a good candidate for omalizumab therapy, this would be two or four weeks depending on their body weight and. Levels. Is available online there is a table, based on their body weight and what their blood level of IgE is. You will have a different frequency every two or three weeks. The other is Eosinophilic, your traditional T two phenotype. They use the listed, which target T2. It is mepolizumab every four weeks. Then you get into more of the nuances. I Reslizumab is a weight based infusion. The other doses — for mepo lizumab if you are 70 kilograms your dose will be the same. R eslizumab may be beneficial for those with a higher BMI. It may address any absorption issues. The downside it is not injectable. There is no at-home version of this. It is an infusion where they are coming in every four weeks. Dupilumab is dosed every two weeks, based on if you’re using severe asthma or steroid dependent asthma, you will adjust the dose accordingly. It’s the only one with an FDA approval for oral corticosteroids. This one is perfectly helpful for the individual where you can’t ween them off prednisone. You get them down to five or 10 milligrams on the symptoms start to have — you cannot taper any lower. Your never really able to get a true count. You don’t know if they have elevated Eo sinophil levels. The other thing I did not put is — has been approved for FE1. If there is airway modeling, or you’re doing monitoring when their symptoms are flaring, that may be a good option for them. Benralizumab the benefit is you do three doses for four weeks, every four weeks and after that it is an eight week dose. If you have an individual who does not want to do home injections because they don’t feel comfortable or don’t have family support or other support to do it, or is coming into the, office to get it done that may be a good option. The C RSwNP, with nasal polyp process, it is critical. This harkens back — sometimes these are so bad you can see them yourself. In other times they require an exam with our ENT colleagues.
But if they have chronic rhino cyanide is with — there are studies going on to make sure these medications will be beneficial but they have only shown benefit and the individuals with upper airway disease and nasal polyps. We will come back to this. This is probably a good thing once you get to the point of determining the individual meets all the criteria for a biologic. This brings us into the newer medication. These are the alarmins. There are three released when we get exposed to typically some stimuli whether it is viruses, in some individuals it is just exercise, humidity, cold air. We release TSLP filed 23 and I’ll 45. Essentially, it is going further upstream. We started at IGE. We moved our way to interleukin four and five. There have been studies on interleukin 13 as well. We move up where things start to get released. So, the headline study of this was the navigator study which showed the target of TSLP reduces exacerbations. Everything to the left of this line means there is a rejection in exacerbations — reduction in . Although there is benefit, it is more powerful, than the individuals with T2 information, they have greater benefit from this because you are turning off a lot of the immune system as well. Eosinophil counts, this is the response, same for exhale nitric oxide. You see this staggered improvement. All of those may help you with your patient. This is true for other tutee agents –T2 agents. If they have these features they are more likely to respond. Interleukin 33 was antagonist. This is another one of the alarmniins. It was looked at medication in addition for individuals on dupilumab. They were not controlled and then were added with interleukin 33 therapy. It is not necessarily beneficial for individuals who do not respond to dupilumab. Otherwise this was looking at the anti-interleukin 33, compared to placebo. It is helpful. It functions at least as well as the other Biologics. I just think that topline other study was looking for an add-on therapy which may not necessarily have it. This paper which came out in the New England Journal has nice figures and tables. The text is a little small but the first part — I think it is the most important. I appreciate that the content of the conversation and discussion is around Biologics. But critically it is to make sure that you have the right diagnosis. You have addressed all comorbidities and avoidable risk factors, you tested for allergens, and have taken care of everything that needed to be taken care of and address the comorbidities. Once you have done all of that you move to phenotyping, as we discussed with Eosinophil counts.
