The RheumNow Week in Review - 15 September 2017 Save

It's the 01/15/2017. I'm doctor Jack Cush, executive editor of rheumnow.com. This is the week in review where we go over the highlights from the past week. This week, we'll talk about what's happening in the world of vaccination and a lot to look forward to. We'll talk about storytelling.

I guess I'll tell you my story about why vitamin D is getting under my skin. At the top of the news, an interesting study from Japan looks at the use of high dose and low dose folic acid in patients taking methotrexate. I did a Twitter poll at one point and found out that, of course, everybody uses folic acid, but interestingly, it's used quite differently around the world. It's not uncommon for patients to be taking ten milligrams per week or more as a single dose or multiple doses outside The United States, whereas United States, we tend to use one milligram a day when we're on methotrexate. The, study that was looked at in Japan looked at over five hundred patients who are, going to start methotrexate and compared those who are on low dose versus those who are on high dose, the dividing point being five milligrams per week or more, and showed that it didn't matter what what dose you were on, whether you're on low dose of methotrexate I'm sorry, low doses of folic acid every week or higher doses of folic acid every week.

It didn't matter with regard to what the outcomes were as far as hepatotoxicity, liver enzyme elevations, etcetera. So, again, use folic acid and avoid the toxicity. I I always say that the that folic acid manages the dangerous toxicity, reduces the rates of hepatotoxicity, reduces, the rates of drug discontinuations. I believe it severely, and dramatically reduces the rates of a rare phenomenon, acute hypersensitivity pneumonitis. A study from, a large cohort of lupus patients, actually it was a meta analysis of 47 studies and looked at thousands of patients with lupus, tried to identify the frequency of the metabolic syndrome.

Overall, they found that the frequency of metabolic syndrome in lupus was twenty six percent and that when they compared lupus patients with those who didn't have lupus, it was increased, that the, odds ratio is one point eight eight, suggesting an eighty eight percent increase in the risk of metabolic syndrome or nearly a double the doubling of the risk if you have lupus. As if there is not enough to deal with in lupus patients already, it's something we do need to be watchful of as far as managing comorbidities. Vitamin D, if you look at the literature this week and vitamin D was out there, guess what? It reduces and manages neuropathy. Actually, what was shown was those who are low in vitamin D have more neuropathy with, rheumatoid arthritis.

It's also been shown that it's associated with multiple sclerosis and alopecia areata. I mean, this magical molecule called vitamin D really is the antikryptonite to mankind, and I'm being quite sarcastic about that. Vitamin D stories are all over the place. It's associated with everything. Why not just, let's say, that vitamin D is probably important in bone health and in immune function and that most people are vitamin D deficient because they live indoors.

And the more deficient you are, more of a sign of unwellness it's associated with. Let's sort of stop with all the associations. I take vitamin D every day. Have I ever measured my level? No.

I think it's goofy, and I think that these kind of reports are really goofy. Goofy or not, what about drug holidays with bisphosphonates? As you know, there's been a quite a move towards stopping bisphosphonates and and giving patients drug holidays, especially if they've been on the drug for a long period of time. A cohort study of a hundred and eighty three osteoporotic women. Now, so they have osteoporosis range DEXA scores, and they've been receiving a bisphosphonate, first line bisphosphonate for three to five years.

And they'll and, and they looked at the patients who went on a, drug holiday versus those who did not. Now there was an imbalance here. This is not a randomized trial. There's no control really here. This is an observational study, but, a minority of people went on a bisphosphonate drug holiday, and and they were followed for a period of time and compared to those that continue to bisphosphonate.

And guess what? Those who went on bisphosphonates had a higher rate, forty four percent higher rate of new fractures. I think this drug holiday thing may end up becoming a big problem in in as we start to look at larger and larger cohorts. But this is a small cohort cohort that tells us that it may not be a wise thing, especially if you need the bisphosphonate because you have osteoporosis. An announcement from Sandoz came this week that tells you that we're gonna get more biosimilars, in this case, rituximab biosimilar.

We've seen a lot of TNF inhibitor biosimilars. Now we're gonna start to see rituximab being developed and soon to be approved. A study of the use of recurrent TB testing in patients who go on ustekinumab. Ustekinumab is an IL-twelve twenty three inhibitor and, bias biology is not supposed to be associated with, TB and opportunistic infections, But, it is in the label, and you do if you're gonna start on Stellara and any other twelve, twenty three, or twenty three alone inhibitors such as guxelkumab, you're probably gonna have to do PPD testing or QuantiFERON testing because it's in the label. It's in the label because it's in the way that clinical trials were done.

Will patients going on those drugs get more TB? The answer is no. And in this particular study looked at the use of repeat testing in a population at high risk. This comes from Korea, which I would call oh, I'm sorry, Taiwan, which is a higher than United States risk, is significantly higher. And I call those TB land, places where TB is endemic and, can be expected.

And in their studies, they had a, with continued use of STELARA, they showed a serial conversion rate that's much, much higher than you expect in United States, but that's because they're in TB land, seven point three percent. So by itself, STELARA does not cause, TB and and shouldn't cause it. It the risk of TB is really related to your exposure risk, as was was as was seen in this study in Taiwan. An interesting article from rheumatology looked at the, biology of vasculitis, especially large vessel vasculitis, including Takayasu's and giant cell arteritis, and made a case for, that there's two things going on in vasculitis, that there's systemic inflammation that is being, prevalent and, and requires steroids and IL-six inhibition. And that's driven by a Th17 response, involves, IL-seventeen and IL-six.

