The RheumNow Week In Review - 01 September 2017 Save

It's 09/01/2017. This is the RheumNow we can review. I'm Jack Cush, executive editor of rheumnow.com. A lot going on in our world. At the top of the news, I think we should talk about, the hurricane Harvey that's hit the South Coast Of Texas, Texas where I'm from.

I was unaffected in Dallas, but many were. I would really strongly urge you to go to the link on the website to donate to the American Red Cross. Or if you just want to text the word Harvey to 90999, you'll be donating $10 to the cause, a very worthwhile cause. I also wanna remind you to be on the lookout for our ACR 2017 coverage. We've been working hard to change the way we do that, to expand what we do, to really excite you so that you can see, what's going on from our viewpoint.

That's coming up. It's gonna be quite exciting. So top of the news, 25 studies have looked at patients who have a, who are have rheumatoid arthritis who are going to get therapy, and it shows that basically there's a very low risk of hepatitis B reactivation when you have a history of of chronic, or a resolved HBV. Those are patients who are hep B surface antigen negative and hep B core antibody positive, suggesting they've seen the the virus in the past and have have a resolved infection. The chance of reactivation looking at a large number of studies is one point six percent, which is really quite encouraging, and it's really not any higher if you take a biologic or specifically a TNF inhibitor.

So it seems that you can use a TNF inhibitor in those patients, but you must use it with caution. Our friend and colleague, Len Calabrese, tweeted that remember that while hep b reactivation is really quite rare, it is also preventable. So you still need to worry about these patients, check their LFTs, look at viral loads. You If think that they're really immunosuppressed beyond rheumatoid arthritis, they probably should see a hepatologist and consider background antiviral therapy before going on a biologic agent. A study of geriatric patients, specifically sixteen hundred and sixty seven geriatric patients who had septic arthritis were matched, ten to one, ten, elderly people, and then versus, the one who had the septic arthritis and showed that the chance of death with septic arthritis in the elderly has increased fifty to a hundred percent, suggesting that, not only that is it a poor candidate to get such infections, but the outcomes are striking.

So aggressive treatment is needed there. The New York Times has reported that the FDA is announcing a, a crackdown on the unscrupulous practices being seen in many stem cell clinics across The United States. We wrote about this before. As you know, there are clinics, mainly orthopedic clinics, but a lot of, other disciplines in medicine are getting into this regenerative medicine movement where they're taking the patient's cells, whether it be from fat, bone, or bone marrow, putting them to culture, repurposing them, you know, tricking them up a little bit, and then injecting them back into the patient to resolve something calling this, stem cell therapy. A lot of these, there have been adverse events and serious adverse events associated with this.

The FDA is of the position that that in some of these clinics, some of these practices are, are unscrupulous. Some of them are dangerous, and that what they're giving back to patients isn't a blood product, but it, in fact, qualifies as a drug or biologic. So this is gonna fall under the scrutiny of the FDA. A study of an uncontrolled study of severe ocular Behcet showed that when they were treated with TNF inhibitors, only about half of them respond to TNF inhibition. Only half of these stay in remission over time.

That's been my experience in using Behcet. I don't see a lot of ocular severe Behcet. So, in that situation, there has been some literature to suggest it may work. But, otherwise, a lot of Behcet's with, mucocutaneous involvement and joint involvement, they don't respond to TNF inhibitor in my opinion. An analysis of the epidemiology of lupus, worldwide shows that really the incidence and prevalence of lupus varies quite a bit worldwide.

But overall, it seems that the incidence is increasing over time. It seems that there are higher frequencies in African Americans, especially from North America where the rate of lupus is twenty twenty three per one hundred patient years. It is lowest in in Africa, interesting, and Ukraine and Northern Australia. An a study coming from the endocrine world shows that untreated sleep apnea increases, diabetes basically and the metabolic syndrome. They looked at this in several ways, including taking patient patients who are on, CPAP and taking them off and seeing what happened to certain biologic measures, and they showed that untreated sleep apnea increased free fatty acids, glucose levels, cortisol levels, and blood pressure, which we know about.

So, again, I don't know about you, but I spend a lot of time, treating and managing sleep and getting patients to go to get studied for sleep apnea, many of whom are resistant. But it it it is something that we should initiate as rheumatologists. A lot of regulatory information in this week's news. At the top of the list, maybe the most important, is that the FDA approved its first gene therapy. This is CAR T, therapy.

It's called KyrmiaH, k y r m I a h from Novartis, $475,000 a treatment. Thank you. And this is being approved for the treatment of young adults 20 who have refractory B cell ALL, acute lymphoblastic leukemia, as you know, has a high mortality rate. If those patients don't respond to conventional therapy, it's about estimated about fifteen, twenty percent. They're giving this CAR T therapy.

That's a chimeric antigen receptor that targets, where they that's injected into the patient's cells, a specific gene that does that, and basically, causes T cells to go after the target B cells, c d 19 B cells specifically to kill them. It kills normal cells. There's a lot of toxicity or symptom management that goes on with this. There's a strong, risk of developing the cytokine release syndrome. And and at the same time that the FDA approved this drug, they also approved Actemra, which inhibits IL six to manage the the the cytokine release syndrome with a dramatic reduction in toxicity and severity and time of those events.

So two drugs being approved at the same time to treat acute ALL. The FDA has also, made a turnabout in its decision about baricitinib. As you know, we reported in July that the FDA was rejecting baricitinib's, application citing an imbalance in thromboembolic events in those that receiving the high dose of baricitinib, where they saw five cases and no cases in the low dose two milligram or in the placebo patients, in the placebo controlled portion of study with thirty thou 3,000 plus patients. The speculation was that they're gonna have to start over. They may have to do studies.

