The RheumNow Week In Review Cocoon Therapy%3F %287.20.18%29 Save

It's the 07/20/2018. This is the Room Now we can review. Hi, I'm Doctor. Jack Cush, executive editor of roomnow.com. This week in the news, the misadventures of methotrexate dosing.

Where do elderly cells go to die? And what's the cost of non medical switching or even worse, non adherence? But before we get into the news, I want to announce that there's going to be a great new regional meeting near you, a rheumatology review run by Arthros. These are regional review meetings that are going be held in Chicago, Washington, Nashville and Boston coming up. You can go to the Arthros website, arthros.org and see these.

On July 18 is the Great Lakes meeting gonna be held in Chicago. The next one's going to be, I have the dates here, Capital City in Washington DC on August 11. And then the following one after that is Music City in Nashville on August 18. So if you're in those regions and within drive time, it's a free meeting, the fabulous faculty and program is unbeatable. I think you should look at it and see whether or not you want to attend.

This week in the news we have interesting information about the prevalence of lupus. This is a Canadian study that looked at the, incidence and prevalence rates of lupus over a sixteen year period beginning in 2000 and ending in 2015. Using administrative claims data, the authors show that lupus is six times more common in women than in men. A number a little bit lower than what you might have quoted in the past, but this is good data from Canada. And they showed that the incidence of lupus in the, population was four point three cases per 100,000 population.

More interestingly, they looked at the prevalence of lupus over time and they showed that it rose significantly two thousand where the incidence with the prevalence was forty eight cases per one hundred thousand in two thousand to ninety cases per 100,000 in 2015. What in the world's going on with the prevalence of lupus? It's hard to say. It could be better diagnosis or more wide use of the diagnostic testing. I don't think so.

I think there may be something here that, may speak to lupus becoming more prevalent and not just, better diagnostic methods identifying patients. But let's see if that gets reproduced elsewhere. A very interesting study, it's a sort of modeling study, it's not really based on actual real data, but nonetheless, I think it was very telltale, Looked at what would be the cost of non medical switching, meaning what happens when we get into biosimilars and we change from originators to biosimilars in an effort to save costs, and that may be forced upon the patient or upon the prescriber. Looking in rheumatology, gastroenterology and dermatology, what they estimated looking at a million insured lives and making estimates based on a physician survey that gave them some non medical switch rates, physician time, health resource utilization, etc. They estimated that the cost of a non medical switch was about $200, per patient, specifically amongst their million patients and the 3,600 who had non medical switching, it was gonna cost that system over $770,000 And that's with a fairly low rate of non medical switching of sixteen percent.

If that non medical switch rate were to go up to twenty five to fifty percent, these expenditures are going to be as high as 1.2 to 2,400,000 just to account for the cost of switching from, for instance, an originator biologic to the biosimilar. An interesting, study also looked at lupus, this time looking at lupus hospitalizations and predictors of hospitalizations, specifically one hundred and forty two lupus patients with one hundred and seventy three hospitalizations for infection. The infection rate was really quite high, the way they calculated fifty percent, and most of those infections were pulmonary infections, lower respiratory infections. The risk factors for hospitalization for infection with lupus included either a very high white count or a very low white count, high CRP, low C4 levels, not C3, and length of hospitalization suggesting that disease activity made you at risk, but also being in the hospital longer made you at risk, nosocomial infections, etc. And maybe having too high an infection, meaning being a marker of lupus, infection.

So, again, this is sort of, I think reinforces what we know, but I don't think I knew that the length of hospitalization was a risk factor, in getting serious infections for lupus patients who are in the hospital. An interesting study looks at systemic sclerosis patients one hundred and thirty two specifically looking at the incidence of musculoskeletal manifestations and shows a high number, not quite fifty percent, but above twenty percent who actually had arthralgias, synovitis, contractures, and maybe even x-ray erosions. They found that rheumatoid factor positivity was seen in fifteen percent of those with limited disease, nine percent of patients with diffuse systemic sclerosis, and a higher percentage, twenty percent who had overlap features of scleroderma. Turns out that if someone had double positivity for CCP and rheumatoid factor, they were not only going to have more arthralgia, they're also going to have more erosions. Think this is important because I've seen lots of patients in my career wherein arthritis, RA like arthritis and severe arthritis was a key early feature, if not the dominant feature throughout the course of systemic sclerosis.

Adherence to biologics is a big issue. Adherence, we talked about adherence in the past to DMARTs and other therapies, it's a big issue across the board. In primary care, patients issued an antibiotic, less than fifty percent of patients will fill the prescription for that antibiotic. Patients tend to be a little bit more adherent in specialty care, but the numbers are staggering and eye opening. This is a very interesting study that looked at claims data and specifically looked at over 10,000 patients who are starting their first biologic.

So these were first biologic DMARDs and biologic naive patients. And they showed that the adherence, non adherence rate, I'm sorry, the one year adherence rate was only forty six percent. By the second year, the adherence rate was only thirty four percent. Again, this is based on claims data and patients filling the prescription. Those are abysmally low, fifty percent dropping out, within the first year, almost sixty five percent dropping out by the end of year two.

