All right, I think we'll get started. It's pretty much about time to turn over. So my name is Chris Hergott. I'm an interventional respirologist at the University of Calgary. I chair the Education Committee for the Canadian Thoracic Society, and you're at the Canadian Thoracic Society Day here at CHEST. This is probably one of my favourite parts of the day, is the lively pro-con debate. We have some boxing gloves up here just underneath the table. We're going to pull those out. No holds barred. So we have the pleasure of two excellent speakers today, Dr. Christelle Godbout and Dr. Pierre Landry. Dr. Godbout is from Quebec City. Thank you. I'm glad she's here, is the head of the Severe Asthma Clinic at the Heart and Lung Institute of Quebec City, and Dr. Landry is a community respirologist, intensivist, and internist practicing in Dartmouth, Nova Scotia, and has a diverse practice and lots of severe asthma patients. So the topic for today, which I hope you'll find appropriately controversial, is biologics should be used for all patients requiring inhaled corticosteroids. Should be a big gasp from the group. So what we're going to do is 15 minutes for the pro side, then 15 minutes for the con side, eight minute rebuttal for each, and then we have a few minutes for a question and answer afterwards. Once that's done, I'm going to get a show of hands to see who's won the debate. And then after that, there will be a large monetary prize that will go to me, and then we can all get together for the CTS reception afterwards. All right. So Dr. Landry, I think you're up first. You are the pro side. Should biologics should be used for all patients requiring ICS? You're keeping the best for last. I'm not able to comment on that. All righty. So basically, by the end of my 15 minutes, I want to convince you all that inhaled steroids are almost a thing of the past. They belong in the MS-DOS days of management. And so I really refer to the pre-biologic days as old school, and I hope that you'll agree with me once I'm done this. Little caveat, I, of course, have some disclosures. A lot of people I like to speak, anyone that knows me knows I love to talk. And so if you pay me to talk, I'll talk even more. But realistically, I see a lot of severe asthma patients. I do not pretend to have a severe asthma fellowship. I work above a drugstore in a suburb of Halifax. But I have a lot of people in biologics there. So today, I want to talk about shifting paradigms in asthma management. So over the last few decades, we have seen a huge evolution in how we treat asthma. We've started with as needed bronchodilators for symptomatic management. We've progressed to some anti-inflammatory therapy. Now that we recognize that airways inflammation is really at the core of asthma as an issue. So whether that be an inhaled corticosteroid on its own or in a variety of combination devices, things like we would try in receptor antagonists, things like biologics, things like azithromycin, it's really changed what we do. No matter what side of the biologic spectrum you think on, I think we can all admit that it's better than this, right? So you know, and I will admit, I have not been around long enough to see asthma cigarettes, okay? But they are there. I like Heather Kellogg's brand. I don't actually know if this is from, you know, the Kellogg's cereal company. But either way, you know, I can't imagine a day where we treat something with an asthma cigarette, right? I don't know if it's kind of like a take two, you know, smoke two and call me in the morning kind of thing like we did with aspirin, but either way, I have a few concerns about that. Steroids of course, being the next step, as you can tell, I'm going with a bit of a cereal box theme. I've got the steroids on the cereal box here. A lot of my patients, you know, have concerns when I say the word steroid, right? There's huge misconceptions about steroids and the treatment of asthma. I have a lot of patients that have historically been told not to take their ICS. I was one of those asthmatics that was told not to take my ICS, that it was bad for me and only to take my bentolin when I was a kid. A lot of my patients still have this concern. But then a lot of patients don't think prednisone is a steroid and don't, and then when you tell them it's a steroid, they're like, oh my God, and I'm like, no, it's not like Arnold Schwarzenegger style steroids, okay? These are a different mechanism of action. We're really using it to quell the inflammatory response. You know, I have no doubt in my mind that oral steroids are important in the treatment of asthma. Same as inhaled corticosteroids. You know, they're indispensable in the flare. The problem is, by the time people get to see me, and I'm sure many of the other people in the room, a lot of our patients have