Running With Data (8.30.2024) Save

Howdy, folks. It is the 08/30/2024, and this is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of rheumnow.com. This week, so much news, so much info.

Let's just tease it by saying we've got tips. We've got tips on steroid management, tips on macrophage activation syndrome, and what to consider, tips on myositis testing. Let's start with something you know, and now you can add to what you know. You know that, the way to reduce the risk of uveitis, either it's onset or recurrence in patients with spondyloarthritis is to use, you know, certain drugs, specifically the the t TNF inhibitors that are antibody based. Right?

More so with adalimumab and infliximab than with etanercept. Well, there's been hint that, the use of IL seventeen inhibitors are also effective in this regard. And then this week, we have the publication of the bimekizumab data. Bimekizumab, the dual IL seventeen a and f, drug that's been approved for psoriasis, not yet approved for psoriatic arthritis or spondylitis. And they presented the results of the the b mobile trials in axial spondyloarthritis, b mobile one and b mobile two, large number of patients, there were three hundred fifty patients, and looked at the occurrence of new uveitis events.

You couldn't have uveitis going into trial. And, yes, if you were on bimekizumab, it was point six percent. If you were on placebo, it was almost five percent. The actual rates were one point eight versus fifteen point four per 100 patient years. And even if you had had a prior history of uveitis and took either placebo or bimekizumab, there was a significantly lower risk, event rates of six versus seventy per one hundred patient years.

So I guess that's the point there is that if you have a prior history of uveitis, and you take a drug that won't protect you, the event rate is seventy seventy percent of people in one year are gonna get uveitis, whereas if you did, a protective drug like bimekizumab, it's much less. Right? It's down now down to six per one hundred. I think that's very useful information. I don't know if you've ever had a problem, with your patients and Pneumocystis urovecchi or PJP infections.

I've had a few in my career, and we've talked about PJP in the past. And so what do we need to know about this? Our recent, retrospective review of fifty eight patients with lupus who had PJB infections was somewhat instructive. First, thirty nine percent of those people died, not good, right? This is an infection you don't want to get.

May and part of that might be that there's often a delay in the diagnosis, it's often not considered early, and it's also a bad infection, it's an opportunistic bug. These events were more common in patients with diabetes and those who required mechanical ventilation, but the mechanical ventilation means that they were sick enough and that they were gonna had a higher risk of dying. Turns out predictive factors for PJP related mortality was having hyperglycemia, diabetes, low complement levels, and thrombocytopenia. To me, that sounds like diabetes plus active lupus. And we've talked about PJP here in the past.

Risk factors for PJP include lymphopenia, high dose steroids. Right? We see more of this in in certain conditions. And then the other one that's that you should remember is rituximab. Not really with traditional DMARDs, or other, biologics other than rituximab.

So, again, I think this is an instructive piece. This week, I was in a discussion talking about how you should stop steroids in someone who's on steroids, and I was trying to make the point, and back it up that, you know, if you're on steroids for less than four weeks, you should just stop steroids, no need to taper. So I did a Twitter poll, and an overnight Twitter poll ran for eighteen hours, I had 133 responses. The question was, how long must you be on prednisone forty milligrams a day before you must slowly wean the prednisone versus stop them abruptly? And your answers, not maybe you, but all your colleagues are all over the map.

The most common answer was two weeks by 50%, three weeks by nineteen percent, four weeks by twenty six percent, and five percent said six weeks. So what's the real answer? Well, it turns out it's hard to know, it's hard to find the real answer, and I did spend a fair amount of time looking for this, and I published this on RheumNow and also on Twitter this week, that the the British, Endocrine Society and the Endocrine Society came up with a consensus guideline that was published about four months ago about the avoidance of adrenal insufficiency, and in there, they make their state their statement that says, number one, to cause adrenal insufficiency, you need to be on steroids at any dose almost or a dose that suppresses your endogenous steroid, that would be five milligrams or more prednisone per day for at least three and probably four weeks or more before you're at risk for adrenal insufficiency. Okay, so that should guide you as far as to when you can abruptly stop steroids and just move on and not play games with steroid tapering. That means steroids at any dose of prednisone greater than five for more than three weeks, might need tapering, but less than three or four weeks, nope, just stop them and move on.

And and I, you know, I don't know about you, but I've had lots and lots of, patients who potentially put themselves at risk by how they abruptly stop steroids. And I gotta tell you, you know, an Addisonian crisis or and real adrenal insufficiency with abruptly stopping steroids incredibly rare, even in people on chronic steroids. But nonetheless, this is the guideline that's out there from the endocrine societies as to how we should behave. A lot more on steroids this week, we published. The RISE Registry did a study, looking at patients who were prescribed prednisone by their primary care doctors before the patient was seen by a rheumatologist.

