The RheumNow Week In Review - 2 February 2018 Save

Hi, it's 02/02/2018. This is the RheumNow we can review. I'm Doctor. Jack Cush, executive editor of rheumnow.com. This week in the news, arthritis numbers on the rise.

A leading woman amongst men in the field of science, you really need to know the story. A vaccine update and what the overuse of drugs and rheumatology, could it be true? At the top of the news, you should know that today, February 2, is Rheumatoid Arthritis Awareness Day. I guess everything, including orangutans, get their Awareness Day, but today is Rheumatoid Arthritis Awareness Day. I think it's important for us as rheumatologists to know this, to expound on this, to celebrate this, and to spread the good word about all the great things that are happening in rheumatoid arthritis.

Sometimes patients just get all the bad news. They got a disease. There's a lot of things they have to worry about. They got to take medicine. But there's a lot of really good news out there about rheumatoid arthritis, and it's up to us, experts in the field to spread that word.

So you need to know about obviously when to monitor for hydroxychloroquine toxicity. There is a new study out from, the ophthalmology journals that sort of updates this. You know, there's been a lot of changes with their new guidelines on monitoring, which not all rheumatologists agree with and not all rheumatologists agree with how they were derived based on limited data. Nonetheless, some of the message still ring true. And that includes those who are at risk for retinal toxicity with hydroxychloroquine, but include those who are on longer duration of plaquenil use with an odds ratio of fivefold increased risk.

Higher daily doses, and there, you know, used to be six point five milligrams per kilogram. The new number is down to five milligrams per kilogram, and you need to do the calculations, especially on your little women who are, you know, in that hundred to hundred and twenty pound range. You may be overdosing them. And then the presence of kidney disease seems to significantly increase the risk of developing hydroxychloroquine retinal toxicity. There's a new auto inflammatory syndrome.

Certainly, you know about the cryopyrin associated periodic syndromes or CAPS. That includes familial cold or inflammatory syndrome in the very young where a whiff of cold air gives them urticaria and rashes. Then there's Muckle Wells that affects kids, adults, young adults with sensorineural hearing loss and periodic fevers. Then there's the horrid neurologic condition, nomenclature, where they have really bad bone neurologic disease. And all of these stem from gain of function mutations within the NLRP3 inflammasome genes.

So now they've discovered a fourth amongst these cryopyranopathies gene. It's actually a disease called caroteneviliitis fugax hereditary. It's been described only in Finland. It is episodic events of eye irritation, redness, some blurred vision lasting for days. But these are recurrent episodes that begin in children and go on to middle age.

It turns out that this is hereditary, hence the name. And the investigators who published this looked at a cohort of individuals all of whom had the syndrome, a familiar history, and they all had the same point mutation in the NLRP3 gene. So suggesting now this is the fourth disorder in the CAPS constellation, if you will. There's a really, really interesting article in Time Magazine that's worth taking the time to read. It is about chemist Gertrude Elion, who was born in 1918.

And as a young woman, she watched her grandfather die of cancer and she devoted her life to science, majoring in science in college, getting a bachelor's degree, and she was going to find the cure or the reason as to why her grandfather died. But she hit the wall and her story is depicted about how a woman who wanted advancement was sort of thwarted in many ways, yet went on to get a master's degree, went on to get a job working in a lab, and then ultimately for Burrow's welcome around 1930 or 1940, I think 1944. In 1967, she was appointed as the head of the Department of Experimental Therapy at Barrows Welcome. And during her career, she developed the following drugs, six mercaptopurine, allopurinol, trimethoprim, acyclovir, and AZT. This is a woman who always wanted to get her PhD but was, discouraged from doing so.

Didn't hold her back. Her story is amazing. It's a good read in Time Magazine. Sixteen twenty five scleroderma patients were followed. And it was a very interesting study because it sort of looked at how you can maybe, categorize a patient based on their initial presentation.