had, you know, five, six courses in a year of prednisone to control their underlying asthma, whether or not it's because of improper inhaled therapy at baseline, right, missing inhaled corticosteroids or combination devices, other triggers in the home, smoking, things like that. You know, by the time we've reached for that oral steroid, we've kind of missed the boat, right? So, you know, oral steroids on their own, I think we know, are quite harmful. This paper here, I'm sure many people have seen this graph, but even 500 milligrams of prednisone in the lifetime of an asthmatic, so that's two courses of five days of 50 milligrams, can really worsen outcomes for all of our asthmatics. And like I said, it's not uncommon for me to see people who've had five or six courses in one year of prednisone, not to mention that, or to have people that have been on 20 milligrams of prednisone for the last 20 to 30 years, right? You know, I worry about this because I worry that we're catching these people too late and we're catching people once the damage is already done. Of course, inhaled steroids, super, super, super important, right? They have been the backbone of our asthma management for years and years and years. You know, I haven't included any pictures of slides of inhaled steroids. I think we all know what the inhalers look like and the variety of ones that we have on the market. I think we stare at them every day with our patients. That being said, I'm not going to doubt that they're efficacious. I'm not going to doubt that they're healthy, but the question is whether or not all patients with asthma bad enough to be on inhaled steroid should be on a biologic. So really, if we're not starting them early, are we kind of missing the boat? Are we letting them get a little far? Here's a little feel-good story about some biologics. I have a 16-year-old patient who was referred to me. This is her original spirometry here. It was done outside of my institution, so I don't actually have the graphs and the numbers. I just have the dictated report. However, as we can see, she has awful, awful, awful asthma. She started developing asthma symptoms at the age of 14, had been on multiple courses of prednisone, some budesonide for motorol, even on a Lama as a second agent, leucotriene, et cetera, and this was still her spirometry when she came to see me. After six months on mepolizumab, this is her spirometry. So she's someone who couldn't climb a flight of stairs without a SABA, couldn't participate in any sports. Her friends had actually, she told me, she said, my friends have never seen me take the stairs. They've only ever seen me take the elevator at school. Anyway, now she's in university. She's coaching, sailing. She's participating in school. She wants to go to med school, she says now. And I think for her, she says that mepolizumab has been life-changing, okay? So I really think that if we start biologics early in people and we don't wait for them to have the chance to exacerbate and keep exacerbating, that we can really avoid some of this underlying damage that's causing them to have fixed airflow obstruction to develop symptoms throughout their life, right? We're going to avoid these persistent symptoms. We're going to avoid the risks of osteopenia, osteoporosis, development of type 2 diabetes, development of cardiac disease, all of those risk factors, and we're really going to hopefully prevent them from getting to that point. You know, I'm not going to pretend this is the cheapest option here because I think we all know it's not. I certainly don't work in a high-resource environment. I have trouble getting inhalers covered for a lot of my patients, let alone biologics. But I think it's kind of time to change our perspective on asthma management, right? So early control, early stabilization, and hopefully maybe treating them so that we can actually resolve the problem of asthma later in life. I will recognize the fact that asthma remission is kind of a lofty goal. There are so many different definitions circulating. They are not uniform. Some of them I think are downright unattainable. We know that spontaneous remission in asthma is very rare as a whole. We know that only somewhere between a quarter and a third of all patients, even on biologics, will obtain remission. But even for that third of patients, that can be a pretty meaningful thing. So I don't know if I've convinced anyone here because I'm not going to pretend this is the cheapest thing. But I hope that some of these stories, knowing that these children, that we can really impact young people's lives, we can really change things, hopefully avoid a lifetime's worth of health care visits and hospitalizations. On another patient I have whose spirometry I don't have here, but a 62-year-old man with a history of asthma, smoked