The RheumNow Week In Review - 12 January 2018 Save

It's the 01/12/2018. This is the Room Now we can review. I'm doctor Jack Cush, executive editor of roomnow.com. This week in the news, what happens when our patients go to surgery? Calcium and vitamin D may not be all that it's cranked up to be, and yes, you actually can predict immune related adverse events in patients receiving checkpoint inhibitors.

A lot of that's in the news lately. The top of the news is an interesting story about what happens when orthopedists sort of double book and try to do surgery. I don't know if you're aware of this practice, I wasn't, but the study from JAMA talked about hip replacement surgeries being done on patients with hip osteoarthritis and the hazards of doing overlapping surgeries, a practice wherein the supervising or head physician, head surgeon, does two or more simultaneous surgeries and supervises the surgeries done by other patients. The outcomes here were complication rates, and in fact, they showed significantly higher complication rates, ninety percent more complications when this practice went into effect. And those are complications all observed within the first year.

Obviously not a good practice to double book and do overlapping surgeries. Dan Solomon and colleagues looked at the cost of care and updated cost of care analysis. This is a meta analysis of many, many papers. It turns out that there were very few that qualified, 12 out of the hundreds they looked at, and only a third of these had what they called good quality data. They showed that the total medical cost of caring for someone with rheumatoid arthritis was $12,509 for all RA patients.

It was actually higher if you're on a biologic DMARC, in fact, three times higher, 36,000, and that RA specific costs were only 3,700 for all RA patients, but up to $20,000 for biologic DMARDs. Again, the cost of care in RA has gone up over time. The cost of care has been supplanted by the biologics. It used to be the cost of care was driven by hospitalizations and surgery. Now it's the cost of the biologics, the cost of the drug therapy.

A new study, looked at, familiar Mediterranean fever patients from an Israeli population, and just did a population analysis of eight eight thousand five hundred thirty four patients. They saw that the risk of developing cancer was in fact lower amongst these FMF patients. The standardized incidence ratio was thirty four percent lower compared to the general population, which is kind of novel because as you know, inflammation drives cancer risk. Almost all the diseases we take care of have some kind of cancer risk, and it's usually not from the drugs. It's usually from the therapy.

It's usually from the disease itself, the inflammation itself. And these studies suggest, well, you know, it may be different in disorders of innate immunity such as FMF and auto inflammatory syndrome compared to disorders of adaptive immunity, which is what you see with lupus, rheumatoid arthritis, etc. So the question is, is it a difference between involvement of the inflammasome or adaptive immunity? One other explanation for this data could be the effect of therapy. And they did not look at that.

They were not able to look at that in this particular study, but let's just say these FMF patients were effectively treated with effective therapies, many of which could have involved IL-one inhibition or drugs to control inflammasome activity. And we do know from a recent study, the study of katekinumab, where it was used to treat patients with heart failure, it was showed that it did reduce heart failure and cardiac events. It was also shown that patients on canakinumab, the IL-one inhibitor, in heart at risk cardiac patients only, they had a lower risk of cancer, especially lung cancer, which has now led to such therapy being tried in cancer trials. So could it be that this lower cancer risk in these FMF patients was because they were being treated? Again, think we need more data on this, but I guess a very interesting finding.

Recently announced data from Horizon about its product pegvodecase shows that up until recently, they were bringing in about over $400,000,000 in sales, and they project in 2018 to do $750,000,000 or above. This parallels the number of patients who have been treated with this drug has increased from fifty thousand to nearly one hundred thousand. So, again, early on there was a lot of hesitancy about using peglodecase to treat patients with severe refractory gout. I think physicians learning more about this drug showing that in fact it can be effective therapy. A tidbit, and this is from my own clinic, I use leflunomide just like all of you, but I might use it differently, and that's because of my working on the drug and clinical trials, understanding the biology of the drug.

Turns out leflunomide has a very long half life. It's somewhere between eighteen and twenty days. As such, it would be a great drug for not once a day dosing, but once a week dosing. And this is what I in fact do in a majority of patients who are on stable doses of leflunomide. So I will start them on twenty milligrams daily, as all of you, monitoring the same way, but after they achieve a response, which is usually six to twelve weeks, and they're on a stable dose, I will switch to once weekly dosing.

I will also switch to once weekly dosing if patients are having problems with either GI symptoms or hypertension or hair loss, in which case I will lower the dose and they'll get received eighty milligrams or a hundred milligrams or sixty milligrams once a week and see if that will be enough to control them. So when I switch to once a week dosing, I use twenty milligram tablets, I say take four or five or six tablets once a week every Friday, and patients do very well. In switching over from daily dosing to weekly dosing, there is no loss of effect, and you'd still continue to monitor the patient, as you normally would in your clinic and still monitor their labs in the same manner. That's I think a helpful way of using the drug leflunomide. A recent study of Swedish construction workers, over 300,000 of them, looked at the incidence of lumbar spinal stenosis surgery.

And this is a very large cohort followed for over thirty one years. In the end, they found that sixteen hundred plus patients went on to receive spinal stenosis surgery and curiously, they find that the rates are highest in those who are heavy smokers. Now, what does that mean? Again, it could be that just heavy smokers is a surrogate for those who have more disease, more comorbidities, less attention to health care, maybe less attention to healthcare services. It could also be that this is, like a lot of studies what we see, where you're dredging for a p value.

You put a large cohort in, you try to find out what's significant, and I often wonder about how real such studies are. Reminds me of all the studies about coffee and the associations of coffee with pancreatic cancer and all kinds of things. Again, it's hard to tell in these post hoc sort of population analyses, especially when it's in claims data. But that's out there, you know, your construction workers should stop smoking so they don't have to have lumbar surgery, I guess would be the take home message. Gabapentinoid use, as you know, is sort of widespread.

