Alive In 2025 (1.10.2025) Save

It's 2025, a whole new year. In fact, it's 01/10/2025. Happy New Year to you. This is the Room Now podcast. I'm Jack Cush.

Another year, another podcast. It's another good year in the neighborhood of rheumatology. This week, starting off the year, we've got reports on RA, vasculitis, gout, lupus, all the things that kind of sustain us. Let's get into it. I want to remind you, Room Now Live is coming up in about a month in Dallas.

I hope you're going to be there. We'll talk more about that at the end. It is a great rheumatology meeting for great rheumatologists. Let's start with an interesting study about cardiovascular risk with osteoporosis therapies. This is a study of a high risk population, 1,000 patients who are over the age of 50 and are on dialysis.

They're at higher risk for fracture, they're at higher risk for a lot of things, including cardiovascular events. And I think that the question is, will they lower the fracture risk? Yes, they do. And will there be a cardiovascular risk? You know, these drugs in this arena have been plagued by the risk of major adverse cardiac events.

It sort of starts with the use of calcium, bisphosphonates not so much, but, you know, hormone replacement therapy had a cardiovascular risk, Romecizumab has a cardiovascular risk, there's been concern about it with parathyroid drugs. So in this particular study, one thousand patients on dialysis over age 50, they either went on denosumab or an oral bisphosphonate for three years, and they were looking at what the benefits or harms might be. And they saw what you'd probably want to see, which is a significant lowering of risk. So adanosumab was better than bisphosphonates at lowering the risk of subsequent fractures, and lowered it by forty five percent. However, it did come with a thirty six percent increase in major adverse cardiovascular events.

Now, is there a risk with denosumab and cardiovascular events? Not previously been reported, but this is a high risk population. And so maybe that's what we're seeing here. But I think that this is a topic that comes up quite often. I don't know if you agree with me, but I think hidradenitis is a disease that we rheumatologists should be treating.

When you talk to patients with hidradenitis suppurativa, they often don't have a home. You know, they're sometimes managed by surgeons, by primary carers, should be managed by dermatology, but not all dermatologists want to manage this really complex medical condition that has a lot of comorbidity. So I report on this, we are going to have a great lecture on this on Sunday at RheumNow Live. This is a phase three study of almost 600 patients who were treated with adalimumab. As you know, adalimumab is approved for use in hidradenitis.

This is a post hoc analysis of one of those phase three studies. And they wanted to see what was the contribution of CRP. In their studies, seventy nine percent of patients had an elevated CRP, high resolution CRP, and those who had high CRP levels did have more severe skin disease. They also tended to have more obesity and higher BMI's. And BMI and obesity is another risk factor for having an elevated CRP, an acute phase reactant.

So in this study, the high CRP patients had higher BMI's 34 versus 28. They also had a lower odds of having an adalimumab response. So the question is, was it the inflammation that made them less likely to have an adalimumab response? Or was it the obesity, which we've talked about before, that contributes to being refractory to conventional therapies? So the lower odds, it was a forty seven percent low, reduced risk of having an adalimumab response.

So is this an activity story, or is this an inflammation, or is this an obesity story? I don't think you can disentangle them in a lot of patients, and I think you're just going have to deal with it. So do you give higher doses? Do you stress weight reduction? Yes and yes.

A Spanish study called the ARTESR looked at giant cell arthritis outcomes over a seven year period. They have twelve hundred patients in this registry with more than two years of follow-up, and they looked at mortality rates. The five year mortality rate in their GCA patients was almost forty deaths per 1,000 patient years, higher in males than in females, fifty nine versus twenty nine per 1,000 patient years. But the overall mortality rate was not that much higher, and it's not significant, it was a little bit higher, but not significantly higher than that seen in the general population. And I think that's really kind of encouraging.

Now, it's age matched, going to be elderly patients versus elderly patients. But I think that this is good news, and it says maybe something to, how, treating this highly inflammatory disorder might help avoid increased mortality. Those who were at higher risk, for mortality were, as you might expect, the males and those who are older, because, yeah, they're closer to death, are they not? That's what happens when you have a birthday every year. You get one step closer to meeting your maker.

Aren't we starting the new year on a happy note? The protective factors in the study was, having a headache, not necessarily having an ocular presentation, but having headache, and and hemoglobin, were protective, meaning having higher hemoglobins had less, mortality risk. Interesting. An EGPA study retrospective review of one hundred and sixty five patients with EGPA and GI manifestations shows that GI manifestations associated with eosinophilic polyangiitis was associated with high eosinophil counts with an eosinophil percentage of greater than almost 20% or greater than 19.5. Patients who had GI massages included those who were who had weight loss, and also had abdominal pain, diarrhea, nausea and vomiting, GI hemorrhage, GI ulcers, rarely obstruction or pancreatitis.

