Osteoarthritis Risky Business (4.18.2025) Save

04/18/2025, and this is the RheumNow podcast featuring me, myself, and I, Jack Cush with RheumNow. We're back to normal, are we not, with the CDC. The CDC issued, actually had a meeting yesterday of its Committee on Immunization Practices, the ACIP Committee. It had been previously, canceled, with the induction of the new Health and Human Services secretary, but they were back in business yesterday, and it was business as usual. They made a few major recommendations.

One, that, the new meningococcal vaccine is different with some expanded strains and indications. They lowered the age to receive the RSV vaccination to those over age 50, it was previously those over age 60, so they added the fifty to fifty nine age group. And they also recommended that the chikungunya vaccine be approved for use in travelers going to high risk areas for chikungunya, the virus infection, temperate climates and whatnot. But they did that because in The United States there have been a few hundred people that have been infected, and mostly travelers, and chikungunya can be problematic, and can have long term articular consequences. There was discussion of, but a tabling of new recommendations regarding influenza and the COVID-nineteen vaccine, and those will be taken up in our the next meeting, which is going to be in June 2025.

There was discussion about limiting the Covid vaccination only to those at high risk, meaning the elderly, but that wasn't fully discussed. We'll see what happens with that in June. So it was business as usual at the CDC Vaccination Committee, ACIP. An interesting report about walking and the risk of developing osteoarthritis comes out of a large UK biobank study of almost ninety thousand people, in this group, who are followed for almost seven years, two thousand seven hundred developed, knee OA that they studied, and they found and they looked at the many things that they collect informationally in this prospective biobank, and one thing was how much average daily walking that they would do. And the takeaway here is that daily purposeful walking will lower your risk of developing knee OA, as opposed to sporadic walking, or people who are walking for other reasons.

But these are people walking for exercise. And on average it took either 5,000 or 7,000 or greater than 8,000 steps per day to lower your incident knee risk by, let's see here, sixteen percent, nineteen percent and twenty six percent. So a lower risk and those were all statistically significant. So eight thousand a day, or more had a twenty six percent lower risk of developing OA. Kind of good news, for those of you who like to walk and wonder if you're doing good things.

You're certainly doing good things for your heart and your lungs, but also for your joints. And you know there is this this data about whether walking or running will cause OA, and again you I think we've covered this in the past, but the bottom line is if you've got a structurally normal knee and your mechanics are normal, the risk of OA is basically no. However, if you've torn your meniscus or your cruciates, and you've got a lax knee, and you've got a genuverum, genuvalgum, and walking on that, there's no protection in general. There's there is an increased risk in those people. An interesting Danish study also looks at risk in OA patients.

In this study of a registry of one point eight million adults and included two hundred and ninety thousand who had either hip or knee OA, and they compared them to one point five million without knee OA that were age, sex and education match controls. And they showed that women had the greatest risk association of with osteoarthritis of the hip or knee, and that being a forty four percent higher risk of cardiovascular disease and cardiovascular events. Significantly higher, forty four percent hazard ratio 1.44. Interestingly, men not as higher risk, but still significant a twenty four percent increased risk. So, men and women who have hip or knee OA longitudinally have an increased risk of cardiovascular events, more so in women, almost twice the rate than men.

I like this report about systemic sclerosis and GI manifestations. We don't often talk about that, but I can tell you that many patients I've seen in the past who had significant GI disease, it can be the dominant form of disease as bad as lung, renal, cardiac, and obviously skin and mobility. But in this particular study, where they had one hundred and thirty two systemic sclerosis patients selected for GI symptoms, they found that over a third of them had these anti muscarinic three antibodies associated with smooth muscle function, I assume, and twenty five percent had high high titers of MR3 positive antibodies. And it turns out that if you had high titers, you had a doubling of the risk of having more diffuse disease. Also, patients with the MR3 antibodies of high titers had worse GI severity ninety one percent versus seventy percent, and more RNP C3 antibodies and U1 RNP antibodies 16 versus six, twenty one versus 2%.

The point is that antimuscarinic antibodies sort of encodes for those with a higher disease severity as far as the GI tract, and maybe more autoantibody associations. Not sure if that's commercially available, but it may be something we have to look to our, you know, systemic sclerosis mavens to see what's their recommendation on this going forward. I like the report in JAMA Network Open this past actually it was about two weeks ago I think, April 3 April 4, about a clinical trial of Kawasaki's patients, and they're all very young. And they all get treated with aspirin and half get treated with immunoglobulin or placebo. And it turns out that I'm sorry, they're all on IVIG.

I made a mistake here. They're all on IVIG and half get treated with aspirin in the usual doses. Turns out aspirin did not change the risk for cardiovascular lesions, and that's why it's always been advocated to do that. But that's an old recommendation in an era prior to the widespread availability and use of IVIG in Kawasaki's disease. It looks like IVIG is a much better anti inflammatory, a much better preventative agent, and there's probably no value to adding aspirin.

