RheumNow Podcast The End Of Arthritis (9.13.19) Save

This is the RheumNow podcast for 09/13/2019. I'm Doctor. Jack Cush, executive editor of roomnow.com. If you're tuning in to find out the end of arthritis, what that's all about, and some clue as to what that may mean, you're going to be disappointed because I just use that as a title to this particular podcast because I didn't really have any unifying theme. I had no catchy title.

So I baited you, brought you here. You can hang up right now if you like. But, usually, what I do is I see a theme, something that's dominant in the news and try to give you a nice title that will give you a feel for this. Don't have one this time. This is a hodgepodge, a mishegoss, a motley collection of different kinds of reports from the rheumatology literature in the last week.

Let's get into it. TycoPA, I don't know if you've heard of TycoPA, it's the Tight Control in Psoriatic Arthritis trial was published a few years ago, and it was the first trial of its kind to show that a T2T regimen might lead to better outcomes in patients with psoriatic arthritis. What appeared in the literature this week was the five year follow ups that the long term follow-up to the TYCOPA study. In the study, they had one hundred and ten patients who either were treated with tight control, that's the T2T regimen, and those who received standard of care, whatever happens. And after five years, the outcomes were surprising.

They were a little bit different than the first report. They showed that both arms, the tight control and the standard of care, achieved similar levels of low disease activity, suggesting that tighter control was not going to yield better long term outcomes. So an LDAS was achieved in sixty nine percent with tight control and seventy six percent with standard of care. There was a higher use of biologics or initiations of biologics, but in the end, there wasn't much difference in biologic use between the groups. And what was different was that maybe tight control gave you less methotrexate use and maybe more biologic use.

This is not a growing endorsement of tight control. In fact, I think it might be a strong argument that it doesn't really have a strong place in our, way of managing patients with psoriatic arthritis. I think it's controversial. I think you should discuss it in your next journal call. A very large study looked at what happens to gout patients as far as developing renal disease and what that means.

The UK clinical practice database, which is a very large dataset, like hundreds of thousands of patients, compared patients, almost seventy thousand patients with gout to about five hundred and fifty thousand patients who did not have gout. These are people from within their database. And they showed that having a diagnosis of gout doubles the risk of having chronic kidney disease. Eight point five per one thousand patient years versus four point one per one thousand patient years. The risk was highest with, you would have guessed it, end stage renal disease.

But although having gout increased the risk of having CKD, it did not increase the risk of dying from CKD. I don't think this is particularly new. I think it's important to know and put a number on it and to worry about chronic kidney disease in patients who do have gout. So Still's disease, as you know, is an auto inflammatory disease. Like other auto inflammatory diseases, there is an increased risk of amyloidosis.

AA amyloidosis can be seen, in patients with systemic JIA and adults with Still's disease. An interesting review of the literature showed that the risk of developing AA amyloidosis was almost one percent, zero point eight eight percent. And this was based on the few cases they could actually find. When they looked at the number of patients, I think it was a total of 16 patients, they showed that the mean age of onset of their Still's disease was around 30. The delay in the diagnosis to time from the start diagnosed with Still's disease to the time they got their amyloidosis was about sixteen or seventeen years.

And renal involvement was the most common feature. I bring this up because I've managed a number of such patients and I've always been of the belief that all that report about amyloidosis is largely something you see on the other side of the pond going towards, you know, the EU. And the fact is that we do see a significant amount of amyloidosis in these patients with auto inflammatory diseases, not just Still's disease. And you need to be on the lookout for them. They will often show up as a change in renal function, hypertension.

They could show up as cardiac disease or GI disease or undiagnosed complications of their original disease. So look for it. I think you'd be surprised. And again, I've seen this in two of my patients. One died from renal failure from their amyloidosis.

So I was talking, to someone this week about drug induced lupus, and I looked something up on the literature and I came across reports of hydralazine induced lupus. Now, don't see much of this anymore because no one really uses hydralazine other than the OBGYNs who are managing pregnancy induced hypertension. I don't really see much hydralazine, maybe difficult cases where it's part of a four drug combination attempt to controlling difficult disease. But nonetheless, hydralazine induced lupus is still out there. And what's notable about those people is they tend to be a little older.

They tend to have a lot of pulmonary and cardiac and pleural pericardial manifestations. But what I saw was a little bit surprising to me. So in the reports, mainly case reports, you saw the usual things, pleural pericarditis, arthritis, anemia, ANA, skin involvement. Yeah, okay, that's what I expect with drug induced lupus. But what I did see, what I didn't expect was a number of reports that showed ANA negativity and instead being replaced by ANCA positivity, including PR3 and MPO antibody positivity.

Some of these patients also have been described as having anti cardiolipin antibodies or double stranded DNA antibodies, and also a number of case reports of true biopsy proven glomerulonephritis, suggesting that the spectrum could be different than what was previously thought, meaning acute disease, lupus like manifestation, positive ANA, stop the drug, drug symptoms go away. Well, some patients have continued on. It raises the question of whether they had hydralazine induced glomerulonephritis or whether they truly had, you know, true lupus that was not yet recognized until they got the drug. Hard to say. But I think that, again, the spectrum has changed.

Look for ANCA positivity, look for hydralazine associated vasculitis. These have all been reported. So an interesting study comes from Ted Mickels and colleagues from the VA system. ACNR published the results of persistence on drugs, and they looked at a cohort of RA patients in the VA study between, I think, about ten year period and looked at persistence on the regimen that was used. The one year persistence of methotrexate and TNF inhibitor over 2,000 patients was forty five percent.

