Lawrence Green, MD, discusses with Kristi Hawley, DO, strategies for selecting treatment options for patients with obesity and psoriasis, as well as patients at risk for cardiometabolic disease.
Dr Hawley is an associate clinical professor of dermatology at Michigan State University College of Osteopathic Medicine and medical director of The Derm Institute of West Michigan in Grand Rapids, MI..
Dr Green is the section editor of The Dermatologist’s Psoriasis Center of Excellence and clinical professor of dermatology George Washington School of Medicine in Washington, DC.
Dr Green: Welcome, everybody. Welcome to a new Dermatologist podcast. My name is Dr Larry Green. I’m section editor of the Psoriasis Center for Excellence as a dermatologist. I’m also clinical professor of dermatology at George Washington University School of Medicine, here in Washington, DC.
Today, I’m so lucky to have Dr Kristi Hawley who’s joining us. We’re going to discuss selecting treatment options for patients with obesity and psoriasis, as well as those at risk for cardiometabolic disease.
Dr Hawley is an associate clinical professor at Michigan State University, College of Osteopathic Medicine, medical director of the Derm Institute of West Michigan in Grand Rapids, Michigan.
Welcome, Dr Hawley. Thank you for joining us so much.
Dr Kristi Hawley: Thank you, Dr Green. Happy to be here.
Dr Green: Yeah, we’ll have a lot of fun, and hopefully, everyone will learn a lot from this podcast.
Dr Hawley, I’m going to start right off and ask if you could discuss with us what we know about psoriasis and obesity, as well as the comorbidities associated with both conditions, such as diabetes and metabolic syndrome? I know that’s a lot, but I know you can handle that question.
Dr Hawley: Sure. Dr Green, we have all come to learn over the years that psoriasis is really complicated now. We used to just think it was a skin disease. Now we’re learning that all these comorbidities are following these psoriasis patients, including diabetes and metabolic syndrome.
It’s really no surprise that a lot of physicians and providers are finding treating psoriasis to be a little big daunting and overwhelming. I’m really happy we can discuss this today and we can focus on diabetes and metabolic syndrome since cardiovascular disease is always getting the hot spot.
There’s been a lot of review articles and studies published trying to elicit the understanding of these diseases, how they’re interrelated. Some of our own colleagues have published data that is claiming that psoriasis patients have twice the prevalence of both obesity and type 2 diabetes, which is astounding.
When I read that, I was like, “OK, is it because our psoriasis patients are more likely to drink, they’re more likely to smoke, they’re depressed? Maybe they don’t have the greatest lifestyle.”
When diving a little bit further, it looks like even when everything’s match-controlled for weight and lifestyle, it appears that psoriasis patients still have an increased prevalence of about 5 to 10% of this obesity and metabolic syndrome.
That does support that there’s probably some sort of genetic mechanism or some sort of underlying shared mechanism. This has also been supported by some twins’ studies also, so it’s interesting.
Dr Green: Yeah, it’s interesting. Basically, they’re looking at all the confounding variables for causing obesity and diabetes. They can eliminate that, and then psoriasis is such independent risk factor in itself.
Dr Hawley: It is. It looks like there’s a lot of shared inflammatory markers in all of these. It’s no surprise TNF-alpha is one of the more notable ones. There is data though that’s emerging that suggests IL-17 and IL-23 may also be playing a role in psoriasis and obesity and diabetes.
We know that adipose tissue is metabolically active. The more adipose tissue you have, it releases more TNF, and then that contributes first to psoriasis and it also creates insulin resistance. There’s this crazy, positive feedback mechanism that’s feeding into each other, and it’s really hard to know what came first.
It makes me wonder if we treat the patients systemically, and we calm down all their inflammation, if we’re going to see positive benefits in these comorbidities in the future. I’m interested to see what comes out.
Dr Green: Yeah, a lot of people are looking at that as well. It is amazing how it’s such a feedback loop like you say. Let me ask you another question. How can obesity impact treatment efficacy and outcomes in patients?
Dr Hawley: We have all experienced how frustrating and heartbreaking it is to try to control our obese patients. They’re a little bit more difficult to get control than our thinner patients. In my experience, these patients tend to have more severe psoriasis, more comorbidities, and are more depressed. It’s so hard for these people. I feel for them.