A few years ago was only about one percent, and now in 2015, it's gone to three point nine percent of adults. And that's is not I I guess it owes to a lot of these off label indications for gabapentin for the management of pain mean, primary indication, of course, was procedures, but it's gone on to be used for pain, for sleep, for, migraine headaches, etc. So, again, gabapentinol use is taking over, especially in an era when opioid doses or opioid use is actually declined, so this may be the new substitute. Another study, interesting study from Canada, looks at those exposed to leflunomide during pregnancy. So in the Canadian healthcare databases between 1998 and 2015, they found over three hundred or almost three hundred thousand pregnancies, rheumatoid pregnancies, and amongst those, there were fifty one who had received leflunomide within the first trimester of the pregnancy diagnosis.

There was another twenty one patients who received leflunomide in the second and third trimester, and interestingly there's no increased risk of spontaneous abortion, malformations, prematurity, or low birth weight. This is a follow on to the data that was published out of Otis, commissioned originally by Aventis to study the effects of leflunomide on pregnancy and took them many years and I think they only had about seventy different cases, but they also did not show an increased rate of malformations or fetal complications when the patients were exposed the infant was exposed to leflunomide. It still remains a serious risk. The patient should not get pregnant while on leflunomide. On the other hand, those who do, both of these studies would suggest that the outcomes will probably be okay for both the mother and the child.

A recent study, as you know, last week on our website we had a lot of discussion about these new checkpoint inhibitors and what happens with them as far as developing immune related adverse events. Last week's report featured some discussion and a commentary by Len Calabrese about what happens when you give these checkpoint inhibitors to patients with autoimmune disease. And in fact, seventy five percent of them will develop these immune related adverse events, arthritis, myositis, hypothesitis, etc. Well, there's an interesting study this week in PNAS that looks at I'm sorry, this is the Journal of Clinical Investigation that looks at the ability to predict these autoimmune adverse events when receiving checkpoint inhibitors. This was done a small cohort of thirty nine or so melanoma patients who were receiving either inhibitors of CTLA-four or PD-one or PDL-one.

They did studies before and after the first cycle of therapy, and they showed there were significant declines in B cell numbers and an increase in CD21 low B cells and also plasmablasts. So it's thought that this could be a significant change that is you can monitor and may be able to predict and do something about these potentially harmful adverse events. What they did show was that the early development of these B cell changes were associated with higher rates of grade three and grade four immune related adverse events. This all occurred within the first six months of receiving either one of those drugs or a combination of those drugs. So it's an interesting development.

There's a problem with these patients. Their identification is getting easier, but their treatment still remains hard. A new report from the CDC talks about how good physicians are at counseling their patients on exercise when they have arthritis. In this particular study, they looked at the data from 02/2014 National Health Interview Survey, NHIS, that involved over 36,000 adults. These are telephone surveys, and what they showed was that 2002, about fifty percent of patients received guidance from their physician about exercise when they had arthritis.

This grew by almost eighteen percent to sixty one percent in 2014. This is a still while that's good growth and a significant improvement, these numbers fall far behind current guidelines and CDC guidelines for exercise counseling. It is estimated that even patients who are maybe more inactive may have even greater loss or deficit in receiving such instruction. The point is that we need to program this into our daily lives when patients have such findings. We need to counsel them in a sort of predictable manner.

Authors recommend a website. They also recommend maybe programming this into the electronic medical record. Another study looked at what happens when early RA patients are studied with regard to adverse events. This comes from NeoRayco study. Ninety eight early RA patients were followed over time.

And again, these had very early RA. They actually averaged five and a half adverse events in the course of this one year study. They had an eight percent risk of developing severe or serious adverse event, and twenty four percent actually led to, of these adverse events led to drug discontinuation. What they really found that was sort of interesting and surprising was that with increasing turtles of dash 28 activity, with increasing disease activity, there were higher rates of SAEs, serious adverse events, NAEs, suggesting that again, it may not be the drugs that are driving risk in many of these patients. It may be comorbidity, it may be disease activity.

It's a complicated equation that leads to why someone will have an adverse event and then discontinue the drug, either temporarily or permanently. And lastly, there's a report from JAMA that did a meta analysis systematic review of 31 randomized clinical trials with over 51,000 participants to look at the influence of oral calcium and or oral vitamin D supplementation on the risk of hip fracture, and they compared that to those who either received a placebo or received no therapy at all, and they showed that there was no significant risk. In fact, if you compare the risk of hip fracture for those who received vitamin D or calcium, the relative risk is one point five three and it overlaps from zero point nine seven to two point four two looking at the confidence intervals. That's just for calcium. Vitamin D, it's a little bit lower.

So it seems to be a little bit of a trend, but it's not significant. In fact, it's even lower if you look at the combination of vitamin D and calcium as it may influence hip fracture, where the relative risk is only one point zero nine. And again, this covers this goes between zero and one point four. So the bottom line is that the routine use of vitamin D and calcium, especially in elderly people, community populations, doesn't seem by itself to reduce the risk of one of the things we're most concerned about, that being hip fractures and disability from that. That's it for RheumNow and go to the website.

You can actually get the links to these studies and read more about these studies. I'll also encourage you for those who don't know about it, RWCS the meeting is coming up in Maui. As you know, RWCS is a an annual meeting run by doctor Cavanaugh and George Martin, and it's a wonderful meeting that starts on February 7 and goes through the tenth. Now, there's a few slots left for those of you who may be interested in going. The faculty every year turns over.

We have new grand teachers who we call the Kahuna, and I think this year's faculty and the program you'll find is really exciting. You can see more about that at r w it's RWCS with dashes in between, rwc-s.com. But that was tough. Anyway, see you next time. Bye.