Obesity QD Clinics Part Two Save

Hello, everyone. I'm Richard Connolly from Dublin, Ireland, and this is QD Clinics for this obesity campaign on RheumNow. So, I'm here to talk to you today about two patients of mine, kind of on the same topic. These were both ladies in their 30s. So, we all know that the big new hot topic in obesity is the weight loss that can be achieved with GLP-one analogues, which are without a bit of GIP thrown in there for good measure.

And these have revolutionized the obesity area. And more recently, we are seeing potential and real, I think, benefits within rheumatology from these agents, both through the weight loss itself, but also seemingly through this effect of GLP-one itself on inflammatory and immune activity within various types of arthritis. But we're gonna forget about all of that for now, and we're gonna go back to the past and talk about the older treatment for obesity, which was bariatric surgery. So this is what both my patients ended up having. So the first of these was a lady, as I said, in her 30s with seropositive rheumatoid arthritis, and she had awful rheumatoid arthritis.

So her disease activity was high. She had lots of synovitis, inflammatory markers were high. But what made her particularly difficult is that she probably had the most refractory case of rheumatoid arthritis I've come across, or certainly one of the most refractory. And I gave her all of our standard usual treatments, all of our unusual treatments for rheumatoid arthritis. What was remarkable is that none of these agents did anything.

They didn't shift her disease activity one single point. She came in every time exactly the same, except that she was often having some side effect from the medication. Nothing terrible, just infections and little bits and pieces. But she definitely felt worse on the medicines than off the medicines. So eventually we had a chat about it and we said, Look, nothing is working here.

I'm making you worse rather than helping at all. Maybe let's just stop doing things for now and we'll see what happens. So she came back to me then. I was seeing her kind of annually just to keep an eye on things. She came back between, I hadn't seen her in a year and she was completely different.

She had lost a shed load of weight. So she'd gone from a BMI of about forty down to a BMI of about twenty five. She told me that what had happened, she'd had bariatric surgery in the interim. But what she was really, really excited to tell me was that her joints are great. And I examined her, there was nothing there.

There was no sign of it is anymore. Checked her inflammatory markers, her CRP was zero. It was something truly remarkable, something that still surprises me. But it seemed for this lady that bariatric surgery, the weight loss had cured her rheumatoid or put it into drug free remission, at least for now. We're now a couple of years out from this and things haven't changed, hasn't gotten any worse.

It's still doing just as well and hasn't needed or warranted any disease modifying therapy. So this is a fantastic success story and something that I said still surprises me, but it was truly remarkable. And then a couple of years after this lady, I had another woman also in her thirties who came into me. This lady had psoriatic arthritis and she was overweight. She wasn't as overweight as the previous lady.

Her BMI was probably low 30s at most. And since she has psoriatic arthritis, we tried a couple of conventional synthetic DMARDs without Well, they did work, but there were side effects that meant we couldn't stay on them. We eventually ended up on biologics. I think on her second biologic, she had a good response went into remission and was doing well. And again, patient's doing well, seeing her every six months, every year, relatively infrequently.

And she also went off and had bariatric surgery. And she came back to me after bariatric surgery. She had lost significant weight again. Her BMI was down through probably low 20s following this. She was very happy with life.

She said she was still on her biologic. She said her joints felt the best they ever had since starting this process. And she asked me, he's like, Can we stop the biologic and see what happens? And as I usually do when somebody asks me this, I kind of went, Yeah, we can, but I mean, the studies all show that eventually you're gonna flare and you're gonna have to go back on the biologic and like, is it worth it? But she was very determined.

She didn't want to try reducing the dose. She said, No, let's just stop it and see what happens. If I need to go back on it, we'll go back on it and we can work from there. So we stopped her biologic and we are now three years down the road. Nothing has happened.

I saw her again recently. No disease activity, no psoriasis, no arthritis, doing fantastically well. Again, it seems purely from bariatric surgery. So I think there's important lessons here that, one, we shouldn't throw bariatric surgery away just because we have these new medicines. It is still a potential option for patients.

The responses to this profound weight loss seen with bariatric surgery maybe do give us some further support for what we can envisage GLP-one analogs achieving in our diseases and the potential benefits of those. So I'm Richard Conway. This has been QD Clinics. Check out RheumNow for all these sessions over this ObesityWonth.

David Lu here for RheumNow. This is my QD clinic about what to talk about in terms of muscle mass and fat mass with GLP-one receptor agonists. So I think this must happen to everyone who listens. You get approached by one of your patients, and this seems to happen to me on a day to day basis. Patient wants to take GLP-one receptor agonist.

