RheumNow Week In Review Gout And Hearing Loss%2C Huh%3F %289.14.18%29 Save

Hi, it's the 09/14/2018. This is the RheumNow Week in Review. I'm Doctor. Cush, Executive Editor of rheumnow.com. This week in the news, the long arm of gout.

What happens when things go wrong? What about headaches for lupus mavens? They're ahead. And which would you prefer? To be managed by an internal medicine resident or physician assistant if you're in the ICU?

At the top of the news we have a study of pregnancy in psoriatic arthritis. This comes from Norway and it looked at one hundred and eight pregnancies and one hundred and three women with psoriatic arthritis. It found out that the vast majority (seventy five percent ) either were in remission or low disease activity state during the pregnancy and for the immediate period thereafter. It was generally after six months that the flares were noted. That seemed to be universal and that is obviously what happens in all patients with arthritis.

Usually by six months they're going off stopping breastfeeding and they're going on to therapy and they used to have to go on therapy because they are flaring. But this is an interesting study because we don't know a lot about psoriatic arthritis and what happens in pregnancy. The same can be said for psoriasis and maybe even ankylosing spondylitis. We do know a lot about lupus and RA in pregnancy. So this is important data that might help you.

Some of these patients, minority, continued their therapies throughout the pregnancy, most did not. So again, I think this is encouraging data for your patients who have psoriatic arthritis and may want to get pregnant in the future. An interesting study looks at early arthritis patients who were either randomized to receive methotrexate or methotrexate plus Plaquenil. Three twenty five patients who were treatment methotrexate naive were randomized to receive either monotherapy or combination and of course you would say that the combination therapy was better. And it was significantly better at six months but it wasn't significantly better at twelve months suggesting that maybe it really doesn't you don't really need to be that aggressive.

Think that this data you look at it, probably say, gee, should probably put everybody on Plaquenil and methotrexate at the same time. It's a safe drug and whatnot. But I don't know that it's worth the extra pills for the patient, and the extra concern for the patient. While again the UR good responses and CRP values were less at six months, they're not much different at twelve months, suggesting you're probably doing the right thing if you start your early arthritis patients on just methotrexate. An observational study looked at the associations of hyperuricemia.

And there's a large population, young adults eighteen to thirty five years of age, and it was shown that hyperuricemia was strongly associated with the development of coronary artery disease. What was interesting about this was it was accentuated with smokers but it was also present with non smokers. In fact, was almost a twofold increased risk of coronary artery disease in young individuals who had hypouricemia. I think this is important because there is this ongoing debate about whether hypouricemia alone is a risk factor for vascular disease, renal disease, hypertension. And if you believe that, then maybe you would be more inclined to treat asymptomatic hyperuricemia.

I must say I've changed my mind over the years. I'm worried about hyperuricemia, especially if it's greater than 10. If it's borderline, I'm probably not going to treat asymptomatic hyperuricemia. There's a lot of experts who wouldn't agree with me on this, but I think there's an accumulating body of evidence that says that hyperuricemia is a very bad risk factor in vascular disease. An interesting study looked at five eighty one gout patients and compared them to osteoarthritis patients and looked at their ten year outcomes as far as cancers and what they found was gout patients had a lower risk of colorectal cancer.

It was zero point eight percent versus three point seven percent almost a four fold higher rate in patients with osteoarthritis compared to age matched gout patients. Now, is this important or not? I think you should know that most studies have concluded that there is an increased risk of multiple cancers in patients with gout overall. This data says it's reduced with the least regard to colorectal cancer and that may well be due to intermittent use of non steroidal drugs. But I think it's good news for patients who have gout.

A strange study looked at the association between gout and hearing loss. They took the Medicare database from 2006 to 2012, used a five percent sample, and looked at the incidence of hearing impairment in people who had gout versus those who didn't. Amongst those who did not have gout, the risk of new hearing loss was eight point seven per one thousand patients. It was almost double that if you had gout, six point nine. The hazard ratio after corrections was one point four four and again that was significant.