Turns out that if prednisone was prescribed before it got to rheumatology care, that those patients were more likely to end up on chronic steroids. This is a study of seventeen hundred RA patients, seven hundred treated, with glucocorticoids, and then, again, showed that the while many of them were on it for, like, a mean of a hundred fifty seven days, the ones who got steroids before they got the rheumatologist were gonna be on it much longer, Suggesting that indiscriminate use by people who don't really know or manage chronic steroids well, should be discouraged. And this gets into the issue about what's the role of the rheumatologist in educating primary care and we want to, but it's not an easy thing to do. And there are many people who try to get involved in primary care education just about rheumatology in general, steroids specifically, it is a difficult undertaking, requires I think a much deeper partnership between the societies, the ACR, the AAFP, ACP, etcetera. There was another report, let me scroll down, about, which drugs are better at steroid sparing.

You know, that we have we we've reported in the past about, you know, with all these great new drugs, biologics, targeted synthetics, theoretically, that they're so good that we should be able to wean our patients off steroids. Turns out we don't. So the fact that these new drugs, expensive drugs, aren't steroids bearing is a little disconcerting because should be one great benefit to better therapy is that you can get off of steroids. Well, in this analysis of where is that now? Seven hundred plus RA patients, They compared patients starting, who were going on a JAK inhibitor versus biologic DMARDs.

Most of them were biologic DMARDs. And it turns out that JAKs were a little better than biologic DMARDs. We're being more able to rapidly reduce glucocorticoids in the first six months and a sixty percent higher odds of being totally off the steroids within one year. I think that was encouraging, but the actual numbers are still not great. Greater than fifty percent around fifty percent with JAK inhibitors around forty percent with biologic DMARDs.

Still a lot of people are on these drugs, it's something that we need to work at. So let's move on and talk about macrophage activation syndrome. I don't usually put up anecdotal case reports because I don't know what we can learn from case reports but I think it was in JAMA there were two case reports of, patients with refractory macrophage activation syndrome who, had failed a number of therapies you would use, and that would include, you know, calcineurin inhibitors, steroids, etcetera. And they were tried with a new investigational drug, a combination monoclonal antibody. I think it's made by Novartis that binds to IL-one beta and IL-eighteen, two mediators of systemic JIA, Still's disease, also big players in what's going on in macrophage activation syndrome.

It turns out that the use of this MAS eight twenty five antibody was very successful in both the acute control of MAS, but also, that there were no recurrences, I think in the year that those patients were followed. So this really speaks to what is your thought process? What is your approach to someone who develops macrophage activation syndrome? The vast majority of those for rheumatologists is going to be patients with Still's disease, it's kids or adults, but it can happen in lupus, it can happen in infection, it can happen in, malignancies and whatnot. Again, the management is steroids and then the old management was choosing between etoposide or cyclosporine, a calcineurin inhibitor.

The new approaches that are maybe safer, and these people are really sick by the way, is the emapalumab, that's the gamma interferon monoclonal antibody approved for HLH. It's called Gamafan, but it's probably gonna get approved for MAS due to Still's disease. I would I would hope in the next year or so, but there's good, you know, Fabrizio di Benedetti in in Italy has done, you know, cohort, you know, I think 16 patients now, where it's had really great effects and hopefully that'll be enough to get it approved. I've talked about JAK inhibitor use in and when you when you have nothing else to use, that might be something to consider. Again, it's not approved for use in MAS, but you can see that, you know, we're beyond the older ways of managing these patients, which wasn't always successful.

We talked last week about RA patients with disease activity having a higher risk of renal insufficiency without necessarily attributing it to RA. It could be due to RA. It could be the drugs we use to treat problematic RA. There was a report this week of retention rates on biologic DMARDs, and that included TNF inhibitors, IL six inhibitors, and abatacept in, four hundred and twenty five RA patients followed for three years, and looked at their retention rates based on their, estimated GFR showing that basically there was almost no change when you use biologic DMARDs that affected it. Now there was a little change with the TNF inhibitors, you know, the retention rates went from forty five percent down to thirty four percent, went up a little bit with IL-six forty seven percent went up to seventy one percent and really, you know, fifty percent to thirty three percent, but overall, there was no change.

There's a lot of spread here and the confidence intervals are wide, but it would basically says that that using, aggressive therapies probably isn't the reason why patients' GFR changes, and that it probably is safe to use biologic therapies in patients with RA and not have to worry about necessarily their renal function. I put in the the citation about RA and activity as well in these notes. I found a I find a lot of I look at a lot of marketing data sometimes and stuff that comes from the pharma companies and agencies that try to serve the educational needs of pharma. And one marketing piece said that the based on their research, this is not a paper, not journal article, but this is marketing research that the global rheumatoid arthritis market was estimated to be worth 20 almost $23,000,000,000 in 2021. And it's said to go up around, I think the number was four or 5% annually and is estimated to reach 33,000,000,000 by 2030.

Why am I telling you these numbers? It's big money. You're a big cog in this big wheel. So many rheumatologists think I'm just a lowly rheumatologist, you know, we only have 5,000 rheumatologists in The United States. We're not too important.

They certainly don't pay us like we're important. And let me tell you, when you control, you know, in all the rheumatoid arthritis industry at, you know, $30,000,000,000 a year or the, you know, the use of the drug, the drug market for rheumatology is probably a $6,070,000,000,000 dollar market. And who influences that more than the rheumatologist? Not many. You're very important.