Doctor, is there anything I should be worried about or anything? Is that okay if I go ahead? Firstly, thank you for asking me. But what am I thinking about in terms of giving proactive advice? And so naturally, I think about the patients that now you think about maybe three or four years ago started a GLP-one receptor agonist and then lost weight and then stopped it a lot of the time and then put weight back on, how their journey has gone and maybe what we could have done better or worse.

I think about the patients who have gone through that process and have managed to lose substantive amounts of weight. Any time you lose substantive amounts of weight, you risk not just losing fat, but you lose muscle as well. Maybe not quite as much as fat, but you certainly lose muscle. That's something that's been borne out in the GLP-one receptor agonist registration studies. We've seen that especially in semaglutide studies and tirzepatide studies.

It's not to say that there's not more fat loss than muscle loss, but you can't inherently miss out on losing muscle mass in that process. The problem is in that point where you stop the medicine and if you put mass back on, which we know happens in the context of stopping that's been well proven, that actually we see that you've put on disproportionately more fat than muscle, especially early on. Now, this is not something that you see in lifestyle based weight loss. It's more progressive and you're able to seem to be able to maintain muscle mass more. And the reason why I talk about this is because it's fundamentally important to a lot of the biomechanical issues that we deal with with our patients in clinic.

If it's going to drive joint pain and joint function, musculoskeletal pain and musculoskeletal function, then we've really got to try and address this proactively. So what can we do about this? Well, basically, trying to think about what we can do proactively to give that advice about muscle mass retention is what I wish I'd given my patients four years ago. We obviously know more now, but isometric strengthening with appropriate amounts of protein intake I think are really the key. And there's reasonably good evidence for isometric strengthening in the context of retaining muscle mass.

We know how important that is in our patients in general, but, in this situation where you're about to really test the body in terms of how it goes with retaining that muscle, it seems all the more important to be proactive about this. Now, I think there are lots of ways about going through this and physical therapy can be really useful and that kind of upfront education. But of course, there are some really good websites as well. I just want to make a plug for two Australian websites mykneeexercise.org. Myhipexercise.org.au, which are free websites with actual plans that are associated with it, exercise plans to really go about and grade eight up, in that case, knee and hip muscle strength.

We know that AAOS, the Orthopaedic Surgeons and the Arthritis Foundation, also have some really good resources online about how to maintain some of this muscle strength. And we don't need to go overboard with the protein either, but we certainly need to have enough to be able to fuel that muscle maintenance. Sometimes there's a bit of talk about ketogenic diets and whether they're superior in this context, and the data for that is actually limited. There's a little bit of poorer quality evidence about it, but really I think getting too far into the unsustainable details is probably not what we're looking to do for our patients. What we're looking to do is give some really solid, achievable advice.

That is when you start the GLP-one receptor agonist not later, but when you start make sure that you maintain a little bit of protein intake, but most importantly, do those isometric strengthening exercises. For plenty more on this obesity campaign and all the fantastic content, you know where to go. Rheumnow.com.

Welcome to ObesityQD clinic. I'm Derek Mueller, PA from St. Clair Shores, Michigan, And today's case is titled of mice and men. A 37 year old female with a history of obesity, depression, and papillary thyroid cancer status post total thyroidectomy with a BMI of thirty five. She was referred to our clinic about three years ago for possible inflammatory arthritis on the basis of recurrent plantar fasciitis, and marginal elevations of, ESR and CRP.

When we first examined this patient a few years back, she had no obvious objective signs of inflammatory arthritis, dactylitis, enthesitis, no axial disease, h l b HLA b twenty seven negative, no personal or family history of plaque psoriasis, IBD, or uveitis. And essentially, she's been managed, symptomatically with celecoxib. However, over the years, any attempt to withdraw or reduce the therapy results in quite significant worsening of her plantar fasciitis. Her orthopedist has managed her with local injections. Unfortunately, the response is fleeting, and, their plantar fascia and corticosteroid injections aren't the most pleasant.

So she really asks at her most recent visit short of surgery, is there anything else that can be done? So this opened the floor for a conversation about things we can do to manage her weight which may have a mechanical impact on her plantar fasciitis. So I pose the question, has anyone, today ever talked to you about GLP-one agonist drugs? She says, can't take those. And I say, why?

What do you mean? And she said, because of her history of thyroid cancer. So is indeed a hard stop in the history of, treated thyroid cancer? Every GLP-one agonist therapy in The United States, semaglutide, loraglutide, tirzepatide, they all carry a box warning for, thyroid tumors. We'll come back to that.

So the clinical question, if your patient has a history of thyroid cancer, can you still prescribe or can someone still be prescribed a GLP-one agonist? And really the whole answer to this question hinges upon what type of thyroid cancer. So we're gonna get into that here next. So first of all, what is even, what's this association with thyroid malignancy and GLP-one agonists? So this really seems to be a story of rodents, rats and mice.

