Caller: With regard to assessing asthma control, is there a benefit to using the ACQ over the ACT or vice versa?

Transcription

1 Dr. Colice: Hello. I m Dr. Gene Colice, an adult pulmonologist and Professor of Medicine at the George Washington University School of Medicine in Washington, D.C. Joining me today is Dr. Anne Fuhlbrigge, a pulmonologist and epidemiologist and Assistant Professor of Medicine at Harvard Medical School. This question-and-answer session is intended for pulmonologists, allergists, primary care and internal medicine physicians, and other clinicians interested and involved in the treatment of patients with asthma, particularly those who participated in the CMEcertified activity titled Overcoming Barriers to Successful Asthma Control. If you have not yet reviewed this activity, you can find it online at Approximately 8% of Americans suffer from asthma. With better control, patients can experience less suffering from asthma symptoms, fewer missed school or work days, fewer ER visits, fewer hospitalizations, and ultimately we hope a more happy and successful, prolonged life. Clinicians can support this goal by providing appropriate evidence-based asthma care, including optimal management with asthma medication and adequate education and counseling. We re delighted to be here today to answer any questions you might have about achieving optimal asthma management with your patients. Caller: With regard to assessing asthma control, is there a benefit to using the ACQ over the ACT or vice versa? Dr. Colice: I m going to defer that to Anne who s really an expert in this area. Dr. Fuhlbrigge: Anne Fuhlbrigge here. So there really are no data that suggest head-to-head that one necessarily gives us better outcomes or better asthma control compared to the other. And so what I m usually recommending to patients and/or physicians who have asked this 1

2 question is that it s really whichever one you re more comfortable with. The ACQ has the FEV 1 as part of it. It can be a seventh component of it. But you can also use spirometry just independently along with the ACT. So I think it s really whichever one you feel more comfortable with and your patients find easier to answer that can be used and used appropriately. I think it s really just a question of using an instrument routinely so that you can compare apples to apples and with it to know whether your interventions have made any impact. Gene, I don t know if you have any particular comments on that. Dr. Colice: Well, Anne, I wanted to follow up on that. You know, I ve been practicing before these tests came along. I sort of developed an approach to asking my own questions. Do you think that these standardized questionnaires add a lot to just somebody who has their own individualized approach to asking questions? Dr. Fuhlbrigge: I think it depends on what the questions are obviously. I think the whole idea of developing these instruments was to make it straightforward and routine, that the same types of information are gathered at every visit. So if you as a practicing physician had developed in your own mind the important questions that do get into some of the different aspects of things like activity limitation or daytime or nighttime symptoms, I think if you use those same set of questions over and over again so that you actually have a nice group of information that you get when you change an intervention either inducing an environmental intervention or adding or subtracting a medication and you know you re asking the same questions; therefore, you get the same answers, then no, I can t say that your own compilation of questions would necessarily be better or worse than the ones that have been validated. The instruments that really have been validated are more just to have something easily available that somebody can use to have a very 2

3 systematic approach to asking the same information time and time again. Dr. Colice: Yeah, I m sure there s a huge benefit with having an objective score. For instance, the ACT you have a number; you can track that over time. Dr. Fuhlbrigge: Some of my colleagues, with the EMRs, they can actually graph like the score and you can get a nice pictorial view of what s happening over time. Dr. Colice: It s a universal language, so if somebody is in Boston and then he or she moves to California, this is something that s easily transportable with them. The new physician or new health care clinician can see that information. Dr. Fuhlbrigge: Correct. And so for someone else looking at the medical record I think it s very clear if the ACT score has been running at a certain level and all of a sudden there s a change. Everybody can truly see that there is something that s happening and need to intervene. So the scoring part of it I think does make it very transferrable and easy to interpret by many different people. Caller: I was curious as to where does bronchial thermoplasty fit into asthma treatment options? And then if you could also comment on when do you actually use it. Dr. Colice: That s a tough question to answer. It s an interesting procedure. It really should be reserved for patients with severe asthma, moderate persistent severe asthma. I would refer you to a recent publication that just came out in the European Respiratory Journal. An 3