So the main manifestations were abdominal pain, eighty percent, diarrhea, forty percent, nausea and vomiting in thirty three percent. Patients who are at greater risk for these GI manifestations were those with weight loss and myalgia and high eosinophil counts. Don't see many EGPA patients, but I think that this is helpful and I'll be looking for more in the way of GI manifestations. I like this report about RA care, and it's a study on nurse led care, NLC, versus usual care, versus rheumatologist led care. This is a meta analysis, or literature review of 14 studies and almost 3,300 patients.

And it showed that nurse led care was highly effective, surpassed usual care, and was equal to rheumatologist led care in both primary and secondary outcomes. And I think that this is maybe a lesson for us as we deal with manpower issues and patient overload issues, that you could have RA patients and protocol protocolize their treatment and have it all being managed by your nurses. And they don't need to be advanced practice providers, although that's certainly another great option in dealing with the demands for care and the difficulty in finding and expanding your practice with rheumatology fellows. So nurse led care working out very well. And by the way, this has been shown in other disorders as well, including gout, is one that quickly comes to mind.

Another RA study looked at the German biologics registry in RA, also called the rabbit registry, that compared from their many, many RA patients, they compared the looked at their RA ILD patients, and they matched them with controls. And they found that high levels of sed rate and CRP were most predictive of an increased risk of incident ILD in RA patients. And surprisingly here is the sed rate and CRP that increases the risk, not dash 28, not tender joint count, not swollen joint count, not global assessment scores. It's inflammation that drives risk. So, you know, we've talked about ILD, it's a big problem, there's a lot of research on it right now.

We just covered ILD, a lot of ACR and ULAR, we saw reports that showed that when you treat RA aggressively, you can thwart the development of ILD. I think that this data ties into that well. Control of disease might help reduce the risk of RA ILD, which one that's present is not good. Poorer outcomes, greater infection rates, higher mortality rates, more difficult to treat, and we don't have an approved therapy for RAILD. So, using sed rates and CRPs as your biomarker makes a lot of sense in managing RA.

An Italian study of almost 500 patients with RAs found that sixteen percent of them met the UR definition of difficult to treat RA, or D2T RA. This finding was unrelated to age, gender, seropositivity, but it was associated with three factors that are of interest to you. Patients who had difficult to treat RA were more likely to have erosive disease, meaning they're the real difficult patients. They're more likely, that's twenty four percent versus eleven percent, double the risk. They're more likely to have obesity.

We've talked about obesity being a factor, a co factor in in non responsiveness, thirty three percent versus nineteen percent. And fibromyalgia, that's the subset of difficult to treat RA patients who are not going to respond to more aggressive therapy, whereas maybe those with inflammatory markers and erosions are the ones that would respond to more aggressive biologic or targeted therapies. But fibromyalgia doesn't. Again, the D2TRAs, a quarter of them had fibromyalgia versus the non difficult to treat, and that was only ten percent. So, again, I think that this is an experience and observations that helps inform what we should be looking for in those who have difficult to treat RA.

A real world study of RA ILD from Italy, the GISAIA study, finds one hundred and sixty five patients with incident RAILD who are also treated with Nintedinib. Now, I find this impressive because most rheumatologists I know in The United States aren't using much Nintedinib. They're sort of waiting, referring to pulmonology, and waiting for someone else to start the patient on nintenden. Now, maybe you are, but I don't see a lot of that where I practice or people I talk to. They and I think this is an interesting experience here, because the sixty five patients with RA ILD on atentenib, what's the outcomes?

And it's not controlled, there's no placebo here, there's no other active control, It's just reporting the observation. Their twelve month retention rate on nantenib was seventy seven percent. That's pretty good. And the drug was said to be effective in eighty percent of patients where they had stabilization of FVC. So the problem here, of course, is side effects are common with nintedinib.

GI side effects are problematic. A quarter of patients here stop the drug because of adverse events, mainly GI. Overall, the GI side effects or side effects were seen in fifty five percent of patients. So I do think that we do need to be considering the use of either tocilizumab or nantetinib, because the other drugs that we use, including rituximab, haven't really proven to be effective in these patients. But we need more research in this area.

We need more trials like this. Speaking of ILD, a post hoc analysis of the DeSear study, a double blind trial in scleroderma, looked at forty eight patients who had systemic sclerosis associated ILD, and showed that rituximab did have an effect on lung outcomes at twenty four weeks, but it was only going to be seen in patients with an elevated CRP. And the CRP elevation did not need to be very high, it just had to be abnormally high. And again, the difference between the rituximab and placebo groups was eight percent, but that was felt to be significant in this trial. A study of lupus looked at fibromyalgia incidents.

How many of your patients with lupus also have fibromyalgia? I got a number in my head that I would have said maybe a third, maybe twenty five percent. This is a meta analysis of 5,000 patients in many studies, and showed that overall the frequency of fibromyalgia is almost fifteen point eight percent, almost sixteen percent. But that lupus patients in the studies had a three point seven fold higher risk of fibromyalgia, and that was significant by the odds ratios. So it's a confounder in management, in drug responsiveness, and also in assessing disease activity.