So rats and mice, their thyroid gland c cells or parafollicular cells are chock full of, GLP one receptors. And just, going back to some basic physiology, these are the calcitonin secreting cells around the gland. So it does seem that in rodents that GLP1 agonist therapy binds to the C cells or parafollicular cells of these rodent thyroid glands. And that seems to enhance the risk of medullary carcinoma in rodents. And that does seem to be duration and dose dependent, in those animals.

And this is really a a receptor purely a receptor mediated phenomenon. Rats, GLP-one receptor knockout mice do not, get medullary carcinoma when exposed to GLP one agonist. And this also happens without interference of the of the RET oncogene that drives human medullary cancer or multi endocrine neoplasia. Okay? So it's a rodent story.

Humans and monkeys rarely have very little GLP-one receptors on their C cells and their thyroid glands. Even monkeys exposed to GLP-one agonist therapy at 60 times. The human exposure for over twenty months did not, in a study did not, show any C cell hyperplasia or medullary carcinoma. So it's species specific. It seems to be an issue at super therapeutic dose signals, and there's really no human or primate relevance that we know of.

So what are the actual restrictions that are on the The US label? So an FDA contraindication to any, commercially available GLP one agonist therapy only contraindicates therapy in two groups. And that's people who have a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type two, MEN two. And again, the logic is that medullary cancer is driven by C cell pathology. Theoretically, you know, we're extrapolating that warning from rodents.

And that's really the whole list. So what's not on the list is the most common types of thyroid malignancies that you may encounter in your patients. So that's papillary thyroid cancer and follicular or differentiated thyroid cancer. So these are different cell lineages, totally different biology. We're not really seeing that as a risk.

So there's no convincing evidence that outside of medullary thyroid cancers, the risk does not exist. Some pharmacovigilant data has suggested a very faint signal for non MTC, perhaps within the first year of GLP-one agonist prescription. But my thought is it might be a selection bias. If you're prescribing GLP-1s to patients and you're asking about thyroid history and you hear about the nodule or a vague family history, that's when people are gonna get scans, they're gonna get tests, and you might pick up on those non MTC cancers. So really the big key takeaways of this and also some extra nuggets.

The actual contraindication for GLP-one agonist therapy is quite narrow. That's people with a confirmed or family history of medullary thyroid cancer or MEN2, multiple endocrine neoplasia. So always ask about personal or family history, and if need be, getting records from endocrine or surgery about a patient's thyroid malignancy history. So papillary and follicular thyroid cancer is not a contraindication. Also, there's no recommendation for routine screening with thyroid ultrasounds or calcitonin screening that's not anywhere in the label that's not indicated.

And then also something to be aware of in patients who have a history of papillary thyroid cancer, or cancer where essentially they've undergone total thyroidectomy, those patients are going to be on some dose of thyroid supplementation or levothyroxine. And if a patient is starting GLP one therapy, that's gonna delay gastric emptying, can shift the absorption of a patient's thyroid replacement therapy. So really important to just be aware of that, that it may be relevant that the patient may need some adjustment of their levothyroxine dose or the logistics of their dosing if you were to prescribe a GLP agonist to a patient such as that. So in this instance, we went through the in our patient, we went through the data, we went through the fact that there was not a legitimate contraindication based on her history of papillary thyroid cancer. So a GLP-one agonist was offered, but she still deferred to double check with her endocrinologist.

So I await our next meeting to flush this out sooner, and hopefully we can help her out with her pain that may very well be driven by biomechanics and obesity. So that's it. Thanks for listening, and keep in touch with RheumNow and all this exciting content on RheumNow's obesity month. Thank you.

Hello, everyone. This is Bella Mehta. I'm a rheumatologist in New York, and I will discuss a case of a patient with knee osteoarthritis. We, as rheumatologists, see these patients almost all the time, and I will talk about this particular patient who was this man in his late forties who presented with progressive worsening bilateral knee pain. You know, his BMI was thirty four.

He also had developed type two diabetes. And over the past several years, I think things got just worse with his pain. In the knees, it was around six on 10, goes up to eight on 10, and it substantially limited his quality of life. He avoided recreational activities with his family, could no longer exercise regularly, and reported sort of problems with stairs, going downstairs and walking extended distances. So, you know, the when when I first saw him, the X rays, you know, demonstrated a KL grade three bilaterally with definite joint space narrowing medially and some osteophytes.

So, again, typically, what we see in these OA patients, he'd already attempted many standard therapies. You know, he had NSAIDs. He had gone to physical therapy a number of times and received corticosteroid injections. Injections. Now these injections did seem to help, and mainly all of these interventions did provide temporary relief, did go from, like, six on 10 to four on 10, maybe two on 10 sometimes the pain, but it was still something that would worry him.

