Marla Dubinsky, MD, and David Hudesman, MD, on Spondyloarthropathy in IBD

David Hudesman, MD, and Marla Dubinsky, MD, talk about the challenges of properly diagnosing and choosing therapeutics for patients with IBD who also present with spondyloarthropathies.

David Hudesman, MD, is codirector of the IBD Center at NYU Langone Health in New York City. Marla Dubinsky, MD, is codirector of the Feinstein IBD Center at the Icahn School of Medicine at Mt Sinai in New York City.

TRANSCRIPT:

Rebecca Mashaw:  Good afternoon everybody. Welcome to another Gastroenterology Learning Network podcast. I'm your moderator, Rebecca Mashaw. Today, we're delighted to have with us Dr. David Hudesman, who is the codirector of the IBD Center at NYU Langone Health, and Dr. Marla Dubinsky, who is the codirector of the Feinstein IBD Center at Mount Sinai and the Icahn School of Medicine.

They're going to be talking about spondyloarthropathy extraintestinal manifestations among patients with IBD. I will leave it to the experts now. Please, take it away, and thanks for joining us.

Dr. David Hudesman:  Thanks, Rebecca. Thanks for the introduction.

We're going to start with a case and then go back and forth, discussing spondyloarthropathies and IBD. Marla, this is a patient I saw in my office a couple of weeks ago, young, 29-year-old female. She came to me, a relatively new diagnosis of inflammatory bowel disease of moderate ulcerative colitis. It was left-sided ulcerative colitis, diagnosed about a year prior to presentation.

She was initially put on mesalamine. Her symptoms had progressed, and her referring provider had put her on vedolizumab. On initial presentation, she was having about 6 bowel movements a day, about 50% with blood and urgency. She also said she had these mild, nonspecific wrists pains and knee pains at that time.

When she's coming in to see me, her GI symptoms are very well-controlled. She doesn't have urgency, her rectal bleeding has completely resolved, and she's having a couple of soft bowel movements a day. However, her wrist and knee pains have become worse. She also is starting to talk about a back pain, which she said she's had on-and-off, but didn't discuss with her last physician. It's become more pronounced as well.

I just want to pause there and ask, when somebody like this comes to your office, they're on a biologic, you're hearing about this joint pain that was there in the past, not a very specific history, it's now progressing, what's the differential? What are the different types of things you're going to be thinking about?

Dr. Marla Dubinsky:  At the beginning, what it makes me remember is at the beginning, we were saying that vedolizumab may worsen extraintestinal manifestations. We were confused as to what this meant. It probably meant that they were always there, just maybe we were missing the biology of this, or not going outside the gut. What we realized is that there is a systemic inflammatory response that we may not get to. There are some extraintestinal manifestations that are independent of even GI disease activity control.

One of the ones that is classic for me is what I'm calling is entheseal-type of inflammation—meaning, it sort of resembles more like a psoriatic arthritis process, and not a rheumatoid arthritis process. It's not quite synovial, it's more where the tendon inserts into the joint, so sacroiliitis or you’re getting wrists, sometimes you get the digits, because the small joints tend to be more like this entheseal, than these big, swollen knee joints. There's often not even swelling. It's often more arthralgias than there is even true inflammation that you see on exam.

It just automatically makes me realize that we have probably the most underdiagnosed problem in IBD is inflammatory back pain. We're not assertively, aggressively searching for it in patients. We're like, "You're on a biologic, you'll be fine. Just go do some physio, and go exercise. Do some back bends and you should be fine."

I think we just don't understand the biology of this kind of inflammatory response. Do you agree?

Dr. Hudesman:  Yeah, no, I think that's a great point. I guess just a side question is, how you ask about these joint pains in your office, because when you say the back pain, I agree completely. I don't know how many times I've run through, "Do you have a joint pain, or skin rash?" and the patient's like, "No, no, no."

Then I'm almost done with the visit, and they start complaining about, telling me, "Oh yeah, my back," after I asked about joint pains a couple of times. I don't think we ask the right way, I don't think we approach it the right way. Is there any trick you use? Just repeat the question in different ways?