Now when you're adding it to a six year old, you know, with strawberry tongue and other Kawasaki manifestations, there's probably not much risk of GI complications, but if you don't need it you don't need it. So I thought that was a very interesting trial in JAMA. A study of how you can predict psoriatic arthritis in a cohort of psoriasis patients. So this is sort of a preclinical population of psoriasis, plaque psoriasis patients, sixty four patients. Not a large study, but it's an ultrasound study.

And they had to have arthralgia, but no synovitis, no steroids, no biologics. And they did ultrasound on them both power doppler and B mode. And they showed that dactylitis was associated with an increased risk of PSA. Now, you know, that's kind of similar to the findings of the Leeds group and Emory and et al, showing that preclinical RA, if you find tenosynovitis, it's a strong, strong risk factor for developing future inflammatory arthritis, aka RA. The same is being seen here, and they define dactylitis as either being ultrasound power Doppler synovitis and B mode enthesitis.

And it was highly significant and had a sensitivity of 87 and specificity of eighty nine percent. So, there is, I think, an important role for ultrasound, especially in patients who just have arthralgia and no proven synovitis, if you want to know what to predict. Especially in psoriatic disease where you don't have a biomarker like ACBA antibodies and high titer or double positivity to up the risk. And we'll talk about that later here in this podcast. Another report on psoriatic arthritis is looking at the reports that we talked about at ACR about IsoKebep, it's a nanobody anti IL-seventeen phase two trial, 172 psoriatic arthritis patients, where they showed that isocepib in the highest doses had a highly significant ACR 50 rates compared to placebo fifty two percent versus thirteen percent.

The forty milligram dose was forty eight percent, although that was not significant, I think. Actually it was significant, but it's less than the eighty milligrams which was fifty two percent. So anyway, looks encouraging. Know, the other outcomes for psoriatic arthritis include improved on his anti IL-seventeen nanobody preparation, smaller structural size thought to maybe have better tissue penetration. That's more of a thought and a buzz rather than a proven principle.

But they did have improvement in all the arthritis parameters, skin parameters, enthesitis, dactylitis and quality of life. Encouraging data from phase two, we'll look forward to phase three. A commercial analysis of claims data on a fairly large population of plaque psoriasis patients looked at first time biologic use, and we're talking about TNF inhibitors and the interleukin anti IL-seventeen, IL-twenty three, IL-twelve 23s, and looked at their use from 2007 to 2021, and their cost. And as you can imagine, there were significant trends back in 2007. The dominant biologic was going to be largely TNF inhibitors, the four TNF inhibitors that were approved at the time.

But over time, with more drugs being introduced, with more head to head trials, especially in psoriasis, the importance of twelve twenty three, and then 17, and then now IL-twenty three, and more recently, although not included in this study, is the dual IL-seventeen inhibitor, you know, showing superiority to TNFs. In this time span, there was a doubling of the use and a doubling of the cost. So from 2007 it was an average cost of a mean cost of 21,000 per year, but by 2021 this would increase to 47,000, and of course this does account, you know, is what's represented here are the annual increases that each of these drugs are doing, and the cost of therapy getting higher, especially with new drugs being introduced. So the final point of this point was yes, trends are changing, and they're changing based on experience, physician choice, but also data head to head data. But in the end, that by 2021 you could have saved 44% on these costs if you had chosen the lowest cost drug within that same mechanistic class.

Not necessarily going with the cheapest, and by the way the most expensive one was Remicade, probably at high doses, was the most expensive drug in the range of costs here. But making your choices based on cost, when you get to this, you know, Twelvetwenty Threetwenty 3, Aisle 17, where the differences are again, no disrespect intended for the head to head trials, which show one being better than the other But the differences are small compared to the savings, which are large. And there are certainly many people getting better. I kind of like this data. I kind of think that we should be faced with cost driven prescribing, because, let's be clear, you're usually tossing a coin.

You don't really know when this is going to work compared to that, and the best you can do on is rely on clinical trial data, which doesn't really approximate what's going on in your practice. So yeah, those sound like fighting words, do they not? You know, I'm ready to duke it out, bring it on. I like this report from an orthopedic journal about the utility of synovial fluid counts in letting you know what you're dealing with. This is a two twenty five prospective consecutive knee aspirations being done for presumed crystal induced arthritis.

In these patients fifty six percent were positive for calcium pyrophosphate, forty four percent were positive for monosodium murine crystals, and twelve cases out of the two twenty five, so that's like five percent, had superimposed septic arthritis. So you know that old teaching adage that just because the patient has crystal induced arthritis doesn't mean there can't be the coexistence of a septic process at the same time, because patients with septa with crystal induced arthritis, it's a risk factor for getting septic arthritis. Just like any abnormal knee surface, just like any abnormal valve surface, you can get seating and septic arthritis. So what they did find that was important was that in the patients with septic arthritis, they were more likely on top of crystals they're more likely about immunosuppression 42 versus fifteen percent. They had a higher mean synovial fluid white count 136,000 versus 22,000.

