Stop Counting Bugs (10.4.2024) Save

It's 10/04/2024. This is a RheumNow podcast. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. You know, a good friend of mine, Danny Ricciardi in Brooklyn, told me a few years ago, what's going on in psoriatic arthritis? There's more drugs than there are than I got patients with psoriatic arthritis well isn't that getting to be the case last year last week we talked about a new drug approved for psoriatic arthritis and spondylitis that's bimekizumab it joins three other IL-seventeen inhibitors it joins three other JAK inhibitors it joins five TNF inhibitors it joins two IL-twenty three inhibitors it's getting confusing isn't it?

What are we going to do about this? Well the good news is this week on the podcast it seems like more than half the podcast is devoted to the topics of psoriatic arthritis and spondyloarthritis So maybe we work our way through the data to get better insights on which drug in which situation will work for you. Or until we develop a moneyball approach to that, Well, we'll discuss moneyball sometime in the future. Let's start with a new FDA approval this week. Actually, it's for a biosimilar.

This one is, comes from Frenzius Kabi. It's called just akinumab, a a u z, or a tolfi is the trade name. It was, approved for use in Crohn's disease, ulcerative colitis, severe plaque psoriasis in adults, and same for, active psoriatic arthritis in adults. So that's a new approval. I think that now makes three ustekinumab biosimilars that are FDA approved in The United States, maybe more than that worldwide.

Another new report this week came out in JAMA. It was a meta analysis, JAMA Dermatology, a meta analysis of who doesn't respond to biologics. Who doesn't love biologics? Well, who doesn't respond might be an important question. And this meta analysis, 40 studies over 21,000 patients, showed the people who were not going to achieve the superlative standard response now in psoriasis trials, and that is a PASI 90 response.

Almost complete clearing. PASI 90 response. You're more likely to not respond if you're older. If you previously been treated with a biologic, and now you're switching, that probably means that you didn't respond well the first time around. If you have a higher BMI, and if you're a smoker.

These data facts have been in play already. This large data set sort of confirms what you should already know. Another analysis of patients with both PSA, almost one thousand patients, and AS, almost four hundred patients, looked at the influence of smoking. And we know smoking is not a good thing in patients taking biologics, not a good thing in patients who have inflammatory arthritis. And in this study, with that looks like a total of almost thirteen hundred patients who had PSA or AS, and somewhere between thirty seven and forty eight percent were smokers, what was the effect of smoking?

None. None when it came to the outcomes of MDA, minimal disease activity, ACR50, and PSA, or in the SPA patients, the ASAS forty, or the ASDAS response. So disease activity response measures were not affected by smoking. I found this really kind of hard to believe, but it's pooled data, multiple sources, large numbers. They did show that patients who were, who were, who had been smokers had a higher odds of drug discontinuations.

That's a measure of lack of efficacy, is it not? Or side effects. And they did have more serious adverse event side effects, especially serious infections. And we know smoking ups the odds of lung infections and serious infections. But you know what?

Smoking did not increase the odds of MACE events, zoster events, or VTE events, things that are often associated with biologic use, and inflammatory arthritis in general. So, of this is a little bit of a head scratcher. But maybe not all inflammatory arthritis is the same. Maybe the SPA patients are different than the RA patients. We need to look at this further.

A study of the oral microbiome in psoriasis and psoriatic arthritis patients occurred in a small cohort study, seventy two psoriatic patients versus 16 controls, and they did saliva analysis for oral microbiome. So they did 16S genome sequencing to see what bugs were in play. And then in in the PSO patients, they sat they found significant increase in certain subspecies. So Capnocytophaga, Campylobacter, Acetobacter, but decrease in Bacteroides. In the PSA patients, an increase in AgriCactobacter, but a decrease in Prevotella.

You're excited about this data. I can tell. You some of you have probably pulled off the road and are repeating this and rewinding it because you just can't believe what you heard. What you heard was what the hell is he talking about, and why is he telling me this information? Well, I wanna point out that I wish I wish there were more microbiome studies, but I wish they would stop counting the bugs.