Dr. Dubinsky:  Yeah, it was funny, I was schooled on this because I was fortunate enough to be with a round table of very smart derms and rheums and ophthalmology experts. They're always telling us that “you never ask it. If you ask it, you don't know how to evaluate it, and you don't send them to rheums often enough.” I said, "Fair, I agree. You don't send them to GI often enough." We can battle this.

She said that inflammatory back pain will not get better the rest of the day. I was asking, how do I know it's not their backpack or their purse that they're carrying that's causing back pain. She was very clear that inflammatory back pain has a specific pattern. It tends to be there in the morning and may be worse in the morning, may get better over the day, but may not be improved with exercise, for example. She said, morning pain longer than 4 months should be considered inflammatory back pain.

These docs were teaching me about things that patients do not think they're joint pains, because a back pain is different than your knee and your wrist, just like your patient. Also, the hip pain stuff was very interesting too, because, "Oh, actually I realize I have some hip pain too, and it radiates from the mid-back down."

Hopefully, through our discussions today, people start thinking about what does back pain mean in the context of IBD. Just because you're on a biologic doesn't mean you're going to get better.

Dr. Hudesman:  Yeah, completely. When I see this, the differential...It could be a little difficult, trying to figure it out. Asking those important questions, as you just mentioned, is this inflammatory back pain, is this sacroiliitis, or spondyloarthropathy.

As you said, we used to think vedolizumab worsens joint pains. That's not the case. We know some of our medications, whether it's an anti-TNF, whether it's vedo, whether it's anything, can be joint pain. We know steroids, even on higher doses or when you're tapering it down, so I'm always thinking of the differentials — is this medication-induced, is this a spondyloarthropathy, and as you mentioned, does it go along with disease activity? Meaning, if we put them on anything from mesalamine to a biologic, and they get better, the symptoms should improve, or is it unrelated, where we need to treat that.

In a patient like this, who has this inflammatory back pain, how are you evaluating them? When are you deciding to refer them to a rheumatologist? Are you getting an MRI? How do you approach that?

Dr. Dubinsky:  Great point, also. Then I'm going to get into the biology discussion, because it does differ also. Even just doing a plain film, you could be able to see some inflammation in the vertebrae or lower lumbar or in the sacroiliac region. You may just plain old send them for a hip X-ray or a sacroiliac, a lower lumbar, X-ray.

Obviously, then an MRI would be the best way to see, is there marrow edema, because you can see some swelling. That's interesting about entheseal as well, as you may see it look different than your classic synovial inflammation, and sacroiliitis in particular.

I also was missing my point, because I used to say, "Oh, I'll add sulfasalazine for people with sacroiliitis who aren't quite responding, or add methotrexate.” I thought I knew what I was doing. They were like, "No, sulfasalazine and metho aren't really the best for sacroiliitis." I'm like, "Oh God, I'm clearly not meant to be a rheumatologist." But I'm a quick learner.

Then we started talking about targets, because we have had also, Dave, folks who don't even get better with anti-TNFs. Sometimes they do need a IL-23 targeted, which is this entheseal stuff or IL-17 even more, because I've had patients with horrible spondylos ank-spond who didn't respond to TNF, IL-23, JAK. Now they have IBD and they're on an IL-17. Someone could tell me that I'm wrong, whatever. I like multiple-dosing these patients with lots of different ways.

I'm starting to understand that not every joint, just like not every Crohn's or UC patient, is the same. The biologic process behind some of these various rheumatic manifestations or extraintestinal manifestations that involve the joints, are very unique.

Remember, ustekinumab failed in the RA studies, knowing that RA is very different. It's not an IL-17, it's not an IL-23, it's almost more an IL-6 process, and TNF, which is common denominator to everything inflammation, but I'm starting to understand.

There was this cool paper that was just published in the New England Journal by Marcus Neurath and his team, who continuously educate us. It's called, basically, cytokine hubs. It allows you to start to understand that there are immune hubs, and which diseases overlap with different immune hubs. Really cool and exciting for nerds like myself who love to think about, why don't people respond to certain therapies.

For us to understand that not all arthritis is synovial, that was clear from what we were saying. These more common arthridities in patients are not synovial. They're more classic, like a psoriatic arthritis type entheseal. That's why IL-23 is very closely linked between IBD and psoriatic and ank-spond more than what happens in RA.

