RheumNow Podcast Better Ways For Gout Treatment (11.8.19) Save

It's the 11/08/2019. This is the Room Now podcast. I'm Doctor. Jack Cush, executive editor of roomnow.com. This week, better ways to treat gout.

Should we expect cancer in our many diseases that we treat? And news for patients with psoriatic disease. Some updates, some new indications, maybe. Let's start off with a study about ANA positive consults. You get them all the time.

Does the patient have lupus or not? A cohort of patients being referred for evaluation of lupus or connective tissue disease showed that having an ANA did slightly increase your risk of getting connective tissue disease, But it did not associate with having fatigue. So they specifically looked at fatigue and other factors and found out that it did not predict the subsequent diagnosis of lupus or connective tissue disease. And this is because about a third of the patients that were referred had fibromyalgia, which probably explained a lot of it. It turns out that fatigue was highly correlated with widespread pain and probably then fibromyalgia.

That would be, I guess, a useful consideration when seeing such consults. We put a tweet up that got a lot of play about methotrexate, an old drug with new tricks. And it's really just a report, a reference to a report that says that we know about methotrexate and its ability in inflammatory arthritis, but you may not be aware of its use and utility in patients who have chronic viral arthritities. And they specifically talked about chikungunya, alphaviruses, parvovirus, even hepatitis and HIV associated arthritis. Methotrexate has been shown to work.

And again, it's sort of a hodgepodge collection of case reports showing its utility, not double blind, randomized, placebo controlled trials, but nonetheless showing where methotrexate may work. I've had a few patients, for instance, with parvovirus where the arthritis actually lasted for more than a year and the patient was on methotrexate for that time. There's a lot of new information about this chikungunya virus and how those patients with chronic arthritis may respond well to methotrexate. So, the Spanish group of investigators have a registry for lupus. It's called R E L E S S E R, Relesser.

They have almost 4,000 patients in this registry. And specifically, looked at the risk of cancer in their lupus patients. So, this was a retrospective study. They did show that the overall SIR was one point three seven, suggesting a thirty seven percent increase in the risk of developing a cancer. It was higher in women where the SIR was almost double that, two point three eight.

And interestingly, disease activity added to the risk of developing cancer. We'd expect that because we know inflammation and immune dysregulation manifests clinically as disease activity, but immunologically, what's it doing? Well, it may increase the risk of developing cancer. And for some unknown reason to me, ACE inhibitor use was actually associated with non hormone sensitive cancers and that was sort of a surprising thing. Now, maybe it's more renal involvement that would use an ACE inhibitor in or hypertension.

I don't think it's the ACE inhibitor that's the factor here. I think it's a surrogate for something else, but something to think about. Speaking of cancer, does it happen in psoriasis and psoriatic arthritis? Well, we have some meta analysis here of patients with psoriasis, 58 studies, thousands and thousands of patients showing an increased risk, an odds ratio of one point one eight or one point two two, a twenty two or eighteen percent increase in all cancers, highest with the most severe forms of psoriasis. The cancers that were increased in this cohort in these studies was colon, laryngeal, liver, lymphoma, non Hodgkin's lymphoma, oral cavity cancers, esophageal cancers, and pancreatic cancers.

So, how can you best manage your gout patients? I've been advocating for years, don't use colchicine. I stopped using colchicine when it went from 4¢ a pill to $6 a pill. And honestly, haven't used colchicine to manage gout in many, many years. It's not necessary.

Yet, the world thinks that colchicine is a drug of choice. Well, not really when explosive diarrhea and belly pain is your main side effect that's commonly seen. So, I manage my gout with nonsteroidals, and if that's contraindicated, I use steroids. And it works out very, very well. And I can use those for chronic prophylaxis when I'm starting urate lowering therapy.

Well, there's a trial called the CONTACT trial that actually did a head to head comparison of colchicine in standard doses versus naproxen in standard doses in patients who had acute gout. And so, the numbers here was like two hundred on one drug, one hundred and ninety nine on another drug. They all had acute gout. What was the outcomes? Well, it turns out both were equally effective in managing the pain and control of acute gout.

Neither one was superior, but there was more side effects with, guess what, colchicine, forty six percent versus twenty percent with naproxen and headache, which was about double, twenty one percent versus eleven percent, again colchicine to naproxen comparisons. And that was those symptoms were being seen in the first seven days. So, again, I advocate don't use colchicine. It's still expensive even though it's generic. But if you like, go ahead, you'll just have more headache, more diarrhea.

It'll give you more headache and your patients also get more headache. Peglodecase is something that obviously is a major advance in treatment of very refractory gout. An interesting study came across of ninety two patients who had gout that was treated with peglodecase and they compared patients who were pretreated with either IV hydrocortisone or IV solu medrol and they showed that there was actually better outcomes when they were given the methylprednisolone pretreatment. They actually had more PEG infusions, so the tolerability of the drug went up. If you were on IV Solu Medrol or Methylprednisolone, eight point five infusions versus four 0.9 with the hydrocortisone.