Counting the bugs is driving me crazy because it tells me nothing. If I have less Prevotella and less Bacteroides, maybe I get less. Well, how do the hell do I get there? You know, I wish they would start counting the things that count. And what we've learned from the mavens in the microbiome field is microbiome may not be as instrumental in causing disease.

It may be more instrumental in causing drug responses to either be better or to be worse. We may be seeing microbiome changes that don't cause disease, but maybe a response to what's going on in disease. You know, there's a lot that we don't know. And I think someone's got to start connecting the dots on microbiome research if we're to continue to listen to Cush try to pronounce 18 letter words that you know he can't do. Let's move on.

There's almost a registry. It's called the Regisponsor study. And I think it's a really good study. Eight sixty six AS patients. And in this study, I found it to be useful that they found that those people who were from lower socioeconomic status groups had a longer delay in diagnosis.

They had a higher amount of bone marrow edema and structural damage, and they had more permanent disability, thirty one percent versus thirteen percent, compared to the patients who were from higher socioeconomic groups. Interestingly, both the high and the low socioeconomic groups receive the same therapies. So it's not the drugs, it's the host, and it's education that clearly influences the outcomes. I'm not looking for better drugs, I am looking for better patients, because better drugs may not be the answer to my problems. If I want the answer to my problems, I usually call Dennis Bedugney.

He's got an article in J Room this month that, where he talks about a cross sectional analysis of a patient survey. I think it's a multi national study, 27 countries, five thousand five hundred axial spondyloarthritis patients. And they found that the main diagnostic delay from symptoms to the diagnosis of axial spondyloarthritis was seven point four years. Seems like that's going down a little bit over time. In this international study, they showed that the highest delay, the longest delay was in South African continents, and also the lowest was in Asia.

Longer delays were associated with younger patients, being female, being diagnosed by a rheumatologist, having more HCPs involved, and a history of uveitis. I would take this to mean, first of I remember when we started getting more and more drugs for spondyloarthritis, the people, the companies that were working on this were calling me all the time to say, Why aren't rheumatologists diagnosing and closing spondylitis? And I agree, we tend to get them after the diagnosis is found incidentally, or accident, you know, by, on a KUB, or they go to a, orthopedist for chronic low back pain, and they find sacroiliitis. Or again, or, you know, it's found in the most haphazard of ways. I wrote a blog that basically said, if you see something, say something.

Meaning, I see spondylitis patients all the time, on the checkout counter, you know, on the train. Again, all kinds of places. I go up to them and I say, excuse me, I'm a doctor. Do you mind if I tell you something about your back? So about 20% of the time I get slapped.

30% of time I get disregarded. But half the time, I have usually a revelation discussion with patients. So I'm willing to risk it, for the biscuit, as they say in hockey. And I think that you should too. But why aren't rheumatologists making more of these diagnoses?

Maybe they have to see a lot of doctors, more ACPs, and then get a complication like uveitis to say, uh-oh, it might could be spondyloarthritis. A study from Taiwan Insurance Claims Data, about a decade old, looked at 30,000 newly diagnosed, AS patients, compared them to one to ten to population controls, and found that if you had AS, you had a higher risk of motor vehicle accidents that led to serious injuries. A twofold higher risk, and that was significant. So, are spondyloarthritis patients worst drivers? What?

Are they taking more chances? Is this fishing for a p value and coming up with idiotic data? It's hard to know. I will support the data by saying early on, when biologics were approved, and around the time they were early a lot of them were approved for RA. And then when they were being started being approved for PSA and SPA, If you looked at the reports and the package inserts, one of the more frequent serious adverse events in the new biologics, especially TNF inhibitors, was injury, fractures, and ER visits.

