RheumNow Week In Review I Wanna New Drug %289.28.18%29 Save

It's the 09/28/2018. This is the RheumNow we can review. Hi, I'm doctor Jack Cush, executive editor of roomnow.com. This week in the news, triple DMR therapy, how long does it last in your hands and how does it compare? It may be that the answer to fibromyalgia is frequency of visits.

And in the Huey Lewis version of I want a new drug, it looks like it may be ustekinumab for lupus. First, you should know that at ACR, RheumNow is gonna have a fairly big presence. We're gonna cover the meeting. You can follow us at acr18.roomnow.com. We're gonna have a lot of interesting, things going on, a lot of new reports, things that'll be novel on the website, including audio clips from leaders in the field that will comment on certain abstracts.

Look for those. You'll see in our booth, we're gonna have panel discussions on key areas of rheumatology, including rheumatoid arthritis and psoriatic arthritis and gout and ankylosing spondylitis. And that's gonna all be held in the RheumNow booth. Look for us on the exhibit floor. But let's go to the news this week at RheumNow.

Horizon announced this week that it's launched a study that is looking at the better use of co therapy in patients receiving KRYSTEXXA for refractory gout. As you know, KRYSTEXXA is highly effective in patients with, topaceous but really defined as chronic refractory gout. And it is limited though by the development in some patients by development of anti PEG antibodies. When that happens, the uric acid levels which would have tanked, gone from ten, nine, whatever, down to almost one or zero start to rise back up indicating that there's an anti drug antibody in play. Some have tooled around with the idea, including Michael Pillinger of using immunosuppressive therapy to curtail that antidrug, or anti PEG response.

Azathioprine has been used. There's actually a study going on that's also been launched, using mycophenolate. I think Ken Segg's running that study. And out in the Great Northwest, they've launched a study using methotrexate as the anti antibody inhibitor. And I think that's something that we're really gonna look forward to because if that works as is expected, then you'll get greater prolonged therapy with less interference by these anti PEG antibodies and less toxicity, and again, more time on drug.

So it's kind of good news. Watch for that in the upcoming year. UT Southwestern has a cutaneous lupus registry that they've been following for years, and they looked at the incidence of autoimmune disease in amongst their one hundred and twenty nine patients. And they found that if you had chronic cutaneous lupus, that you had an eighteen percent risk of other autoimmune disease led by autoimmune thyroid disease. It seems to top the list for most associated autoimmune disorders.

Risk factors for, the development of other autoimmune disease includes being white, never smoking, a positive family history of an autoimmune disease, and of course, being ANA positive. Systematic review of 10 studies looking at undifferentiated arthritis in patients with preclinical RA or arthralgias in at risk individuals, look specifically at whether there's a value to therapy, whether it be corticosteroid therapy or DMARD therapy. So 10 studies, almost, eleven hundred and fifty patients with with, either arthralgias or undifferentiated arthritis. There are two meta analyses that actually specifically looked at arthralgia only patients and could find no evidence that only arthralgia patients, without any other risk factors would benefit from either steroids or DMARR therapy. On the other hand, patients meeting the definition for undifferentiated arthritis, meaning they usually had synovitis, and, of course, being, you know, maybe at risk for RA, there seems that there may be a benefit when DMARDs or steroids were used that they lowered the ultimate development of rheumatoid arthritis by as much as twenty seven percent with an odds ratio of point seven three.

Again, we really are in an era where we don't know what to do in at risk individuals. Who are they? First degree relatives of someone who has rheumatoid arthritis, those who have seropositive with arthralgias, those who may have one joint or a marginally elevated acute phase reactant, do you jump right in and use methotrexate or a DMARD or even more? Again, those trials are underway, but this is early data from what's been done and looked at by meta analyses to see if you can get some guidance. The bottom line is arthralgia only probably does not merit DMARR therapy, but that if people look like they have undifferentiated inflammatory arthritis, yes, that does seem to make sense.

And it's just a report appeared in the literature that caught my eye. It's called burning mouth syndrome, BMS. It's a variant of chronic pain. It's said to affect as many as four percent of people in Sweden, which I find hard to believe, But when they characterize these these patients, they tend to be middle aged, or elderly, women more so than men. Patients present with severe burning or stinging, usually involving the tongue, but throughout the mouth has also been described.

They often have metallic taste and abnormal taste sensation, dysgeusia, and they often have, dry mouth and it may be associated with skin disorders, nothing specific. To me, this sounds like another variant of fibromyalgia, patients who present with as very difficult to define pain syndromes are just strange, and I don't mean that in a derogatory sense. I think the altered pain perception, through central mechanisms leads to pain that is often hard to describe and often can be creepy crawly things on the skin or things that don't have dermatomal distributions, or in this case, I've had patients with unilateral focal facial pain associated with fibromyalgia, bad sleep, etc. Whether that's a variant of that, wasn't looked at in this particular thesis that was done, but I think it's interesting to note that it's out there. Data comes from the American, Veterans Administration that looked at their RA population between two thousand and six and twenty twelve and specifically looked at what happens when you escalate from methotrexate incomplete responders to either receiving triple DMARN therapy or methotrexate plus a TNF inhibitor.

And while the patient responses to both drugs in a short term seems to be, like the other study seems to be good, when you measure response by persistence on drug, it is the the the biologic plus methotrexate that outperforms triple. So at one year, the the methotrexate TNF inhibitor of forty five percent were persistent whereas only eighteen percent were persistent on triple therapy. And the interesting thing about non persistence on triple therapy was that a lot of it seems to be related to toxicity from sulfasalazine of all things. So that was sort of two bits of information. Number one, very low persistence rates on either drug in patients in the Veterans Administration, and eighteen percent, on triple therapy, you can say, that means it doesn't work.

