RheumNow Podcast Upadacitinib FDA Approved For RA (8.23.19) Save

It's the 08/23/2019. This is the RheumNow podcast. I'm doctor Jack Cush, executive editor of RheumNow, coming to you from Bethesda and the NIH second symposium on auto inflammatory diseases. I'll talk about it at the end. They say you are what you eat.

Well, we're going to talk about how your genetics may shape your microbiome. How could a MDA five positive dermatomyositis patient be any worse than they already are by being MDA five positive? And new drug happenings, drugs are busting out all over the place. This and more. We'll start with a report about knee osteoarthritis, randomized controlled trial, not a very good trial, but you know, I'll put it up because I can put up any kind of trial I want.

This is a trial of curcumin versus diclofenac. It's five hundred milligrams TID of curcumin versus fifty BID of diclofenac in knee OA, one hundred and thirty nine patients. The endpoint was just four weeks, twenty eight days. And guess what? They were equally potent.

Now, is that a win or not? Well, you know how many of your patients love drugs and how many of patients love natural products. Curcumin has been proven over and over to be as effective as nonsteroidals. This study and others show, however, that it has less toxicity. So there by itself is probably enough to consider that as a therapeutic alternative in patients with osteoarthritis pain.

The CMAJ, the Canadian Medical, Journal has an interesting report of an association between GERD, This is a study of over 3,000 patients. So it's not small, but shows an association, statistical association between GERD and TMJ disorders. I mean, it's a long way from your stomach to your jaw. Somehow they might be connected, but I'm not getting this connection. It turns out that if you, that GERD is a risk factor for getting TMJ, with almost a threefold increased risk and that such patients often have higher rates of somatization, anxiety and sleep disorders.

Now I get the association between TMJ and sleep disorders and fibromyalgia. Patients with fibromyalgia have a lot of TMJ pain. They often see oral maxillofacial surgeons. It's one of the things that they deal with and they're not surprised and they're surprised not knowing how to deal with it. But again, where GERD ties into this, I'm not sure.

I don't know if these kind of association studies from large databases are real or not. Do you see this? I really don't, I'm going to be looking. Analysis of pediatric, patients with JIA and FMF, looked at how often they get infusion reactions when they're receiving biologics. So this was, a cohort of, patients who had received over 32,000 either injections or infusions over a long period of time, looking at the rates of adverse events and specifically the rate of, serious adverse events, anaphylaxis.

What's your number? How often do you see anaphylaxis in patients, either adults or kids taking biologics? They looked at eight different biologics. Turns out the rate was about three point nine percent in kids, and most of the events were associated with either tocilizumab or rituximab. I find both surprising.

Rates of anaphylaxis has got to be less than one percent in my patients, in my hands. But, you know, this is research. They were specifically looking at this and using an, sort of administrative data to, come up with these numbers. You may be wanting to look at this on your own. MDA five is a variant of dermatomyositis.

These are patients who have severe cutaneous disease. They're at risk for severe lung disease. The presence of lung disease with an MDA five antibody and dermatomyositis, is a bad prognostic finding. In this particular study of thirty one MDA five positive patients, they looked at those who developed pneumomediastinum, about half the group, and those who didn't, and showed that having pneumomediastinum, which sounds like a bad complication of lung disease, no matter what your problem is, they nonetheless had a higher risk of mortality, liver dysfunction, even worse respiratory outcomes, and abnormal CT chest scores. So again, if you MDA five is not a reason to toss in a towel, it is a reason to worry.

But I would say that development of pneumostinum would be a worrisome finding and should be, treated aggressively if that's found. A group looked at gout patients and the association of urate lowering therapy and what that may do to the bones over time. Eighty seven gout patients on urate lowering therapy had serial X rays and had serial deck scans, dual energy CT scans, looking to quantify uric acid deposits, but specifically uric acid or tophi associated erosive disease. Interestingly, over two years, X rays showed no changes, over time in whether you were on urate lowering therapy or not. However, if you look at those same patients over two years, but instead looked at deck scans and quantified erosions by deck scanning, there was a significant reduction that was associated with the use of your rate lowering therapy, suggesting that, there is a strong benefit to urate lowering therapy, one that's not so easily identified by routine radiography, but would be identified by finer techniques, especially one as specific as dual energy CT.

So what about microbiome? You know, it's a lot of research being done on the microbiome. This particular study looked at 107 healthy subjects and looked at six ninety six twin pairs from The UK twin cohort. And they then also did microbiome testing on all these patients using the usual technique sixteen s ribosomal RNA sort of bacterial sequencing to find out what the microbiome was in these individuals. And it showed that the presence of b 27 and the HLA Doctor beta-one alleles had a significantly distinct association with microbiome changes, suggesting that your genes, your class two and class one MHC molecules can shape what your microbiome may look like and therefore may be important in disease pathogenesis and onset.

Last week when we went to press with the podcast, we did not yet know about, but soon found out about that upadacitinib, a new JAK1 inhibitor, selective JAK1 inhibitor, was approved by the FDA for use in moderate to severe rheumatoid arthritis, not responding to methotrexate and DMARDs. The drug's name is RINVOQ, r I n v o q, and it's going to be yet the third, JAK inhibitor that will be approved in the rheumatoid arthritis space. They were given approval for the fifteen milligram once a day dose. It has a lot of the same warnings and precautions that you see with many biologics or any other JAK inhibitors, but I'll go over them anyway. It's important to know with a new drug.

