Opioid Deaths are Down (2.28.2025) Save

It's the 02/28/2025. This is the RheumNow podcast. Hi, I'm Jack Cush, executive editor of roomnow.com. Deaths are down, Aisle 33 is up, and weight loss makes the news again this week on the podcast. MMWR came up or I think it was MMWR, but was certainly a CDC report this week that there was an unprecedented drop in overdose deaths in the last twelve months, down twenty four percent in previously, a hundred and fourteen thousand, now down to eighty seven thousand.

This is a big drop. And, you know, with the, you know, the war on drugs, the, outcry over fentanyl related overdose deaths, all the measures being taken to combat this issue, you know, they're starting to take hold and show up in these kind of statistics. Yet, even though there's a 24% drop, and that is a big number in public health, overdose remains the leading cause of death in Americans up to age 44. So young Americans, even thirties and forties, it's still a big issue. So we need more work in this area.

And, you know, you're not using narcotics the way you might have used them ten years ago because there is this outcry against it all. I don't know if you've, seen, Cochrane reviews before. They kind of take on the big ticket items, the issues that people may be talking about. And they did a review recently of TNF inhibitor use in JIA. Now, a number of the TNF inhibitors are approved for use in JIA, largely for polyarticular JIA.

And while this review, based on nine clinical trials, some of whom work against placebo, some were against methotrexate, some involved methotrexate. Nine trials, almost 700 patients, kids between the ages of eight and 15, disease duration from one to six years, showed that a no brainer here, that TNF inhibitors do work in JIA. The shocking thing to me about this was in their, you know, extremely rigid, well done methodology, they didn't have enough evidence to say that they could endorse TNF inhibitors as far as their long term safety and long term abilities in controlling pain, function, and controlling disease. And that's because they just went with the data, and the data were usually six and twelve month studies. They were doing no longer no long extension trials.

So, I think it's an endorsement, certainly for TNF inhibitor use. It has become a mainstay in all rheumatology, including pediatric rheumatology. But it does say that we do need an exceptional effort in studying JIA. You know, if a drug is to be FDA approved for use in adults with RA, PSA, whatever, then the company that goes after such an approval is mandated and obligated to be doing the similar trials in patients with JIA. And we've seen a very slow rollout of trials that do support the use of biologics in JIA, but they have limited duration.

We do always need to make an extra effort, I think, in getting drugs approved for pediatric rheumatology, especially for JIA. I was at RWCS two weeks ago in Maui. Great meeting run by Artie Kavanaugh. Great set of speakers. William Bugby from Scripps Clinic, a really fabulous academic orthopedist, gives great lectures, did a review of a number of different topics in orthopedics germane to rheumatology, and actually sort of set everybody straight on what the actual survival is of hips and knees that they're replacing.

You know, it was said back when I was a fellow in 1984 that if you got a replacement hip and knee, you know, it was going to last ten to fifteen years and then we don't know. And they've been using that line for a long time. But the fact is the newer hardware has been so refined and procedures have become so refined that the expected durability or survival of an implant is much longer. And Doctor. Bugbee showed data that it was really in the twenty to thirty year range, getting closer to thirty years.

Well, that's backed up by a report this week from Peking University looking at their long term follow-up of two twenty six patients who were having total knee replacements, showing that survival rates were ninety four percent at ten years, ninety two percent at fifteen years, ninety percent at twenty years, and seventy two percent at twenty five years. So, overall, these patients did very very well, while there was a doubling or tripling of function with the use of arthroplasties. But between ten years after the implant and twenty years, there was somewhat of a decline in function. I don't think it was due to the implant. I think it was due to the age.

You know, most of these people getting implants are, what, 50, 60 years of age? Go twenty five years out, function declines when you're in your 70s and 80s. This is a good report, and this is kind of what you need to tell your patients who are contemplating, hip or knee replacement. If they are contemplating hip and knee replacement, you should look at my blog. I think it's a really good blog.

It's about the importance of rehab after knee replacement. It's called My Physical Terrorist. And, I'm a big proponent of rehab after knee replacement. Bugby said that actually the data isn't that strong to support it. And that's why most orthopedists don't recommend it.

But I'm telling you, I still don't know what I want to believe that. I think rehab prehab prior to surgery and rehab after surgery is paramount. And that's what I'm going to stick with. Sorry, Doctor. Bugbee.

Kawasaki's disease, you know, a tough disease. It's a pediatric condition. We adults are going to see it from time to time. A really good study from a Swedish registry of almost 1,800 patients compared the course and disease of those Kawasaki patients to almost 18,000 controls. And they showed a very clear correlation between infections and the risk of subsequent Kawasaki's.