This takes us through what we discussed which is if they are not Eosinophilic, your thinking about TSLP therapy, unless they have allergies then you can do IgE therapy. To the nuanced component, there is some data that some individuals don’t have an elevated Eosinophil count, but have an elevated nitric oxide, they will benefit the therapy of dupilamab. It will offer more benefit. If there Eosinophil count is very high, over 1500, you want to make sure nothing else is going on. Depending on your patient’s history, possibly parasitic infections. Then you are going to be reassessing this within four to six months. Some individuals will get a response after their first injection, that is the exception. Most will take two to three to see if you have — if you are responding. Given at least four to six months to ensure that — to clarify if there is any response or not. From a side effect profile there are benign medications a small number of patients will have a reaction. But it doesn’’t matter. We used to see the first injection in office with that is no longer required. Sometimes it can be helpful practically just to give them instruction on the self injection and get them comfortable but from a side effect profile it is no longer necessary. So what we’re left with is really a fantastic treatment that has developed over the last 10 to 15 years and changed the landscape of asthma patients — treatments for debilitating, disease when you get to that level of severe asthma. It’s a very positive development. In terms of limitations, one of them is we don’t have any head to head studies. We looked at outcomes among asthma studies dating back over the last few years. This was not limited to Biologics. Just things as simple as asthma symptoms/asthma control, we only reported in half the studies. It is hard to compare when you have that pure severe Eosinophil ic asthma. We really don’t have data to guide that. One possible solution, this is work we did with allergy and asthma network, a nice input of patients and patient advocate groups which was important for a report like this with the core outcome set. These outcomes are likely the most important to have a broad array of stakeholders which are severe asthma exacerbations, change in asthma control, and asthma specific quality of life, and asthma specific hospital stay or admission.
There are nuances among the study as far as what Eosinophil count they used, for inclusion criteria, what medications the individuals run a baseline that makes it very hard to compare, is one medication better than the other, without a randomized controlled trial which will probably knock and –will probably not happen? There is limited data to guide which biologic in terms of what we can use. One is the closet allergic phenotype with an elevated IgE, testing. Upper airway symptoms, again with having nasal polyps. If they are steroid dependent or have reduced lung function dupi lumab will improve FEV1. You have an individual or otherwise wants to reduce their frequency of injection, it is good for that population. From that same paper I alluded to that was in the New England Journal this is just a clinical review paper. They have this paper which is good. If you are trying to determine make a quick assessment about an individual with the expense of sounding like a broken record. Once you have ensured that it is intense asthma, you have addressed the comorbidities, ones who are trying to figure out which biologic to use, that figure in this table are good references to help cut that. The other limitation is that there are individuals that have highs symptom burden which they do not actually exacerbate. These are looking at how symptomatic individuals are in this is their rate of exacerbations. What you can see is there is no increase. Day-to-day symptoms are not a great Corlett for frequency of exacerbation. There is this population where they have these day-to-day symptoms but are not exacerbating a lot. These medications don’t actually provide much benefit in those individuals. There is some improvement in asthma symptoms from day-to-day but really the main benefit of these medications, the biologic medications is to reduce exacerbations and reduce oral corticosteroids dosage if it is a chronic therapy. The other part is, fortunately when you get people in that pure wheelhouse for this with T2 immunity, not everyone will respond. Fortunately most people will at least half will have a great response but about 10, depending on the study, 15 to 70% of them will not show response despite being other criteria. There is this question of what to do with them. We cannot predict this because there is no way to know. You get a feel for it I guess. But that is not reproducible. What we are left with is observational retrospective data which are asthma centers that have encountered these individuals and they have said, OK we have tried this person they have met the criteria, let’s start by switching them to dupilumab. We have done the same thing here. Basically, some groups this is the group at the University of Rochester that have recorded on this. This is 83 individuals not on a biologic. You get a great response. Exacerbations go from five to one, you are dropping your steroid use. Then, this is individuals that fall into the category of, OK they were on a biologic and it didn’t work and we switch them to another one. You get a response and this is consistent with what we experienced anecdotally. It even though you are using two I/O five therapies, one seems to work better than the other. If you are switching it is probably best to switch from an aisle five to an aisle four. So, you are targeting a different pathway. To sin — this is a nice schematic. I’m not intending to go through this in detail but, the general take away is if an individual does not respond to the biologic you use, you revisit are you using the inhaler the right way, is there a comorbidities going on? What you are sure about this there is value in switching to another biologic but you have to be upfront with them to let them know you don’t know how effective it will be, but you need to try something different, they may benefit from it. The other limitation of this is the cost. The average expense is $10,000 to $30,000 per year.
