Alexis Ogdie, MD, on the Impact of Obesity in Psoriatic Arthritis: Part 1

In the first of two videos on the impact and treatment of obesity in psoriatic arthritis, Dr Alexis Ogdie reviews recent research on how obesity affects the severity of disease and the effect of weight loss on patients with PsA. 

Alexis Ogdie, MD, is associate professor of medicine and epidemiology in the Perelman School of Medicine and director of the Center for Clinical Epidemiology and Biostatistics and director of the Penn Psoriatic Arthritis and Spondyloarthritis Program at the University of Pennsylvania in Philadelphia, Pennsylvania.

Obesity and Psoriatic Arthritis: Weight Loss Strongly Linked to Improved Disease Activity

• Obesity and psoriatic disease (psoriasis, psoriatic arthritis [PsA]): Across 3 cohort studies, obesity increases PsA risk ~1.6–1.7× vs general population, independent of psoriasis severity/duration. Obesity is also associated with lower likelihood of achieving minimal disease activity (MDA; ≥5/7 criteria including joint counts, enthesitis, patient-reported outcomes) after biologic initiation, potentially due to functional limitations and proinflammatory adipose cytokines (IL-6, TNF).
• Dietary weight loss and PsA outcomes (Di Minno 2014 RCT, TNF inhibitor initiators, 6 months): Mediterranean vs free diet showed similar overall MDA rates, but weight loss magnitude drove outcomes: 5–10% weight loss increased MDA likelihood 3.6×; ≥10% weight loss increased odds 6.67× vs no weight loss, regardless of diet type.
• Diet interventions (Rosenberg single-arm VLCD; DIPSA randomized trial, n=90, 12–24 weeks, stable therapy): Very low-calorie diet and structured diets (DASH, Mediterranean, standard advice) improved clinical outcomes; differences between diets were not statistically significant. Across studies, patients who lost weight consistently had better skin and joint outcomes, with modest weight maintenance and stable clinical benefit up to 12 months.

Hi, I'm Alexis Ogdie. I'm a professor of medicine and epidemiology at the University of Pennsylvania. Today I'm going to talk to you a little bit about obesity and psoriatic disease. We've been studying obesity and psoriatic disease for probably over a decade now. We know that obesity is a risk factor for both development of psoriasis and development of psoriatic arthritis, and there's been a number of studies on that now. In fact, 3 separate cohort studies in different populations have demonstrated this risk. So among patients who have obesity, their risk of developing psoriatic arthritis is about 1.6, 1.7 times the general population, and that's even after accounting for body surface area of psoriasis, duration of psoriasis, and other risk factors as well. So obesity is important for development of PsA, but in addition to that, we've also known that obesity is associated with a lower likelihood of achieving minimal disease activity.

So what is minimal disease activity? MDA is achievement of 5 of 7 different targets. And these are things like swollen joint count of 1 or less, tender joint count of 1 or less, enthesitis count of 1 or less, having a good patient global, low body surface area of psoriasis, a good patient pain assessment, and a good HAQ score or function score. So 5 to 7 of those means you have MDA. Well, if you're obese, you're much less likely to be in MDA and less likely to achieve it after you start a new biologic therapy. And this is due to multiple different things. One of those factors may be just literally the weight. So you're not quite as functional if you're obese. If you have obesity, it may be harder to get up and down the stairs or to exercise more, et cetera.

And then also it may be that there may be some fat distribution of drugs. Now, supposedly, most of the biologic therapies aren't supposed to have much fat distribution. It's supposed to say mostly in circulation, but regardless, we've seen from studies that we just don't get the same level of response.

And then finally, obesity or adipose tissue is actually an inflammatory organ. It produces interleukin-6 and TNF, which are some of the same cytokines that are driving joint inflammation. We also know that if patients are obese, they're more likely to have a higher level of body surface area.

So naturally, this begs the question, if you lose weight, do you get better control of the disease activity, both for the skin and the joints? Well, there's been a number of studies over time, particularly those that are focused on dietary interventions that have demonstrated that weight loss works. It's a good measure, it's a good intervention for improving the skin disease and for improving the joint disease.

There have been 2 prior diet studies in psoriatic arthritis. One was led by Di Minno in 2014, and in that study, that team randomized patients to a freely managed diet or a Mediterranean diet among those with obesity who were initiating a TNF inhibitor. They then followed them over the 6 months, and they found that the diets were relatively similar in terms of who achieved the ultimate goal of MDA, but the Mediterranean diet was a little bit better. But beyond that, they found that it was the amount of weight that was lost that was most tied to whether or not someone achieved MDA or not. So if patients lost 5 to 10% of their body weight compared to those that didn't lose weight, regardless of what diet, they were 3.6 times more likely to achieve MDA. And if they lost 10% or more of their body weight, they were much more likely than those who didn't lose weight to achieve MDA, and that odds ratio was 6.67, so pretty phenomenal impact of weight loss.

But achieving a 10% body weight loss is really difficult. The next trial was Rosenberg et al in Scandinavia, and they didn't do a randomized study. They did a single arm trial in which they gave all the patients a very low calorie diet. So basically people drank shakes for, I think it was 12 weeks, and then there was a ramp off period after that. Maybe it's 4 months. But in any case, many of the patients lost weight, and of course they did better. So the results were quite similar to what was seen in Di Minno. And many of them actually maintained their weight at 12 months. They did have still a lower calorie diet that they followed.

We recently connected a dietary intervention, and that study was called DIPSA. We randomized patients who were a stable on therapy, so a slightly different patient population. So we wanted to know for those patients who were stable on therapy, not quite ready to switch, but not quite doing well enough to feel good, we randomized them to 1 of 3 diets. The first one was a DASH diet, which is the American Heart Association diet. There's lots of resources online. It's a pretty easy one to follow. The next one is the Mediterranean diet. So we used the PREDIMED diet that was published in the New England Journal several years ago. We supplemented with olive oil and nuts. And then the third diet was, this is what is healthy, go on your way after a single nutritionist visit. So then nutritionist helped all the patients in the study of 90 patients in total to what they're constructing their diet.

What we found is over 12 weeks, there wasn't that much difference in weight loss across the 3 different studies. In fact, the Mediterranean diet maybe even had a little less, but not statistically significant. However, the patients in the DASH diet did do slightly better as did the Mediterranean diet, but it wasn't that much different. But again, we saw that those who lost weight, regardless of which of the dietary arms they were on, did better. We then followed patients out to 24 weeks. We kind of removed the regular check-ins with the nutritionist in those 2 intervention arms, and we found that there was a slight bit of weight gain, but it was mostly stable after that, and the clinical outcomes were basically stable after that as well. So patients did better with a dietary intervention. Almost everybody improved that actually stayed on the diet or did the diet, and it didn't really matter which one you were on. DASH diet did slightly better, but not statistically significant. And that's important to remember because the other one is literally handing a patient a form that says, this is what is a healthy diet. So cutting back on sugars and making sure to eat a wide range of different foods, et cetera. So eating better helps. Weight loss still helps more though.