later in life, ended up in our ICU at the Dartmouth General Hospital three times in two months, intubated with severe respiratory failure. Absolutely crazy, just super sick. Everyone's saying, he's COPD, he's COPD, he's COPD. But once we actually look back, well, smoking history, not that much. Responds dramatically to steroids, right? Riparoring eosinophils, you're on mepolizumab, no emergency visits, no exacerbations. Fixed airflow obstruction still sitting around the 27%, right? But he's symptomatic. He's much more improved symptomatically. We know that we're never going to resolve all asthma, but I do think for a lot of people, maybe we can control off-delete asthma with biologics. Anyway, happy to hand it over to Ms. Denham. Thank you. Just to let everyone know, there were lots of note-taking over here for the rebuttal. I think it's, yes, it's going to be good. I'm ready. But, okay. So you finish early. You don't have a lot to say for the pro side. Can you tell where my biases are? But, yeah. So you left me more time for my con side. So as you all probably guess, I will convince you efficiently in the next 15, and I have 20 minutes now, that we should indeed not extend the use of biologics for everybody who requires ICS. Here are my disclosures. So it's going to be very simple. I'm not going to go, like, into all details and patient cases. Like, it's really easy. Why shouldn't we broaden the use of biologics? It's a matter of lack of efficacy and state bankruptcy. So let's start with the efficacy part. So it's going to go in three parts here. So let's start with the walk-down memory lane. So you can see here all the studies that led to the development of mepolizumab in severe asthma. A lot of them are very famous, like DREAM, MENSA. But that's not the one I want to talk about. I want to bring you back all to the beginning here, when the two first studies that GSK did to develop mepolizumab. So the first study involved 24 mild atopic asthmatics, so non-severe. And they received one injection of mepo, and it was higher doses. And they had allergen challenge after that. And guess what? Well, it decreased eosinophils. So it worked. Like, the drug did its effect. What did it do clinically? No effect on bronchial hyperresponsiveness, and no effect on the late asthmatic reaction, which involved T2 inflammation. So no clinical effect in non-severe asthmatics. Then they did a bigger study, more than 300 moderate asthmatic, again, non-severe asthmatics. They all had ICS. And they received three dose of mepo. Yet again, decrease in blood and sputum eosinophils. So the drug worked. It had biological effect. Clinical, let me tell you, no effect on FEV1, no effect on symptom score. And if you look closely, actually, placebo did a bit better than mepo here. And no effect on exacerbation. So it really didn't work. And I see Renata is here. And she likes to say GSK was ready to throw the baby with a bat while after these two studies. And it actually took two investigator-initiated studies to define the population in which these drugs are effective. Tell me, severe eosinophilic asthma, not non-severe. Go to the next part, the Forgotten Study. If I'm talking about the BISE study, B-I-S-E, does anybody know what study I'm talking about? There is one here, Andrea, but I'm pretty sure most of you, they don't know there's this study. It's actually a phase 3 study. It's the only phase 3 studies in recent biologics that studied non-severe asthmatics. Non-severe asthmatics. And it's not well known. I think you can guess why. So again, more than 200 asthmatic that were symptomatic despite low dose, low or medium dose ICS or low dose ICS-LABA. So all non-severe asthmatics. They received Benrazumab for 12 weeks, so three months. And no effect on lung function unless you think ATMLs is significant. No effect on symptoms and no effect on exacerbation. So just doesn't work in non-severe asthma. My next point, my next items refer to using the right tools for the job. So I believe, I hope, you all know that movie, The Shawshank Redemption. Just raise your hand if you know. Okay, a lot of them. Good. So it's a very great movie if you have not seen them. It's old, but I suggest it for your next movie night. But it's a story of a guy who gets out of prison using a rock hammer. It only takes him 19 years. But that is because he didn't have the right tools to get out of prison. Imagine what would happen if he had a sledgehammer. But then, obviously, there would have been no movies. But my point is that biologics are like rock hammers. They're precise tool and designed to target inflammation that is left after ICS and LABA. And I'm sorry to hit you with the confusogram here, but it's just to illustrate a very valid point. That is, inflammatory pathways in asthma are multiple and complex. And each