4 expert panel looked at the management of severe asthma, and they were very clear in their recommendation. They said that bronchial thermoplasty should be reserved only for patients undergoing trials because I think it s fair to say that we don t really have enough information about the wide spectrum of patients. The number of patients that were studied with this approach was small. We have long-term follow-up out to a couple of years, but we don t have it with a control population to understand the full benefits There are some risks with this procedure, so the immediate days after the procedure the patients are at increased risk for an exacerbation. I would characterize it as an interesting emerging new therapy, which really needs more carefully done studies to understand how it fits into our armamentarium. Anne, what are your thoughts about this? Dr. Fuhlbrigge: I actually tend to agree with you. And the whole group of clinicians that I work with here at the hospital certainly has it as something that we can offer patients, but many patients who are referred for consideration of bronchial thermoplasty are looked at very closely to make sure there s something else that can be done before considering moving ahead with bronchial thermoplasty itself. We are looking at all the medications that have been tried, looking at adherence, looking at technique, all the things that we know can impact how a patient does before saying, Okay, we ll move on and do bronchial thermoplasty in this patient. It s something that s considered, but we have to go through many other steps before we get to that point. Dr. Colice: I agree. I ve been referred patients for consideration for bronchial thermoplasty and for everyone that I ve evaluated, there are things that were missed or not done or the patient didn t understand. And, when we really went back to the basics, we can get these patients under control. So it s not something that I have actually ever referred a 4

5 patient for and I m very cautious about it right now. Caller: My question is regarding the use of tiotropium for asthma. When do you use it and do you use it instead of a long-acting beta-agonist? Or could you just talk a little bit about the use of this medication? Dr. Colice: There s a very nice study by Steve Peters in the New England Journal of Medicine. There have been other studies looking at the use of tiotropium in difficult to control asthma. It does play a role. It can be used in conjunction with an inhaled corticosteroid, as well as an inhaled corticosteroid and a LABA. So it does provide additional benefit. It is not approved for use in asthma yet and they re working towards this. But I must caution you, if you re going to use tiotropium, certainly the patient should be on an inhaled corticosteroid as well. There are certain situations in which tiotropium might have advantages over a LABA. For instance, I saw an ophthalmologist with difficult to control asthma and he had a hard time with a LABA because of the tremor. And we put him on tiotropium and he did very nicely with that approach. There are patients who are on inhaled corticosteroid and a LABA and are struggling. In those situations I will consider adding tiotropium and have been pleased with the results on certain occasions. So I think it s an exciting new therapy. I think it s going to actually have more widespread benefit than the bronchial thermoplasty. The one situation that I think is still problematic is if you have a patient who s on inhaled steroids, they ve not responded, you ve added a LABA and you ve not gotten a benefit; it s tough to know in those patients whether you should stop the LABA and try tiotropium, leukotriene receptor antagonist, or continue the LABA and add on to that. I don t think we have enough information yet. I d ask Anne if she has any thoughts about that as to how she might handle this. 5

6 Dr. Fuhlbrigge: I do know a colleague who has finished a trial recently but the results are not available for publication looking at the use of tiotropium in patients who are considered at least from prior literature to be higher risk than those identified in the SMART trial where there was a potential signal of increased problems and exacerbations with LABAs. If you remember, in that study there was also some increased potential risk in black individuals. And so a colleague actually is just finishing up a trial looking at the use of tiotropium instead of a long-acting betaagonist in patients self-identified as black and looking at whether or not there really is a benefit in that particular population. So that should be out soon and we may have some additional information there also. But we don t have the final results on that yet. That s another area that is being actively investigated as we speak. Dr. Colice: So to get back to hopefully the answer to your question, I think that tiotropium will be approved for use in asthma. I think it can be used either as an add-on to inhaled corticosteroid or as an add-on to inhaled corticosteroid plus a LABA. There are good studies that show that there s added benefit in both situations. The more problematic issue, and I think Anne nicely referred to this, is who you decide to add Spiriva to, who you decide to add a LABA to, who you decide to add a leukotriene receptor antagonist to the initial steroids. And I don t think we know the answers to that yet. Dr. Fuhlbrigge: I agree. I don t think we have a definitive algorithm that says a patient who s on inhaled corticosteroids and you want to add another agent, who should you direct to each of those three options. And I don t think we have clear data from studies that say exactly in this person that I should do X and that in this person I should do Y. And so it may be something where you talk with the patient about the risks and benefits of each and then start one and, as we have talked about before, 6