So realizing that secondary fibromyalgia is a frequent comorbidity in SLE will make your life easier. Again, we have reports of the wonders of JAK inhibitors. This is five randomized controlled trials looking at JAK inhibitors and whether or not they're effective in vitiligo, with the endpoint being repigmentation in vitiligo patients. So in this five trial 1,500 review, it showed that greater than fifty percent improvement in total vitiligo score was 2.7 times more likely on a JAK inhibitor, or that seventy five percent improvement in facial vitiligo was almost fourfold higher when patients were treated with JAK inhibitors. So, JAK inhibitors had same amount of side effects as did the placebos, although there were more skin associated AEs, and by that, I would assume that they are meaning herpes zoster.

So, yet another example of where JAKs may work, and we're going to have a great discussion on JAK inhibitors at RheumNow Live. We got a whole session, four lectures. John Giles talking about oral surveillance three years later. Matti Feldman talking about what happens when JAK inhibitors go generic. Yes, it's going to happen.

Christina Charles Schulman is going to talk about dermatomyositis and JAK inhibitors. And Joseph Marola, a RheumDerm guy at UT Southwest, going to talk about Tick 2s and their effects. So I think you're going to enjoy that at RheumNow Live. A report from Arthritis Care and Research looked at a twelve month study randomized trial of one hundred and seventy nine gout patients who started on allopurinol to lower the uric acid levels. Now, you know, when that happens, in the first six months, you get a lot of mobilization of uric acid and an increased rate of flares.

So the first six months, it's probably not a good idea to look at flare rates. But in this trial, the period from six months to twelve months, they found that flare rates went down significantly, that thirty eight percent of patients had no flares, nineteen percent had one flare, and forty three percent had more than one flare. So still flares are a problem in even patients who are on urate lowering therapy with forty three percent having two or more flares between six and twelve months after starting allopurinol. The bottom line is that flares contribute to the impact of gout and ultimately gout outcomes. And it is something that we have to co manage when we're using urate lowering therapy.

Another report on gout looked at what happens when you lower uric acid levels in patients with CKD, stage three CKD. And they found that if you lowered the uric acid to target levels of less than six, you also lowered the future risk of severe kidney disease, worsening of their CKD, or even better, end stage kidney disease. And that was significant. And last, my last report on gout looked at colchicine and whether it lowers the mortality risk overall. You know, there's a number of studies out there that most studies showing that it does lower overall mortality, some show showing that it does lower cardiovascular mortality risk and MI rates.

And then you do know colchicine was approved last year for cardiovascular risk reduction. So in this very large database, of almost ninety nine thousand, almost one hundred thousand patients initiating urate lowering therapy, seventy four percent male, eighty five percent, white, two thirds I'm sorry, the average age was 63 years. They showed that colchicine prophylaxis in these hundred thousand gout patients was used in sixteen percent. And in those that received colchicine, they had a significantly lower, lower rate of cardiovascular events, an eighteen percent lower rate with a hazard ratio of point A two. Those on colchicine had a rate of twenty nine per one thousand patient years.

Those without prophylaxis thirty five per one thousand patient years. So it did lower gout flare rates, it and then in this case, it did significantly lower cardiovascular event rates. So don't be afraid to use colchicine. We have talked about GLP-1s. Somehow between ACR and the holidays, we missed this report from New England Journal about the use of GLP-one receptor agonists in knee osteoarthritis.

This is a sixty eight week trial of four zero seven patients who were enrolled to receive semaglutide weekly. Going in, the average age was 56, the BMI was forty, the Womax scores was 71 out of 100 for their knee OA pain. So there was a significant reduction in BMI of almost 14% on the semaglutide versus only 3% on placebo, that was highly significant. And those that were on the GLP-one drugs, there was a significant reduction from 71, and a drop by 41 down to 30 out of 100, whereas there was only a 27 drop in those that were on placebo, and that also was significant. So we've talked before about GLP-1s and their efficacy in gout, in RA, in lupus, and now also in knee osteoarthritis.

You might have seen the report this week, sort of a nationwide assessment of electronic health records, in over 10,000,000 people and six large medical systems around the country, looking for the frequency of autoimmune disease, and they had a list of one hundred and five autoimmune disease. They found that five percent of the population has an autoimmune disorder. This is actually less than what I reported last year, where I think it was as much as ten percent, but a lot of this has to do with how you do it, right, with the methodology that's employed. Again, they did see, not surprisingly, that autoimmune disease was twice as likely in women compared to men, and that of those who had autoimmune disease, two thirds had one autoimmune disease, twenty five percent had two, and eight percent had three. You know, the main ones were, as you might expect, RA, PSA, thyroiditis, I think were the top ones on the list.

So if you're interested in that, you can find the citation on the website. Again, room now live, February eighth and ninth, all day Saturday, half day Sunday. I think you want to be there. We've got a great session on JAK inhibitors, as I mentioned, with Madeline Feldman, Joseph Marola, Christina Charles Schulman and John Giles. We're going to have a great panel discussion on this.

We hope to see you in Dallas. Tune in next week. Happy New Year.