biologics, they target only a small and narrow part of that confusogram. So you have IgE, alveolar asthma, NTL5, NTL5 receptor, even dupilumab and NT2 slips. So they left a lot of that graph untouched. So they're like the rock hammer. It's perfect for finishing the job. But when you need to get through the wall, you need a better tool. You need the sledgehammer, which is ICS. For me, ICS are like the sledgehammer of the anti-inflammatory therapy. They act on multiple level to improve asthma control and asthma symptoms. So they reduce the number of a lot of inflammatory cells that you can see here. They also decrease multiple chemokines and cytokines. They restore the epithelium integrity and reduce mercury secretion. They reduce endothelial leak. They decrease the activity of inoles decreasing phenol. So they act even in the known, the T2 low inflammation of asthma. So they hit really the whole inflammatory cascade. What about LABAs? What about LABAs? They're like wedges, I like to say. Because they're complementary to the effect of ICS. So we usually believe, or a lot of us believe, that they only act through relaxing of smooth muscle. But in fact, they have a lot more effect on the inflammatory pathway. They inhibit the release of histamine of mast cell, inhibit plasma excitation, decrease trafficking, they increase mucociliary clearance, and they even have a neuromodulatory effect to decrease bronchoconstrictor response. So together, ICS and LABAs, well, they hit the whole inflammatory pathway and cascade, and they're synergetic as ICS decrease the tolerance and side effect of LABAs, and LABA potentiate the effect of ICS. So you can bet with these tools and Digiframe, and the Shashank Redemption, would have gone out of prison within a week of being incarcerated. He wouldn't have needed his rock hammer. I could stop here, but, yeah, I have time. And why not crush him up? So let's talk about the money side of things. So we're talking about how, if we widen and broaden the use of biologics, it will lead to state bankruptcy. So you all had patients that came to tell you that, well, inhalers are expensive, they can't afford them, and it's really, really costly. And I've shown here how much the Quebec government pay for them. I know that private insurance, and even in the U.S., it's much more than that, but just to give a reference here. And it's true that when you look at that, ICS LABA treatment can add up to $1,500 a year, which is quite a lot. But do you know how much biologics are costing a year? I'm telling you, it's between $25,000 to $30,000 a year. So this is a big number, and it may be difficult to conceptualize a bit. So let's transform these numbers into tangible things. So instead of a year of Omadisman, you can buy a small car, maybe even a Tesla. Instead of a year of Mepo, you could buy almost a Bitcoin, but by the way the Bitcoin is going lately, probably a full Bitcoin soon. Instead of one year of Wresley, you could buy a mid-range-priced Rolex for the guys here in the room. Instead of one year of Benra, two tickets for a safari in Africa, a one-week safari. But talking about tickets, I don't know if there are Swifties in the room or parents of Swifties complaining how expensive these tickets are. Well, instead of one year of Benra, you could go to multiple concerts. And finally, instead of one year of Dupy, this is for people like me, you could buy at least 10 pairs of designer shoes. There's a very big shopping mall just right next to the convention center, so with that, it's a very good afternoon of shopping. So that's how much they cost. But now look around in the room. So we're a couple of people. One out of 10 of the people here in the room probably have asthma. And maybe even more. You talk about your past as an asthmatic, but I don't know. It seems that I attract asthmatic. All my residents are asthmatics or have a cat and are allergic, but that's another story. But yeah, asthma is a very prevalent disease. But thankfully, 90% of asthmatics, they're non-severe. So they wouldn't be eligible for biology. Imagine if then, if we widen their use and extend their use to these non-severe asthmatics, that mean we will increase the number of people treated by tenfold. And with the health minister budget already to the roof, well, that's bankruptcy assured if you do that. And not only that, but we know that a third of patients with a diagnosis of asthma are not even asthmatic. So, and this is a very good study, I think most of you know, and it has been replicated twice. But if we extend the use of biologic, it means that probably more than a third of patients who will end up on these very expensive medication will not even need it. And my last point, last argument, ooh, I almost broke the computer here. So it's just about the relative cost of severe versus