And certainly, we know scleroderma has both limited and diffuse disease, and we know that both often have Raynaud's phenomenon as a presenting feature. Of these sixteen hundred plus patients, eighty three percent of the patients in this cohort presented with Raynaud's as their first symptom and seventeen percent did not. Clearly, there was a big difference in survival between those that did have Raynaud's as a first symptom versus those who did not, such that when you looked at survival at twenty years, eighty three versus seventy two meaning those who had Raynaud's as first symptom had a better survival. This continued on even after thirty year mortality rates where the numbers were seventy one versus fifty percent. This is actually survival rates.

So the idea is that you can, probably do better if you have Raynaud's as an early manifestation. Now they did look at their overall population and showed that mortality was associated with a number of features that you might recognize as being the bad prognosticators in scleroderminous disease. That includes being older male, having diffuse cutaneous disease, having interstitial lung disease or pulmonary hypertension, past renal crisis, and cardiac involvement. But nonetheless, I like the story here and that the first symptom Raynaud's does have some predictive value in predicting long term survival. In a large cohort, one hundred and sixteen patients with polymyositis dermatomyositis who happened to have also interstitial lung disease.

They looked at them and characterized the group. Interestingly, fourteen patients died within the first six months. This is a bad player. ILD and PMDM has poor, poor outcomes, and I think it's underscored by this first line in the more an early line in this paper. They also went on to characterize those who are at risk for early death, and that included those who had upper lung lesions, an eightfold increased risk, hypocapnia, sevenfold increased risk, and the presence of serious infection.

They found that serious infection was seen in up to a third of patients, and that also had a high poor outcome. Predictors for serious infection include high serum KL6 levels, high dose corticosteroid use, and the combination of immunosuppressive, and steroid use with a fivefold increased risk for serious infections. What is serum KL6 levels as you might ask? I didn't know what it was either. It actually is a large molecular weight glycoprotein made by type two pneumocytes and has been associated as a prognostic finding and an association with, the different forms of pneumonitis and interstitial lung disease.

So, it's not something that we are aware of, it's something that the pulmonologists are probably aware of. An interesting study comes again from the French Air Registry. As you know, the French have a number of different registries and their Air Registry is one that looks at the use of rituximab in patients with rheumatoid arthritis. In their twelve seventy eight patients who have received rituximab, they looked at those who went on to actually receive a full dose in their first cycle, where they received one thousand milligrams times two, two weeks apart. But then they looked at those who went on to receive low dose and compared them to high dose.

So reduced dose, for instance, five hundred milligrams times two, two weeks apart versus the usual dose a thousand times two. And again, the low dose group was only about fifteen percent of the overall group. But when you looked at them down the road, there was similar outcomes in survival. The five year survivals were both around fifty five percent for either group. And it was also shown that those who received the subsequent low dose rituximab therapy had fifty percent fewer serious infections, less total rituximab use, and hence there was a financial savings associated with that.

So, you know, this might color some of the ways we actually use this. I think some of us are using low dose rituximab when we're faced with some financial constraints, but this may be the safer better way to use the drug. There's some recent epidemiologic data that's out there that we should probably be aware of. In 2008, and this was recently published in an epidemiology journal, between 02/2014, The US population numbers for arthritis grows from fifty six point one million to sixty five point one million. Associated with this was an overall increased direct cost of care and an increase in out of pocket expenditures.

In 2008 was $585,000,000,000 and went up to $645,000,000,000 by 2014. The out of pocket expenses, really didn't change that much, 83,000,000,000 to around 71,000,000,000. The investigators here surmise that the numbers have gone up, but the number and the cost of care is really driven by the numbers going up with who develop arthritis. Another interesting epidemiologic study comes from the Scandinavian Journal of Rheumatology, which looked at the risk of developing gout, over a twenty five year period. And they showed that the gout numbers actually have risen thirty percent during this twenty five percent period.

