The RheumNow Week In Review - 25 August 2017 Save

It's the 08/24/2017. This is the RheumNow we can review. I'm doctor Jack Cush, executive editor of roomnow.com. This week in the news, pregnancy tops the list. We have information about the safety of IL-one inhibitors in pregnancy.

As you know, the TNF inhibitors have sort of dominated the picture on pregnancy so far. They're being class B pregnancy risk and others being class C pregnancy risk. There's a lot of data about TNF inhibitors that's out there. Very little data about the IL-one inhibitors led by Kineret and Ilaris and Rolanicept. But, one group got together and collected data on, a number of pregnancies, specifically looking at there were 11 paternal exposures to IL-one inhibitors and 31 maternal exposures to IL-one inhibitors.

On the maternal side, it was 23 anakinra and eight kanikinomabs. And most of the, for instance, the anakinra cases ended up in live births. I think it was twenty one out of twenty three. A few of the cases of kanikinomab, I think there was one miscarriage. There was one renal agenesis, along with an ectopic neurohypophysis as a potential, defect.

But overall, the experience was good. And again, albeit very limited, there's some encouraging data there about the IL-one inhibitors. Another study comes from the Scandinavian countries where a number of countries got together and pooled data on four thirty five juvenile idiopathic arthritis patients and looked at the incidence of uveitis. As you might expect, the incidence was twenty point five percent. Ninety percent of those were asymptomatic.

And the predictors for developing uveitis was number one, age. If you were less than age seven and you had JIA, you were more likely. Also, ANA positivity and antihistone antibody positivity were tended to be predictors of developing uveitis. Interestingly, it was the younger females and not the males who had a risk of developing uveitis. A study from the Canadian, actually in Ontario, group of rheumatoid arthritis patients, in fact almost four thousand six hundred patients looked at adherence to medicine.

And in their data set, they showed that fifty nine percent were thought to be adhering to biologic therapy. I think that's actually pretty good. Although most of us think one hundred percent of our patients take the drugs that we give them, the data is pretty clear. And I think with biologics and rheumatic disease drugs, it's quite disappointing. So fifty nine percent is not too bad, but at the same time, it's not too good either.

And we have significant challenges in the world of convincing our patients about the efficacy, safety, and the need to take the medicines we prescribe. Interestingly, they found that if you're non adherent, you're more likely to receive steroids, although the difference wasn't that great. It was sixty seven percent if you were non adherent versus fifty six percent, for the adherent patients as far as taking steroids. A Swedish early inflammatory arthritis study looked at the things that would influence the onset of rheumatoid arthritis. They found that oral contraceptive use, either ever or, past oral contraceptive use, decreases the risk of ACMA positive rheumatoid arthritis.

They tried to assess whether or not breastfeeding might also decrease this risk, and they were unable to do that. Their resultant, or their conclusion was that it really had no effect. So, again, the odds ratio having ACMA positive RA was down about sixteen percent, if you were exposed to an oral contraceptive. In the world of regulatory medicine, Ironwood, who took over the rights to Xerampic, lisinirad, from AstraZeneca, Ironwood, who is developing and promoting that drug, has now announced the FDA approval of the combined drug of lisinirat and three hundred milligram allopurinol. Two hundred milligrams of lisinirat, three hundred milligram allopurinol, all in one pill, and it's called Duzalo.

It's a doozy. The question is, do we really need the combination therapy? I'm not big about combination drugs, especially if we start mixing old drugs together and causing high cost. I get chorus, lisinirat has to be prescribed with a urate lowering therapy, either allopurinol or febuxostat. This is making it convenient for the patients and I'm sure quite expensive for the patients and the insurers as well.

My main gripe with lisinirat is that its use is predicated on proving that the patient is not controlled on standard therapy when the evidence is really clear that most of us don't do a very good job of optimizing the use of urate lowering therapy, including good old cheap allopurinol. But there are patients who may benefit from more aggressive therapy and maybe this combination would be beneficial. Again, how it's going to find its utility in the current marketplace remains to be seen. I experimented this week on Twitter with the use of Twitter polls. I've been looking at those recently, think it's kinda interesting.