non-severe asthma. Yes, it may be worth using biologics in severe asthma, because the direct medical costs, as you see here, per year, it's much more in severe asthma than in mild asthma, for example. Mild asthma is a third of the cost of severe asthma, and it's a tenth of the cost of biologic per year. So imagine if we could extend the use to mild asthma. That means, like, that prescription drug, blue thing, will go up to the roof, and it will certainly not be cost-effective. But is it really cost-effective in the severe asthma population? It's far from certain. So this is the ICER, it's an independent U.S. organization that evaluates different medications and tests, and they examined the biologic therapy in asthma. And their conclusion is that biologics, their value of biologics is around $350,000 per quality gained, and with a threshold of $50,000 for cost-effectiveness, well, that will mean that even at the current price, they're not even cost-effective in many severe asthmatics. They would have to be discounted 75% to actually be worth it, and I'm talking about severe asthma here. Imagine non-severe. So with that, I'm going to conclude that prescribing a biologic in non-severe asthma is just like buying a fake and broken, because it doesn't work, Rolex for the price of a real. So it looks fancy, but it doesn't work, and it's way overpriced. You better go to Walmart and buy a Hello Kitty watch. It's going to be very, very effective. It's going to give you the time for a fraction of the cost, and just like ICS and LABA. And I'm going to conclude with a personal cheap shot, because we're in a proper debate. I can't believe you didn't bring that up. So I must say I digged a lot to find some dirt on you. I hope you didn't find much. I didn't find anything. So I'm like, okay, that's how boring he is. Because like, yeah, I'm much less boring than that. Wonderful. Thank you. All right, Dr. Landry, it's time to take the gloves off. time for your rebuttal. I'm pretty mean as you can tell I mean I think everyone saw that my second year of residency applying to Karma's was not very kind to me that's where that picture is from I still have the same shirt and stethoscope though although I think I spilled something on it at one of my Karma's interviews so I don't wear it anymore you know we have heard a lot about data and a lot about science and a lot about facts and cost comparisons and things like that as you know Nova Scotia is the richest province in Canada you know I see a few of my you know people that were all my co residents here as they can all attest to we have the most advanced health care system in all of Canada and we certainly have the means to provide biologics to everyone so you know but where's the romance in it right does anyone like their inhalers has anyone ever told you oh yes might be designed for motor I'll change my life for my you know I love this I love this inhaler you know I feel like I'm a new person you know I've taken this inhaler and I can I play sports and I've gone to college and you know I finished my course no no one says that right but with biologics sometimes you put people on it they go to school they you know they don't need their handicap parking pass anymore they don't end up intubated and ventilated in ICU but inhalers no one takes them anyway right let's be honest or is that just me with my non-adherence so you know there's also a thing about the sledgehammer I think if he used a sledgehammer the prison guards would have caught on movie would have ended way sooner it wouldn't have been as fun so where's the fun in just giving inhalers to everyone who doesn't like giving needles to people right I think we all do right flu shot kovat shots pneumonia vaccination a biologic why not right it's just another needle there's definitely no there's definitely no you know vaccine fatigue or anything like that going on these days right you know and yes well I might not have any cost data because let's be honest it's really not there I'll be the first person to say it's just more fun I think we should have fun I think we should make a nice romantic asthma journey for all of our patients right just you know let them you know let them live these you know these wonderful lives where the breathing is easy and they don't have to go in prison and Shawshank Redemption and you know they can go on expensive shopping trips funded by their private insurance plan and things like that when when we stop their biologic for lack of efficacy all right thank you all right dr. W you have the final word so you talk about how much biologics change life and it changed life of your patient just want to hear these patients that got their life changed by biologics were they severe or non severe asthmatics yeah that's what I guess so so that because just as it wouldn't change