I find this interesting because the numbers of patients developing gout in The United States has clearly gone up in multiple studies that have looked at this. And most feel it's driven by multiple factors, including earlier diagnosis, but especially by obesity and dietary change. Well, it seems that it's also affecting the Scandinavian countries, the Nordic countries, as was titled in that paper. There's a new study that talks about the effectiveness of influenza vaccination. This comes from the Canadian Medical Journal, where they actually took, it was a group from multiple Spanish cohorts, and they looked at patients who received no vaccine versus one vaccine versus repeated annual vaccines.

And they showed that for those who received a vaccine followed a year later by a vaccine or repeated annual vaccines, that it was thirty one percent effective in preventing hospitalization from the flu, seventy five percent effective in preventing ICU admission due to the flu, and seventy percent effective in preventing death from the flu. So you may not get it right every year, but repeated vaccinations does have a public health benefit that you should be touting to your patients, especially your patients who are at higher risk. The new guidelines on zoster have just come out. They were published in the MMWR and the CDC, last week. These are the updated guidelines, twenty fifteen guidelines, on zoster vaccination, and the news here is that we have a new vaccine.

We have the new Shingrix vaccine. This is the recombinant inactive Zoster virus vaccine and it does have certain advantages. So the details of the ACIP meeting on a regular basis and what their proceedings were, what they discussed, how they came up with some of their guidelines are discussed in this fairly long paper but are summarized on our website. They really asked three questions and the three questions that they asked at their October 2017 meeting was, is the new vaccine, the Shingrix inactive vaccine, recommended for immunocompetent adults over the age of 50? The vote was 14 in favor, one against.

Is the new vaccine, the Shingrix vaccine, recommended for immunocompetent adults previously vaccinated with the Zostavax, the live virus vaccine from Merck, and the vote was 12 in favor and three opposed. And then when they asked, Is the new vaccine preferred over the old vaccine? Is Shingrix preferred over Zostavax? And the vote was in favor of Shingrix, but only eight to seven. So that is their recommendation going forward.

If you want to look at some of the reasons why this was favored, you can look at the report book on our site or at the CDC site. But as you know, this new vaccine, the inactive vaccine, has certain advantages. While it is a two shot vaccine and a little bit more costly, but not much more costly than Zostavax, it requires two vaccines and it does have more constitutional side effects with it. But it is much more effective in a wider number of patients in all age ranges and all the way up into the 80s, whereas the Zostavax loses effectiveness with time. They both seem to have a four or five year duration to their effect.

And I think because it is inactive and has a potential wider use, especially amongst those who are immunosuppressed, it seemed to get favor with the ACIP group. Now, one of the problems here, of course, is that this has never been studied in our patient populations in rheumatoid or psoriatic and immunosuppressed individuals. And from what I understand, discussing this with Lenny Calvary's, the company has no intention of actually doing the studies. If you're talking to GSK, the makers of this new vaccine, you should pressure them. We need to see data about how to use these drugs and are they the same?

Are these guidelines the same when it comes to, our population? You got to love guidelines that are drawn up by a committee that doesn't involve us, any of us. And there certainly are many rheumatologists who are very into this topic, and who are doing studies in this area. If you want me to be part of the solution, need to include me earlier on would be my advice to guidelines committees. So again, I think that there's good news about new vaccinations, but we do know another report from, I think the JAMA Dermatology looks at the use of I'm sorry, the risk of developing herpes zoster as measured by, emergency department visits for this over a, seven year period.

So they looked at patients in ED visits between 2006 and 2013, and they showed an eight point three percent rise. So zero point one three percent in 2006 to zero point one four percent, which is an overall 8.3% rise. So there might be an increase in the rates of zoster in our population that could be from better recognition, more education, more drugs to actually treat this. What they did show was that the growth was primarily seen in young people between the ages of 20 and 59. So be on the lookout for Zoster.