You should be aware of the box warnings for serious infections, including tuberculosis and opportunistic infection. Don't start the drug having an active infection, and then hold or invoke if one serious infection develops, not a routine infection, but a serious infection. Patients should be tested for the risk of TB, and should be monitored for TB. Again, the risk of TB, this is my opinion, not in the package insert, risk of TB with JAK inhibitors is not nearly as high as it is with TNF inhibitors, but because JAK inhibitors will inhibit gamma interferon to some extent, there may be a higher risk than with other biologics like abatacept or rituximab. So monitor for TB and test for TB lymphoma malignancies, as you see all the other packaging inserts.

And what's new here is the risk of VTEs, thrombotic events, including deep vein thrombosis, pulmonary embolism, arterial thrombosis were seen in patients with RINVOQ or upadacitinib. Now their numbers in their clinical trials and the development program were really quite low. I didn't expect that that would be a box warning here. The FDA, think, is going forward and now making this a class effect. I don't think because they they added it, as you know, a box warning to tofacitinib with some of its recent safety data.

It was part of the, approval for baricitinib. I think you're gonna see it with filgotinib if and when that gets approved in, the many months to come. So I think it's a class effect now with JAK inhibitors, which is one of the warnings which says patients at risk with thromboembolic events probably shouldn't be given this particular JAK inhibitor. And they have other warnings, and this is not box warning, just regular warnings about monitoring for lymph lymphocyte counts, hold the drug and don't use it if lymphocyte counts are less than 500 or if the absolute neutrophil count is less than 1,000. Use caution in patients who have an increased risk for gastrointestinal perforations.

As you know, IL-six inhibitors have a risk of GI perforations, but so do JAK inhibitors. And that's in the package insert or that's been seen with the other drugs that have been studied, including tofacitinib. So that's a warning here as well. The drug is going to be soon available. Its price is going to be a whopping $59,000 a year or $5,174 a month.

You say, wow, that's going be a lot. Just like all our other drugs, there's going be a copay program. It won't be that much for people who have commercial insurance. You're paying cash, you're in trouble. By comparison, it's on par with what's out there for other drugs.

So for instance, the price of Humira is 62,000 a year. Brazeljanz is almost $54,000 a year. And the price of, Olumiant or baricitinib is a bargain at $25,642 a year. That's sort of their commercially advertised price. So again, look for this drug.

I think it is an important addition. I think it may change how we use JAK inhibitors now that we have three in the marketplace, and maybe four in the future. Lastly, other big news about SKYRIZI. SKYRIZI is rizenkizumab. It's an IL-twenty three inhibitor also from AbbVie.

It was approved in April for use in psoriasis, not psoriatic arthritis, just psoriasis. They published the results of a head to head trial of SKYRIZI versus Humira showing that their IL-twenty three inhibitor is significantly better. AbbVie is banking heavily on the success of SKYRIZI, rizikizumab, and also upadacitinib or RINVOQ going forward. And as Humira will go off patent in the next few years, it's all patent outside The US. It's certainly on patent in The US till 2022, I believe.

So in this particular study with SKYRIZI versus Humira, six zero five adults with plaque psoriasis, moderate to severe getting the usual doses, the week sixteen results looking at a superlative outcome of APOSI ninety had a seventy two percent for the rizenkizumab and forty seven percent for adalimumab. Look for this in your psoriasis patients. I'm sure that's being developed for psoriatic arthritis. The trials are being done, but again, it's really right now just for skin psoriasis. Lastly, we'll talk about pregnancy outcomes in JIA patients.

When I've done, analyses of our patients, my patients who get pregnant, certainly we see RA patients, some PSA, some spondy patients. You know what? We have a lot of patients who had JIA and who are now adults, young adults, and they get pregnant. The question is what happens with them? The data here was pretty good.

Ninety eight women with JIA and their pregnancies and twenty one males with JIA and their pregnancies. They looked at those who were exposed to DMARDs. Half of them were exposed, I believe, to a biologic And the majority of them really were JIA, but there were other pediatric patients who grew up. At this point, I think they were average 23 with thirteen years disease duration, and their rates, as a result of being pregnant, were not higher. In fact, we're on par with population based expectations.

So spontaneous, abortion was thirteen percent, fifteen percent or less is about right. Congenital anomaly was three point six percent. Their numbers range from three to six percent in the general population. That's pretty good. They did have a slightly higher rate of premature birth twelve percent and c sections at thirty seven percent, but that's been seen in other inflammatory diseases like rheumatoid arthritis.

Again, this is a German study. I think this says that your JIA patients can go ahead and get pregnant and expect to do well even if they have been exposed to a DMARD or a biologic. Look for the war on RA part four, where I talk about Glenn Frey, the Eagles, and why we need to step up like the Eagles did to become notable. I'm now at the NIH Auto inflammatory Conference. You can I'm going to write about that in the days to come.

You'll hear more about that. A lot of great information. Look to NIH to look at the videos that they're going to post for you to watch for free. Also, as a result of having this meeting, I developed another website called stillsnow, stills, now.com. You can use it to get information about Still's disease, the criteria.

I got a cool, diagnosis calculator. You check the boxes on symptoms. It'll tell you whether you meet Yamaguchi criteria, the Cush criteria, or the ILR criteria. Still'snow.com. That's it for this week at RheumNow.

We'll see you next week. Take care.