By comparison, the persistence on triple DMAR therapy, methotrexate, sulfasalazine, hydroxychloroquine was only eighteen percent. In their analysis, they showed that the reduction was largely due to toxicity, mostly from sulfasalazine, suggesting that maybe it shouldn't be part of the mix. It also suggests that triple DMAR therapy doesn't, again, fare as well as combination therapy. And the question is, is that reality based on lack of efficacy and development toxicity, or is that, reflecting the rheumatologist belief systems that say that, Gee, it's just not as good. I don't use very much of it.

I'd rather use a TNF inhibitor. I think this is a strong bias against triple DMAR therapy that's not quite deserved because the data on it are very strong. This data, based on real world use in the VA system, argues against its utility long term. You may have seen the report at the start of the week actually came out exactly a week ago on Friday, when the FDA announced the, approval of, OVEF or what's called Nintetinib, a tyrosine kinase inhibitor used to treat idiopathic pulmonary fibrosis has now been approved for systemic cirrhosis patients who have significant interstitial lung disease. The approval follows a number of different studies, mainly in a five hundred plus patient study, the senescence study that showed there was a significant difference after one year on entetinib, and where they showed about a forty six percent reduction in progression of their, FVC progression, compared to those who are on placebo.

When you look at the actual numbers, the data, you know, there's not a lot of difference. The differences are small, but it's about half as much progression when you're on this particular drug. Again, it does have some toxicity. It is going to be an add on, but it is remarkable in that it is basically the first drug approved for this condition. What is also remarkable is the fact that while it has shown pulmonary benefit, it has no effect on other manifestations of systemic sclerosis, and that would include skin manifestations.

So look for this. I'm sure you'll be visited by your local Boehringer, Ingelheim rep sometime soon. A very interesting study, Arti Cavanaugh brought this to my attention that appeared in Alzheimer's rheumatic disease that I missed. That brings up an important point. You know, a lot of you read the literature.

If you find an interesting article that you think everyone should know about, send it to me, JackCushroomNow dot com. I'm always looking for good things to report on. You could be a reporter for RheumNow, as far as I'm concerned. This particular report looked at septic arthritis and how it should be treated. It's a very large study coming from Switzerland where they took one hundred and fifty patients, the vast majority of whom had wrist and hand septic arthritis, bacterial septic arthritis, and they either received two weeks of IV antibiotics or four weeks of IV antibiotics.

All patients underwent some sort of surgical lavage, sometimes more than one. And then that was followed by a myriad of different IV antibiotic therapies, either twelve weeks or four weeks, followed by PO antibiotics. And when you looked at the overall cure rates, it was about the same for both, meaning ninety nine percent with two weeks of IV antibiotics and ninety seven percent with four weeks of IV antibiotics and really no difference in, toxicity or other adverse event rates, or sequelae. So again, this argues that maybe we don't need quite so much, you know, four weeks, six weeks of IV antibiotics with bacterial arthritis. I think we need more studies like this for it to change the standards of care, which do call for longer courses of IV therapy.

Another interesting study also appeared in Alzheimer's disease this past week. Bimekizumab as add on therapy in patients with rheumatoid arthritis are a patients who did not respond to cerdulizumab. In this particular study, I think they had about 100 patients, what's the number, something like that, 100 patients, half actually, everybody went out to open label cerdulizumab. And after eight weeks, if you were a responder, you were not going to be in the study. If you were an incomplete responder or non responder, you stayed on the cerdulizumab and half got placebo and half got bimekizumab.

Bimekizumab is an antibody, a monoclonal antibody that binds to IL-17A and IL-17F. And the idea is it's a dual inhibitor and maybe it's better than a single inhibitor, which is what we have on the market right now. As you know, this therapy has been studied well in psoriasis and psoriatic arthritis and shown to have some really impressive results. What's also known is that other IL-seventeen inhibitors have not worked in rheumatoid arthritis, although many postulated that it would. So why they studied this here, I don't know.

It seems like an odd idea, but interestingly, the data was pretty clear. So eight weeks of therapy, you get randomized, the next twelve weeks from eight to 20 was where they evaluated the efficacy of bimekizumab or placebo as add on therapy. And guess what? Patients who were more likely to achieve LDAS was more likely to be seen with bimekizumab sixty one percent versus forty eight percent with placebo. The relative reduction in -twenty eight CRP was -1.41 versus -0.82, again, with cerdulizumab and placebo.

This sort of reawakens the issue about whether IL-seventeen inhibition might be advantageous in patients with rheumatoid arthritis. I'm assuming we're going see more studies on this. Our last report comes from JAMA, and makes you a better doctor overall, maybe even a better rheumatologist about how you should screen patients who are about to have total joint replacement. Fairly large study basically looked at claims data of patients undergoing, arthroplasty, I think it was mostly hip and knees, which you know is like being done in a bazillion people right now. And what's also known, and I'm sure you know this, is that diabetics and uncontrolled diabetics have a higher rate of perioperative and postoperative complications coupled with their arthroplasty.

This particular claims based study looked at how many patients undergoing arthroplasty had preoperative or perioperative, testing for diabetes, either serum glucose or hemoglobin A1C levels. And it was shocking how low it was. If you didn't have diabetes, it was only done five percent of the time. If you did have diabetes, it was done twenty six percent of the time, if you were not on insulin, and forty three percent of the time, only forty three percent of time if you were on insulin, suggesting that this is probably something we should be doing in patients undergoing major surgery, like a joint replacement. It's easy, it's cheap, and it may help to avoid, unwarranted complications in the future.

That's it for this week. Go to the website, check out the citations. You can read more on these great reports. We'll see you next week on RheumNow.