Dr Green: Do you do anything different for patients with psoriasis and obesity in terms of treatment? Do things change? I know some of the biologics are weight-based and that may make a difference. What else would you do besides, if there is weight-based dosing for a biologic? How would you treat them differently?
Dr Hawley: That’s a really great question. It’s hard to pick a one-size-fits-all treatment for these patients, but there are a couple of things to consider based on what’s out in the literature.
One of the first things is that psoriasis is an independent risk factor for the liver fibrosis, regardless of any comorbidities. You add obesity on top of it and the risk of non-alcoholic fatty liver disease is really high.
It was interesting. There was a study that showed that 96% of patients who’ve used methotrexate, who have these risk factors and have psoriasis, develop hepatic fibrosis. I was like…that’s frightening, especially because I use methotrexate a lot.
Because of this, I try to steer away from methotrexate in the heavier population that has all these comorbidities. In terms of the TNF agents, the fixed-dosing TNFs are a little less efficacious in our heavier patients, but there’s a lot of data coming out that shows that they can protect against some of these comorbidities.
They may improve weight circumference and glucose and lipids, but again, may not work as well for skin and joints. Remicade, I know that’s old school, tends to fare well in the heavier patients because it is weight-based dosing. That’s always something to consider if you have a patient who is heavy and can’t respond to anything else that you’ve given them.
Dr Green: Kristi, you mentioned TNFs. What do you think about other biologics in patients with psoriasis and obesity? Are they effective? Do you change things? Anything else you do? Do you think they prevent fatty liver disease or cardiometabolic complications?
Dr Hawley: Based on what’s out in the literature, it looks like the IL-17s might fare a little better across all weight classes. In one of the studies, ixekizumab, or Taltz, seemed to perform the best across all the weight classes, so that was really nice.
Unfortunately, in the studies, it doesn’t look like it’s improving lipids, fasting glucose, or blood pressure. While it might work great for skin and joints, the data just isn’t there yet to show that it’s improving these other comorbidities like the TNFs are. The data’s lagging and it could come, but at this point in time, it’s just really not there yet.
Another one that we were so excited to hear about was apremilast, or Otezla, because in clinical trials, we saw weight loss, but we’ve all been a little disappointed that it hasn’t really come to fruition in practice.
For me, it’s my skinny patients who lose weight and then they’re upset that they’re losing weight. There is data that demonstrates patients on Otezla can decrease their hemoglobin A1c, so that’s great. If somebody has diabetes, it might help them in that level.
Dr Green: Actually, that’s an important point, Dr Hawley. The hemoglobin A1c for patients who are diabetics or prone to be diabetics, in that respect, Otezla can make a difference. I agree with you. I’ve never been impressed that much with Otezla and weight loss.
I usually tell my patients that read that in the package insert, I want to tell those patients it’s a great medication. I tell them don’t necessarily expect to have weight loss with Otezla, but expect to have your psoriasis improve. I couch it that way, and I totally agree with you on that respect.
Speaking about weight gain and weight loss, I want to ask a little more about weight gain. You mentioned TNF inhibitors have a lot of evidence to show that they potentially reduce fatty liver disease and other complications of obesity seen in psoriasis patients.
There’s also evidence that TNF-alpha inhibitors can cause weight gain. Are there any treatments that should be avoided in patients with psoriasis and obesity? TNF-alpha inhibitors, we’ve shown how they’re good. What about potential weight gain? What have you learned about that?
Dr Hawley: This is a really interesting and controversial topic. A couple of years ago, maybe 10 or so, they were publishing data that TNFs were causing weight gain. There was this large, systematic review and meta-analysis that was just published this year actually— so really perfect timing –that looked at TNF agents to see if that was true.
Apparently, across other disease states, in most disease states, TNF inhibitors do not cause weight gain. Interestingly enough, in our psoriasis patients, there is a risk that it can increase weight and BMI, which, to me, is totally counter-intuitive considering that we’ve learned that TNF can increase adiposity and all these other things.