And what I did first was I threw out a tweet that said that leukocytosis, aka palpable herpura, is most commonly associated with a lot of things, infections and drugs. Of all the things associated, actually antibiotics lead the way. In most studies, maybe as much as two thirds of cases are related to antibiotic use, including ciprofloxacin and cefazolin, and you can go on and on and, you know, and penicillin like drugs have been all linked to this as have been infections for which patients receive antibiotics. So gets a little murky there. But, anyway, as I tweeted that out with a reference, I also, threw out a question to the Twitter world, and the question actually comes from JAMA.

And you can look in the current issue of JAMA and see this question that says, a 30 year old female has non itchy, non painful palpable purpura in the lower extremities and abdomen. This she's had these lesions on and off for the last eight months, and the patient has a history of hepatitis B that's been treated with antiviral therapy, tenevir, and asked the audience, what would you do next? So I posted this question, and we got about 40 responses right away. And the choices were treat with prednisone, treat with topical steroids, reassured, observed, and the fourth answer, which eighty eight percent of people chose, was the right answer, was, evaluate for systemic, illness and vasculitis. So you might see Twitter polls.

I think that they're interesting. This week, we had a great article from Doctor. Kevin Winthrop, who's sort of the infectious disease specialist to the rheumatology community and to many. Kevin has a great deal of experience. Used to work for the FDA.

He's now at the Oregon Health Science Center in Portland, and he wrote a nice review article on the management and diagnosis of nontuberculous mycobacterial infections, NTM. This used to be called atypical mycobacterial infections. And in his nice, relatively quick read article, he covers five questions, including, when to suspect, NTM infections. He says these are most common, almost exclusively seen over the age of 40 and more so in females. People are at higher risk include those who are tall and thin, those who have, chronic lung disease.

Rheumatoid patients are at greater risk as are patients who are on chronic steroids, and as are patients who are on biologics. You know, NTM infections outnumber TB infections in almost every population, whether it's HIV, cancer, immunosuppressed, RA patients on biologics, non immunosuppressed patients. NTM infections are more common and we should worry about these and, strongly consider these. How do you screen for them? There isn't a blood test and there isn't a skin test.

Usually the issue comes up either based on symptomatology or an abnormal chest X-ray. Kevin Wright said if you have an abnormal chest X-ray, you should consider doing a non contrast CT and getting some AFB from the sputum and seeing if you can prove the diagnosis there. There are American Thoracic Society guidelines on how to prove whether an MAI or other NTM infection found in sputum is in fact clinically meaningful. And lastly, the management of these infections can be difficult. You never fully eradicate them.

The most common amongst them is, MAC, and, and he recommends that a macro a macrolide antibiotic along with that would be like Zithromax along with ethambutol and rifampin for as much as twenty four months may be indicated. As you know, these drugs when you have these infections of patients on TNF inhibitors, you have to stop TNF inhibitor, same could probably be said for steroids. So you should really avoid TNF inhibitors, especially when you have these and never go back to them because you never fully eradicate. And TNF inhibition leads to the, flourishing of these bugs, especially the, mycobacterial species. So you could go to other biologics which have a much, much lower risk for mycobacterial infections, and that's a that's found in other discussions on RheumNow.

So another great report I think came from a follow-up to what was reported at EULAR, an S3 report of the Govibrant study. This is what happens when you give IV golivimab to patients who have psoriatic arthritis. As you know, golimumab in the subcutaneous form is already approved for use in psoriatic arthritis based on clinical trials that show an ACR twenty, fifty, and 70 response rate of fifty two, thirty two, and nineteen percent. The interesting thing is that this much larger trial with gave much greater results. And, of course, there's no head to head here, but it looks like ivigolimumab is a throwback.

I asked Artie Cavanaugh, the lead author on this paper, what he thought about it. He said, this is a lot like the old days when it was easy to prove a drug worked because the ACR twenty fifty seventy on IV golimumab, was 75, 44, and 26. Clearly better than what we saw or what's in the literature for SubQ. Now there are no head to head trials. Whether you should use SubQ or IV is really up to you.