There has been cost-effective analyses on this were the more severe individuals. It’s likely in that benefit because of the health care utilization and quality of life. Nonetheless, still a very expensive medication. Fortunately, the manufacturers of the medications have various programs that, assuming your patient will fill out certain forms, generally are able to be much more affordable in terms of the actual out-of-pocket cost a patient will pay. Lastly, although it may not matter to some individuals, other individuals have difficulty with at-home injections. Most of them, for the transition to having a self injector pen which is prefilled. This is enhanced, the ability to do it at home. And hopefully, most offices will have the bandwidth if needed to have individuals coming to the office but for the most part, patients will prefer to do this at home and all the — and not the end — and not the inconvenience of coming in. Move — which is moving beyond T2 pathway of asthma. Some examples of this are asthma COPD overlap, which has had focused studies on. Recently there was an encouraging study for Eosinophil COPD, addressing some of these comorbidities that individuals with asthma and obese are different. Medications targeting them may be helpful. Sex differences. There are hormonal and asthma differences between males and females, that may lend itself to specific therapies. Imaging phenotypes, using things like CT scans to identify particular phenotypes of asthma that can be treated. There are studies called the precise study which is an adaptive study. They measure proteins in the blood. Based on the protein you get a specific treatment. That brings us to this other thing of, can we actually predict how a particular individual may respond to a medication? We have some guidance on which biologic to start. But it is not a huge — it is not definitive. Can we transition them to transition medicine? This person could benefit from dupilumab or — I put a fingerprint there whether it is imaging, genetic testing to try to better bring study, the try to figure out how to do this more effectively. So in terms of take on points — I will be glad to address any questions. I think I am probably up to seven, I was targeting for five, foot I wanted this rash but I wanted to say you are ensuring accurate diagnosis. That is 80 to 90%, maybe 95% depending on the population of the individuals with asthma. It is ensuring you have the right diagnosis, addressing comorbidities making sure they are using inhalers the right way and avoiding any exposures possible. As i have mentioned, assessment therapies of comorbidities, which can interact with severe asthma. Lastly, as we discussed, there are some but limited data to guide which biologic.
This is summarized here which is if they are allergic, if they have nasal polyps, or other allergic comorbidities, like food allergies that have not been reviewed here, if they are steroid dependent, or have reduced lung function, and the frequency of injections. Just this table, as a nice reference for this. So, with that I will close. I think you all — thank you all for attending and for the Allergy & Asthma Network to providing me with the platform to review this.
De De: Thank you Dr. Vick Tejwani. I’m am going to start with a couple of questions we have from our attendees. One of those was looking at access. What are some of the access issues you’ve encountered when prescribing biologic treatments?
Dr. Tejwani: That’s a great question. I think the the biggest access issue is more of a global access issue which is unfortunate that patients don’t have a primary care doctor they are not being referred to a pulmonologist. They are just kind of getting repeatedly prescribed prednisone , maybe utilizing the urgent care or they are getting prednisone. That is really the funnel the narrow point. Once they are in our group and seeing an allergist and going through everything, despite the cost of the medication with enough persistence both on the backend of our administrators and the patient, we are able to get it. But, that being said, all of that takes time. That takes an individual with one navigating the health care system to get there. Two they are responsible for some of those forms which carries a certain educational threshold and socioeconomic threshold have the time to navigate all of that. Once they are in, we can fortunately work with them to get something. But I do think there are some hurdles to get to that point, and there are exceptions where we can’t get it right. Generally, the manufacturers they each have their own assistance program for patients. If they fill the forms out, they can usually happen.
De De: Great. We to have a helpline with prescription drugs for asthma. That may be a resource we can share afterwards. The other question that is interesting is someone is asking what have you heard or seen in regards to inhaled Biologics in studies or have you seen anything like this?
Dr. Tejwani: Great question. I have seen some oral medications but, so far none that really our meeting muster. I think there is an idea that to try to do that. There is a nebulized medication, which just came out for COPD. Then for asthma there are other oral medications being studied. To my knowledge I have not seen any inhaled Biologics that have been tested yet.
De De: Right. We to have some testimonies here within our question-and-answer. It is amazing to see the testimonies that patients have shared with us or health care providers. They have had success with Biologics. People are asking for a copy of the slides, I would have to say that will be available after today as one of the supplemental documents. The last question here is which of the Biologics helps most of reducing airway move — airway remodeling?
Dr. Tejwani: I think the short answer is we don’t know. I would may be due pillow Mab, because of FEV1. That is just me speculating. We don’t really know the answer. In may meet the threshold because it is higher up in the inflammatory pathway. We just don’t have an update on that yet. I think that is a great question. , any of these which does most questions, we cannot answer definitively because of the absence of any head studies.
De De: Absolutely. It says do you see any future role of targeting TGF be — TGF B.