And it had fewer infusion eight versus forty two percent, forty two percent being with hydrocortisone, suggesting you should be using the longer acting steroid when pretreating patients going on pegilodecase. So, does treat the target work in gout? We do know that hyperuricemia in gout patients is correlated with a risk of death and cardiovascular events. Study of almost 1,200 patients that were enrolled in a gout study or gout registry, These patients were ninety two percent male, average age was 60. They had disease for almost seven years.

The entry baseline SUA was nine point one milligrams per deciliter. And they in the prior year had an average of three to four flares. And they looked at the patients and their ability to achieve a target uric acid of lower than six milligrams per deciliter or zero point three six millimoles per liter. And they showed those who achieved the goal, got it down to that very low SUA, they actually had a lower mortality rate. So, those that didn't had a higher mortality rate.

The hazard ratio was 2.33 and the same for cardiovascular mortality two point zero five. So, almost a two to three fold increase in mortality if you do not achieve your goal in lowering uric acid down to that target. Again, why that's not in the guidelines from the American College of Physicians? I don't know. I guess they don't read the research.

So, there is new data that came out from the European Medicines Agency, the EMA, the European FDA equivalent about tofacitinib and the risk of clots, as you know. And it's now a black box warning on all JAK inhibitors, tofacitinib, baricitinib, and upadacitinib. And I guess it's deemed to be a class effect. We know RA patients have a slightly increased risk of venous thromboembolic events and it may be in some cases, not other cases, a little bit higher with the JAK inhibitors. So, the FDA slaps a black box warning on this.

And it got a little dicey because earlier this year, tofacitinib, no mention in their product label, no warnings, but then they have this long term trial in high risk RA patients where they either receive tofacitinib at five BID or 10 or adalimumab and they showed that there was a higher rate of VTEs, especially with the ten milligram dose, but even with the five milligram dose and a higher rate of cardiovascular events and death in the higher dose. So, this changed the warnings in The US and also in Europe. As you know, the only indication in both The US and Europe for a ten milligram BID dose of tofacitinib is for ulcerative colitis. Well, the EMA comes out and says, Really, you should not use that ten milligram dose in anyone who has a high risk of venous thromboembolic events. They basically have said that there's an increased risk of VTE, DVT, PEs at both the five and ten milligram BID dose when you compare tofacitinib to a TNF inhibitor.

So, the bottom line is that although this is a rare event, somewhere between one in one hundred and one in one thousand patients might come down with a VTE. If you're someone who has a higher risk of VTE, you should not be taking a JAK inhibitor. And I think that's something to be discussed with your patients. A pre release on information that will probably be presented in the next few days at the ACR meeting, the EXCEED study. This is a study of Cosentyx, head to head of Cosentyx versus adalimumab in patients with psoriatic arthritis.

Again, unique in that it's a head to head, it's a fifty two week study, cefukinumab versus adalimumab. It's a phase three trial, over 800 patients were recruited. The primary endpoint was an ACR20 response and it was not different between the two drugs. Now, if you'll remember, ixekizumab earlier in the year had a report in Annals of Rheumatic Disease showing that ixekizumab, another IL-seventeen inhibitor, was superior to adalimumab in psoriatic arthritis patients, but they had a co primary endpoint, meaning they had to improve as far as an ACR50 and as far as a PASI 100 skin score. They met their primary endpoint, their co primary endpoints, by basically winning in the skin but being equal in the joints.

So, this data on the EXCEED study is not any different than that seen with ixekizumab, equivalent articular responses when IL-seventeen inhibitors are compared to a TNF inhibitor in patients with psoriatic arthritis. I think that's good news, although it did not meet its primary endpoint, I still think it's good news, another good option for us. Our last report is about upadacitinib, which obviously was approved earlier this year. They have a new phase three trial called the SELECT PSA two trial, where they recruited patients to treat active psoriatic arthritis who previously failed and were incomplete responders to a biologic DMARD. They either received fifteen or thirty of opacitinib or placebo, and not surprisingly, the fifteen and thirty milligram dose was significantly better with basically an twelve week, ECR twenty, fifty seven, thirty two and nine, almost sixty, forty, 20.

And it had about a Posse 75 response of about 50%. So, JAK inhibitors are not as great at skin as they are at joints. They're fabulous at joints and that's why these drugs have been approved in psoriatic arthritis, but not necessarily in psoriasis. So, opacitinib is not yet approved in psoriatic arthritis, but this is encouraging data that says it might be. That's it for this week on RheumNow.

Go to the website, check out these citations. This week, we're going be at the ACR covering it. Go to roomnow.com. Follow the emails we'll send you every day with the highlights of the meeting. We're going to have top 10 lists of best abstracts.

We're going to have a lot of videos, a lot of podcasts, a lot of good articles written by the faculty you've seen in past meetings. I think it's going be an exciting week at the ACR. Check out what we do. Talk to you then. Bye.