It'll be interesting to see how this plays out and whether they'll get an FDA approval for the use of IV galimep. They also had good responses in the skin, Posse 75 response of 59%, and they had great X-ray responses where those that were just on background therapy, placebo methotrexate, had worsening of their X rays, had two sharp units, over, I I believe it was fifty two weeks, whereas those that were on ivigolumab had a lessening minus point minus point four sharp units. So, again, very much as already said, a throwback to the old days when it was pretty easy to prove and you had great X-ray results. A great report was seen this week from Dan Solomon's group and, those at, at the Harvard, Medical School on treat to target, and whether it's being utilized by rheumatologists. In their study of six forty one RA patients from 11 medical centers, and specifically the charts of forty six, mostly rheumatologists, they looked at whether or not in the care of rheumatoid arthritis, rheumatologists are adhering to the components of treat to target, which means have a goal, measure and treat to that goal, have the shared decision making and show that therapeutic decisions were based on the goal.

There are four components. And they looked for those and amazingly, found that two thirds of the doctors and the charts they surveyed didn't meet any of these components, meaning treat the targets got no traction in the rheumatology community. More, I guess, shocking is that only like zero point three percent actually had all four components in play. This is interesting because actually most of us believe that we do measure. Most of us believe we do treat the target.

Our surveys from Jeff Curtis and I that we're gonna publish soon, it's in press, and Jay Rheum says that fifty four percent of rheumatologists do some measure ranging from a HAC to a DAS to a gas to a C Dye or whatever you it is that you like to use. But the evidence that we use that measure in decision making in our study was very scant. A few other studies says also not likely, and in this study says that you don't even do them. A lot of comments, after this was posted from rheumatologists saying that this is sort of a, a waste of time or a scam or something perpetrated by industry, and they have no time for it. And I don't believe that actually.

It only takes sixty to ninety seconds to perform these metrics, and it's even easier to have a standard that you're treating to. And the standard should be low disease activities or remission. And so again, I think it's surprising that this advance in rheumatoid care and something that's in the guidelines for both the ACR and UR guidelines, has largely been discarded by US rheumatologists. A nice report from Olga Petrina was posted on, the analysis of lymphoma risk in patients receiving TNF inhibitors or not receiving TNF inhibitors, all of whom having rheumatoid arthritis. As she points out in the title, it's the rheumatoid arthritis and not the biologic or the TNF inhibitor that drives a lymphoma risk.

They looked at data from nine registries and looked at those who are not on drugs versus those and really show showed number one that RA patients have a higher risk of lymphoma, largely B cell lymphoma, but also T cell non Hodgkin's lymphomas more so than the average population. And that RA patients on TNF inhibitors, the risk is the same as if you're not on TNF inhibitor. Hence, it appears that the lymphoma risk is driven by RA and is rheumatoid arthritis dependent and as other authors have shown, is probably more dependent upon disease activity and inflammation overall. To close this session, we want to give a special acknowledgment to the loss of one of our, leaders and colleagues, Doctor. H.

R. Schumacher, Chief of Rheumatology at the VA Medical Center in Philadelphia, professor of medicine, a leader in the rheumatology community, you know, an icon in the world of gout and crystal analysis, a major teacher, clinical trialist, a guy who spent most of his life being both a scientist and a clinician. We've got a bit of a tribute to him and a link to two other memoriams written by a lot of our colleagues. So we will miss Ralph and those many of you are gonna have to work real hard to fill his shoes. And lastly, go to the website and look at therapeutic update.

We did one a few weeks ago on the cirucoumab FDA hearings. We just posted one on the tofacitinib FDA hearings. He's got almost 700 views in two weeks on YouTube, so you can look at the new one on the website. Be sure to go to iTunes and give us a good score and a ranking, you know, the big thumbs up kind of deal because, If if you get if we can be highly ranked, maybe we'll get famous. Who knows?

That's it for this week on rheumnow.com. Tune in next week for more good news.