Matthew Baker, MD, on the Association of Osteoarthritis With Atopic Dermatitis
Dr Baker discusses research indicating that patients with asthma or atopic dermatitis have a significantly higher risk of developing osteoarthritis over 10 years of follow-up.
Matthew Baker, MD, is the clinical chief in the Division of Immunology and Rheumatology at Stanford University and the codirector of the Stanford Multidisciplinary Sarcoidosis Program in Palo Alto, California.
TRANSCRIPT:
Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your host, Rebecca Mashaw, and I'm happy to welcome back Dr. Matthew Baker, Clinical Chief in the Division of Immunology and Rheumatology at Stanford University in Palo Alto, California. He's going to review the findings of a recent study that he and colleagues conducted into the association of osteoarthritis with atopic dermatitis. Thanks for joining us today, Dr. Baker.
Dr. Matthew Baker:
Thanks for having me. It's a pleasure to be here.
Rebecca Mashaw:
What interested you in studying the incidences of osteoarthritis among patients with atopic disease?
Dr. Matthew Baker:
I think just in general, we're very interested in studying osteoarthritis, because it's such a common problem. It can be quite disabling for patients, and there are few effective treatments. Really, treatments have been focused on alleviating pain and preventing progression to joint replacement, but there are no disease-modifying drugs that can actually prevent or stop the progression of osteoarthritis. So we're very interested in studying osteoarthritis in general. And specifically, we looked at patients at this concept of whether allergic disease or atopic disease may play a role based on evidence that comes out of the lab of Dr. Bill Robinson here at Stanford.
And in his work, we've shown that there's an increase in a particular type of cell that's associated with allergic diseases called mast cells. And that when you look, if you take tissue out of a joint of a patient with osteoarthritis and look at the synovium or joint lining, you see actively degranulating mast cells and it's differential compared to, for instance, rheumatoid arthritis where you really don't see this degree of mast cell.
And further studies in the lab have shown that if you actually take mice and you knock out just selectively the mast cells and then introduce a model of osteoarthritis where you destabilize the medial meniscus, that the mast cell knockout mice actually have attenuation of developing the osteoarthritis. So we've seen this evidence in animals and in the Petri dish essentially with human data, but we wanted to extend that with epidemiologic data to see if there's a signal in large populations of humans.
Rebecca Mashaw:
That's really interesting. Would you give us a brief overview of the study?
Dr. Matthew Baker:
This was a retrospective cohort study. We used claims data, so this is insurance claims data from Optum, which is a large provider that encompasses over, I think, 80 million insured lives or something to that degree. And then also, we also recapitulated the study in electronic health data from our institution here at Stanford where we had a little more granular data including things like body mass index. And so we analyzed patient data from roughly 2010 to 2020. And the idea was to create cohorts of patients who did not have existing osteoarthritis or atopic disease and then follow them, create a cohort of patients who go on to develop atopic disease, either asthma or atopic dermatitis or both, and then have a comparator cohort of patients who never go on to develop an atopic disease. And then compare, do some methods such as propensity score matching to make the two groups as similar as we can across a number of variables, and then to look at our outcome, which is the development of osteoarthritis.
And so again, the primary analysis was done in insurance data. So we're really defining these things using things like ICD codes, which have inherent limitations, but there are standardized ways to try to identify things like osteoarthritis. We identified patients with 2 or more ICD codes for osteoarthritis separated by 7 days or more. And we could also tease apart the subtypes of osteoarthritis, whether it was affecting the knees, hips, hands. And so we just followed these patients as long as we could. Up to 10 years was sort of the mean duration of follow-up to see who developed osteoarthritis.
Rebecca Mashaw:
And what did you find?
Dr. Matthew Baker:
We found that if a patient had asthma or eczema, there was a 58% increased risk of developing osteoarthritis over that period of about 10 years of follow-up. And then if they had both asthma and eczema or atopic dermatitis, the risk increased to an odds of 115% of developing OA. So it was interesting to see that kind of additive effect if you have 1 versus 2.
And then we also did, as a nice sort of comparator, asthma is obviously a pulmonary disease, but asthma we think is driven by these allergic pathways, at least in a large subset of patients. And another pulmonary disease would be COPD, which is not really driven by that allergic pathway. So we did another comparison where we looked at COPD versus asthma, and we found that the asthma patients had an 83% increased risk of developing OA compared with COPD, sort of further supporting this concept that it's really the allergic pathway that may play a role.