And I explained that by saying they felt so damn good that they ran out, and then went bungee jumping, or speed racing, or bicycling, and they were happy to break a leg, fall off their bike, or be in car accidents. I think this data kind of supports that once you relieve people of the burden and the disability of inflammation, all bets are off on what may happen to them. Maybe they live a little riskier life. I don't think that they're worse drivers. That I know is not true.

But again, this could be fishing for p values. I'd be interested in what you may think. ASAS came up with recommendations on how to order imaging in patients you suspect as having spondyloarthritis or sacroiliitis. This was guided by a task force and a long consideration, literature review, questions, Delphi process. And they recommended, I think, five or six things.

One, in your request for imaging, whether it's radiology, a radiography, or MR, or even CT, you should be putting in necessary clinical information: age, sex, B27 status. Something about how long they've had back pain, where it's localized to, whether it's inflammatory or not back pain, or whether there's been a recent change in their axial status and complaints. Three, whether there's been, whether the person is engaged in physical activities that could be important in the diagnosis, or recent childbirth. Four, if there's access to prior imaging that could be used to compare new imaging to, that would be important. Five, note if there's contraindications to imagings, or you're concerned about that, or the contraindications to the use of contrast agents.

And lastly, what's your suspected diagnosis? Or if the patient previously has a diagnosis of spondyloarthritis, and whether you're doubting that, or wanting to confirm that. A comment by Eugene Fung from Waco said, You should also put in your request what protocol you're looking to do. Do you want Ferguson views, simple AV views, some special protocol in doing MRI that may be important at your site? That's also important.

I must say that I get very upset when I send my patients to radiology, and I give them a history, I always do, and the radiologist, who may not be a musculoskeletal radiologist, comes back with the report, No fracture seen, arthritis present. Oh my god, I'm about to blow a pupil. What were they thinking? It comes from rheumatology clinic. Again, you got to help them.

Ask them what you want. Give them necessary information so they can be better diagnosticians. Radiologists are very bright, even if they're not musculoskeletal experts. You got to help the story. In Korea, they did a study this week that shows there's a link between RA and migraine.

That gives me a headache, and it's not related to seropositivity. This is a study of forty six thousand RA patients compared to two hundred plus thousand population controls, and found that the adjusted hazard ratio is one point two one. It's significant, A twenty one percent increased risk of migraine. Vascular disorder. Rare of vascular disorder.

That's the only way I can connect these. Again, fishing for p values or real. I can't say in my almost forty years of seeing a bazillion RA patients that migraine, I see a lot of migraine, but I see a lot of migraine and other disorders as well. So could just be that patients who see doc more doctors more regularly are more likely to get diagnosed with all sorts of things, migraine being one of them. But look for it.

Tell me what you think. A report out of Canada in the Journal of Rheumatology also looked at RA, but this time looked at early undifferentiated polyarthritis patients, and looked at them over three time points, or three years. Ninety eight to two thousand and four, two forty five patients. The next group was two thousand and five, twenty ten, two sixty six patients. The next group, 2011 to twenty twenty two.

That regardless of era, the patients referred for polyarthritis had many of the same referral symptoms, many of the same findings on exam, and they tended to be treated exactly the same. But key things that came over this longitudinal trend analysis. One, the duration of symptoms to being seen decreased from, actually, it increased from two point nine months to four point one months. Seropositivity went down from fifty four to forty two percent. Erosion scores went down from 18 to nine, and most of that was in seronegative patients.

But steroid use increased over time from eighteen to thirty three percent. It's a mixed bag in that early undifferentiated polyarthritis group. Maybe we're getting better at investigating them by doing serologies and doing earlier x rays. I think the time frame to referral is not too bad, less than four months. That's not bad.

Steroid use is a problem, and we talked about that in the past. Patients coming from the primary care sector are getting too much steroids before they come to see you. And by the way, that could be your fault, because you take forever to get patients in to see you. If the wait to see you, someone in your clinic for a new, I think it's RA, and I'm a primary care doctor, if the wait is less than two weeks, you're a great rheumatologist. But if you think you're a great rheumatologist because the wait is six months, you stink at what you do.