This is an evolving, cool space for us to think about understanding that, maybe your traditional thoughts on “anti-TNF works for everything,” or, "All arthropathies are directly related. Just get the gut going and then send them to the physio," we're learning a whole lot more, that we need to understand the differences in these arthralgias and arthropathies, and that our traditional approach, even with our biologics, may not always be the answer.

Dr. Hudesman:  Those are some great points. I agree completely.

Then, just to echo some of the things you said, first is appropriate diagnosis, especially for the axial spondyloarthropathy, sacroiliitis. That's when you need to get rheumatology onboard. Versus, let's say, it's a reactive arthritis, you put them on a medication, their joints get better. You don't need to rush them into that.

We published this past year in the IBD Journal, looking for Crohn's patients, which we were doing MR enterographies, can we use that to look at the SI joint?

The gold standard is doing an MRI of the SI joint and L spine. It was interesting, in our study, it was retrospective, about 250 patients, but we saw that just under 18% of our patients did have evidence of sacroiliitis, just on an MR enterography.

Sometimes you order an L spine, you have to deal with insurance. You're not used to doing that, but just talking to your radiologist and asking them to look at that, you could pick that up. About half of them were complaining of inflammatory back pain, but the other half weren't. If we just took a little closer look on some of these routine tests we're already doing, we might be able to pick it up.

Then I agree completely on the management strategies here, is an axial different from peripheral. Then even within axial, there's different approaches. It just shows, particularly in this case, that maybe if you investigated a little bit upfront, you would say, "OK, maybe an anti-integrin or vedolizumab wouldn’t be the first medications since there are these joint manifestations."

Dr. Dubinsky:  Yeah, definitely. I love that paper that you wrote, because we find things and we have to want to be proactive with all our IBD patients. We're all starting to try and figure out, "How do I choose which therapy first?” Well, here's another way to segment patients. If you have an extraintestinal manifestation that does not parallel “just get your mucosa healed,” you need to think clearly about what your first therapy is going to be.

Your paper helps people know that, "Oh, shoot! One, I should make sure that my radiologist read it correctly and I can rule out that almost 1 in 5 patients may have inflammation, and half are going to be asymptomatic. I should know that before I decide which biologic strategy I'm going to go with." I think your paper was so critical on that. Now we're understanding that we have different targets now that we can maybe use, and use these findings on MR, even when asymptomatic, to make the decision as to what treatment they should use.

Dr. Hudesman:  That's great. I guess, maybe just get your thoughts on, we take away the back pain in this patient, but the peripheral symptom...How do you approach them? What medications do you like to use in those situations?

Dr. Dubinsky:  I approach it similarly. I explain to patients...they'll say, "But I have no swelling," or I say, "Listen, let's talk to a rheumatologist, let's have you seen by one of our rheumatologists. Let's make sure that we're all calling it the same thing, that I understand that we're dealing with a more IBD-related reactive, maybe, arthritis. Maybe, that's possible too.”

We have that, that if we do treat the IBD, the joints should get better. I just want to make sure that I'm not missing something, because I'll even tell you, even patients where I would use infliximab, the rheumatologist may have said, adalimumab will do better if it's psoriatic arthritis, the Humira approach for sure, as well as obviously ustekinumab, potentially.

One thing they do tell us is that ustekinumab, while it may melt the skin away, it's not as good for the arthritis. Even understanding that, which is why I say, let's refer it to the professionals. I think our lesson is, engage them early, regardless of if there's joint inflammation or not visible. These patients have real maybe at that entheseal, around the joint, rather than your classic. We need to think differently about how we classify arthritis and IBD, and engage early the rheumatologists, so you don't get progressive joint damage, especially around the hips.

In my pregnancy clinic, patients who've had longstanding sacroiliitis that was not correctly treated, that we even talk about the risk of pushing too long when you have a vaginal delivery. If you've had longstanding inflammation in your sacroilial and hip region, you don't think about it, but pushing too hard and too long could be a problem. We have to talk to them about maybe C-sections.

There's a lot of implications even in other aspects of IBD management, by us not managing correctly these inflammatory back conditions, for sure.

Dr. Hudesman:  Those are all great points. I want to thank everybody for listening. Thank you, Marla, for doing this. This was great. Hope to speak with you soon.

Dr. Dubinsky:  Yeah, thank you so much.