their life if they were if they were non severe if you heard correctly and like you have so much no argument to back up your view that you have to rely on emotional emotion instead of a facts and so like you're talking about all of your patients like I've barely seen one or two study to back you up so it's just about emotion of people they like injection and things like that it's not a valid argument and let me tell you if your patient prefer injection good for them I had a patient it's really true just to two weeks ago I wanted to prescribe a biologic you look on the internet and said well that biologic is made with ovary of amst of Chinese hamster you're never gonna put that into me doc so I didn't think about your anti-vax patient they will never have a flow shot or a biologics prescribed either and if you have billions to invest because you tell told us that Nova Scotia is super rich and can definitely afford biologics for the whole population well why not invest it in what's really worth it which is good diagnostic tools how long do you do your GP has to wait to prescribe a spirometry in Nova Scotia yeah so you can bet that just a few patients of biologics they can say if it could increase the amount of spirometry they could do it in your province access to CREs and even like full coverage of ICS so we can pay for ICS in full so they wouldn't be in any affordability problem with that and you mentioned at one point that like the danger or the effect of OCS but you know what's very effective to decrease exacerbation and OCS use in non-severe asthma yeah ICS and smart therapy 50% decrease in exacerbation so it's really more worth it than a bile and over like price biologics that wouldn't even work in that population so I think I made my point and I am going to look at every hand raised when they he asked if he wins if I'm gonna go and see you personally to convince you otherwise I'm gonna have to say this is a safe space please I'd ask you to sit down and just relax a little bit okay thank you both to our combatants let's give them a round of applause no one will be hurt in this debate just so we all are aware of that yes just the hamster does anyone have any questions for our two combatants here at the back there do you want to step up to the microphone and perfect from Calgary first question how many pairs of shoes you said you have so the question is do you see the use of biologics not necessarily in severe asthma but asthma that's not controlled so nowadays we're talking about remission whatever the definition is going to use is going to be do you see it as a potential tool to achieve asthma remission regardless of severity have you heard at my to my talk in the last like 20 minutes I tried to convince you that it just didn't work like in the non severe asthma even on control so the patient that were randomized in the trials I talked about they were all non severe and on control and it just didn't have any effect on exacerbation and long function and asthma control so it's just not a question of control or on control but a question of what's underlying the disease and if it's not severe and using just something that will act in a narrow part of the cascade will probably not work but that's my so what's what's your what's your clinical experience because mine it's not actually that that's why I asked the question I've had several not lots but plenty of asthma patients not severe not controlled that done extremely well in biologics so let's I remove I will remove my hat of the con side here okay so don't listen just him so thank you I do believe though like personally that it may have some efficacy probably not every biologics I didn't talk about on that is a map that did study non severe asthmatics and it had some effect so I did choose my studies to present and you didn't so I don't know but yeah so some biologics I do believe may have an effect in non severe asthma I just depend like where they act but yeah I had to make my point great any other questions all right so the question is biologics should be used for all patients requiring ICS so pro is dr. Pierre Landry can I have a show of hands all right she's writing all this down just so you know and then con dr. Christelle babu all right wonderful excellent thank you so I hopefully you all appreciated that it's a kind of fun to do and make a little fun of each other and go through some of the science which is great so I appreciate it thank you again to both of our combatants all right so this ends our CTS session for today thank you for coming please fill out your evaluations in the chest app and just as a reminder the CTS members reception is at 530 tonight at the Hilton Hawaiian Village coral ballroom number one thank you you

biologics

asthma

treatment

outdated

long-term damage

quality of life

efficacy