Seemal R. Desai, MD

 So Milind, let's start with you. How is the advancement in the knowledge about pathophysiology? You talked to us about mice and heavy chain myosin binding protein C [MYBPC3] sarcomere variance at the very beginning. How is further understanding of that pathophysiology led to the development of new therapies?

 You take a genetic abnormality, recognize it, dissect it, and then understand enough about it to then go and develop a precision tool to work on it. So what are we talking about? We know we briefly talked about in HCM [hypertrophic cardiomyopathy], what is happening is there's excessive actin myosin cross-bridging that happens at a myocyte level which results in the hypercontractility. This is a good lesson in life—not everything that is vigorous is good. So bottom line is we know there's a lot of hypercontractility; there is a fair bit of inefficient use of energy and stiffness, excessive fibrosis. All those things lead to the pathophysiology of hypertrophic cardiomyopathy. To top it off, this excessive hypertrophy and hypercontractility results in the outflow tract obstruction that you see so. I think we need to take the microscopic and the macroscopic perspective together and working on a precision drug like the cardiac myosin family of inhibitors. What do they do? These types of drugs reduce the actin myosin cross-bridging, so they don't shut them all off. Otherwise, you know we won't have a heart that is beating. So they shut enough of them to reduce the edge of hypercontractility so from hypercontractile you become appropriately contracted. It makes the heart utilize energy more efficiently. In doing so the most important part at this point of time is that it reduces the outflow tract obstruction, which then has a lot of downstream positive impact, including improvement in symptoms, quality of life reduction in MR [mitral regurgitation], improvement in diastolic function, LA [left atrial] volume reduction, and mass regression. Most importantly, we are in the business for making patients feel better and perhaps avoid invasive therapies that may have heterogeneous outcomes, so it helps reduce the rate of septal reduction therapy. We are just getting started here as you very well know, we are getting started here.

Transcript is AI-generated and edited for clarity and readability.

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Milind Desai, MD, MBA, comments on the broadening knowledge in the oHCM space, leading to the development of new therapies.

Advances in oHCM Therapy

 Andrew, take us back to the patient who maybe hasn't had a good response to the beta blocker or calcium channel blocker, even a combination of those 2 agents. How do you approach talking to a patient and selecting the right septal reduction therapy [SRT], and what are the challenges that come with those invasive therapies?

 So when I talked to a patient about the pharmacologic therapy, I say none of the drugs that we know of significantly reduced the degree of hypertrophy. If we're talking about something definitive to address the hypertrophy, that's when we start talking about septal reduction therapies. The 2 most commonly used ones now that have a good track record and experience would be either surgical myectomy, which has been available for more than 60 years, or alcohol septal ablation, which has been around for more like 25 to 30 years, I tell patients. That the decision oftentimes is up to them between what they think would fit best with their lifestyle. But we may recommend 1 or the other based on either their comorbidities and their ability to get through a cardiac surgery, perhaps favoring, then a less invasive alcohol septal ablation procedure or their anatomy. There are some anatomies where it is not just the sigmoid basal septal hypertrophy that could be addressed within alcohol septal ablation, but more complex hypertrophic cardiomyopathy [HCM] anatomies, particularly those that have concomitant mitral valve disease, which can happen in 1 in 5 patients with hypertrophic cardiomyopathy, where a surgical approach would address multiple different components of that outflow tract obstruction. So I think we try to give a best recommendation, but oftentimes there is equipoise about what would be the most effective in terms of alleviating their symptoms and patients will ask the right questions most of the time and decide, OK, this one I think is fits with my current plan for my health.

 Great, and Milind I’ll just end this segment with talking a little bit about access to septal reduction therapy and high-volume centers. I know you recently published some work on this. What's your opinion on where myectomy is are done and where they should be done?

 So this is an important question to answer because of substantial heterogeneity in outcomes based on a given centers experience. The paper that you alluded to looked at SRT landscape in the USA and what we found amongst are there are also multiple other publications that have shown that if you go to a highly experienced center for an SRT procedure,your mortality rate is like in the 0.5% range, often many years it is 0%. But if you go to a low-volume center, that's just doing occasional procedures like this, the mortality can reach all the way up to 16%. That's a big number and that's just mortality. In hospital or in post procedure mortality, VSD [ventricular septal defect], uncorrected problems, persistent gradients, all those things aside, 16% mortality. So it is important SRT works. When it works, it is a really gratifying result in an operation, but you have to find the right center. The unfortunate reality of the landscape in USA that was, I think, the punchline of the paper is in spite of the inverse association between outcomes and surgical volumes or procedure volume. Seventy percent of US patients with obstructive HCM went to lower-volume centers. So clearly there's an unmet need to consider broadening the tent of available options.