You need to rethink the referral process. I've had to ask me about it some time. A study about gout comes from the NOR gout study, looked at non adherence, and its effect on poor outcomes. This is a five year observational study of only one hundred and sixty three patients, but basically showed, overall, the adherence to urate lowering therapy was very good for the whole cohort. However, the ones who were classified as non adherent, not surprisingly, three times the number of flare rates, thirty three percent versus ten percent.

And they were, had double the rate of not being at target. Again, these are being treated by rheumatologists. The ones who were adherent, only forty five percent were at target. The ones who are not adherent, eighty seven percent were not at target. Again, even we rheumatologists need to do better.

Interesting study this week in JAMA, Network Open looked at something I don't know a lot about, whole body electromyostimulation. I think someone made that up. But if you look at the report, they show you some kind of gear that the patient wears with patches sewn into a vest and something around the waist. These are electrodes, and the electrodes stimulate muscle. And they treated, seventy two overweight, symptomatic OA knee patients.

Half got this, whole body electromyostimulation three times every two weeks for seven months. And the other group didn't get this, and they had usual care with one physical therapy referral. And guess what? The electromyostem patients had significantly less knee pain, by nine points on a 100 scale. That's something to be proud of.

Highly significant. And they won significantly in four or five other secondary outcome measures. In essence, I don't think you need to be going out and ordering these devices, because what these devices really represent is strength training. And I've been saying for years, I should have had this up in my clinic before I left the university practice, big sign in the waiting room that this is the year of getting strong. If you're getting stronger, you're getting you got a chance of getting better.

If you're not working at getting strong, I don't care what your problem is, that means you're getting weaker. And that is a recipe for doing worse. More pain, less mobility, more reliance on assist devices, more need for pain med it's just a mess. Strength has got to be your mantra. And put that big sign up in your waiting room.

This is the year of getting strong. Ask me about how to get strong. My last report is about declining use in postmenopausal women who are getting hormone therapy. This was a JAMA article that got a lot of play this week. This is looking at over thirteen thousand postmenopausal women in the NHANES study in two different eras.

And they basically showed that of this thirteen thousand, half of them were 65, the other half were 65. And they found that nineteen ninety nine, twenty seven percent of women in this group were taking hormonal therapy. In 2020, only four point seven percent. That's almost an eighty five percent reduction in hormonal therapy. And you know the story behind this.

It became into question around two thousand, but there's a risk of cardiovascular issues, that there's not the protection that you suspected, and then there's other secondary issues in older people. Well, a lot of that data has changed. And you should read the report in RheumNow to get into this. What we do know is that, again, the number right now is really, really low. Back a long time ago, it was mostly women 52 to age 65.

We now know that it's usually people 52 where the people are using post menopausal hormonal therapy, which is indicated for symptomatic management of post menopausal symptoms, right? And it has some positive effects on bone. But as they get older, you obviously may not want to use that when they're above 60 or above 65. Where they found that the change in hormonal use decreased by twenty five percent in the 52 group, that in the fifty two to sixty five, it dropped even more and by thirty one percent. But there were fewer people on it over the age of 65 who only dropped ten percent.

Again, use of hormonal therapy is highest in Caucasians, whites, lowest in racial and ethnic minorities. So something to consider going forward. I don't know how much hormone most of the hormone therapy, most common one used was estrogen over time. But in recent years, there's been more combination estrogen progesterone use. So talk to your local osteoporosis maven about what this means and how it might color your treatment.

I want to remind you ACR is coming up in six weeks. RheumNow is going to be covering it. We're really excited about it. We're gearing up for it. Hope you'll follow us.

Also, the website roomnow.live is open for registration. That meeting is February eighth and ninth in Dallas, Texas. Artie Cavanaugh and I look forward to seeing you there. It is the most interactive of rheumatology meetings. This is where you come and you teach your peers and you teach the faculty what they need to know.

Look for the final schedule. It's coming up soon. Take care. Bye.