The RheumNow Week In Review - 22 December 2017 Save

It's the 12/22/2017. This is the RheumNow we can review. I'm doctor Jack Cush, executive editor of rheumnow.com, wishing you a very merry Christmas and happy holiday. I hope there's a lot of time off for all of you to rest and recollect on the on the last year and make plans for the New Year. Next week, during the holiday week from the twenty fifth to the first, we will be on hiatus on rheumnow.com.

We will be posting some of our best of articles and blogs during that period. So you can still tune in and maybe find something that you might have missed in the past year. In this week's Christmas weekend review, a lot of inform information about psoriatic arthritis at the close of business last Friday, the makers of tofacitinib, Pfizer, announced, a new indication for Xeljanz, that being psoriatic arthritis, which is now indicated for use in active psoriatic arthritis affecting adults either, to be used alone, as monotherapy or in combination with DMARR therapy or methotrexate. Again, it has the same dosing, the same indications, the same warnings. It does, however, warn about combined use, and there's a lot of talk and little information about when you use a DMARD like Xeljanz in combination with another DMARD or even better yet, a biologic for which there really is no data.

So the FDA does warn about combining the use of this drug with other biologics, cyclosporine or azathioprine, which it terms as powerful immunosuppressants as, again, these really haven't been studied. So it is a good addition. It's based on the OPAL data, which was impressive, presented at ACR and ULA this year. It does substantially add to our arsenal of drugs for problematic psoriatic arthritis. It is not indicated for use in psoriasis where it has not been shown to be effective, only at the very high doses of ten milligrams BID, is not an approved dose.

So do not use it for psoriasis and skin. Yes. Use it for arthritis and joints. Also this week, a JRheum article about the follow-up to the SPIRIT p one study with ixekizumab, also known as Taltz. This was, the results that followed a twenty four week double blind trial of ixekizumab versus placebo versus adalimumab.

And then in the extension after twenty four weeks, the placebo and adalimumab patients were crossed over to ixekizumab eighty milligrams either every two weeks or every four weeks. And, again, at the end of one year, their ACR twenty fifty seventies were equal whether you receive 80 twice, every twice a month or four times a month q two or q four weeks. With ACR twenties of sixty nine percent on q two and of sixty nine percent on q four. So it looks like the ongoing dose should be, eighty milligrams, every four weeks. Also published this week was a meta analysis of a number of different trials that looked at the efficacy of IL-seventeen inhibition, and all that's out there for psoriatic arthritis and basically showed compared to placebos, there was at least a twofold greater ACR 20 response in patients who received an ACR twenty I'm sorry, patients who received an IL-seventeen inhibitor.

And across the board, they showed no substantial increased risk for new signals, and no increased risk for infection, serious adverse events, tuberculosis, invasive candidiasis, or other, infectious complications. So sort of a a good news for those of us who are getting into the IL-seventeen business and finding its utility, especially in psoriatic disease where it works great for the joints and it works great for the skin. A Swedish analysis looked at, conduction disturbances I'm sorry. Looked at TB and other infectious risk amongst thirty eight pay thirty eight thousand patients with ankylosing spondylitis, psoriatic arthritis, or spondyloarthritis, and they compared this thirty eight thousand to almost two hundred thousand in general population looking at those who were biologic naive, those who were on biologics, and specifically looked at the TB risk and basically showed that there was, for those that were biologic naive, meaning this is disease only associated risk for SPA, PSA, AS, there was no increased risk of TB with an odds ratio of about one point two. But when you added a biologic, in this case, most most of these were TNF inhibitors, that it did increase the TB risk sevenfold, an odds ratio of seven point five.

This is not dissimilar to a lot of the data that we've quoted in The United States and other non endemic regions where there may or may not be a constitutive risk of the disease to get TB. RA, it's a slightly increased risk. It appears from this data, it's not increased in AS, PSA, and SPA. But then when you add a TNF inhibitor, it takes your constitutive risk and magnifies it. In RA, that could be as much as ninefold.

Many studies showed exactly this number around sevenfold increased risk when you add a TNF inhibitor. So, again, there is something there that you need to be aware of. And, again, of course, we know the TNF inhibition especially is very, very important to the generation of granulomas and the maintenance of granulomas, which is why there is, a risk once you add a TNF inhibitor. Again, the risk with other biologics, including IL seventeen inhibitors, is very, very little more based on where someone lives rather than the biologic. An interesting study from looked at the, association of psoriatic arthritis in juvenile, psoriatic disease and to look at their weights.