 To add to that, the number of cases of either form of SRT that would be in the higher tertile of volume is still surprisingly low. So when we talk about when we talk about high-volume centers, I think if you said that to a patient they would say, "Oh you're doing 50, 100 a year,” we're talking about in the highest tertile that you're in the teens perhaps. So there are a very high number of low volume centers and I used to feel a little bit uncomfortable when patients ask me how many of these have been done here this year How many of these have been done? But now I think it really should be almost publicly reported information. Because really across all of cardiology, there's such a strong relationship between volume and outcome. So I think the patient is actually doing their homework when they ask that question.

 It's a different connotation when you're looking at the patient straight in the eye and saying, “Yeah, our center does about 40 or 50 of these a year”, versus this is a surgeon who’s done 2500 of you know, so there are connotations to this, and that should be addressed. And like Andrew said, it should, I think it is the narrative will shift now with available newer therapies to sort of you know publicly report these types of things.

 It’s us to have really open conversations with their patients as they're weighing these very, you know, heavy and sometimes life-changing decisions. So Michelle, are there other current unmet needs in obstructive HCM?

 I'll give you about 2 minutes to answer that.

 So I think there's so many things we still need to know preventive disease, modifying therapies, clinical trials that focus on patient reported outcomes with information on the differential impact of therapies based on sex, race, ethnicity, and not specifically for obstructive HCM, but for all HCM patients. Accurate sudden cardiac death risk assessment, wider access to genetic counseling, which is an essential component of genetic testing and guidance on things like exercise sports participation. I think this is what makes the field exciting for us. There's so much we have still left to learn.

 That was wonderful. You gave us about 20 things to do for the next decade.

Expert cardiologists share approaches to the challenges that come with septal reduction therapy, as well as access to oHCM treatment.

Septal Reduction Therapies in oHCM

So, this has been a tour de force of an amazing discussion. In the last few minutes let's get some sort of final parting thoughts and, really, I would love to have your thoughts about where we are in our disease state understanding, anything we talked about clinically, and kind of your hopes and dreams for the future of this disease and, really, for skin disease. We know that there are so many skin diseases out there that we treat that don't have FDA-approved therapies. Ted, I'm going to start with you. I'd love to have some final few minutes of your thoughts.

 Thank you. What a wonderful panel, and Dr Desai, thank you so much for leading us. It was really a very thought-provoking discussion. I learned a lot personally, so thank you to everybody here. I do want to say as a principal investigator, as someone who runs quite a few of these vitiligo trials, recruitment can be difficult. For those people who are watching this, if you don't mind helping the local sites out with recruitment because we all want to get these drugs in the hands of our patients as quickly as possible. Some of the latest medications that are available are in clinical trials right now. Using the investigational sites in your area can be helpful, and for those of us who are really trying to get the latest, we rely on you. So that's one thing I would say, thank you for letting me do that. Otherwise, I think the topical ruxolitinib is a wonderful first step in treatment for an autoimmune disease that has sorely needed something particularly for itself. I'm so happy that we – as I said, that ruxolitinib, has opened the door and now there are so many others that are in development. I think that what we'll see is similar to what we've seen in psoriasis. We're now kind of experiencing an atopic dermatitis, where there's just going to be a rush of highly efficacious treatments that will both systemically and topically allow us to treat the entire patient and really elevate their quality of life, which is what is most important.

: I would say my biggest take home – first of all, this has been such a wonderful panel. Like you, I learned from everyone and thank you for moderating this. I think it’s a very exciting time to be treating patients with vitiligo. I’ve been treating vitiligo for 20 years and I will say, as I mentioned, it was hard when patients – 10, 15 years later, there really was nothing new. There really was nothing new for so long and so this is a very exciting time. I'm very hopeful, optimistic, excited to see the results from the newer trials that come out, and, like you said, we're going to get not just 1 new FDA-approved treatment, but I'm sure in the future, many. That will be such a change for a disease that I feel like was neglected for many decades.

Heather, let me just ask you, since you are really engaged with social media and getting the right messages out there, have you really found that social media has been a wonderful way to talk about vitiligo? Hasn't that been your experience because you've done some great work on that?

 Yes, so I do think social media is great for rare diseases because, although vitiligo really isn't rare – it's actually not that rare – but for diseases that people don't talk about much, I think patients can feel very isolated. If you're a vitiligo patient and you feel isolated, you might have 1 family member, a distant family member, who has it, but you might not have anyone else to talk about it with. One of the biggest impacts I think social media has is that it allows people to connect and to share things that even us as physicians wouldn't be able to share: the best textured make-up, the best – what lasts longer? What doesn't rinse off in the pool? Those types of things are the things that you can learn on social media. From a physician standpoint, I really do try to make an effort to do a lot of education so that they're getting the correct information and not the old wives’ tales and remedies that have no data and no proof. From our perspective as physicians we can give, create content that's accurate and valid and also introduce new concepts because this new topical has just been introduced in the last year, so for people who haven't seen their dermatologist, they got burnt out and haven't been in in 2 years then say, “Oh there is a new treatment now, let me go and make an appointment with my dermatologist.” I think social media plays 2 roles from our perspective and a role in education. From a patient's perspective, it's a way to connect with other people and really get further insights beyond what we can offer our patients.

