The Best Rheumatologists (7.19.2024) Save

It's 07/19/2024. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. Let's begin with roll call.

Alright. Doctors Liu, doctor Calaveris, doctor Calaverice, doctor Cappellini, doctor Bingham, doctor Mira. Oh, this list? Yeah. This is a list of all the experts who taught me about IRAE, immune related adverse events associated with checkpoint inhibitors.

You know, we all see it. Not a lot of it, but we all see it. And it's good to have these experts out there teaching us. We had two reports on IRAEs this week that were synonymous. And these reports basically attested to the fact that when your patients with autoimmune disease get cancer and then are prescribed a checkpoint inhibitor, like a PD one or PD L1 antibody therapy or CTLA-four therapy, your adverse event rates are higher in your autoimmune patients.

So one was a study of one center, this was published in PLOS, almost five hundred patients that were going on anti PD-one, or L1 or anti CTLA-four antibody therapy. And they found that amongst the five hundred or so that about six percent or twenty eight patients had pre existing autoimmune disease. When you compare those who had pre existing autoimmune disease and the rates of IRAEs, which as you know, psoriatic arthritis, myositis, you know, hypothesitis, IBD, etcetera, that IRAEs associated with these therapies were higher in the autoimmune patients, fifty seven percent of patients versus thirty five percent in the non preexisting autoimmune patients. But interestingly, that, autoimmunity did not have any, was not affected by these IRAE events and that was I think kind of interesting and good news and outcomes and mortality were the same. Another was not a single center, but instead was a meta analysis, actually a systematic review of almost 24,000 patients.

And the patients with autoimmune rheumatic disease had about thirty percent higher rate of IRAEs and that this was seen in overall IRAEs were seen in sixty one percent of patients with this and that's kind of similar to the other one, fifty seven percent. Most of the side, but the interesting point here is that most of the IRAEs are mild, maybe moderate, never life threatening, not associated with death or really poor outcomes, the majority are treated with manageable doses of steroids and only a minority required either DMARDs or biologic therapy. And more importantly, that, this occurrence in, autoimmune patients with IRAEs had no effect on cancer outcomes. The treatment of the IRAE had no effect on the cancer response. Overall, in that cohort that, developed these IRAEs, thirty two percent were hospitalized, mortality rate was incredibly low, zero point zero seven percent.

So that's seven per ten thousand. So very, very small. So, again, I think this is particularly germane to us as rheumatologists who we do see these patients in consultation. And you should know that maybe your patients who go and get these therapies may be at slightly higher risk. A new announcement this week that I think was expected, and that is AbbVie based on the results of their successful trial of padacitinib in giant cell arteritis has submitted regulatory applications to the FDA and the EMA to, for the consideration of upadacitinib in the treatment of adult patients with active refractory giant cell arteritis.

So that's the application has begun. Could be somewhere within a year before we see something positive on that or negative. We'll wait and see. An interesting study is a follow-up to last week, we talked about air pollution, causing higher rates of lupus. And I said, as I mentioned, it's been associated with RA.

This week, I got another one. This one from a fairly large, almost 500,000, UK Biobank cohort found that long term exposure to air pollutants, and that was all kinds of nitrogen, nitrous nitrous oxide kind of things, was associated with either anywhere from about twenty to fifty percent increased risk of developing psoriasis. Moreover, those who had a genetic predisposition to psoriasis, I don't know what that is. What's CW six? And where exposure had an even greater risk of incident psoriasis.

So, again, this unusual interplay interplay, and and I think this is a big thing. I'm gonna write soon an article about environmental rheumatology and I think it's something we should be paying attention to. Two reports on methotrexate this week, we just love methotrexate in rheumatology, do we not? This is almost a 200 patient study where they actually studied GI symptoms. Do you really need to do that?

Well, they did it and they did it formally using something called the methotrexate intolerance severity score, the MISS score. And they basically identified that amongst all these hundred ninety two patients with RA on methotrexate, GI intolerance of some sort was seen in fifty six percent. Yes. You would have guessed that nausea, and pain, I don't know what that is, occurred post methotrexate. I'm not sure what that is.

I think maybe they misclassified that, but I see fifty percent of people with CNS blah kind of things. Anyway, they did see that this was more in people with African American descent in patients with fibromyalgia, those on steroids, those on JAK inhibitors. Interesting. Anyway, what they found was that the MISS score, the methotrexate intolerance severity score was unrelated to the route of administration, oral versus I'm prior or preexisting GI disease, age, or the methotrexate dose. I've always thought there might be an influence of dose on GI symptomatology.

