The RheumNow Week In Review - 26 January 2018 Save

It's the 01/26/2018. This is the RheumNow we can review. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week in the news, MPO antibodies has a unique association you probably were not aware of.

More on dermatomyositis and juvenile myositis and what their associations are that you also may not be aware of. And speaking of what you may not be aware of, do you know what the cost of your biologic therapy is in psoriasis? We'll tell you. So at the top, we have good news for those of you in The EU. The EMA has actually approved the use of another IL-seventeen inhibitor, ixekizumab, also known as Taltz, for use in patients with active psoriatic arthritis not responding to disease modifying drugs.

This is good news as follows what's happened here in The United States and expands the market and availability of IL-seventeen inhibitors, which is going to be an advantage for patients. Now that you have several, the question is, will you switch between them? I would say give it a try because certainly that's what we've done with TNF inhibitors, but we need some good data about switching. An interesting study comes from claims data that looks at the rates of septic arthritis in patients visiting the emergency department in hospitals in The United States. So these rates actually turned out to be quite stable between 02/2012, but the overall rate is zero point zero one percent or one in ten thousand ED visits is for septic arthritis.

Now, by comparison, that's obviously a lot less than what you might see in gout, but it's not that much less because the rate of gout seems to be about eight and a half per ten thousand. So I think that's sort of a sizable number, maybe more than I expected. But nonetheless, it turns out patients who visit the ED and have septic arthritis, the vast majority are hospitalized, over eighty three percent. And it turns out those who are more likely to be hospitalized are those who have, not surprisingly, comorbidities. So be on the lookout for septic arthritis.

According to an interesting report by the Rheumatology Network, which tried to tell us about the manpower issues in rheumatology, An interesting quote: There are 5,400 rheumatology providers. This actually includes almost 400 NPs and PAs in The United States compared to almost 4,900 rheumatologists in The United States. Now, when you really consider that not all those 4,900 rheumatologists are practicing prescription writing rheumatologists, that makes the number of advanced practice providers to rheumatologists at a ratio of one to 10. I think that surprises me, surprises I think a lot of people who may not yet employ or use advanced practice providers to extend your care and services. An interesting study of fifty eight patients with either GPA or MPA shows an interesting association with bronchiectasis.

However, this association was really seen only in NPO ANCA positive patients, not in those with PR3 or other forms of ANCA. So NPO ANCA females and those with peripheral neuropathy were more likely to have association with bronchiectasis. If you look at the reports that are coming out of bronchiectasis, we certainly see this in rheumatoid lung and other lung conditions, but bronchiectasis seems to have a high association with a lot of our inflammatory autoimmune disorders. There was a study of nearly nine thousand patients with either polymyositis or dermatomyositis and looked at their risk of venous thromboembolic events. Now, I don't know if you have a belief on this, but we certainly do know that VTEs, that that would include PEs and DVTs are increasing in patients with inflammatory disorders.

And not surprisingly, the same was seen here in patients with inflammatory myositis, where the odds ratios were over four for either VTEs in total DVTs or pulmonary emboli. Another study of juvenile dermatomyositis looked at rates of comorbidities and the rates were astounding if you look at the report. This is based on inpatient database analyses And it showed that of those who were hospitalized with JDM, now of course that might be a more severe case, and this might skew the data somewhat. Nonetheless, the odds of having hypertension 22 fold, obesity almost six fold, diabetes almost eight fold, hyperlipidemia five point eight was a hazard ratio, lipodystrophy one hundred and fifty one meaning that you really only see that in JDM and rarely in anybody else. The idea is that JDM and really myositis in general has a whole host of hazards, not just VTEs like the last report, but now comorbidities.

I believe that my patients with inflammatory myositis have a higher rate of steroid toxicity as well. And there's some data to support that. A nice report that appeared this week was a review of drug induced syndromes in rheumatology, specifically drug induced lupus. And the list here, this is sort of checklist of things you should know, hydralazine, procainamide, isoniazid, minocycline, diltiazem, and TNF inhibitors. The other lupus like disease that's associated with drug use includes subacute cutaneous lupus erythematosus.

I've seen more cases of this in the last few years than I have of actual drug induced lupus. Here, the drugs inducing this tend to either be hydrotheriazide, terbinafine, or any of the proton pump inhibitors, and even the TNF inhibitors. So be on the lookout for patients who may have drug induced syndromes. So here's an interesting study of patients with lupus from the Nurses Health Study, and it specifically looked at the onset of lupus and the especially those who were double stranded DNA positive and what the associations may be. And, of course, this is maybe some data dredging here, but interestingly and maybe not surprisingly, they found out that patients who are smokers and current smokers more were more likely to be double stranded DNA positive twice as much more likely.