I just have to say kudos to you, and Brittany, and Nada, and Ted, all of you guys who do that to put out the right messages about board-certified dermatologists and sending the right messages because there are influencers out there who aren't medical professionals who are giving the wrong information to our patients. Many of our organizations that we're all a part of have really championed this. The AAD [American Academy of Dermatology] has an incredible “Your Dermatologist Knows” social media campaign that started in the past few months. It's been incredible because we have to really band together to get the right info out there so then patients know what the right question is to ask, when to seek treatment, and when to have hope. Brittany, would love some of your final thoughts.

 I feel like so many – I agree with everything really that's been said already. I do really feel optimistic that in, right now lots of patients come and maybe they come to see me for something else, and they have vitiligo and I'll say, “Oh have you treated that,” and the patient says, “Oh no, I've been told there's nothing to do for it over and over.” They've sought treatment and somebody said, “It's no big deal, that's cosmetic,” patients have felt dismissed. I really do think that that tide is changing. With an approved therapy there's all this awareness now that this is an autoimmune disease. It's just like anything else we see, and it really warrants treatment. With the advances in the scientific understanding, we now have a pathogenesis-directed treatment. I really think in 5 or 10 years that patient experience is going to be very different. We're going to have multiple fairly reliable and effective therapies. We also are going to have patients who are coming in earlier, and probably going to do better, because they're getting treated at the beginning of their disease, rather than 20 years down the road where it's going to be a lot harder to repigment them. This longstanding vitiligo may be something that slowly kind of goes away over time, which is kind of exciting.

: Super exciting. I am optimistic that we will have a cure for vitiligo in our lifetime. I'm really optimistic of that so we're going to hopefully keep going for that. Nada, what would you say? You're so passionate, like me, about this.

 Absolutely. This has been an amazing panel. I echo what everybody said. I think the exciting thing is that as we're understanding the pathogenesis more we are going to have more of these targeted therapies. Similar to what Ted was saying, the way we see that the treatments are blossoming for psoriasis and atopic dermatitis, I think vitiligo is next in line. Ruxolitinib is the beginning of that, and it's not just topical and oral medications, but procedural therapies. The transplantation process for vitiligo used to be quite involved and there's a treatment that's in studies right now that once that gets approved will allow people to do procedural therapies in their office much easier than before. I think the other really exciting thing is seeing the voice of individuals with vitiligo really getting amplified, and seeing public representation of vitiligo increase. We're really seeing that help decrease the stigma that comes with the disease. Winnie Harlow was one of the first people to kind of really come out and model without her makeup. That was a huge statement for people with vitiligo that, “I can do this, and I can feel good about myself, and I know that I look great and not feel that I have to have hide- behind makeup or anything else.” Mattel came out with the Barbie. There are dolls with vitiligo, CoverGirl hired their first model with vitiligo, “Call of Duty” now has a character with vitiligo. So, just across all these sectors of society, this public representation is huge, and I think it's so important for us to be able to advocate and support our patients in every regard for getting treatments, but also for not getting stigmatized for their disease and making the public know what is and be educated about it. I think there's a movement happening all in the right direction and it's very exciting to see.

I couldn't agree with all of you more. I think now is just such an incredible time. This has been a fantastic panel. I am so hopeful about vitiligo treatments for our patients. I hope we'll be able to have the opportunity to do more of these discussions in the very near future. I'm sure we're going to be having lots more scientific data that's going to be rich and fulfilling for us to be able to share for our patients. So, Dr Lain, Dr Woolery-Lloyd, Dr Craiglow, Dr Elbuluk, thank you for joining me. It's really been a pleasure to be with you all today for this exciting discussion and thank you all for watching this HCPLiveâPeer Exchange. If you enjoyed the content, please subscribe for our e-newsletters and to view upcoming peer exchanges and other great content right to your inbox, make sure you visit HCPLive.com. I'm Dr Seemal Desai. It's been my pleasure to be your chair and moderator for today's discussion. Thank you for joining us.

Expert dermatologists share final thoughts on treatment of vitiligo and topical ruxolitinib. 

Key Takeaways on Vitiligo Management 

: So, Ted, we talked about access to therapy and wanting for clinicians and dermatologists to be able to get new treatments in the hands of their patients. Talk to me about some tips, tricks; ways that you've been able to motivate your patients and what can we share with our colleagues on access to therapies and how they can get some of these?