Why would there be an association between hearing loss and gout? Maybe that's the reason why they don't follow our advice. They just didn't hear us. So you have a gout patient I told you to take the allopurinol! So is it that?

Or could it be again that hyperuricemia leads to microvascular disease? It turns out that vascular disease is often an etiologic factor in many cases of hearing loss. Again, this study is not well explained as I'm going go into later when I talk about depression and lupus but I think it's interesting data and it will lead me to look for hearing loss in my patients and maybe to ask them about their hearing especially before I give them what I think is crucial therapeutic advice for the future. There's a small study but nonetheless a single center study that looked at 10 patients who developed autoimmune diseases autoimmune, immune related, adverse events associated with the immune checkpoint inhibitors the PD L1 inhibitors, etc. In their 10 patients they had oligoarthritis, polyarthritis, tenosynovitis.

Half of them were ANA positive, a bunch of them had CRPs. The things they wanted to take from this is that the onset was about six months after the onset of therapy for their cancer. All of them required steroids, some of them required high dose steroids. And the mean time to resolution was really quite long. 9.2 was the average mean time to resolution.

This is a low frequency event that we in rheumatology are seeing more and more of and these people do represent a significant therapeutic challenge. We've recovered this in multiple reports in the past. If you have such a patient just do the search on, roomnow.com for either IRAEs or checkpoint inhibitors and you'll see a compilation of multiple reports that really describes the syndrome. Some very disappointing data comes out, this last week from AstraZeneca and Medimmune who, as you know, have been developing the, type one, alpha interferon, inhibitor, anifrolumab. As you know two years ago they made a big splash at EULAR presenting the data that looked really really good thirty four percent SRI4 responses on anifrolumab versus seventeen percent highly significant.

That was a phase two trial. Now they have two large phase three trials called TULIP one and TULIP two. TULIP two is in progress, TULIP one has been wrapped up and they gave a preliminary report. Now the sad part is I'm not going to tell you the values I am going to tell you that this was a study of I think two hundred and four sixty patients who were randomized to receive placebo or two different doses of anifrolumab one hundred fifty or three hundred milligrams every four weeks. The primary endpoint was the SRI-four at twelve months.

They did not achieve their primary endpoint suggesting it does obviously doesn't work. They also provide no further data and tell you it's going to be released at an upcoming medical meeting. I assume that means ACR twenty eighteen in Chicago. So look for that data at the ACR meeting, about anifrolumab and not meeting its primary endpoint in patients with lupus. Again, it might be interesting to note whether that was only seen in people who had a signal for anifrolumab viz.

You know, not all lupus patients have the same biology. That was shown quite nicely by Virginia Pasquale who suggested there might be five different types of lupus, one of which has a high signal for interferon or interferon driven disease. An interesting study comes from, the Karolinska Institute where they do very good, research in Sweden. In this study they looked at the role of diet in the onset of patients who who get Rheumatoid Arthritis specifically they looked at, seventeen hundred cases of incident RA and compared that to age matched controls two to one. So basically three thousand six hundred non RA controls.

And what they found was that the risk of developing RA was highly associated with those who were consuming a Mediterranean diet. Now, in their studies they actually have a dietary questionnaire, 125 different questions or so, and they could actually develop what was called a Mediterranean score if you will. And those who actually had a high Mediterranean diet were much more likely to not get rheumatoid arthritis. This mainly was seen or only was seen in men and not women. The overall reduction for the whole population, the whole study was about twenty one percent, I think.

The odds ratio was zero point seven nine. These results, however, only applied to men, where there was a fifty percent reduction in men and also those who were seropositive for either rheumatoid factor or ACPA, where there was over a thirty percent reduction in those individuals, again, who were men or seropositive who are on a high Mediterranean diet. So very interesting, and maybe that's important for patients who are at risk, patients who have a strong family history of RA, patients who may be seropositive but have no symptoms, maybe it's something that we should be advising because we really don't know what to do with them therapeutically. We're waiting on those studies to be done. Another quizzical study comes, from the Nurses Health Study that shows a significant association between depression and the onset of lupus.