7 you then monitor what happens and you see objectively do you really have some improvement or not. And then if there isn t, you can try one of the other agents and reassess. Caller: What about the role of genomics and biomarkers? How is that going to potentially impact the direction of how therapies are chosen and used in these patients? Dr. Colice: Wow, that s a tough one! Anne, do you want to handle that first? You handle all the hard ones. I ll handle the easy ones. Dr. Fuhlbrigge: I don t personally do a lot with the genomics and genetics in the research world, but I have several colleagues who are deeply immersed in that at the Channing laboratory. And obviously the excitement there is that we will over the next few years have additional information that will allow us to look at pharmacogenetics and pharmacogenomics and say, This particular med has a higher risk in this patient, or This particular med has a much better chance of having a therapeutic impact. Although we don t really have the tools right now, my colleagues are actively investigating this to be able to tell us exactly that. In certain situations these are the high-risk patients or these are the patients that will have a significant benefit from this particular medication. And that obviously will be tremendous, but we aren t quite there yet where we can send off a sequencing and decide that this drug is for this patient and another drug is better for a second patient. Dr. Colice: Yes. I agree. Dr. Colice: So, Anne, in your presentation you talked about symptom perception in the asthma patient and how sometimes that can be impaired. So my question to you is how often do you do spirometry in the 7

8 outpatient setting? You re doing the ACT, the ACQ, you re getting those results, and you re getting objective information. But under what circumstances would you say, Hmm, I d better get spirometry because I m just not sure that these answers are giving me the entire situation. Dr. Fuhlbrigge: Well, I think it really depends a little bit on the patient because I think there are some and I hope I emphasized, but perhaps I didn t as well as I should have that the perception can be different between patients. But it seems in my practice at least there are some patients who are, shall we say, poor perceivers and others who are not. Although there certainly can be some variability from time to time, it s more one group of individuals I worry more about being poor perceivers of their level of obstruction. And so in that particular group I use spirometry more routinely to make sure I understand how they re doing, because I can t rely as well on what they re telling me on a questionnaire. Whereas other patients who have a very good ability to perceive when their lung function is changing and really can note the symptoms and adjust appropriately, I don t need to use it as often. I mean there are some recommendations that patients with asthma should certainly be getting spirometry intermittently, approximately at least every year or so. What I would say is kind of a minimum in a patient who has active asthma that you re managing, even if you think that they perceive their symptoms well. But in that subgroup who I really feel are poor perceivers, then I tend to use it much more routinely. And I may even use it in some patients at every visit if I can do it quickly in the office right there, because it just helps me know for sure that what they re telling me on paper is exactly what I m measuring via lung function. At least at a minimum we can do peak flows if we don t do spirometry. We can also use peak flow to help us in that regard. Dr. Colice: Anne, do you have any questions for me? I sort of put you on 8

9 the spot. Dr. Fuhlbrigge: I guess one of the things that you talked about in your presentation, which I think is something that is still an issue when we re educating our colleagues about all the different inhalers, is what is your approach to the different inhaler devices and being up to par? Do you have ready placebo devices to help teach your patients and how do you go about making sure that your patients really know how to use the various different devices? Dr. Colice: We don t have placebo devices so we ask them to bring their own devices in, and we look at them as they use their own devices. It s a tough issue because patients will misuse every device, no matter what you think about. And you think, well we ve got that covered. They ll do something completely crazy and you ll just say, Wow, how did that happen? In general I like patients to use the same device for both their reliever and their controller. Now since most relievers out there are metered dose inhalers that means that I would give them a reliever metered dose inhaler and a controller metered dose inhaler, because I think it s easier when patients are using the same device for both. I think there s good information out there that suggests that if you use a dry powder for your controller and a metered dose inhaler for your reliever the likelihood of them making errors goes up. There s one sort of trick with that, though, and that is the color of the inhalers. The 2 most commonly used metered dose inhalers are the same. So ProAir is the most commonly used albuterol and that s red. And Symbicort is the most commonly used dual combination controller, and that s also red. So you have to be aware of that, because patients can get confused if they have the 2 same red devices. So that s something to think about. I like the small formulation inhaled corticosteroids and metered dose inhalers, because there are good studies that show that the lung deposition with 9