And that's quite different than the the the inflammation that you see in blood vessels, where that's more of a Th1 response where your IL-twelve and especially gamma interferon can mediate a lot of vascular, inflammation and what happens, in the vasculature. So, for instance, you may control systemic inflammation, but patients may go on to still have vascular events, that are driven by a different biology. This needs to be considering when managing and, monitoring patients with, large, especially large vessel vasculitis. It's an interesting read. AbbVie announced this week that their Select Beyond study, a trial being done in patients who have, received advanced therapies, including TNF inhibitors, and then were given a JAK their JAK inhibitor, their JAK1 inhibitor called upadacitinib that their, results were really good.

They had a fifty two percent, low disease activity state and a thirty two percent remission rate at six months, and, you know, really good ACR twenty, fifty, 70 scores. But the caveat here is that there was an imbalance in safety signals, specifically serious adverse events were seen only in the fifteen and thirty milligram dose groups and not in the placebo group. They had five percent SAEs and seven percent SAEs when you were on upadacitinib. And the same can be said for deaths that there was one death in fifteen milligrams, one death at thirty milligrams, and none in the placebo population. These numbers are small, but unfortunately, there is an imbalance and that will, shine the light on this particular kind of outcome as they look at the total data set.

And they did note that they had very few events that were thrombotic that were being seen and none in their prior trial. In the second trial, there was, I think, one thrombotic event. So that's good news. But again, this is good news and a little bit of bad news, but nonetheless, I think, that we need to see more data play out over time. A study of 200 scleroderma patients compared them to a 100 normal controls and looked at, esophageal motility studies and basically showed that severe esophageal dysmotility, is not uncommon in patients with scleroderma.

And it isn't actually seen with limited disease and, diffuse disease, even localized disease for that matter. But nonetheless, the association with severe dysmotility is mostly seen in those with long standing disease, those who have coexistent interstitial lung disease, and those who have higher GI scores and those who have lower health related quality of life scores. The good news, that came out of the FDA this week was the, unanimous vote by the advisory committee to, approve the, new GSK herpes zoster subunit vaccine called Shingrix. And that is, in follow-up to their ZOE 50 and ZOE 70 trials that were published and written about earlier in RheumNow. These were published in the New England Journal.

Again, it was unanimous vote. It was the vaccine is a very good, outcome as far as not being 90 effective at four years out and that there's no loss of efficacy, with increasing age of the population. It also reduces, significantly reduces the risk of, postherpetic neuralgia also over ninety percent. And again, these results are maintained in a very, very old, greater than 70 years of age population. One of the downsides of this is that it will be more expensive, and that it will require multiple injections that have a fairly an issue of constitutional manifestations, myalgias and arthralgias and, you know, other things, other constitutional things, it'll make it a bit of a a pain in the neck.

But and it's, but the good news is that this is an an inactive shingles vaccine compared to Zostavax, which is a live virus vaccine, this vaccine, when it is available, could be used in patients taking DMARDs on biologics who have immunosuppression, etcetera. Now mind you, there are no trials being done in patients who with with that particular profile, for instance, rheumatoid arthritis on biologics. But based on the biology, it should be safe to be given in such a cohort. But again, it's been recommended for approval by the advisory committee. We await the decision of the FDA panel.

A nice article written by Cassie Calabrese this week says that it's flu season and rheumatologists should get in line and should be vaccinating their patients. She makes a strong case for the fact that sometimes we believe that primary care is doing it, primary care thinks that we might be doing it. The bottom line is the patient falls between the cracks and doesn't get vaccinated because no one is taking responsibility and pushing it. So it is our responsibility. These are our patients.

They are immunosuppressed by steroids and maybe by other drugs that we use. It is best to get the flu vaccine done in September and October, but it's never too late. You can be giving it even as late as, late January and February. The flu season does peak in January and February, but it can even go out as far as next May 2018. She makes a strong case for us taking responsibility as well for pneumococcal vaccination, including the use of the Prevnar thirteen vaccine.

So again, read that. It's an interesting article. It gives you some tips on how and when to do this. And then today, the last day or the last of the week, I published a blog of my own on storytelling, really because I was pointed that way by Ronan Kavanaugh, about the value of storytelling in medicine and how it's become a bit of a popular, avocation, if you will, amongst, physicians to either write or speak, and tell their stories about patients, patient care, and their medical experiences and the inside of that. Ronan has a series he's starting in Ireland that's going to be called Bedside Stories, so you can read about that.

But story is a tremendous way of teaching, selling, convincing, and having an impact on a population. It is replete in our society. It's used in television and movies. Story is a three act play, a beginning, middle, and end. An introduction, a twist, and then a resolution.

Story should be employed more frequently in not only in our lectures and how we talk to each other, but also in maybe how we educate patients who often have a hard time understanding, the medical terminology and the complexity of the numbers and the biology of what it is that we intend to do with them with regard to their care. Look at it. You too can be a storyteller. That's it for this week on roomnow.com. Go to the website to look at these links and others.

Follow us on roomnow.com. Look forward to what we're going to present at ACR. You'll be surprised.