RhThe RheumNow Week In Review Fateful Outcomes In Rheumatology %287.13.18%29 Save

It's the 07/13/2018. This is the RheumNow Weekend Review. Hi, I'm Doctor. Cush, Executive Editor of roomnow.com. This week we're going be talking about disappointing results with an anti IL-twenty three drug, surprising outcomes for those who have inflammatory back pain, and sort of the fate of outcomes in several disorders that will be surprising to you the rheumatologist.

Also want to give you a reminder about regional meetings in rheumatology that you should attend. I'll tell you about that at the end. At the top we have a study from Canada this is from, John Esdal and Diane Lacalle's group that did a population based study in Canada that looked at the monitoring of hyperlipidemia in RA patients and controls. They looked at over 5,000 patients in both groups and showed that not surprisingly both groups were not very good with regard to monitoring for hypolipidemia, but that RA was in fact less than that seen with the general population. This is a reminder for us to be involved in the comorbidity management.

Although this study came from primary care ordering of tests, same has been seen in other studies by rheumatologists who do monitoring. Again, this is a big issue in our population and it's probably not being attended to. An interesting meta analysis of multiple studies that looked at the associations between non neurologic autoimmune disease of which there's many and its association with psychosis revealed some surprising results. Surprising? Real?

I don't know. What they found was that there was an overall association between psychosis and non neurologic autoimmune diseases with a twenty six percent increase in such patients, and mainly an increased risk for developing pernicious anemia, pemphigoid psoriasis, celiac disease, and Graves' disease. Again, somewhere between a twenty three percent and ninety one percent increase over control populations. Interestingly, showed a lower association between psychosis and ankylosing spondylitis and rheumatoid arthritis where there was either a twenty eight percent or thirty five percent reduction in risk. The question is amongst all your patients with autoimmune and inflammatory disease, how much psychosis do you really see?

I gotta say in my practice I really don't see many. I certainly can't compare to the numbers that were seen in this meta analysis of 27 studies. But is this p value fishing or is this real? Again, I can't say I'm not surprised that psychosis patients have a myriad of other problems, but would that be a whole lot different than the general population? I don't know that I believe it, it's for you to consider in your assessment of these patients.

An interesting study comes out of Australia where they had an early arthritis clinic that studied the delay in referrals from symptom onset to GP referral to referral to the rheumatologist to referral to actually receive a TNF or non biologic DMAR therapy. Again, studied a large cohort of patients and what they found was a significant delay from symptom onset to rheumatology review meaning rheumatology evaluation of twenty six weeks. I find this surprising because most of us think we're doing a really good job of early diagnosis and early treatment because patients are being referred earlier. Well, in my experience, the referral is really related to how open your schedule is. If you have a six month wait time, you're not getting referred to anyone because you're not marketing yourself as an early arthritis doctor.

However, if you're seeing patients within a week of their calling in for any reason, you're likely to see a lot of early patients. Well, in Australia, again it's a significant delay. It turns out that the most important part of this delay was due to patient delay in seeking help. It was almost two months or more before they sought help from their GP and then referral to the specialist came after that. GP delays were associated with low disease activity, and those who were socioeconomically disadvantaged.

We know that, being younger in a lot of populations, equates to not seeking help for musculoskeletal symptoms. So I think that the whole issue of referral still merits significant attention, and maybe better promotion of rheumatology services. What was seen in their study was that patients seen within sixteen weeks were more likely to actually be treated better. An interesting study looks at early RA patients an orthopedic journal that looked at MRI outcomes in RA patients. From a clinic of 150 early RA patients, they found seventy six patients who had achieved remission at one year.

And they looked at the MRIs done at baseline and during the course of therapy and then at one year. And they showed that despite being in clinical remission, the majority of patients who were in remission still had evidence of MRI inflammation. Now we know this to be true. Other studies that look at those who achieve, definition of DAS or bullion remission or ACR Ular bullion remission or C. Dye remission still do have residual swollen joints.