10 them is really improved. So my approach usually is start out with a metered dose inhaler, albuterol. For inhaled corticosteroid, I preferentially use a small particle inhaled corticosteroid. And then when I m going to the dual combination to try and use one that s a different color from the albuterol inhaler I m giving as rescue. Now dry powder inhalers are great. They re good and this is just my preference. I much prefer to use the metered dose inhalers, the nebulizers for a variety of reasons, but that s my usual approach. Dr. Fuhlbrigge: When you re going from a step 2 to a step 3 patient where you re going from a low-dose ICS to then having to either add on a LABA or increase to a medium dose ICS, would you preferentially usually go to a medium dose ICS so you wouldn t have to change to a device that has a combination product? Dr. Colice: I prefer to go to a medium dose ICS, and we actually have something that we re just finishing up now that looked at this pretty carefully; the patients we give increased dose ICS compared directly to an ICS LABA actually do pretty well. So I think the evidence is there to support that approach. If I do need to go to an ICS LABA, especially step 4 or step 5 or step 6 I will, but I m just mindful of the one I use and make sure it s easily differentiable from the albuterol that the patient has already got. So that s a little trick that I don t think everybody realizes. Dr. Fuhlbrigge: I think that s a very important point, though, to emphasize that making sure that patients can easily tell the 2 apart and make sure that there is no confusion between them. Dr. Colice: I always ask them to show me the medicines. And they ll bring out their ProAir and they ll bring out their Symbicort and they ll say, Here s my reliever. Here s my controller. And I say, Well, which one do 10

11 you take when you re short of breath? And about 50 percent of the time they get it right. Although you make the argument with Symbicort that may not be as important, but really you do want to have them use the right one. So it s interesting. Dr. Colice: Many people do not consider asthma as a serious condition; therefore, controller medication adherence is a major barrier. So I m going to ask Anne, how can we as asthma educators effectively get this point across? How do we make sure that patients actually take their controller medications? Dr. Fuhlbrigge: I think that s a very difficult area and one that I think a lot of us spend a lot of time thinking about. I think one of the things that people have shown is that if you really include the patient in the decision making about their health care and about decisions about their medication regimen and changing medication based on their symptoms or what you re finding, they many times will buy into that therapy and be a partner in that much more effectively. There s also a lot of interest in studying how we use medications and unfortunately we don t have the final answer on that, but there is a lot of interest looking at do we need to have all patients with asthma taking controller on a daily basis. I know there are some trials going on right now looking a little bit more closely in the mild persistent asthma population to say, Can we have a more sophisticated way that we deliver the medication that allows patients to take it when they need it but maybe not have to take it routinely every day? Unfortunately, that is still being studied so it s not ready for prime time yet. But everybody is actively thinking about this process. Dr. Colice: I ll just tell you a little anecdote. I saw a patient a couple of years ago, a very intelligent, 40-year-old woman came to me and she said, You are the fifth pulmonologist I m coming to see. And as soon as 11

12 you hear that you say, Uh-oh! I m in big trouble. So I said, Okay, tell me your story. So she says, I have asthma. I go to see a pulmonologist and they put me on inhaled steroids; my asthma would get better. I d stop the inhaled steroids and my asthma would come back. So I was sort of dumbfounded and I said, What do you think about that? They say you always learn from patients. Well, this patient s response was a great learning experience for me. She said, Stupid pulmonologist. So I said, Wow! That really hit it home to me that we really have to get across to the patients that asthma is a chronic disease. And I was able to do it with this patient and I would call her, I would her every couple of weeks initially, every couple of months. I convinced her that she had to take her asthma medications on a regular basis. It s been about 5 or 6 years, and she s been perfectly well controlled for all that time. But it really struck home to me the responsibility that the health care clinician has to have in teaching patients that asthma is a chronic disease that needs to have regular medication use. Dr. Fuhlbrigge: I agree with you, by you just asking that question of that patient and having her explain what she was thinking, that got you and she to have a dialogue that I think then allows you to have her understand better what was really needed. Dr. Colice: Exactly. Caller: How might treatment strategies for the Th1 phenotype differ from the Th2 phenotype? Dr. Colice: That s an interesting question. Anne, do you want to handle that or do you want me to handle it? Dr. Fuhlbrigge: I can start it; you can finish off. I think we don t know for 12