Again, the KL score was grade three, and he would ask me. He's like, oh, it's just grade three and not grade four. So and I'm also too young for eventual joint replacement. But I always would talk to him, and this is another point that I make to all my patients saying KL grades in knee osteoarthritis may not correspond to the amount of pain the patient has because pain is so multifactorial, and the joint damage may not completely contribute to the pain joint damage on an X-ray. So, you know, we've been trying we were trying to manage this patient with conservative treatment because he did not want the joint replacement, which made sense.

And at a routine visit with his endocrinologist, he was started on semaglutide to improve glycemic control. Again, I think they tried to get some of the other GLP ones, but then insurance approved the semaglutide. So over the following year, he experienced substantial weight loss and improved metabolic health. So he had around his BMI went from, like, say, thirty four to, like, twenty eight, and his knee pain dramatically improved. What surprised him was not just simply changing his weight, but overall the kind of energy that he had.

He reported walking longer distances, you know, returning back to exercise, participating in activities that he previously avoided, and his pain declined to, like, around one on 10. And he'd never he then did not need as much NSAIDs. Maybe he would still take it occasionally, but we particularly stopped giving him the corticosteroid injections because he was doing fine. Again, I I think that, you know, this sort of tells us that even with that KL grade three, once his, you know, weight was reduced, it did help his pain component for his knee OA. And, you know, primarily, we thought obesity contributed to knee OA through excess mechanical loading across the joint, across the knee, which is like, you know, for every one kg increase in weight, I was taught, like, your knees have to sort of take in four kgs to sort of compensate.

So, certainly, biomechanics matter, but that explanation is incomplete. And especially she's seeing these dramatic effects, we know more. Again, we now recognize that obesity is associated with metabolic inflammation and changes throughout the entire joint. And, you know, fat cells produce inflammatory mediators which can influence, you know, overall the whole joint outcomes, pain sensitization, bone remodeling, all of these things that affect quality of life. This explains why opacity is associated not only with knee OA but also with OA in joints that are not particularly exposed to substantial mechanical loading.

For example, hand OA. There are some early studies showing that, you know, patients who've substantially lost weight, their hand away symptoms have also gotten better. So obesity is not simply making the knee work harder, but also changing the biological milieu within the joint itself. So and the other thing sort of that I take away from this is that, you know, as the patient lost more weight, it was not just the number on the scale, but that, you know, and number on the scale of the weight as well as in the on the pain, but also function, which is sometimes not talked about enough, I feel, in our field. So he returned to exercise, reduced his reduced his pain medications, and started doing activities that were getting increasingly difficult prior because of his away.

So this this his experience actually is like if you take a trial patient from the STEP nine trial, which is the original NEJM trial, which talks about how patients with knee OA improved after getting GLP ones, He's basically he's he's, like, one of the prototype within those curves on the STEP nine trials where it shows that patients who were on this improved pain significantly versus those who were on a placebo did did not. Again, you know, they they they found the delta or the clinically meaningful finding, which was pretty large in those patients who were on these drugs. Again, you know, there are recent imaging and mechanistic studies that have shown that improvement in, you know, inflammatory as well as structural features, including changes in the synovium and the cartilage, have been associated with the GLP one drugs, but, again, these are small studies in different models, mice models, whatnot. Again, there's some data you know, again, very few patients in these studies with MRI showing those changes. There's more to come, and, you know, we will see more and more data emerge out of this.

But I think that the idea that obesity treatment will have biological effects in a disease like OA, in addition to the mechanical ups, of course, are great. And, again, even with sort of disease like OA that we feel that there's less or not many demodes or, like, things that change trajectory, you know, treatment of obesity can change trajectory. And, you know, even though his radiographs did not normalize, obviously, because he had some damage, some osteophytes, but his his function and pain improved. His daily life changed. So, you know, the conversation of the patient's sort of health trajectory changes.

If if things you know, if there's a motivated patient, if things work right, and and the goal is not necessarily to reverse the osteoarthritis. It is just to help patients have less pain, move better, and and slow the progression of making of the joint damage being worse. So, you know, again, we think of obesity as a comorbidity, but I think we should start thinking about it as something that we can disease modify using this. And for many patients with knee osteoarthritis, obesity is more than a risk risk factor. And as our understanding of osteoarthritis evolves, we are moving away from this concept of osteoarthritis being a purely mechanical disease and more towards something that affects the whole joint and it's influenced by many factors weight, obesity is the big one, but metabolism, inflammation, body composition, all of that contribute and sort of treating the patient, thinking about all of this together might be something that would help improve outcomes.

So with that, this is Bella Mehta signing off, and please follow me more on Twitter at Bella underscore Mehta. Thank you.