And and those who had a long history of smoking also had a almost a twofold increased risk of being double stranded DNA positive for lupus. So again, is not a good player when it comes to both the onset and the expression of disease and sort of fits with that model of preclinical RA where one may be at a genetic risk then is exposed to an environmental stimulus, smoke, nutrition, etc, alterations of microbiome. And this is what we're seeing in lupus now, smoking and alterations of microbiome. Greg Silverman had a plenary session at the ACR talking about how the microbiome is shaping not only the onset but also the expression of lupus with more severe disease, specifically nephritis. Lupus mothers who give birth to children are more likely to have low birth weight children.

It turns out that active lupus is more likely to be associated with a fivefold higher risk of preeclampsia and an eightfold higher risk of preterm birth. Those numbers are actually higher than what we see in rheumatoid arthritis patients, but it is in parallel to what we expect out of active lupus. We do know that if you have active lupus, you're less likely to conceive or have a problematic pregnancy, and this would be evidence of that. An interesting report about referral comes from Scotland, where the local guidelines are that patients who have early onset RA should be referred within twelve weeks of presentation of symptoms. In their review of the data, only forty four percent of patients were referred to a rheumatologist within the twelve week timeframe, suggesting that there are significant delays there.

There were some comments about this on Twitter from The UK saying that they were doing much better at getting their patients in in a faster manner. But of course, that's, you know, people boasting and not real data comparisons. But again, while I think there is the belief that we're diagnosing RA earlier and getting patients referred earlier, there really isn't a lot of good data, I think, to support that. And I think that since we're not seeing early RA or promoting this early RA in The United States, There are a lot of patients where there are delays, and I think that's something we continue to need to work on. So what is the price of biologics?

I mean, I remember when these were $18,000 a year. As you know, these go up every year. I mean, Humira leads the way in pricing with increases of about 6% per year. These are the numbers for psoriasis treatment. And while the treatments may be slightly different than that in RA or IBD, psoriasis treatments are nonetheless almost similar.

Who leads the way? Giselkumab with a six month trial costing 29,000 or 58,000 for a year. Taltz also being almost 29,000 at 28.6. Next is Humira at 26.6, meaning the price of Humira for a year of therapy is over $53,000. Enbrel also 26.6 or 53,000 for a year.

Next, what's slightly behind it is Cosentyx at 26.5 for six months, Stellaris 19,000 for six months, Remicade 14,000 for six months, a real bargain. But guess what? If you go buy a similar and use Inflectra or Inflexis, it'll either cost you 11,000 for Inflectra or only 9,000 for Rinflexis. So, again, you can see now how the biosimilars might be big game changers in the future for many diseases that we treat. As you may have seen last week, the New England Journal report had a lead article about the use of steroids, specifically hydrocortisone and high dose in patients with septic shock.

And while there were no higher death rates or change in mortality, being patients didn't have less deaths or have more deaths that didn't change mortality, it did seem to change the course of therapy where they had faster resolution of septic shock, less time on mechanical ventilation, less time in the ICU, fewer transfusion. So this is important because, you know, there is this wide held belief that steroids can be really detrimental in patients who are having active infections. And sometimes in patients who are hospitalized where you don't know what the cause is, whether it's a serious infection or a serious rheumatic disease, my contention is there is no harm in using steroids in such patients. I think this data sort of supports that. So there's a lot of talk in the GI world about monitoring either drug levels or anti drug antibodies as a way of assessing efficacy or the loss of efficacy in patients treated with TNF inhibitors.

This is, as you know, a big issue in patients receiving monoclonal antibody based therapy. So it was a fairly large study, done, which this week, talked about the rates of secondary failure. And in this particular study, they looked at patients who what's the number here? The number of patients that were studied were five seventy patients. And this is sort of a retrospective observational study of patients receiving either etanercept, befiximab or adalimumab.

Of these patients, these are five seventy patients who had a secondary loss of efficacy. So they previously had responded and now they lost their efficacy, so they're secondary failures. And they did not find any evidence of anti drug antibodies with etanercept, but with infliximab and adalimumab, the rates of anti drug antibodies was either twenty seven or twenty nine percent respectively. Now, you can either take that as a, you know, bad news or good news. I take that as good news and sort of suggest that anti drug antibodies is only partly to blame in patients who have secondary loss of efficacy.