I looked into it a little further because I wanted to understand the science behind it. Apparently, TNF can either induce anorexia or it can induce overeating or appetite. What they’re thinking is that it’s dose specific. At certain doses, it can induce increased appetite. They’re actually looking at TNF inhibitors for anorexia nervosa patients, which I think is so cool.
In the clinical trials, or in this meta-analysis, there was only an average weight gain of three pounds in these patients. For me, three pounds isn’t enough to not use a TNF in this population considering what we are seeing with the comorbidities.
Dr Green: That’s really interesting and a really great answer. Thank you for doing all that research. A lot of us have always wondered, including me, especially, how TNFs really fit in with psoriasis and obesity, with interval weight gain, which, as you said is small, and all these positive things that can happen for patients with obesity.
There’s a lot of good information for the practitioner to use in the future to make a decision on the best biologic to use for a patient with psoriasis. Let me switch topics just a little bit. Let me ask you about the role of integrating lifestyle interventions with traditional medications for patients with psoriasis.
Dr Hawley: It’s no surprise that any improvement in lifestyle modification—diet and exercise— can really help mitigate their skin involvement. It can help their medications work better. It can decrease their comorbidities, increase their lifespan.
There’s actually studies out that show that if you have a family member with psoriasis, if you eat healthy and you exercise, you are way less likely to manifest psoriasis. What they’re showing is that a lot of people who gain weight later in life develop psoriasis at that point when their lifestyle goes downhill. It’s no secret for all of us that, with all skin diseases, if you can improve your diet, you’ll be better off.
Dr Green: Kristi, you brought up a lot about the role of integrating lifestyle interventions in patients with psoriasis using medicine. Weight is a very sensitive subject in everyone, especially patients with psoriasis, and as you mentioned, these people experience social stigma.
How do you counsel your patients about being obese or weight loss? Do you bring it up? Do you think someone else should bring it up? How do you approach the obese psoriasis patient?
Dr Hawley: That first visit, when you diagnose psoriasis is really difficult for our patients. We have to explain to them that they have this new diagnosis that’s lifelong, that we can’t cure. They have to carry along these comorbidities with them in the future, establish with primary care.
You can see in their faces how stressful it is. You’ve completely changed their life in that one minute. I take that as an opportunity to let them know that I’m going to be there for them, that I’m there every step of their journey, but that they can play a role in their own health too.
I touch on it gently. I say, just by doing small things, by changing your diet and exercising, you might be able to decrease how many medicines you have to go on. You might even extend your lifespan. That’s it. We don’t have time to worry too much on it. I let that sit with them.
When they come up for follow-up appointments, I follow up on it, and then I offer resources. I’m not a nutritionist. I know what I’m supposed to eat, but I don’t know how to tell anybody what to eat.
I refer them to a nutritionist that I already have a relationship with, that I know isn’t going to talk them out of going on medications, that’s really important, and hope that eventually, when their skin starts to clear, they’ll start to find the confidence to go out on their own and take control of their own disease.
Dr Green: That’s great, and great advice for all of us who are out there practicing is to establish a relationship with a nutritionist for these patients who need help and know that we’re there for them. That’s great information to add. Thank you, Dr Hawley.
Do you have any other thoughts that you would like to add? Anything you want to talk about in terms of treating psoriasis patients who are also obese?
Dr Hawley: I know that psoriasis patients can be really difficult to navigate. There’s so much to think about. The idea of a one-size-fits-all treatment or biologic for all patients just isn’t a reality because of things like this.
What I recommend is bring these patients back often at the beginning of your treatment courses. Get to know them and then chip away at the comorbidities slowly. You don’t have to do it all in one visit. Eventually, when you get them controlled, and they start to feel confident in their relationships with other doctors, you can see them less.
Dr Green: Thank you. Thank you, Dr Hawley. Thanks for being with us. As you know, guys, Dr Hawley’s an associate clinical professor at Michigan State University, College of Osteopathic Medicine, and certainly, a rising star in the psoriasis treatment world.
I appreciate all the research and learning you’ve done and have shared with us on treating psoriasis, especially today, talking about psoriasis and obesity. Any other questions or comments that you guys have, please submit in the feedback box. We look forward to hearing from you. We want to hear from you.
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