The rates were lowest with golimumab and highest for infliximab, not surprising infusions are going to actually probably urge patients to stay on a little bit longer. But even in patients who were effectively treated, what they used here was a formula that Jeff Curtis and colleagues developed where you could sort of guesstimate effective therapy based on a number of different parameters. And using that parameter, there was thirty percent of patients who were effectively treated with their biologic. Yet, even with the biologic they had a fifty nine percent adherence rate, and suggesting that even in face of disease, control, patients were not being adherent, a high percentage were not being adherent. This is abysmal data.

What we need to do to improve this remains to be seen, but is a gigantic challenge in healthcare, if not rheumatology. A population based study in Latin American countries, eight of them specifically looked at the incidence, the frequency of musculoskeletal and rheumatic disorders. So looking at the indigenous people in these Latin American countries, the overall rate of musculoskeletal complaints and disorders was thirty five percent, a high high number. I'm not sure what you quote when you talk about the frequency of musculoskeletal complaints, it's been as low as twenty percent, sometimes higher. This is thirty five percent.

What was that broken down to be? The thirty five percent, thirteen percent were for back pain, nine, ten percent for osteoarthritis, six percent for regional pain, only one point three percent for rheumatoid arthritis goes along with our estimated prevalence of rheumatoid arthritis generally in our population, but only zero point one percent with spondyloarthritis. So good numbers to quote when trying to get a handle on the frequency of musculoskeletal complaints in a large population. Are you aware of the study of senolytics? That's S E N O lytics.

It really is looking at the study of how you can affect senescence as it relates to, ultimate outcomes in health, that if you can, cure senescence, meaning prevent aging, that patients may in fact do better. We do know that that senescence cells will develop that senescence cells actually can be taken and transplanted into young mice and it will impair not only their function, physical function, but it will also impair their mortality, that there are higher mortality rates when patients have, or animals, including humans, actually have lots and lots of senescent cells. So this specific study that was published in Nature is a very interesting one cause it looked at young mice and old mice, gave them senescent cells, showed bad things whether they were young or old. And then it used a therapy, a cocktail, a senolytic cocktail that included dasitinib, a JAK inhibitor, and quercetin, an antioxidant, and that these have been shown in other studies to actually reduce the number of circulating senescent cells. By giving this cocktail, what they did was they lowered the number of senescent cells and what they then showed was that you had improved physical function and improved survival like thirty five to sixty five percent improved survival or physical function and survival respectively.

So impressive numbers and an impressive way to, reverse aging and to get to that sort of cocoon therapy. Look up the movie Cocoon to figure out what happened there. An Australian safety study analyzed methotrexate, overdosing and problems with methotrexate missed dosing. Specifically, found, identified from their database twenty eight cases where methotrexate was missed dose and what the consequences of that were. Turns out the vast majority of these were cases wherein methotrexate usually given once a week was now given daily, erroneously daily.

And the net result of that were high rates of adverse events including pancytopenia, thrombocytopenia, neutropenia, stomatitis, mucosal ulcerations, and lots and lots of GI effects. We certainly know this happens in practice in patients who are on a stable dose but they reduce their renal function, they get a surge of methotrexate levels that can become toxic. But it also happens in these scenarios where there's an error in dosing and patients who should be taking it once a week on Saturday are now taking the same dose every day, or they're spreading out their doses all throughout the week, which is also quite, dangerous. Those who are at risk were non English speaking individuals, those who are confusing the daily dosing of folate with the weekly dosing of methotrexate, and those were wherein mistakes were identified either by physician instruction or the pharmacist instruction. Interesting tweets about this online, Janet, Pope actually had one of the best one.

This is why she writes the prescription for methotrexate to specifically state methotrexate six pills every Friday. You give it only on the day that you want it used as opposed to saying once a week that could be misinterpreted by either the patient or the pharmacist. Again, another lesson learned about methotrexate. Speaking of methotrexate, what happens in those who don't respond? A good study looked at predictors of methotrexate non response.

This is specifically the rheumatoid arthritis medication study, a UK study that looked at over a thousand, ten fifty early RA patients and those who had undifferentiated arthritis who went on to receive, either subcutaneous or oral methotrexate. They showed that non response was seen in forty three percent of individuals, pretty high number, and that this was correlated with A, seronegativity, B, high HACS scores, and higher disease activity measures and overall, associated with higher anxiety scores. Not surprising with seronegativity and disease activity associations, but anxiety being something that would, curtail and limit responses is something new and something to take note of. Our last report comes with the, about the unsafe practices with Ambien and its use in The United States. In 2015, three point eight million Americans received a prescription for Ambien and many of these did not follow guidelines recently set out by the FDA which include one limiting to short term use because of a loss of efficacy, two using lower doses for those over the age of 65 and using lower doses for women, because they have a higher blood levels, and then there are increased risks when combining Ambien with other CNS depressant drugs.

Again, a study of the Medicare expenditure survey in 2015 revealed that women were more twice as likely as men to be, missed dose with regard to Ambien and to receive Ambien and that, forty one percent of patients on Ambien were also taking other CNS depressants. That two thirds of patients were using higher doses instead of the lower doses, and that two thirds of patients were over the age of 65. Sadly, there was a high number of individuals who were actually not following these recommendations and were not, three quarters were not following these two or more of the above recommendations regarding, Ambien use. So something to consider when you're prescribing this drug in those especially of fibromyalgia, etc. That's it for this week at roomnow.com.

Go to the website to get these citations and read more about these interesting articles. Tune in next week for the podcast and the video cast of the RheumNow Weekend Review. Tell your friends to sign up. Talk to you next week.