And then, as I mentioned, our claims data did not include things like body mass index, which we know is a major risk factor for developing osteoarthritis. And so we wanted to validate our results in both an independent dataset, but also a dataset that provided this extra layer of data. And we found very similar results in that EHR data, again, showing an increased risk of OA for patients with atopic disease.
Rebecca Mashaw:
When you describe patients as exposed or nonexposed to atopic disease, what exactly does that mean?
Dr. Matthew Baker:
It basically just means, again, we initially selected patients that didn't have any known history of osteoarthritis because we wanted to see that as the outcome, but also no prior known history of atopic disease. And then as we followed patients in this massive cohort of millions of patients, some developed atopic disease, and then they suddenly then become the exposed because unlike a therapeutic study where the exposure is the drug, our exposure here is having a diagnosis of atopic disease. So those exposed patients had atopic disease and the nonexposed throughout the whole time we followed them, never had a diagnosis of an atopic disease.
Rebecca Mashaw:
You noted in your conclusion that future interventional studies may consider targeting allergic pathways for the prevention of OA. Can you tell us a little bit more about these allergic pathways and how they might be involved?
Dr. Matthew Baker:
Yeah. So we think, again, the fundamental cell type that at least our laboratory data supports and we hope that this adds support to, is that mast cells may be playing a role. So one idea would be something like a mast cell stabilizing drug. There are several older drugs that do that, things like cromolyn or ketotifen, and there are newer antimast cell drugs being developed. You could also block downstream mast cell mediators like histamine with antihistamines or upstream activators of mast cells such as IgE. There's drugs that do that that are used for allergic asthma, like Xolair.
So I think, really, fundamentally targeting the mast cells is where our hypothesis lies right now. It is also possible that some of these allergic cytokines like IL-4 and IL-13 could play a role. I think we have much less data there right now, but the nice thing is that if that was the case, there is already a therapy that blocks that pathway, dupilumab or Dupixent. And so we're very interested in replicating—or not replicating but doing additional observational work—looking at whether patients who have been treated with dupilumab may be protected against OA. The problem with that is that it hasn't been around long enough yet to have enough follow-up time to really do that study, but I think someday that would be a really interesting question to ask.
Rebecca Mashaw:
Sounds like you have a really rich field there for pathways to examine and also for additional medications and therapies for other conditions that may show some promise here.
Dr. Matthew Baker:
Yeah, I think that's the idea that there have been many attempts to develop a new therapy for osteoarthritis, both pain and disease modification. As I mentioned, particularly disease modification has unfortunately been completely negative to date. And so I think many people in the field do have this idea of could you potentially repurpose a drug that's already in existence? It would be a much lower bar to do that, especially if you could find something that was safe and obviously effective. And so, we're interested in looking at these pathways and others involving drugs that are already on the market for other indications.
Rebecca Mashaw:
Most patients who have asthma or atopic dermatitis are likely to be being treated by a pulmonologist or a dermatologist, not a rheumatologist necessarily. It seems to make this an ideal case for the need for multidisciplinary care and interaction.
Dr. Matthew Baker:
Definitely, I think most of us are big fans of multidisciplinary care, and it's great to have lots of specialists involved. In this case, I don't think we're there yet. This paper was not meant to suggest we change practice in any way. It's really more hypothesis-generating. I think we need follow-on studies that test the hypothesis and hopefully confirm it. And then the idea is really to say this is a hopefully worthwhile endeavor and to actually do interventional studies, prospective studies to find a treatment that can help patients.
Rebecca Mashaw:
It seems that a lot of people accept generally that OA is just a natural part of aging. Is that really the case?
Dr. Matthew Baker:
Yeah, we think it used to be thought of that OA was really just a degenerative wear and tear disease that most people would develop over time. We certainly know people who have been particularly active or activities that are traumatic to the joints are likely to get it sooner. But more recently in the last decade or two, we have, I think, a more nuanced understanding that there really is this chronic, low-grade inflammation in the joint. It's more than just degeneration over time.
And so some people will develop it earlier and some may never develop it. And I don't think we fully understand why that is. But we do know certain risk factors are at play. Female sex, obesity, some cardiometabolic factors all play a role. And then, as I mentioned, trauma, different sports activities and jobs and just the anatomy of some people predisposes. And so I think yes, in a sense that most people at this point will get it as they age. It's incredibly common. There's, I think, over 50 million people in the US with it right now. But I don't know that it's necessarily inevitable. And I think we all hope that we will have a way to prevent it in the future.
Rebecca Mashaw:
Well, thank you very much for spending the time with us today to talk about this. It's very interesting. And we'll be looking for follow-ups. Thank you.
Dr. Matthew Baker:
Great. Thanks for having me.
