Joshua Baker, MD, on Obesity and Response to Advanced Therapies in Rheumatoid Arthritis

In this podcast, Dr Baker talks about his recent research into whether obesity affects response to different types of medications for the treatment of rheumatoid arthritis.

Joshua Baker, MD, is a rheumatologist and an associate professor at the University of Pennsylvania School of Medicine.

Watch Dr Baker's video on intramuscular fat in RA here.

TRANSCRIPT:

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Mashaw. I'm very pleased to introduce my guest, Dr. Joshua Baker, who's an associate professor of rheumatology and epidemiology from the University of Pennsylvania.

He's going to discuss a recent study he conducted with colleagues on the effect of obesity on response to advanced therapies in rheumatoid arthritis.

Thank you for spending some time with us today, Dr. Baker.

Dr Baker:  It's my pleasure. Thanks for having me.

Rheumatology and Arthritis Learning Network:  To start us off, would you explain the outlines of this study that you did on tumor necrosis factor inhibitors versus non-TNF biologics among patients with RA, and how body mass index, or BMI, may affect response?

Dr Baker:  Sure. There are a number of studies prior to ours looking at the association between obesity and response to therapy in rheumatoid arthritis. Many showing that patients who are obese have a lower response, so we'd expect a lower response among obese patients.

The reasons why that is are fairly complicated and maybe not worth going into here. It is important to note that that is something that's been observed. It's also been proposed that the issue might be particularly important for TNF inhibitors due to the way they work. A number of studies have shown an effect among patients on TNF inhibitors, but not as much in other studies looking at other drugs.

The thing that's been missing is a true head-to-head study where someone's looked at TNF inhibitors and non-TNF inhibitors among obese patients to see if there's a difference in response when you compare them directly.

That was what we set out to do, both to characterize the association between obesity and response to therapy, but also to look at a direct comparison between two different classes of drugs within obese patients.

RALN:  What other types of drugs did you take a look at, other than the TNF inhibitors?

Dr Baker:  We looked at TNF inhibitors as their own class, because there's so much interest in that class. It's hard to look at every single class of therapy because the numbers get small.

What we looked at is we combined non-TNF advanced therapies into a category and called that non-TNF biologics, which is commonly done. We were not able to look at or we did not look at many of the individual therapies that make up that group.

RALN:  You mentioned that other studies have been done about the impact of obesity on treatment for RA. What particularly interested you in this topic of research? You mentioned there had not been a head-to-head. Was that the key motivator here, was to get that head-to-head comparison?

Dr Baker:  Yeah. What I observed in the literature was that we see this association between obesity and response to therapy. Some studies show it, some studies don't. Overall, there's a lot of differences in the results of different studies based on simply what population is being studied or how the study was done.

It's really difficult to know whether differences that we're observing between therapies is really due to the therapies themselves versus differences in study designs between different studies. I've really been, for a long time, been interested in doing a direct comparison within one population to really try and get at that question. That's what spurred this specific project.

RALN:  Can you tell us a little bit more about CorEvitas, the source of the data that you used in the study?

Dr Baker:  Sure. CorEvitas is a very large and powerful registry study, which was designed to really perform post-marketing studies, and to be able to evaluate the effect of therapies really in the real world. After they come to market, what's their real-world effectiveness and real-world safety?

This is an ideal setting to do this study because it's set up to really look at effectiveness in the real world. We were able to take advantage of this powerful registry to look at and use some of the outcomes that they've collected to do a real-world study, looking at the question.

RALN:  Let's get to the essentials. What did you find out in this study about the impact of obesity on the response to therapy in RA?

Dr Baker:  We did find that obese patients were somewhat less likely to respond overall. We looked at the whole population. It seems to be a BMI of 27 had the best response.

When your BMI goes above that or below that, your response starts to get lower. People who are more obese certainly had modestly lower response rates overall in the study. We also saw that underweight patients also had lower response rates.

The real interesting part of the study, though, was that there was really no difference whatsoever between TNF inhibitors and non-TNF inhibitors. The effect of obesity essentially was the same. That lower response rate that you see with obese patients was the same regardless of the therapy used.