 I really think it all starts with documentation in the progress note. If you look at the endpoints for the clinical trials and who this cream is indicated for, this topical is indicated for, that will dictate how you should document in your chart as well. I document an f-VASI [facial vitiligo area scoring index], for example. I document a t-VASI [total vitiligo area scoring index]. It's not hard. It is the number of handprints, multiplied by the degree of pigmentation. So, for example, these patients in order to get in a clinical trial had to have an f-VASI [facial vitiligo area scoring index] of 0.5 % and they had to have at least, I believe, up to 10% and that's why the 10% is the cut off, up to 10% vitiligo in the rest of the body. If you understand that, then you can document appropriately in order to have the ammunition to go back to the payer to say, “Look, they meet criteria for this and by the way, this is the only thing that is FDA-approved for this indication. What do you want me to do?” So, I kind of go back with those 2 and then finally, we have a biologic coordinator. We have someone who, unfortunately, we pay in order to get these drugs approved, which is counterintuitive, but we do it anyway. That person is very good at utilizing all the promotions and rebates and the opportunities that the pharmaceutical companies provide in order for us to get these drugs into the hands of our patients.

That's a whole other multihour discussion because the amount of overhead that it costs our practices to have individuals like that, but guess what, if we don't then the patients aren't going to get the therapy. It's the unfortunate nature of the system we're in. Heather, what are some of your thoughts on this topic?

: So, I agree with everything that you said. The other thing that I really try to utilize are the patient assistance programs, because they're there for a reason. I think sometimes we underutilize them because “Oh, it wasn't covered, I'm so sorry,” but we really have to, in some ways, change gears and say it wasn't covered, but they also have a patient assistance program. A lot of times it's very simple; it's a one pager that you fill out and they send it in. They just basically disclose their income. Sometimes they request documentation, sometimes they don't, though. Sometimes they don't even request documentation. I think that we need to take much more advantage of that because that's there for us to use for those reasons. Instead of saying, “It's not covered, let's try something else,” I try my best to go with those patient assistance programs when I have difficulty with insurance.

I think that's a really good point because I will admit that sometimes when we're frustrated doing prior authorizations and after a really busy day and answering multiple call backs and path reports, etcetera, that's the last thing on my mind. You're absolutely right and probably that biologics coordinator or that 1 staff person in your office is the point. Do you all have a point person in your practices or at the university that helps? Brittany, do you have someone?

I sort of have one of my medical assistants who's become our de facto person and she does a great job. Nada, what about you?

 Yeah, we have a coordinator who helps in that role. I think it's been mentioned, it is very time consuming and so getting authorization is – it's a necessary thing we have to do, but unfortunately, it does take a lot of staff time and physician time to get our patients sometimes what they need.

: It makes sense. One thing that I wanted to mention earlier that we talked about, and I think coverage is a great place to put this, is there's been great papers. In fact, there was one that just came out in the literature last week that talked about dyslipidemia and metabolic syndrome and other systemic comorbidities with vitiligo. We have a form letter in our practice that if we get a denial, we just print out the form letter. I put it on a letterhead, I sign it, and we actually staple the PDF of these papers and send them to the insurance company. We'll still get denials and then I say, “Well did you get on the phone with the medical officer? Did you not read the paper that I just sent you?” This is a systemic disease. Have you any of you tried tactics like that?

: Absolutely, I've definitely sent papers to them. There's also a great one that was in the JAAD [Journal of the American Academy of Dermatology]; “Vitiligo is Not a Cosmetic Disease.” I love to send that paper when they send back the rejection because they're trying to call it cosmetic. The other thing, you and I are on the board of the Global Vitiligo Foundation and so we have letters that we've written on there, which can – so that you don't even have to go through all that work, that you can print. That basically will help you to try to get authorization for topicals. We have one now for ruxolitinib, we have for phototherapy, with citations included in the letter so that's just to help all the physicians out there with trying to get coverage for their patients.

So, I'm so glad you plugged the Global Vitiligo Foundation, and the Global Vitiligo Foundation is a non-profit so I'm just going to say, an incredible resource for clinicians and for patients. Support groups are very important in vitiligo. There are some amazing vitiligo support groups out there on Facebook, on social media. World Vitiligo Day is now highly organized and propelled forwards because of patients. If you have a patient who really wants to feel connected with other vitiligo patients, a great opportunity is through the support groups. I'd encourage everyone to send their patients to the Global Vitiligo Foundation website. Obviously, my conflict is I'm on the board of directors, so is Dr Elbuluk, but this is a nonprofit that's really designed to help advance our understanding of vitiligo and really empower patients. The patient voice is so important, especially as we continue to advocate for more NIH [National Institutes of Health] funding, for more research dollars and really wanting to advance the field of the disease.

Experts in dermatology comment on the need to promote access to emerging treatments in vitiligo.

Seemal R. Desai, MD

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