And we know that patients with psoriasis and psoriatic arthritis in adults have a significant association with obesity and other comorbidities. And may mainly, they wanted to look at whether this also occurs in children. In fact, that's what they saw. Amongst their 320 kids in that registry, twenty percent were obese and thirty three percent or one third were overweight, suggesting that this is, well, we certainly know that obesity is a big problem in the pediatric population, especially in North America, but that this carries through to those with juvenile PSA. The FDA issued a warning this week.

It was a re maybe a reissue of an old warning about the use of gadolinium or gadolinium based contrast agents where they were studying them. This was based on an announcement they did in 2015 where there was shown some concern about the use of these, these agents for, renal disease and CNS things. But, basically, they now say, in this reissue that healthcare providers should limit the use of gabalinium, as an enhancement agent only when contrast enhancement is necessary for diagnosis and that you should also consider avoiding the use of repetitive MRIs that use gadolinium based contrast agents. Surprising bit of data came out this week, made the news, New York Times, etcetera, about, life expectancy, in The United States. You know, most of us have been touting the wonders of our great care and advances in medicines and and and medical care, that's led to a greater life expectancy in each generation, and that's steadily gone up in the last, thirty years.

But for the second year in a row, life expectancy has gone down in The United States based on 02/1616 statistics where, it dropped from 2015, a life expectancy of seventy eight point six years to in 2060 I'm sorry. It dropped from seventy eight point seven years to seventy eight point six years. This is this is the only time in recent history where there's been a consecutive year drop in life expectancy. And, again, this data comes from the CDC and the the Center for Health Statistics. The New York Times had an interesting article.

It's probably worth a read for those of you who are perplexed by the issue of non adherence and noncompliance with medicines. They go through a lot of the data, including the data that patients are, you know, especially in general care, not likely or general practice, likely to fill a prescription, at least half of patients, and that those who do don't usually take it the way they're supposed to. There may be a little bit better performance in chronic diseases and subspecialty care, but not much. But, again, when they review the data, it seems like the only thing that really affects, adherence is the price of drugs. That when you try to incentivize the patient, have pill bottles that beep, have all other kinds of ways of tracking and reminding patients, they're not that, as effective as when the drugs in fact are cheaper, which I guess the patient feels that there's more value, in the amount spent to the amount of derived benefit.

So, again, that maybe that needs to factor into some of the explanation that goes on. There's a clearly an educational gap on this issue of non adherence. A nice, review from JAMA looked at the incidence of tinnitus, a big problem for a lot of our patients. We know that nonsteroidals do, significantly cause a high rate of tinnitus. But, in their review, twenty one point four million Americans have tinnitus.

That, that amounts to almost ten percent of the population, adult population. A quarter of them have been having it for more than fifteen years. Thirty six say thirty six percent say that it is constant, and seven percent say it is their biggest medical problem. So, interestingly, in that article, nonsteroidals didn't play a big role. What seemed to play a role on, risk of tinnitus were those who worked in office and industrial and other work environments where loud noises were a big part of their work.

And it also another big, contributor are loud noises in recreational time or recreational environments, and obviously, not steroids would be in that too. So things to think about, when dealing with patients with tinnitus. Maybe you should advise them about how what what's going on in their work environment. Many of us are certain based on thousands of patients we see each year that tell us that when the weather changes, when the barometric pressure drops, my arthritis gets worse. And it's we're we're we're used to our our our patients becoming weathermen, and, being fairly accurate, at least according to them.

But another bit of research actually comes, has been published that says, that in an analysis of claims data where they try to link up patients who, went to doctors and, patients with musculoskeletal conditions who went to doctors, and then they link that up to the, rainy days and changes in barometric pressure either for the day that they went to the doctor or the week proceeding, they could actually find no association between, rainy days and such weather changes and musculoskeletal visits to the physician. You know, this is a lot like the diet data where patients can swear that a certain diet makes a difference, but most of the diet data is not very encouraging. And same thing for weather changes. It's hard to figure out, do you believe the research or do you believe the patients? I gotta live with the patients.

I'm believing the patients. In Olmsted County, the Mayo Clinic, they actually took another look at their rates of gout, and and and they showed, as you would expect, that in, different decades, the rate of gout has gone up significantly. We know that over time, the frequency of gout has gone up in many different cohorts, including the Mayo Clinic cohort where from, between eighty nine, the rate was sixty seven. In 2010, the rate was a hundred and thirty seven cases per 100,000 individuals. It's gone up.

But what they also showed during the the new the news here, the great news flash is it's not just gout that's going up, it's the comorbidities associated with gout also went up during the same time period. There was a, a a rate of of of hypertension rose from fifty four to sixty nine percent. The rate of diabetes rose from six to twenty five percent. Morbid obesity rose from ten to almost thirty percent during the same time period when obese when when, when obesity rates are going up and and and gout rates are going up. So, again, there's a tie in there.