And this was mostly upper respiratory and GU infections and some GI infections. They showed a clustering early on before Kawasaki's. In the month before Kawasaki's. A five fold increased risk of having an infection that leads to Kawasaki's. And that even with remote prior infections going out six to twelve months, there's a thirty percent increased risk.

So five fold would write immediately before and even a thirty percent odds ratio one point three in the six to twelve months. Infections are playing a role. And why is that important? You can't do anything about it, right? It's like the weather.

You talk about it, even what can you do? But I do think it says something important about what the mechanisms are that lead to Kawasaki's. And this should be instructive to researchers to investigate this further. I'm not advocating for antibiotics in the early phases of Kawasaki's. We need to research, again, the role of infection and what that's doing to trigger what becomes Kawasaki's.

A Medicare study of 2,300,000 participants in Medicare showed that amongst practitioners who were high users of telemedicine, they overall saw more patients. They had more overall patient visits, and that was an increase in face to face and also outpatient telemedicine visits. But high telemedicine users were less likely to do a lot of screening tests, which are felt to be low value screening tests. So, a modest but significant reduced rate of screening tests for cervical cancer, ECG, pre op and post op ECGs, CMP, CBCs, TFT's, and imaging of uncomplicated low back pain less likely to be done by those who do more telemedicine. Is that because they're not in the office and they don't know what button to press?

Is that because they're just practicing more cost effective medicine? There are many of you who are no longer doing telemedicine. I think you should. Overall, high users of telemedicine also spent less money on care. Think about it.

What makes nodules get better? I don't know. And we're talking about rheumatoid nodules. I can tell you what makes them worse. A report on two zero eight RA patients looking at what made them worse.

And these were RA patients where they looked at lung nodules because they all had chest CTs. And it turns out that ACPA positivity and not rheumatoid factor positivity was associated with nodule progression. So being ACPA positive, there was almost a fourfold higher rate of nodule progression. And that means increase in size over time. Turns out that what didn't affect nodule progression?

The use of conventional DMARTs like methotrexate or biologics or targeted synthetics. Again, the head scratcher in what do I do about these nodules? And I wish I had a good story for you. I have a great story about a patient with severe pulmonary nodules that was causing recurrent pneumothoraces in a seropositive RA patient. We treated him with cytotoxin and cyclophosphamide and rituximab and resolved the problem.

But that's an N of one. There isn't really literature to support much of what we did, but that seemed to work in my one patient. Interesting study about GERD symptoms in patients with RA that they was associated with higher tender joint counts. What? GERD?

Associated with higher tender joint counts and higher visual analog scale scores. I assume that's global scores. But it also was associated with lower methotrexate use, and hence the higher tender joint counts and higher VAS scores. Turns out that GERD scores were not related to NSAID or steroid use in this analysis. So it turns out that GERD could have an impact on methotrexate dosing and subsequently on disease activity.

I've never made that association, but, and I don't often attribute GERD symptoms to methotrexate use, but I think some people do. Interesting. Another interesting study this week was about a small cohort, seventy eight patients who had rheumatoid arthritis and ANCA, a positive ANCA test. These were over age 60, mostly female, two thirds rheumatoid factor positive. Forty five percent were P ANCA positive, forty two percent MPO positive.

And you know what? Some of them just had a positive test. But some of them did have actual ANCA associated vasculitis in addition to their seropositive RA twenty nine percent. Forty five percent had GPA, thirty six percent had MPA, five percent had EGPA, thirty one percent renal involvement, thirty six percent upper respiratory involvement. Those were most common.

Patients who had both RA and ANCA associated vasculitis were more likely to be seropositive with rheumatoid factor, be NPO positive, have nodules and inflammatory eye disease. It is a subset I've seen maybe two cases like this, and basically you treat what they've got. You treat the RA, but you're gonna have to I wouldn't treat the ANCA, but if they had either GPA, MPA, EGPA, right? Or renal involvement, yeah, I'm gonna step up and treat it as an ANCA associated vasculitis. Interesting.

Another interesting report was linking IL-thirty three to patients with lupus one hundred and twenty patients versus sixty controls. IL-thirty three levels were significantly higher, almost like four times higher in SLE patients compared to controls. And having elevated IL-thirty three levels correlated with SLEED I scores, disease activity, and the risk of organ damage and renal disease. IL-thirty three is part of the IL-one family. It is both pro inflammatory and somewhat anti inflammatory.

It's made by endothelial cells, keratinocytes, dendritic cells. It can drive a Th2 response. It can drive autoantibody production. It is not unique to lupus. It's seen in RA, multiple sclerosis, all kinds of other conditions.