So this is not surprising but the numbers they came up with were forty three percent had synovitis and thirty nine percent still had bone marrow edema, nine percent with tenosynovitis. They did show that a third of the patients did progress to develop erosions and this is more likely to occur in those who had bone marrow edema. Our friends at Healio reported that in a study of GPA patients that compared adults and kids with GPA 200 plus kids versus 5,000 adults and guess what kids had worse disease. They had thirty percent more hospitalizations and kids were more likely to have two to three fold higher rates of leukopenia, neutropenia and hypogammaglobulinemia. Just like lupus these kids are probably more at risk, and should be worried about more.

An interesting study comes from an NIH funded, the Rochester epidemiology product that looked at patients who developed low back pain in Olmsted County. And this studied patients between 1999 and 2003, and specifically they looked at a very high number, five thousand three hundred patients with back pain. Of that number a surprisingly low number one hundred and twenty four had new onset inflammatory back pain and you know how to define that. After thirteen years of follow-up only one third or thirty one percent of the inflammatory back pain patients went on to develop, spondyloarthritis. Thirty percent, therefore will develop spondyloarthritis but a higher percentage will not progress to spondyloarthritis.

So forty three percent will not progress to spondyloarthropathy. This may explain why the prevalence of inflammatory back pain is high at three-six percent, yet the prevalence of spondyloarthritis is a fraction of that somewhere between zero point four and one point three percent according to Michael Ward and his co authors. An interesting stat came out this week about testosterone use. I'm sure you see a lot of this amongst your patients but what was interesting to me was that between 02/2011, T cell centers, people getting on this bandwagon, making money off of injecting men with testosterone, the amount of testosterone use in The United States rose threefold. I mean, it tripled in a ten year period.

And this was mostly done in men who really didn't have a good reason to be on testosterone. However, in 2013 there were two major studies showing that testosterone use was associated with higher rates of myocardial infarction and CVAs suggesting that, well, Gene might want to think twice about this. Well interestingly from that date onwards testosterone use dropped by 50%. So there's still a lot of this out there, it's still not necessarily being done with the right indications, but I think advising patients that there is a risk associated with testosterone would be the smart policy going forward. So, regarding the fate, that's one of several stories that tell you about the fateful outcomes of people.

There's an interesting study on the fate of seronegative rheumatoid arthritis from Tulikki Soka and colleagues in Finland. They actually had over a thousand patients in their early arthritis clinic from one center. And of that early arthritis patients, who had early rheumatoid arthritis, I should say, four fifty three of them were seronegative. And they looked at the ten year outcomes in that population. And I think that they were surprising.

They found that three percent either converted to seropositivity and went on to develop, erosive disease. Only about eleven percent remained unclassifiable as seronegative RA, so you could say that only fourteen percent remain seronegative RA, and that's low compared to, I think, what most of us see in The United States. But what happened with the rest of the population was sort of surprising. And that includes that sixteen percent went on to develop and be reclassified as polymyalgia rheumatica, ten percent as having osteoarthritis, and a third of their patients went on to have a spondyloarthropathy psoriatic arthritis, reactive arthritis, spondyloarthritis or ankylosing spondylitis. So again, there's a hodgepodge of one-two percent of GCA and other diagnoses including gout and pseudogout.

But they were relatively low single digit low percentages. So the idea here is that not every patient with seronegative RA remains a true RA patient and that reconsideration of diagnosis is paramount in the longer you manage such people. An interesting study comes from, a cohort in The UK that looked at refractory RA using the British Society of Rheumatology Biologics Register, where they have thousands and thousands of patients. Amongst their 13,000 RA patients that are taking a biologic that were enrolled, they were able to classify eight sixty seven of them, or six percent, as being biologic DMARD refractory. They define that as those individuals who went on to require a third biologic DMARD.

So they have some very interesting data about what the prescribing practices were. This was not a controlled protocol. This was whatever the doctors wanted to do. Early on, the vast majority, sixty percent, went from a first TNF inhibitor to a second TNF inhibitor. Later on, they were more likely to switch to another MOA looking at two different time frames, 2001 and 2007 and 2008 and onwards.