Gout I I believe gout is part of the metabolic syndrome and and should be considered as such, but, we need better data to make that claim, but I'm sticking by that for the time being. More on gout. Allopurinol, was studied, this week by Nicola Dalbeth and other researchers from Auckland, New Zealand, where they did an interesting study where they it was a follow-up to a study that they did, and they really looked at allopurinol initiation in patients and and who had gout and hyperuricemia, and they looked at whether you, initiated, right off the bat, the escalation of allopurinol or whether you waited and then escalated after a time, all trying to achieve a target serum uric acid of less than six. The interesting thing about this particular study was they showed that when you when you looked at renal outcome, baseline renal outcomes, renal function based on creatinine clearance, Creatinine clearance did not influence the outcomes. And so if you were a creatinine clearance of less than 30 cc's or between thirty and sixty or greater than 60, you basically had the same rate of success, in achieving your target, serum uric acid, roughly around seventy to seventy five percent for all the groups that looked at, and they were not significantly distant, different.

The bottom line being that even in the face of renal impairment, allopurinol dosing doesn't need to be adjusted and doesn't need to be worried about as much as it we need to worry about it with nonsteroidals or, with colchicine in patients who have renal impairment. They said that and if anything, patients with renal impairment actually needed less allopurinol to achieve serum uric acid levels. And those who had normal renal function, no evidence of CKD, they actually required higher doses of allopurinol. The range was some difference of between two hundred and fifty and four hundred and fifty milligrams per day between the renal impairment group, lower doses, and the normal renal function group where they use four fifty milligrams per day to achieve that target level. Overall, I noticed that that even though it was a protocol and and they were using urate lowering therapy, the the rates of of success were sixty five to seventy five percent.

So we're still have a long way to go in achieving, our goals in treating gout, and that's very important to know. The risk of gout was looked at by Hyun Choi and others from Harvard who tried to do a newer analysis of flare of either the, onset of gout or flares of gout or recurrence of gout based on uric acid levels, and they showed, not surprisingly, they're closely linked. And they specifically looked at recurrence of gout was was low when the uric acid was less than six, only 12%, and high, 61% when the uric acids were greater than nine. When they looked at patients who are on urate lowering therapy and who had achieved their goals and were supposedly controlled, rates of flares and recurrence were only three point seven percent for those that were that were on, that had uric acid of of six, whereas the recurrence rates of even though they were they were supposedly controlled and on urate lowering therapy, when the urates were levels were nine or above, it was a again, a sixty one percent increase. So, again, it tells us some data that we already know, but it gives us some hard numbers that we can quote with patients.

Two last bits of information, is the rates of of of knee replacements in rheumatoid arthritis patients has changed over the years. This is a study from the Danish, registries and where they linked up their surgeries with their RA patients and their biologics. They instituted a change in their RA treatment guidelines in 2002. So they divided up those patients treated before 2002 and those after 2003, and looked at hip and knee replacements. And they showed that while, knee replacements were going up and up and up until 2003, then they went down in the biologic era.

Hip replacements were already changing and not seemingly affected by biologics. So this is, again, another bit of evidence suggesting the the powerful cost savings behind biologics. It used to be that the number one cost to the extreme cost of RA care was surgical care. And what we've done is we've replaced the cost of surgery with the cost of biologics, but the patients are better off and don't need surgery. Lastly, a nice report from, Jeff Curtis and colleagues looking at a way of predicting serious infectious risk in RA patients.

And in that particular study, what they did was they took and and established a, a comorbidity index. And based on, usual comorbidities and if you had two or more comorbidities in this comorbidity index and you were on steroids, you had a significantly higher predictable risk of serious infection. So, again, they looked at the this was data drawn from the rapid one, rapid two trials with cerdulizumab, and and and their comorbidities were things like age, diabetes, COPD, asthma, etcetera. And there was a score that you could get those weighted scores, and they call this an a c AACI index. So if you had a two or more with steroids, you had nearly a threefold higher risk of getting an SIE.

So, again, yet another way of predicting the risk of a serious infectious event in RA patients, and then RA patients. You know, if you wanna look at RA patients going on a biologic, you need to look at the rabbit wrist registry, which will do the same thing, take the same parameters, it into equation, and show you rates that are quite surprising. So that's it for this week on rheumnow.com. Hope you have a great holiday. Go to the website to see the links and read more about these news reports.

We'll have more for you in the New Year. It was a great year this year. Thanks to you. We appreciate all your comments and input. We'd like to get more of that as we go forward.

We'd like to make this, a very valuable resource for you and your education. Have a happy New Year.