They showed that doses that are probably being used in RA, which I have to assume was as low as maybe seven and a half or 10, but as high as twenty five, that that range didn't seem to matter when it came to methotrexate toxicity of the GI type. Another study looked at methotrexate in patients not responding to methotrexate, hundred and seventy four RA patients, and they they were started on tocilizumab and what was unique about this was having high GM CSF levels, sort of pro inflammatory cytokine with a lot of hematologic inflammatory effects. High levels at baseline were an independent predictor of poor response to tocilizumab. Now is this to say that that it's the converse of a high IL six levels might be an indication of better responses to tocilizumab? No.

It's not. And, actually, high CRP levels and IL six levels has not been consistently shown to be predictive of responses here. But in this study, maybe this is a marker of more severe patients rather than patients who won't respond to tocilizumab specifically. So these patients, also had higher DAS scores, and had higher cytokine levels and sed rates, also at bedtime. So it might just be disease severity.

But I like this kind of predictive variable research because we need more of that in knowing what therapy to choose next. A retrospective study looked at lupus nephritis and the influence of ANCA positivity. We reported here before that there's a minority of patients with lupus, you know, and in this particular study, thirty a hundred and fifteen patients had biopsy proven class three, four, or five lupus nephritis, and thirty percent were ANCA positive. In that cohort, ANCA positive lupus nephritis patients, they had higher disease activity scores. They had were more likely to have proliferative three and four lupus nephritis, require more immunosuppressants in the form of cytotoxin and mycophenolate, and they were, actually, they were actually okay as far as achieving remission, but they did require those immunosuppressants, and they required more of them.

So it might be a subset, and you remember that research that was presented at by Andrea Fava from from Hopkins where he showed p r three staining in the kidney, and that is p r three staining that is exemplar is exemplifies the degranulation and the damage that goes on within the kidney. So it probably pays to check ANCA levels, and you probably should be worried about c ANCA and p ANCA. But, again, there's enough reports out here that I'm changing my test ordering and staging of lupus patients, especially if I think they may have kidney involvement. Speaking of kidney involvement, can you give the urate lowering drug febuxostat to patients who have chronic kidney disease? You know, the package insert says that you can, but it doesn't really talk about its use in the most severe forms of CKD, like CKD stage three or lower.

Anyway, a meta analysis of 16 studies showed that when febuxostat was used, it actually lowered the risk of future renal events and lowered the risk by forty four percent. These patients on febuxostat with gout, of course, had slower rates of decline in their eGFR's. They had reduced urine albumin to creatinine ratios. So by controlling urate load, maybe it lessens urate associated kidney disease or hypertension related kidney disease, and the outcomes as far as kidney function are good. Still doesn't answer the question that I started this little diatribe with, which was if you have high level CKD, you know, can you safely use rebuxtat?

And and I would, unless they were on hemodialysis or anuric, I would. I would just start at a lower dose and follow kidney function. But, again, patients would, again, creatinine clearance is, of 60 or higher, and I I would probably say even lower than that, certainly do well on febuxostat. I found this study kinda odd because I know nothing about it. Microwave ablation therapy.

You know, they do cardiac ablation therapy, and they do other ablation therapies, and this was a study being done, in a small cohort, twenty two patients with 24 active knees who were presenting with chronic or recurrent monarchitis. So this is sort of an orthopedic study and patients with chronic monarchitis, not responsive to whatever you do in those people. And I know don't know about you, but I've tried everything but the kitchen sink, and they still recur. And it's a really tough group. Anyway, 24 knees treated with microwave ablation, and they, prior to the ablation, they required, I think, five, intra articular aspirations and or injections in the prior six months for a total of a 129.

In the six months following microwave ablation, only seven required intra articular, aspirations without therapy. And the rates dropped from about one a month to point o three a month, and that was highly significant. No complication rates. Where do I get my microwave ablation therapy? Do I get it at Sears in the microwave department, or do I call the crazy scientist orthopedist in town?