Dr. Tejwani: I was very interested in this as the early part of research I did. I think, possibly the issue, which it is a protein in particular, it is response thing — it’s respond is for smooth muscle remodeling. I think the challenge with it is unlike some of these targets which, fortunately, sometimes when my patients here at biologic they may be diagnosed with lupus and we are targeting with interleukin one that have other benefit. Interleukin four and interleukin five, the Eosinophil pathway is not really that useful. Although it is deleterious when it gets out of whack, the challenge is that it has likely beneficial immune components to it or does have some beneficial immune components to it. How to target the specific downstream pathway that is bad from TGFB, where you leave the good part of it alone?
De De: That is really interesting. Thank you for bringing that to my attention. Someone is asking if you could please repeat how soon after injection from Biologics should patients seen improvement?
Dr. Tejwani: Are usually counsel my patients on waiting six months before they reach a verdict. These — most of them will see benefit before that. These are individuals that by the time they are this point have been struggling for some time, naturally frustrated and looking for a cure. The reason I say that to them is I just don’t want them at three or four months they don’t feel better and it just turns out that they needed another couple of months. I would say, on the counseling side I think as a provider you want to give yourself six months to give yourself a cushion, but at three to four months they should start to see benefit. I will come to the slide, after four to six months they say. But on the counseling side you are good on six months.
De De: Great. A person always asks, what if a person misses an injection? How will that impact?
Dr. Tejwani: Great question. One thing we did not touch upon is stopping Biologics which is another limitation, which is how long and what do we need to do. So, I have some patients that for example when they aren’t week three or four they will start to feel symptoms getting worse as they are nearing the four-week threshold. Generally speaking, once you have gone somebody — one’s — once somebody’s at this point they should not miss an injection. It will likely be harmful. The caveat is if they miss it for some reason, they are traveling, or there is some lapse in renewal. From a practical perspective, we let our patients know now and try to keep them on our radar, four-month 10 or 11 — for month 10 or 11 to start the renewal process. The renewal typically starts 12 months. If they miss it for whatever reason, it is a natural experiment. Just because if they miss it and they don’t feel much worse, you might want to revisit how much they need it. Usually patients that are on this, even if they missed one, within a couple of weeks they will feel the difference.
De De: We have time for two more questions. One of these is, is there any likelihood of certain genetic profiles, we did not touch base on genetics, are there certain genetic profiles with severe asthma that respond better to the biologic?
Dr. Tejwani: I think, yes. But not ready for clinical practice. The two longer answer to that is there are efforts to develop something like a polygenic risk score, beyond using a snip or a variation of a single gene and say let’s take these 10 genes and create a risk for the individual. The other thing is we talked about IL 33 therapy. That has been studied in COPD. With the study they looked at genetic variations in interleukin 33 as a modifier to therapy. It seems that individuals with certain mutations have a better response to IL 33 therapy. There will be, whether it is genetic, there is also studies where we do nasal swabs and look at RNA, I think some combination of this probably within — hopefully five to 10 years. Maybe longer.
De De: That will be it. An interesting day, when we can see all of the DNA and what is going on with our patients. One more question. You and I talked about it a few minutes ago. The consensus statement that came out from HTS, about the concept of remission, what are your thoughts on the concept of remission when it is regarding these Biologics treating asthma?
Dr. Tejwani: It is great. I think it is nice to have definitions of things, particularly in the research space. From a practical and clinical perspective, this is something we’ve all done, maybe not articulating it, but we have individuals, where I am seeing them every one to three months, then they go into remission. Now we have a definition for this and we are spacing out visits. We are not checking in is often. It is great to have an agreed-upon consensus definition. In terms of the implications here, I think what it will — it can help guide us on, we have limited data on it, and I touched upon it, is one to stop this. We don’t have great evidence on it. If somebody goes into full remission for two years, hypothetically, or whatever duration of time we agree upon, then maybe we try them off the biologic for example. That is where I think it could play another role in asthma therapy — biologic therapy. One, monitoring response. The biologic should reduce emission. After some period of time in remission, can. The biologic or see how they will do — can we stop the biologic or see how they will do without it?
De De: Thank you for your time. We are at time. We appreciate everyone attending. We have another webinar next week on September 26. We will welcome the doctor from, spirit health, he will discuss exacerbated respiratory disease, ERD. Look for upcoming webinars in October. You will receive an email from us and it will come from zoom in a few days with a link to the recording and evaluation in the supplemental resources. Thank you again from all of us at allergy –Allergy & Asthma Network. Join us as we work better to breathe together. Thank you.
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