But, if linked to lupus, maybe we'll see therapy in the future that will target IL-thirty three. There is such a monoclonal antibody out there that's in clinical trials, mainly in sinusitis, rhinosinusitis and bronchiectasis. I haven't seen it in lupus or RA yet. Itipekumab Itipekumab, an IL-thirty three monoclonal antibody. You may want to look for that in your next visit to the ACR or ULAR.

I like these next three reports. We wrote about them a little bit more extensively on the website. The misdiagnosis of dermatomyositis appeared in JAMA Dermatology. It's a report of two sixty patients, two thirds of whom had dermatomyositis and one third had CADM, right? Clinically amyopathic dermatomyositis.

That's a worrisome group, right? That's what we used to call that dermatomyositis synomyositis. A lot of those are MDA-5s and other patients, and they may have more severe lung disease and not so much in the way of skin. But in these two sixty patients, one hundred and twenty five of them were previously diagnosed with another inflammatory skin disease. Most of them were dermatitis, some were eczema, some were with cutaneous lupus, But they evolved.

And they evolved to either DM or CADM over time. And the other thing is that a lot of these patients are first being seen by dermatologists. And then later, the myositis diagnosis shows up. Turns out that the CADM cohort were probably the more worrisome of the group because they had more misdiagnoses than the dermatomyositis, they had longer diagnostic delays, and they had more of the dermatomyositis associated malignancy that we often worry about. So, misdiagnosis is a big issue.

I think setting up easy referrals between you and your dermatology colleagues could maybe cut down on this, or certainly shorten the duration between diagnostic delays. Another interesting study this week came of an analysis of the FDA adverse event reporting system, what we call MedWatch. This is a They're dredging for associations here. And they found two two thousand and eighty reports of TNF inhibitor induced lupus. So, drug induced lupus caused by a TNF inhibitor.

They found it with all five of the TNF inhibitors: infliximab, etanercept, atalizumab, cerdulizumab, and galimumab. And what they noted here was that while the range range in drug induced lupus manifestations range from mild to severe, that they said ninety percent had either serious or life threatening disease or death. So a lot of these people probably are skewed in reporting to the FDA, right? More likely at the more severe cases being reported, maybe the mild cases don't get reported as much. But nonetheless, severe stuff can happen, and that includes, by the way, nephritis and hematologic manifestations and life threatening pericarditis, etc.

There were two different patterns here. One, that the time it took from starting the TNF inhibitor to getting lupus was longer with infliximab, adalimumab, and etanercept, like seven months or more. Or shorter with galimumab and cerdulizumab. Why that would be? It's got nothing to do with the half life, I'm not sure.

It's hard to know. Were probably deaths occurred with all five TNF inhibitors, but occurred a little bit more with cerdulizumab and etanercept. The overall strength of association was greatest with infliximab, followed by adalimumab, followed by cerdulizumab. Okay? I don't know if I agree with some of the associations that talk about arthritis associated with adalimumab, nephritis associated with etanercept in children, and blah blah blah, because now we're getting down to small numbers and there's no real control group here and it's hard to know what this means.

What you need to know is that, again, one of the most common causes of drug induced lupus is this paradoxical reaction to a TNF inhibitor. It can be mild, but it can also be severe and may include serositis, worsening of arthritis, or even renal disease, including reports of glomerulonephritis. A report in JAMA from Nancy Lane's group looked at postoperative weight loss and its effects on implant survival after a patient undergoes an OA patient who's obese undergoes either hip or knee replacement. This was a large database study that looked at three thousand seven hundred patients who qualified as being obese with hip or knee replacements. And they categorized, and they had patients in here who took the usual drugs for weight loss: Orlistat, GLP-one agonist, Rimonobant, I'm not sure which one that is.

And they showed that, if you had stable weight after and by the way, these patients started their weight loss drug after they had their joint replacement surgery. Those who had a stable weight, the risk of revision surgery was five point six percent. Those who had small to moderate weight loss, two to ten percent, had about a twenty percent reduction, where it was four point four percent. And that was almost significant. It was about a twenty five percent reduction.

But if you had larger weight loss, more than ten percent, it was down to three point seven percent as the risk for revision surgery. And that's a forty three percent drop that was significant. So, loss prior to surgery: still important, right? But the ACR hip society I'm sorry, the hip and knee society guidelines on joint replacement surgery say that obesity shouldn't be a deterrent for doing surgery. So, lose weight before, but do the surgery, and it's okay to lose weight after.

And maybe to even use these drugs. I found this really interesting. Anyway, that's it for this week on the podcast. Hope you enjoyed this information. Tell your friends about us.

Give us a good ranking wherever you listen to your podcasts. We'll be back next week with more from the wild, wacky world of rheumatology. Take care.