And these time frames actually showed significant differences in physician prescribing behavior. What they did show was that early on, six point seven percent in that first cohort actually had refractory disease and it took them almost eight years to achieve that. On the second cohort, it was only four point eight went on to develop refractory disease but they got there in a lot faster time frame, two years, suggesting that there was more switching between the classes, as doctors have gotten more aggressive over time. After they got their first and second TNF inhibitor, the vast majority would use, rituximab. But that was mainly in the first era.

In the second year, used much less rituximab, eighty three percent versus like fifteen percent. And then after rituximab in The UK, tocilizumab was the next best used drug and then abatacept close after that. What the, authors correctly state is that some of these patterns of use more reflect the introduction of those new agents into the marketplace rather than a true preference of one drug over another. Interesting study about Rizankizumab. Rizankizumab is a selective IL-twenty three inhibitor.

It has now been studied. There are other IL-twenty three inhibitors. Tremfya or guselkumab is approved in The United States for psoriasis. And these are being developed in psoriasis and spondyloarthropathies. This specific drug was actually studied in ankylosing spondylitis patients, 159 patients who were biologic naive and never received the biologic and were given either placebo or one of three different doses of rizanquizumab as an injection.

And guess what? At week sixteen, I think was their endpoint, it could have been week twelve. But this was a twenty four week study. Their first endpoint was, I think, week 16. The results were the same.

Only about a quarter of patients responded and basically placebo did as well as the drug and didn't make any difference what dose of drug you were on. So that's sort of surprising data that this IL-twenty three inhibitor doesn't work. We know that IL-twenty three inhibition works great in psoriasis and psoriatic arthritis that twelvetwenty three works obviously well in psoriasis and psoriatic arthritis. And actually has shown good effects in patients with emphysitis. Again, twelvetwenty three as a target may not be ideal for patients with ankylosing spondylitis nor spondyloarthritis but we need more studies on this.

There are studies going on with other agents looking at this. Hydroxychloroquine as you know has been a big issue for many of us. We're looking at these new guidelines from the ophthalmologist that look at ideal body weight prescribing, and worrying about doses greater than five mgkg of ideal body weight versus actual body weight where a high dose is greater than six point five mg per kilogram as a total daily dose. They showed in a very large UK database amongst 21,000 new users of hydroxychloroquine that, thirty seven percent of patients with ideal body weight, thirty seven percent of those with, normal body weight and forty four percent of obese patients were being overdosed meaning over those limits. But then when you apply actual body weight it's fifty three percent of normal and ten percent of obese patients were being excess dosed with hydroxychloroquine.

This is more likely in women as you know if you're not paying attention those thin, frail women under one hundred and twenty pounds a day if you're using usual doses of hydroxychloroquine you may be in trouble with actual body weight dosing. So pay attention to that. Again, these guidelines are correct or not remains to be seen. I'll end with two interesting things. One, you should look at, Maddie Feldman's blog on prescription drugs and the effect on access to biosimilars in The United States.

She goes into how drugs are sold, how they're priced, what the involvement of pharmacy benefit managers is. It's an eye opener, it's a great read and something you should really understand if you use biologics or are considering the use of biosimilars. Lastly, there's a great set of meetings coming up in September excuse me, in July, August, and September. These are being run by Arthros. I'm involved with Arthros in establishing good, state society educational meetings.

We have regional meetings going on in Chicago, we're calling that the Great Lakes meeting. We have a great meeting going on in Nashville. So Chicago is going to be on July 28. Nashville is going to be on August 18. We have a great meeting in DC that's called the Capital City Meeting.

On August 11, August 18 is the Music City Meeting in Nashville, and on September 29, the Down Eastern Meeting in Boston. Fabulous faculty. I'll be moderating the first program where our faculty is myself, Artie Cavanaugh, Kevin Winthrop, Michael Weinbach, Joel Block, and Andreas Reif, I believe, on that faculty. You can go to the arthros.org website to register for any one of these meetings coming up in the next few months. That's it for this week on rheumnow.com.

We'll see you next week.