And maybe if you want to test for these and to explain that, you're going to pick up less than thirty percent. But you're going to need to find out why the patient's not responding and there are probably other factors in play. You might also ask, is this disease specific? They actually looked at both spondylitis patients and patients with rheumatoid arthritis and found similar data. They what about the issue of background DMARDs where it would not be used in spondylitis but would be used in RA?

Know, DMARDs should protect you against anti drug antibodies. It turns out that protection was very little. So of those who were on combo therapy with a background DMARD, the antidrug antibodies was 16%, and if you were on monotherapy without background DMARDs, it was 26%. While those are significantly different, again, it's a small player in the overall picture of non responsiveness. So it remains to be seen what the efficacy is going to be or what the utility of anti drug antibodies are going to be in rheumatology patients.

So there's an interesting study of Cimzia that's out there that was reported by Desiree Vanderheit, I believe in the annals of rheumatic disease. In this particular study, gave patients, three twenty five patients specifically, either Cimzia or placebo and follow them for out to four years. They previously reported on the efficacy of this trial showing that obviously cerdulizumab worked really well in twelve weeks, which was the primary endpoint. What they did in this trial was that they also looked at MRI scores of inflammation of the SI joint, and they also did, regular X rays and scored them at the different time points starting at baseline week twelve, six months every year thereafter. And basically what they showed was that over a four year period, there was significant improvement in the SI inflammation scores on MRI.

In fact, that was seen as early as week 12. But that same benefit that was seen by week 12 and those on the TNF inhibitor was maintained throughout the four year period without much change, suggesting that, again, there's probably something important going on here. Again, MRIs are very hard to prove benefit, but using the technology that's advanced as far as the scoring, Walter Maximovich developed SPARC scoring for SI joints on MRIs has been very valuable. They also showed that the X-ray changes really had very little progression, which is also important over a four year period. There was some progression in the SI scores, but it was not significant.

So overall, eighty one percent of patients with ankylosing spondylitis in this trial, and this is also included patients with non radiographic axial SpA, but eighty one percent of patients with ankylosing spondylitis really did not change their X-ray scores over a two year period. That's encouraging data, in this trial with a TNF inhibitor. By the way, this is similar to the data that was seen with secukinumab, the IL-seventeen inhibitor in the measure study where they, showed a seventy nine percent protection, I believe, over, a two year period. So again, that's encouraging data about the use of aggressive therapies that may be able to forestall the radiographic changes associated with these diseases. So we have two last reports.

One is a novel one that you might want to look at, and it's called Problems with Drug Storage. And this comes from an abstract they saw at last year's EULAR meeting and is now in publication in a GI journal, the Journal of Gastroenterology and Hepatology that talks about a paper by De Jong that looked at a cohort of patients receiving a golimumab and the golimumab had a temperature sensor attached to it. And basically in their trial, they showed that only about eleven percent of the patients given golimumab were able to store the drug correctly at the right temperature. Those that didn't were all over the map. You know, it was too cold, it too hot.

You know, Just Right was sort of lacking. And that's what the purpose of the paper was. There's another paper that was also published a year ago that showed the same thing where their numbers were a little bit less. Only about seven percent of patients actually stored the drug correctly. So you should read the paper to take some perspective to figure out whether this is going be an issue for you and your patients, especially your patients who may not be doing well.

Because we do know that if the drug gets, thawed or goes to room temperature and goes back in the refrigerator and goes back and forth, or it gets frozen and unfrozen, it may change the protein structure and the efficacy of these drugs. I think the one tip that I think you should take away is make sure to remind your patients not to store the drug in the CRISPR. The CRISPR is that bottom box in the refrigerator. It tends to be colder, significantly colder, and the recommended storage conditions for these drugs is somewhere between two and eight degrees centigrade. So that means up to about 36 degrees Fahrenheit is is about the right temperature.

But the CRISPR is usually two to five degrees lower and has variable humidity controls for newer versus older refrigerators. But the CRISPR is a bad place to put it, and you should remind your patients of that. Lastly, the US Senate Finance Committee voted to approve, mister Alex Azar, previous head and president of Lilly, to become the new US head Secretary of Health and Human Services, where he'll play an important role in drugs and drug development and health care of The United States, the population and whatnot. You should look at the, the video that we have on the RheumNow website where we, I interviewed him at the last ACR meeting. Interesting interview.

A smart fellow. I I I sort of like this appointment. I think he's got some nice progressive ideas. He's all for transparency and pricing. I think you should look at the video.

It's on on the website. That's it for this week in roomnow.com. Make sure you go to the website to check out these links, learn more about these topics. We'll see you next week on RheumNow. Be sure to subscribe on either YouTube or iTunes or SoundCloud.

Thank you. Bye.