13 sure at this point in time but you may have seen some of the recent work. I know surely Sally Wenzel has published on this and others about sub-defining phenotypes within the asthma umbrella and that there really are differences between patients, but one area is obviously the potential of Th1 more focused phenotype than a Th2. And so the work is still ongoing to say what parameters we can clearly identify in the clinical world to say this patient needs slightly different therapy from this patient. So I don t think we can say there is a clear algorithm; just say that one versus the other is treated tremendously different from a patient who s Th1 versus Th2, but certainly there is a lot of work undergoing right now to better understand those subphenotypes within asthma. Gene, I don t know how you go about from your day-to-day practice trying to help identify that sub-distinction in asthma. Dr. Colice: Well, it comes up all the time about individualized medicine or personalized medicine and are we there yet. We are there to a certain extent in asthma with omalizumab, with the anti-ige monoclonal antibodies. So there you have a clear group of patients with elevated IgE that might respond to that particular compound. We re at the cusp, we re thinking about a lot of different things, for instance, with the anti-il-13 products. We ve got sputum IL-13 levels, we ve got periostin levels, but I would agree with you, Anne, we re not quite yet at the level where we re screening patients for Th1, Th2, individual cytokines, and being able to then say this is the therapy for you. It s going to be a couple of years. But when we get there I think it s going to be a huge step forward for us. Caller: How do you educate your patients about how triggers can change their asthma over time? Dr. Colice: The most common trigger that I see on a regular basis is the allergen-related triggers, the seasonal patients who will pretty clearly tell 13

14 you that in spring and fall they ll have problems. I like to have these patients seen by an allergist, I like to have skin testing just so that we can confirm all of this. Then it s really a question of timing your visits so that you can see them before problems begin. This gets back to something that Anne mentioned before. You know, not all of my patients will I have on inhaled steroids all year long. So there are some patients who will clearly have a seasonal component, and I might have them off their steroids during the winter or summer seasons when they re not having problems. I ll time their visits before and we ll start them on inhaled corticosteroids before the problems, and many times we can control things pretty well there. The other trigger that I see commonly is pets. It s amazing to me how patients refuse to get rid of their pets. It s not something that you can adjust your therapy on; it s something that you really have to talk about with the patient so that you can eventually get to the point where you can get rid of their pet. And when you re able to do that you see oftentimes a marked improvement in overall asthma control. So those are the 2 biggest triggers I see in my practice on a regular basis. There are occasionally aspirin-sensitive patients and that s something that you really have to make sure you educate these patients about. But that s a very infrequent problem. Anne, what are your thoughts about this? Dr. Fuhlbrigge: I think the other thing potentially that the question was regarding is how to help figure out what triggers are for a given patient. I think that it just goes back to really sitting down and having a conversation and trying to help the patient map out when they are having more trouble so that you can help them work through where were they, what happened, and can we think of something that might have been consistent in the times they ve had more trouble with their asthma. I think of it as a little detective work, which can be kind of fun but it also can be difficult, because sometimes they re just not clearly aware of what 14