As you know, the Nurses Health Study has come up with a lot of good data, they come up with a lot of goofy data. Again, two hundred thousand women, one hundred and ninety four thousand women followed for almost twenty years in two different studies. And in that time frame they actually had one hundred and forty five new cases of lupus. Turns out that women who had depression depression was proven three different ways: a clinical diagnosis given by a doctor, consuming an antidepressant and they had a score that included in their questionnaire that was highly associated with, depression. Either or all of those scores were associated with a two fold increased risk of lupus.

Overall, the hazard ratio was 2.67, that was significant. Turns out that no matter how you slice and dice this into different subgroups it was over a two fold increased risk. Again, unchanged by body mass index, smoking, contraception, whether you're post menopausal, whether you're on hormones, etc. I don't know how to explain that. Why would depression patients be getting lupus?

Is that something that you see? I don't think I really see it. We know that depression is part of neuropsychiatric lupus. We know that there is some literature about immune abnormalities seen in patients with new onset depression. I don't know if you've noticed this but I've certainly noticed this as one who often is looking for new onset disease, RA and lupus, you find a lot of new onset positive serologies coming from the psychiatric clinic in patients who have depression.

So there could be something to this, but I think what you really need to take from this is that this is not proof. That such observational studies really are hypothesis generating and need to be proven in a randomized trial. That would be an intervention trial. Take depression patients, follow them prospectively, see what happens, make an intervention regarding depression, see if it changes the risk of lupus. Obviously very hard to do and maybe you're all left with.

But again, in the nurse's health are not truly representative of other women. They tend to be younger, more white, thinner, more access to health care, better diets, better health practices, etc. So again it's hard to say what this kind of data means but it is nonetheless interesting. New England Journal this week had a very important paper about, BMS Bristol Myers Squibb new product. It's a TYK2 inhibitor, it's called BMS-nine hundred eighty six thousand one hundred sixty five.

They haven't yet purchased the name I guess. And this is a twelve week trial of a TYK2 inhibitor. TYK2 is part of the Janus kinase family. If you're talking about JAKs there's usually a discussion of JAK1, JAK2, JAK3 and TYK2, the tyrosine kinase that is involved in transmembrane signaling, the generation of cytokines especially IL-six, IL-ten, IL-twelve to name a few. This is being developed on a number of different disorders lupus, maybe inflammatory arthritis, in this case, patients with psoriasis.

A twelve week study that looked at multiple doses versus placebo in two sixty seven patients with plaque psoriasis, who were moderate to severe. And they found really impressive results. The placebo response rate for a PASI seventy five response was seven percent on placebo, but if you're taking six-twelve mg per day of the TYK2 inhibitor they saw a PASI 75 rate of sixty seven-seventy five percent. No impressive safety signals, that would distinguish it from anything else being studied in psoriasis. Is this meaningful?

I think it's too early to tell how it's going to stack up against TNF inhibitors, other JAK inhibitors, as you know tofacitinib was approved for psoriatic arthritis not for psoriasis. And certainly IL-seventeen, IL-twenty three, IL-twelvetwenty three. This is one study, two sixty seven patients, we need more studies. But this is good news because I think we're going to see this kind of therapy in rheumatology and it's not just going to be limited to, only, those who have, psoriasis. Let's just say, and this report with a quote that I put on Twitter this week.

It's sort of a follow-up to all the tweets I did last week coming from my white coat ceremony speech, sort of inspirational things about patient care. And this week's quote comes from me. Providing medical care is more of a commitment to the patient than a commitment to science. Empathy, understanding, and listening are incredibly hard when you think you have all the answers. That's it for this week at rheumnow.com.

Go to the website to read up about these reports. We'll talk to you next week. Take care.