I think that these kind of data which are really self reported, observational, they often reflect what the doctor thinks. If the doctor doesn't say good things about triple therapy and is pessimistic and says negative things, guess what, patients are gonna drop out, have side effects, etc. So again, I think that, it's not surprising to me that methotrexate and TNF nodes do well, it is surprising to me that the triple DMAR therapy did not do as well. Speaking of fibromyalgia, a really, difficult study to read, because of its implications. A very large EMR based study of almost 9,000 patients with fibromyalgia specifically looked to quantify depression, severe depression so severe that suicide was an issue.

In fact, they found thirty four actual suicide attempts and ninety six events of suicidal ideation. It was higher in patients who were obese and those who had drug dependence problems, and it seemed to be prevented by the frequency of outpatient visits. I know that, fibromyalgia can be difficult to manage and many people will tend to space out those visits, and you know patients with fibromyalgia often do have a lot of need for interaction with medical providers. So it seems that frequency of interaction could be a very beneficial thing in this often difficult to manage population. I tweeted this week something, that I thought was fairly mundane and mainly for our European colleagues that the European Commission had approved its fifth, adalimumab biosimilar.

This one was called Hulio unrelated to the TV network. Hulio, comes from Mylan and Fujifilm as the maker and there obviously are now addition to Humira, there are other biosimilars from other companies including, for adalimumab including ones made by Amgen Sandoz, Samsung Bioepis and Boehringer Ingelheim. So I thought this was interesting and it's a new addition to the market in The EU. On Twitter, someone commented, what a shame that we don't have biosimilars, this is all the fault of PBMs. That's an incorrect statement.

PBMs may have some issues in our healthcare economy, but the reason we're not seeing adalimumab biosimilars and, etanercept biosimilars is really because of litigation. Right now, those are being held off. They are approved in The United States and they're not on the market because there's a lot of legal battles all going on behind the scenes regarding patent and whatnot. We do see three versions of infliximab that are on the market, now, but the other ones are as hung up in litigation. Maybe PBMs will play a bigger role but they're not to blame right now.

Analysts of Internal Medicine had an interesting article about the misuse of opioids. They did a study of a large population, adult population between 2,000 six and twenty fifteen and looked specifically at 31,000, 32,000 prescriptions for opioids, found that five percent were for cancer pain, sixty six percent were for non cancer pain with a good indication. However, twenty nine percent the opioid was prescribed without a pain diagnosis being on record, suggesting that this is part of the problem. These have become little bit too reflex. And again, the more we talk about it, we're guilty of it here at RheumNow.

The more we talk about this opioid epidemic and the horrors of it, the more the patients who have real pain are going to suffer because it's gonna get more and more difficult for people with pain to be appropriately treated. Lancet this week published the Arrive study, spelled a r r I v e. Don't know what it stands for. I always think these contractions are a little bit hokey anyway, but it is a prevention trial with aspirin and compares placebo to low dose aspirin over twelve thousand patients with a moderate cardiovascular risk. And they basically showed that whether you're on placebo or low dose aspirin, there was no difference in fatality rate, no difference in a combined cardiovascular endpoint that looked at, heart failure, hospitalizations, MI, CVAs, etc.

So that sort of failed. The only thing that stood out was that there was a twofold increase in GI events and those were taking, aspirin compared to placebo. And the critics of the study said that maybe this wasn't a good study because the event rate that was observed was far lower than what was predicted when they were powering the study. So again, the value of daily aspirin in patients appears to be dwindling with all the recent studies. Some recent studies showing that aspirin is really only indicated in people who are at high risk and had prior events.

For you and I who've never had a cardiovascular event, the use of daily aspirin may have no benefit, may only have a small degree of harm. An interesting study comes from the state of Florida about knee arthroscopies, being on a decline. Specifically, they showed in a, time frame, I think it was of 2002 to 2015, there was almost nine hundred thousand knee arthroscopic procedures performed in the state of Florida, but that these have dropped from two thousand two to two thousand fifteen by a total of twenty three percent, and the drop was mainly seen after 2008 when they were starting to go on there were a number of studies on record showing that arthroscopy was failing in a head to head trial, against placebo when it was being done for either knee pain or meniscal tears or knee osteoarthritis. Turns out that conservative management was better than surgical management in those situations, and this is when it started to be changed, change the behavior by orthopedist. I know that in my community, I've sent a lot of patients to the orthopedist with a meniscal tear and the plan has been conservative management, not arthroscopic surgery.

So again, these are on the decline and you're probably seeing this in your practice. Lastly, an interesting study about ustekinumab, the IL-twelve twenty three inhibitor being tested in adult patients who are ANA positive who have moderate to severe active lupus, and are enrolled to receive ustekinumab or placebo on top of their background therapy. The primary endpoint in the study was the SLEI2K Responder Index also called the SRI4 response at week twenty four. They screened a 166 patients, a hundred and two were randomized to either or placebo. The week twenty four results were heavily in favor of ustekinumab with an SRI four response of sixty two percent in ustekinumab and half that at thirty three percent with the placebo, and that was highly significant.

This is very encouraging data, although it is preliminary. The numbers here in this trial are small, a hundred and two patients, but it's very encouraging. There's a good biologic rationale for why IL-twelve twenty three would work in lupus patients. But as you know, you know, lupus trials are hard to do. They're even harder to reproduce.

Ask anifrolimab, looked great in its initial phase two and didn't look so great in its repeat phase three. So, we'll wait to hear more about ustekinumab and lupus in the future. Right now, it's still investigational. That's it for this week at RheumNow. Be sure to tune in to the website to get these links and learn more about these important reports.

We'll talk to you next week. Goodbye.