You got new guidelines, got new tools. There's a lot that we can do there. As I will remind you, if you are using the live virus vaccine, the rule is you need to be off of a biologic for at least two weeks and probably four actually, probably four weeks and then maybe the whole, dose duration of the drug, and then you can vaccinate and return to it, two weeks later. So theoretically, you could do it in between infliximab infusions, which I really wouldn't recommend. So there's in the area of skin and dermatology, there's a nice report on the MDA five antibody in patients with dermatomyositis.

In fact, there's two reports, and I think they're really quite instructive. I don't know if you're familiar with this MDA five antibody. It has been associated largely reported in the Asian populations. It has been associated with, those who have CADM or clinically amyopathic dermatomyositis, we used to call dermatomyositis, synomyositis. And they studied 20 consecutive patients with dermatomyositis, 20 consecutive patients with polymyositis.

And what they showed was the MDA-five antibody was only seen in 30 of patients with dermatomyositis, never seen in patients with polymyositis. And again, many of them had this pattern of no clinically manifest myopathy or weakness, so hence they're the amyopathic dermatomyositis patients. But they tend to be younger, they tend to be more male, and they tend to have shorter duration in their studies. And again, the bad news is that the presence of that antibody portends a real serious risk for severe lung disease with poor outcomes and rapid progression and very aggressive ulcerative skin lesions on the fingers usually. Another report from the American Journal of Medicine also this last month looked at patients who had both the MDA five antibodies or those who had aminoacyl tRNA synthetase, one of the, anti synthetase autoantibodies in the myositis antibody panel.

And what they showed was the presence of the MDA-five, antibody, was associated with progressive interstitial lung disease, rapidly progressive interstitial lung disease, way more than with a tRNA synthetase like sixty percent versus twenty five percent. And they also are associated with better worse survival and a higher rate of ILD progression if you have the MDA five antibody. So this may be something that you want to look at especially patients who have no myositis but yet have classic Gottron's lesions and ulcer lesions on the fingers. And then you want to look at their lungs to make sure that they don't have developing interstitial lung disease that is progressive. Now there's two more reports that look at the use of drugs in our patients than shows the overuse of drugs, or the new use of drugs, if you will, in the case of ankylosing spondylitis.

This is a report in J Rheum from John Ribel and a bunch of colleagues, where they used a grant to characterize the therapies that patients with ankylosing spondylitis are showing, and they showed a substantial number of ankylosing spondylitis patients who were taking opioid narcotics. And the factors associated with opioid use, especially chronic use, including having a longer disease duration, a history of smoking, a lack of exercise, higher disease activity by the FASDi and the FASDi, depression, and cardiovascular disease. In the end, they said that opioid use was tended to be associated with more of the subjective measures associated with disease as opposed to the objective measures of activity and inflammation that are often seen in ankylosing spondylitis. So I'm sure we have these patients and that you might want to pay attention to them and find out whether that opioid use is appropriate or not. And lastly comes an online study of non steroidal use.

This is an online study of almost 1,500 individuals where they kept daily diaries on nonsteroidal use, especially as they started. And almost 1,300 of these people were using over the counter ibuprofen. Overall, they found that fifteen percent of the population were using larger than recommended daily doses for the over the counter nonsteroidals, and thereby, you know, sort of putting themselves at risk. So this is something we need to be aware of, especially when counseling our patients about the use of nonsteroidal. Many of our patients do use over the counter drugs.

Again, they need to be counseled not to mix them and to be sure to use appropriate doses, doses that you would in fact recommend. That's it for this week at roomnow.com. You can go to the website and read more about these articles, get the links, download them, put them in your files. Next week, RheumNow is going to be at the Rheumatology Winter Clinical Symposia, RWCS meeting that Artie Cavanaugh runs in Maui with a premier faculty. We'll be covering the event with a lot of videos, live reports, and a ton of tweets.

Tune into RoomNow for news and education from RWCS in Maui. See you next week.