15 might be the trigger in that particular case. I think there isn t really any absolute way to do it except for really talking with the patient and trying to figure out what the common thread in the times when their asthma is more controlled versus uncontrolled. Dr. Colice: I should mention also exercise because exercise is a very important trigger, and we don t think about that as much as we should. Exercise-induced bronchospasm is something that s also very important to consider. Emotion, stress, all of those things can certainly be triggers as well. Caller: Where do you think the monoclonal antibodies under development would best fit into current treatment options? Dr. Colice: Anne, I ll take this one if you don t mind. Dr. Fuhlbrigge: Yes, okay. Dr. Colice: There are a whole host of these monoclonal antibodies. Of course we already have omalizumab that s available and has got a fair amount of use around not only the United States but around the world. Of course none of them are approved yet, and there is a whole list of them I ve mentioned anti-il-13 or anti-il-5 products. I think it s very intriguing. They re still undergoing to a large extent the phase 3 confirmatory trials, so we re not going to probably see an approved new product for another year or two or three. And once we do that, it s going to be very interesting to see whether these products are going to be limited the way omalizumab is to specific phenotypes. So omalizumab is for patients with elevated IgE levels, skin test reactivity positive, certain weight characteristics. Will that also apply to these newer monoclonal antibodies, for instance, anti-il-13? Do you have to have an elevated 15

16 sputum IL-13 level? Do you have to have an elevated periostin level? I expect that that will be the case and then that will be the lead-in to personalized medicine. Now all of these are being tested in conjunction with standard therapy, inhaled corticosteroids, LABAs, et cetera, so it s not going to preempt us from taking our usual approach to asthma. This will be add-in therapy for patients who are having difficulties despite standard therapy. Anne, do you have anything that you want to add? Dr. Fuhlbrigge: One of the things to consider with many of these newer agents is they do have a significant cost associated with them. I agree with Gene that they re going to be probably within a subpopulation at least to begin with, that we need to really justify that we need to go to this level of resource in order to get the asthma under control. So, I think it s not something that will be readily available to just pull off the shelf for any asthmatic. But we ll really need to look at a subpopulation who we think really needs to move to this cost level and the potential risk. Any of these agents have a small risk associated with them, so it s also important to think about that. Caller: Is there a particular subset of patients where it s generally more useful to add a long-acting beta-agonist than a leukotriene modifying agent when the patient s not well controlled with an ICS. Dr. Colice: Wow, that s a wonderful question. So there was a wonderful article by Steve Peters in the New England Journal of Medicine a couple of years ago where in a cross-over fashion they looked at patients who are not controlled, they re on inhaled steroids, they tested them with either a long-acting beta-agonist, an anticholinergic, or increased doses of steroids. And different patients responded differently. Some patients responded better to LABAs, some people responded better to the LAMAs, some people responded better to the inhaled corticosteroid. It s pretty 16

17 hard to predict beforehand, unfortunately, which one is going to respond better to which. The best study that recently came out about the LABA versus leukotriene modifier came from David Price and that was also in the New England Journal of Medicine and that was a so-called real-life study. And they surprisingly found that LABA and leukotriene modifiers provided about the same results in care outcomes, and they attributed that to the fact that the leukotriene modifier patients were more likely to take their medicines than the patients who were on LABA. All these potential add-on agents, and I mentioned long-acting muscarinic antagonists because we ll probably see that approved for use as an addon therapy to asthma in the future, provide some benefit in selected patients, but I don t think we know for sure how you can predict ahead of time which patient is going to respond better. Anne, do you have any thoughts about that? Dr. Fuhlbrigge: I agree. You had talked a little bit before about personalized medicine, and this is actually obviously the area we want to be a little bit more confident in that we can predict who is going to respond better to drug A versus drug B. I think right now the best we can do is think about a systematic way we can evaluate a patient so that when we try a new medication we evaluate whether or not it really truly has had an impact on their control. And, if it hasn t, then we take that medication away and try another option that we have. Dr. Colice: Yeah. Dr. Fuhlbrigge: I think, unfortunately, right now we still are at the trial and error amongst the different medications at each step that are available for a given patient. We don t have a clear direction that absolutely drug A is better than drug B in a given setting. 17

18 Dr. Colice: It s an interesting one that s not generally appreciated now. But when the leukotriene antagonists were being developed they tried to phenotype patients to see which patients they thought might respond better to these than to others, and they were never able to identify a group of patients that would respond better in the development of those products. Thank you very much, all. And we greatly appreciate your joining us today and asking your questions. All the best to you in your asthma management. 18