So, you need to know your worth when it comes to what you say goes when it comes to managing these patients and the use of, better newer therapies, or I should say potentially better and newer, but certainly more expensive therapies. I found an interesting cohort study about the association between GERD and outcomes in patients with systemic sclerosis. So while ninety six percent of patients, five hundred patients roughly had evidence of GERD, Turns out and there was always been this issue about whether GERD influences the onset of ILD. And I wonder how that happens. Is that through some kind of reflux and aspiration that, is this then the in the inciting event, again, the mechanics haven't really been worked out, but it's always been hinted.

Right? So this research says that GERD did not influence the diagnosis of ILD in scleroderma patients or its severity. However, GERD treatment with either PPIs or H2 blockers was associated with improved survival in scleroderma patients. That's like a backdoor answer to the problem. So this is a curious area.

I don't think we have all the information, but this one cohort analysis says maybe, maybe not. Something for you to consider. Let's look at myositis and ILD. We do know that myositis patients, I'm talking about PMDM, who get ILD, they like RA, like lupus have a much higher mortality rate, much higher complication rate, much more morbidity with pneumonias, etc. A study of one hundred and ninety myositis patients versus myositis mimics over four hundred showed that if you look to predict ILD, doing myositis, specific antibody profiles increases or having one of those like JO-one for instance, increases the risk of ILD six fold.

Having a ROW-fifty two antibody increases the ILD risk eight fold. Having dual positivity with both of those increases the risk of ILD 20 fold. Wow! I gotta tell you I've never been a big believer in doing myositis, specific autoantibody testing because it didn't really change my my thinking some of this data does. So maybe it changes yours, maybe it doesn't.

Two more reports, I like the report this week, from Doctor. McCoy talking about Sjogren's disease, specifically seronegative Sjogren's patients. Her report in RheumNow, actually published somewhere and we wrote about it, was that one third of Sjogren's patients often do not have an antibody, antibody positive either with Rho, SSA or LAH, we like to lean more on SSA. And one of her questions is, you know, how do you diagnose that with reliability without doing a labial biopsy, you know, a focus score greater than four or whatever. So she did an autoantibody panel looking at IgG antibodies, looking at SSA negative Sjogren's patients, Sika controls without autoimmunity and then patients who had autoimmune features.

There's about two hundred patients overall and she found that antibodies to d two d t d two or the the d aminoacyl tRNA deacetylase. D t d t this is new to me, that's why I'm stumbling. DTD2 antibodies were more prevalent, significantly more prevalent in, autoantibody negative Sjogren's disease patients meeting criteria otherwise compared to the both control groups at a fairly high significance level. So that and there was another autoantibody profile, anyway, like this research because I think sometimes we're, we think we're on thin ice when diagnosing Sjogren's syndrome and there are many of you out there who think that maybe we're not diagnosing enough Sjogren's syndrome. I'm not so quite convinced but I'll listen to people who are and people who are the experts on this and hopefully make up my own mind, but I like the idea that research is being done on this.

The last piece I want to talk about is the risk of inflammatory arthritis, IERA or JIA, based on prior exposure to antibiotics. I have written about this four times in the last, I think, two or three years with two good reports, showing antibiotic use portends the risk of RA or inflammatory arthritis and two other reports showing that it increases the risk of JIA. Oh my, well, got another one, right? And this one is, a study of almost thirty thousand new onset inflammatory arthritis, half of them being RA and the others being PSA, SPA, and they were compared to basically, 285,000, population controls. And they showed that, prior antibiotic prescribing was found in forty two percent of the inflammatory arthritis patients compared to only thirty one percent in the background population.

Basically, this suggests almost a, about a fifty percent higher risk when, amongst the patients who ultimately develop RA, PSA, or SPA, and it was like forty eight percent, sixty seven percent, and fifty two percent. What's the deal there? And I guess the real question is, does that just mean that people get antibiotics or sicker people and sicker people are gonna develop other things downstream, autoimmune disease, inflammatory arthritis, cancer, you know, they're more likely to get hit by a bus. It's really maybe a nonspecific, marker, or is there something to it? Does antibiotic, chronic antibiotic therapy are repeated?

Some of those reports I mentioned before, not this one, did say that more exposure was associated with higher risk. So does antibiotic exposure change microbiome? And does microbiome, changes in a certain host, lead to the development of preclinical disease than clinical disease with external factors like diet, smog, smoking, God knows what else. Again, these are, you know, interesting ways of considering how we get to what we've got. What we've got are people with inflammatory arthritis.

How do we get there? If we really want to affect that outcome, we're not gonna do it with a brand new expensive IL-twenty nine inhibitor. Sorry, I like having more options. If we really wanna affect the outcome, need we need to be in the prevention business. Who's going to be more inclined to investigate or affect, prevention than the rheumatologist?

I don't know. So yeah, it's your job, it's your concern, I'm giving you the information, you gotta run with it. Start running people, we'll talk next week. Bye bye.