I don't know. We need to see more research on this. And lastly, a study from Amsterdam looked at two hundred and three lupus patients and tracked their, prior, associations of tracked their, being infected either with minor infections or major infections and and whether or not that influenced minor flares or major flares of lupus. So what they found that there's the incidence of major, infections was six point three per one on patient years I'm sorry, five point three per one on patient years and a minor infection sixty four, so almost ten ten or 11 times higher. But that if you had major or minor infections, you had, like, almost a doubling of the lupus flare rate and only did major infections really lead to and that would be hospitalizable infections, IV require IV antibiotic requiring infections lead to a higher rate of major lupus flares, and that is a seven point four fold higher rate.

That's the hazard ratio of seven point four. Pretty interesting. I like this report that we put up this week on scleroderma, siniscleroderma, and this is, I think it was reported at Ojama, but a co large cohort of 25,000, almost 25,000, systemic sclerosis patients. And in that cohort that they found, ten percent of patients, and this is actually meta analysis, I guess, of many studies. Right?

There's not no one's got a cohort of twenty five thousand scleroderma. So many studies, grouped together. The range in these studies was zero to twenty three percent. The median was ten percent incidence of systemic sclerosis, synae scleroderma. So you have systemic sclerosis proven by criteria and or biopsy, but they have no sclerodacty and no skin involvement.

So what do they have? Forty six percent had interstitial lung disease, pulmonary artery hypertension in fifteen percent, renal crisis in five percent, and cardiac diastolic dysfunction in twenty six percent. That while this is an interesting subset, how do they behave? Well, they behave more like limited scleroderma than diffuse, and, actually, survival was basically equal to that seen in limited systemic sclerosis, right, the CREST variant, but was, certainly a lot better than patients who had diffuse disease. So I don't know about you, but I've seen those patients, and it's good to know we'll have more information about that.

You may have seen, I think, the the EULAR report on the EULAR recommendations on the treatment of systemic sclerosis. I think about 800 of you have read that article. I think it's a good fast read. Doctor Francesco Delgado from Leeds, he leads the scleroderma research effort at Leeds, and he did the presentation on behalf of a 27 member ULAR task force that included 18 rheumatologists, I think, a few methodologists, a few fellows, etcetera. They sort of, looked at the problem of scleroderma management according to eight domains.

One, Raynaud's management. Two, digital ulcers. Three, pulmonary hypertension. Four, skin fibrosis, five, ILD, six, musculoskeletal and joint involvement, seven, GI involvement, and lastly, renal crisis. I think you should look at the report.

I have to if I was gonna go over the treatments and they recommend, it would be another thirty minutes, and I don't think you want that. But surprisingly, interesting placements and good data. A lot of one a quality evidence, one b quality evidence for the use of mycophenolate, cyclophosphamide, but also rituximab and even tocilizumab and certainly, nintedinib. Okay? They didn't have perfenidone on this list, but they did have a lot of a lot to say about the use of p, p d five inhibitors and bosentan and iloprost and IV and others, especially in managing Raynaud's and digital ulcers.

It's a worthwhile quick review. So you can go to look at the table at the bottom of the report that I made for this where you can read the text. That was a report actually came out of MedPage today. Lastly, you may have seen, I think it was two days ago that The US News and World Report published yet again the 2024 list of the best hospitals in rheumatology, and I listed for you the 20 best hospitals. The top five are really unchanged over the last five years.

Johns Hopkins has been at the top of the list for seven years in a row, and the other five spots kind of change and move around a little bit. This year, the order was number two Cleveland Clinic, number three Hospital for Special Surgery in New York, four the Brigham in Boston and lastly the Mayo in Rochester I guess all right all Mayo's get included in that list so again this is kind of exciting stuff we certainly know that our hospitals our medical schools they love to say that we're the best that we're on the top of the list and you know, but you know is that where really all the best rheumatologists are? I think in my unofficial review of this perplexing issue that is of such great interest to you that you've listened this far into the podcast, my estimates are that these top 20 hospitals only have about half of the best rheumatologists. The other half, come from the rest of you. And, other stats that I've acquired, one third of you who are the best rheumatologists have unspeakable, unspellable names.

One quarter of you, strangely, have cats as pets, and at least half of you wouldn't wanna be on any such best rheumatology list. So it's about bragging rights, which seems to be important to universities and academic centers and teaching hospitals and actors. But I don't think Rheum's, you and I are so easily impressed by these lists. Think we're glad to say that my institution's on that list. And I think that, you know, all that glitters is not all that great, and that's why I like hanging with rooms who their greatness is achieved at the patient level at each visit every day.

Congratulations on all your hard work. That's it for the podcast. Go to the website to check out these citations and more, and we'll talk next week.