Another way of looking at that might be to say that among obese patients, there was no difference in the TNF inhibitors versus non-TNF inhibitors, really suggesting that the effect of obesity doesn't appear to be specific to one therapy versus another. It's something that we're seeing for all.

RALN:  Am I correct in thinking that a BMI of 27 is slightly overweight?

Dr Baker:  Yeah. This is a question that comes up all the time. Many times with obesity research, we see what we call a U-shaped curve where it's worse to be obese, but once you get down to a lower weight, it starts to also look bad. That's true in RA frequently.

The likelihood is that it's not that the ideal weight is 27 or the ideal BMI is 27. The likelihood is that there are a number of people that were heavier and lost weight due to a medical illness or more severe rheumatoid arthritis.

It's an epidemiologic bias of how we do research that there are many people that are quite sick that are thin, but it's not the being thin that's bad. It's the way that you got there that's bad. That's true. The finding that the ideal weight is 27 is certainly inflated and probably not a biologically true number. It's really just an effect of this weight loss in more significantly ill people.

ALN:  That was one of the more interesting things that I noticed in your article was that the patients who were underweight were also showing a lower response rate. It may be that patients on either side of that mid-range, for various reasons, are already responding at a lower rate to these therapies, and that's what you're seeing. Is that correct?

Dr Baker:  Yeah. We absolutely saw lower response rates in the underweight folks. That's consistent with some other studies. We've seen that for other ways of measuring response, like for how long you stay on your medication, when you start it, things like that. We also see higher mortality rates in thin people with RA.

It fits within the concept of thinner people are truly sicker and may have become thin because they've had more severe disease over time. By nature, their disease is simply refractory leading to both poor response, but also to being thin. It wasn't too surprising to see that underweight people had a lower response rate. It was somewhat surprising to see how strong that effect was.

In clinic, it may be a helpful way of identifying people that might have been adversely affected and might have a lower likelihood of responding once you start therapy.

RALN:  Is that thinness a measure of frailty?

Dr Baker:  We couldn't measure frailty in this particular study, but weight loss and being thin can be features of frailty. That's very likely to be part of this is that we have a number of frail people in that category. They're less likely to respond partly because of the frailty, but also all the things that led to frailty in the first place, so yes, absolutely.

RALN:  How could this information then be applied in a rheumatology practice? You touched on that just a moment ago.

Would you suggest that the practicing rheumatologist pay attention to patients who are obese and how losing weight may help them respond better? Also, on the other side, pay more attention to those underweight patients who may be a bit more frail?

Dr Baker:  You said it well. There's a couple of takeaways. One is, don't worry about weight when deciding between different therapies because it didn't matter. That's one thing is you shouldn't be worried about making a treatment decision, or at least which treatment to use, based on someone's weight.

Number 2 is can we intervene on the weight itself to improve outcomes? I believe that's the case. Question is how effective it is to get people to lose weight. That's its own challenge.

We certainly, as rheumatologists, should understand how bad obesity is for a lot of the outcomes we care about and try and intervene on that. As we get new therapies that may be more effective for weight loss, that we engage with those and we use them to help our patients.

The third part is just that, really, people that are thin, it does make sense to think about those patients a little bit harder. Make sure you're adequately managing them.

You may already know that they're still ill, but identifying that these thin folks are at higher risk of having poor response may be helpful in clinic to really try and know who you need to watch a little bit more closely and figure out why they're thin in the first place.

RALN:  Is this one of those good applications for multidisciplinary care and bringing in a dietitian to work with patients if the practice will allow that?

Dr Baker:  If we could do that more frequently, we would do a lot better by our patients. Other than expensive medical therapies, to also provide resources for nutritional support and weight loss would be tremendous for our patients. Part of that is simply just making those resources available to physicians and also patients. We have work to do in that realm. We need to do a better job of that.

RALN:  This has been really interesting. We'll look forward to seeing what else you find out about this subject as you go on. I know you've done a good bit of research on body composition and RA. Thank you for joining us today to give us the insights into your newest research.

Dr Baker:  It's my pleasure. Thanks so much for having me again.

Reference:
Baker JF, Reed G, Poudel DR, Harrold LR, Kremer JM. Obesity and response to advanced therapies in rheumatoid arthritis. Arthritis Care Res. Published online February 10, 2022. https://doi.org/10.1002/acr.24867