That's 22,000 with just crystals. Most of crystals were calcium pyrophosphate. Yeah, I know you said you've seen monosoramurates with sixty seventy thousand white counts, but all in all, all the crystal arthritises, you know, it's going to be inflammatory, very inflammatory, but not like the one hundred and thirty five thousand seen with the superimposed staph or septic arthritis joint. They found no difference statistically between septic and aseptic joints, but numerically it's impressive ninety one percent versus sixty nine percent. I've always taught and looked at the data that said the higher the poly percentage on your synovial fluid white count, the higher the risk of infection.

Meaning that PMN percentage is greater than eighty five percent. I'm worried about infection all the time. And that was reflected here, although in this analysis it was not significant. So, the takeaway message here is that when they did all the math and other analyses that a sodium fluid white count of greater than 50,000 had a strong predictive value, ninety two percent sensitivity for the existence of septic arthritis on top of crystal arthritis. Specificity was ninety percent as well, and the area under the curve is ninety six percent.

I still like poly percentages being a big thing. They didn't make such a big thing about it in their paper, but you know, they can't all be right as opposed to you and I, and we're always right. Last report: predictors of developing RA. A European study: fifteen years of enrollment, six seventeen seropositive arthralgia patients recruited between 02/2019. Thirty nine percent had rheumatoid factor, thirty one percent were ACPA positive, CCP positive, and thirty percent were double positive.

The meantime to develop arthritis in this cohort that were followed longitudinally was nineteen months, and it happened in a third of patients. So think about this. We talked before about at risk arthralgia, preclinical arthralgia, know, clinically significant arthralgia patients that if you are seropositive you got at least a third risk thirty percent, thirty five percent risk of developing RA. In this study, where again they're seropositive, they have a thirty four percent risk of developing RA. Thank you very much.

Risk factors for developing inflammatory arthritis were: A) being first degree relative fifty percent higher risk. Intermittent symptoms, I'm not sure what that means. I guess it means it doesn't go away, but it comes and goes sixty four percent higher. Symptoms of greater that are less than twelve months, meaning they're relatively new. Morning stiffness greater than an hour reported joint swelling, meaning the patient reports joint swelling, although you don't see it, then they can be right.

Fifty one percent higher risk. High appetiters 4.65 hazard ratio. That's four and a half fold higher. Double positivity for ACPA and rheumatoid factor is 6.8 fold higher. And they showed that if you had any three of these above your risk of developing arthritis was fifty eight percent.

So, think this is starting to frame who we're supposed to be worried about when it comes to, clinically significant arthralgia preclinical patients. Obviously the seropositivity is important. We said from the previous psoriatic arthritis test I would get an ultrasound looking for tenosynovitis. But again, the most strongly positive predictive is high titer ACPA and double positive ACPA and rheumatoid factor. And it doesn't have to be that both of those are high titer, they just have to be double positive.

And that lateral one is the most important. That's it for this week. Wait, we have more! There's an Ask Cush Anything report. This is from, Mexico, Doctor.

David Vega Morales. Hello, Doctor. Cush. Have you ever seen erythema nodosum in a patient with secukinoma? I had one, and I want to know if you have seen this.

Thank you, Doctor. Morales. I've never seen that, but I went and I looked it up. There's one case report in the literature, and that's without going to the secukinumab drug development database to see if they got any reports, but that's really quite rare. The one report that's out there is a case of secukinumab causing Behcet syndrome, and one of the manifestations of Behcet's was E.

Nodosum. I want to consider this, while it seems temporally related to the initiation of therapy with secukinumab, I want to say that think about this from the onset of E. Nodosum. What causes E. Nodosum?

It's infections. You know, in my experience, it's always been TB and fungal is the leading candidates. It's drugs. Most of those are antibiotics rather than immunosuppressors. Although current literature suggests that checkpoint inhibitors have been reported to cause, enodosum as a manifestation.

And then autoimmune diseases or inflammatory diseases, of which Behcet's is on the list, but highest on the list is probably IBD, Crohn's and ulcerative colitis. Now, let's consider secukinumab. You probably gave it for either psoriasis or for, spondylitis, and we know that one of the side effects of, IL-seventeen inhibition is the induction of colitis. I would say the more likely scenario here is IL-seventeen inhibition in this patient probably is producing either overt or subclinical colitis that you could prove by you doing a camera study or colonoscopy or taking a better history. And then that is the cause for the the instigator behind the E.

Nodosum event. Obviously, the treatment here is going to be withdrawal of that therapy, but if the patient must be on it, are probably going to have to investigate that even more fully. That's the end of the podcast. We'll talk next week. Take care.