This is gonna delay the approval of drug to either 2019 or 2021 depending on who you read. But in negotiations and discussions with the FDA, Lilly and Insight, have announced that they're going to resubmit a new NDA for baricitinib in January 2018. The FDA will have six months to review that data, and come back with a decision about baricitinib, which as you know is an oral JAK inhibitor that, is a once a day dosing, is felt to be, you know, a big player. This changes the mix right now. We only have one JAK inhibitor, tofacitinib.

There's filgotinib and, updacitinib or, the the one from, ABT, four ninety four from, AbbVie, and those are in development. Those are we're going to jump ahead of of baricitinib. Now they're probably gonna be a little bit behind baricitinib if baricitinib goes through the process and can explain that those venous thromboembolic events probably are at a rate that is commensurate with what's seen in RA patients who have an increased risk of venous thromboembolism. Another, regulatory action, much to my surprise, I didn't know this was brewing, but another adalimumab biosimilar was approved from, Boehringer Ingelheim this week by the FDA. It's called c y l t e x o.

Anyway, again, it's not likely that's gonna hit the market anytime soon. There's a lot of litigation going on with this and Amjevita, the other adalimumab biosimilar from Amgen, and litigation over patent protection and whatnot. It's gonna be a while before we see an adalimumab biosimilar. Certainly not in the next six months would be my estimation. Canakinumab was nice report that we've been waiting for.

There's several reports going on in the in the cardiology literature where they're testing the hypothesis that control of inflammation will control the risk of cardiovascular events. So we have trials going on in methotrexate and Plaquenil in this study, the CANTOS study, with an IL-one inhibitor, canakinumab. So the results of that were published at, presented at a cardiology meeting in Spain and also published on New England Journal showing mecanakinumab given to a thousand 10,000 patients with who are at high risk for cardiovascular events. They've had a prior MI. They have an elevated high resolution CRP level greater than two milligrams per liter, and they're followed over I think it was two years, and, actually, it's three point seven years of follow-up.

And they showed that the overall, those who received either a hundred and fifty milligrams or three hundred milligrams of canakinumab every twelve weeks had a, sixteen, fifteen percent reduction in cardiovascular events. That was significant, and it was just not only the events, but death from cardiovascular, events were also seen. Another offshoot to the study showed that those who were treated with canakinumab also had a lower risk of lung cancer. Both the onset of incident lung cancer and death from lung cancer was lower in patients who were taking and there, the reductions, I believe, were close to fifty percent reductions. These are all interesting results.

The problem is that canakinumab as priced currently is over a $115,000 a year, And so it's not likely it'll be used as routine prophylaxis for cardiovascular, prevention, nor for cancer prevention. So we need to understand the biology of what's going on here or, find other ways to use IL-one inhibition to these benefits. This current issue of the, arthritis and rheumatology used to call it arthritis and rheumatism. I don't think that was a good change. But ANR, let's call it, has three articles devoted to the topic of shingles vaccination.

The first one comes from Kevin Winthrop and Jeff Curtis who did a study in a 112 patients who were going to receive tofacitinib, and they were randomized to receive either live virus vaccine or placebo. And they showed that it was safe to use the live virus vaccine, and then wait two or three weeks and then give tofacitinib with no untoward reactions. The The only untoward reaction seen in this trial was one patient who developed developed disseminated herpes zoster, and that patient had, no innate immunity to zoster. They they they when they checked there was this was basically, first time exposure for that patient. And so that rare event was was seen in this trial.

But overall, it looks like that practice of vaccinating before, the use of tofacitinib was quite efficacious. And that's currently my practice. Not only do I do this in patients over the age of 60 who are eligible to receive the vaccine, I urge anybody under the age of 60 who needs this this drug to get, the live virus vaccine, as soon as possible whenever possible. There are two other reports. One was just a regenerative view of the large number of studies done with tofacitinib showing that the rate still is consistent at about four, zoster events per 100 patient years.

Most of these were involving one dermatome and weren't serious involving the eye and etcetera, that the rates were higher in certain regions such as Southeast Asia and I think the Ukraine, and then also, were higher in patients who took steroids. And then the last one was, an editorial that I wrote, called, fear fear the infection, value the solution, when it comes to herpes zoster. In it, I review who's at risk, how these patients should be approached, and the practice of vaccinating, which is patients need to be off of biologic therapies for at least two weeks and maybe as much as four weeks, and then, receive the vaccine, and then they can go ahead and get the the the biologic restarted, the tofacitinib restarted, two weeks later. So, again, be off four, vaccinate, and then restart two weeks later is the practice advocated by the CDC and many. Please be sure to take a check out our our new therapeutic updates.

The last one we posted was with Phil Meese, Alan Gabowski, and myself commenting on five questions on the FDA hearing regarding the use of tofacitinib in psoriatic arthritis, where it seems like that's gonna get approved, and it'd be interesting to hear the perspectives of those who are either there or viewed the results and have some perspective by being past FDA members such as, Givo and myself. So that's it for this week at rheumnow.com. I'll leave you with these words of wisdom. The job is not you nor is your income car or good looks. You are your principles and what you do when those principles are called into question.

I dreamed up this little quote. It's I I kinda wrote it, but I wrote it after listening to a podcast by Malcolm Gladwell, who has a podcast called Revisionist History. The link is on the website. The podcast in particular that led to this, almost thoughtful, quote, was about a doctor in at the Mayo Clinic who spent his life doing research on diet and the role of fatty diet in cardiovascular disease. And that, many years after his death, the solution, the answer to the question was found in his basement.

So it's called the episode is called The Basement Tapes. It is about, values and work ethic and and about principles. See you next week. This is rheumnow.com.