Lupus Delights Save

It's the 09/18/2020. This is the RheumNow podcast. Hello. I'm doctor Jack Cush, executive editor of roomnow.com. This week, we're number two.

I know we like to be number one, but number two ain't too bad. Pregnancy and COVID. Not as good as I previously thought it was. There's some sobering information here. And a number of lupus delights worth hanging around for.

Let's talk about this week's reports. At the top, Doximity came out with a survey that looked at healthcare providers and where telemedicine is is today and where it's come from and where it's going. And they came around with a top 10 specialties list of those who use telemedicine most. Who's number one you say? Endocrinology.

Number two, rheumatology. Number three, gastroenterology, followed by nephrology, cardiology, GU, neurology, geriatrics, hem onc and pulmonary. It looks like cognitive disciplines are taking to the phones and to the video thing. Surgery, not so much. Procedural things like ophthalmology, not so much.

I think this is a big advance for rheumatology. I think this will change the way we do our practice. I think if you're not plugged into telemedicine, you should be. There are a lot of advantages here both for your patients and for you. You can expand your practice.

I've actually heard of practices getting rid of employees and nurse practitioners and PAs during COVID, when in fact they should be expanding their practice certainly by using more telemedicine. So, we have a number of COVID reports that we should run down. First is the association with nonsteroidals. Remember that crazy French directive that said, you should not use nonsteroidals if you have COVID based on nothing. Well, there's actually a Danish cohort study, of those taking NSAIDs, those not taking NSAIDs, one to four, MATCH study showing no higher risk of mortality, hospitalization, ICU admission, mechanical ventilation, need for renal replacement therapy.

Again, it was sort of an idiot kind of recommendation. Don't know where that came from, but don't heed any cautions regarding nonsteroidals and COVID. I think a nice report, has come out about Remdesivir in combination with patients who are receiving Baricitinib. This was a, NIH run trial, it's called the ACTT-two trial, over a thousand patients randomized to receive, either remdesivir alone or remdesivir plus four milligrams of baricitinib. And again, the, outcomes were good.

The Baricitinib Remdesivir outcome actually had a better time to recovery in those who are hospitalized with severe COVID-nineteen infection. There are a number of Baricitinib trials in progress. Baricitinib looks good not just by being an anti inflammatory cytokine inhibitor, but also because it blocks endocytosis and uptake of the virus by cells. So, again, we'll see more of that in the future. Again, I keep telling you, we're waiting for all the randomized controlled trials.

They're going to start coming out in September, October, November. I think we're going to start seeing them soon, I hope. There's a proof of concept study that adds to the already existing uncontrolled or not completely controlled data about colchicine in COVID. This is another proof of concept study, one hundred and forty consecutive COVID patients were randomized to either receive, everyone got standard of care, which includes antiviral therapy, etcetera, and then others, received colchicine, others did not, in addition to standard of care, and overall survival rate was better at twenty one days, and those who received colchicine plus standard of care, colchicine being, a drug that acts on the inflammasome and that may have protective effects here. Again, the survival rate is eighty four percent versus sixty four percent highly significant, but again a small study.

There is much larger studies being done by Montreal Heart Institute, I want to say, and NYU, look for that. There's a, I just published today, an update about pregnancy and COVID-nineteen. This is spurned by two reports appearing in MMWR from the CDC, one about five eighty seven patients, the other one, I don't know, one hundred and fifty patients. These were, pregnant patients who were COVID positive. In the larger study that was from March till August, patients were accrued, over five hundred, and in patients who were COVID positive, fifty five percent were asymptomatic.

However, the forty five percent that were symptomatic included a bunch, you know, fifteen percent who were hospitalized in the ICU, you know, I think there was like one or two deaths. I mean, so the idea is that because you're pregnant, you know, you're not necessarily free. And there were a few fetal losses. The smaller study that was paid where patients were accrued from eight medical centers in The United States, that was between March and May. They found that if you were hospitalized with, for obstetric reasons, eighty one percent of patients were asymptomatic when they were COVID positive.

However, if you were hospitalized for COVID reasons, guess what? A lot more were symptomatic and those were the ones who had more trouble. So the idea here is that, you know, unlike Zika virus where there's a known bad outcome, especially for the fetus, and women who are infected with the Zika virus, we weren't seeing any negative reports with this particular virus, the SARS CoV-two, but now we are seeing that it is playing a role in what happens to pregnancy. There has been some fetal loss, There have been some intrauterine growth retardations. I did reference a Lancet article about how these patients should be approached in an algorithmic way.

You can find those citations on the website. So moving on from COVID, DSH, I know we don't talk a lot about DSH, you know, it's a diffuse idiopathic skeletal hyperostosis or Farrestiase disease. A cohort study of, nearly four hundred DSH patients looked at calcium artery scores and showed that a high percentage of these patients, a quarter of them had very high calcium artery scores, CAC scores are greater than 400. The point being that it looks like dish patients carry a reasonably high risk of coronary artery disease. Now, is it related to their age or is it related to DSH?

This report doesn't go into it. Wasn't designed to answer that question, but it is something you should worry about in your DSH patients. An interesting study came out, on again COVID, '19. I put this in the wrong spot, but these were, this was from a dermatology journal, two thirteen patients, with image that they followed thirty six percent tested positive for COVID when they compared COVID test positive, COVID test negative, no higher rate amongst the COVID positive IMiD patients immune mediated inflammatory disease, no higher rate of hospitalizations, mortality, ventilation, and it was not shown that immunosuppressors were all part of the risk. This is what we've saying all along.

Our patients are doing well as long as they're well controlled, as long as they continue to take their drugs. So, a study of rituximab and ILD was reported this week. It's a small study, 31 patients uncontrolled, but it's a prospective, I think it was consecutive patients that were treated with rituximab. And in this particular study, they showed that rituximab treated and these are patients who are refractory. RA patients who had refractory ILD that was progressing not controlled by usual RA therapies.

The choice was made to institute rituximab therapy. And in those people, there was, a modest decline in, force, FVC and also DLCO, improvements of eight percent and twelve point seven percent respectively, while they were able to lower their prednisone use while getting rituximab. I don't think that's been answered yet whether rituximab is truly effective in ILD. We don't really have a truly effective drug in reversing the process in the ILD with RA, or even with any other of our autoimmune diseases. At best, we might find a therapy that halts the progression, and that would be certainly a great thing to say.

Well, right now, don't have a good head to head trial proving that Rituximab is effective here, I've used it, I'm sure you have too with hope because you don't have hope, you don't have many other options. We need more options in this arena. I don't know that Nintedim is going to be the answer. Hopefully, they'll examine RA patients specifically with ILD. They have an autoimmune ILD study that they've done, but I don't think it answers this question.

So I don't know if you manage gout patients and wondered about the use of dual energy CT scans to show you those bright green deposits of monosorium sodiumurate in places that you didn't expect it, quantifying the amount of of deposition of crystals that are seen in patients. Well, this particular analysis came up with a study in twenty seven patients that looked at over 4,000 DECT, dual energy CT identified lesions, these bright spots that show up in these twenty seven patients and basically showed that there is a difference in their their specificity, meaning that not all things that are bright, not all shiny objects here are gold, not all shiny objects here are due to gout. And specifically, what they showed that, it was much more likely based on the characteristics that were seen, high density, large volume, low deck ratio was thought to be specific for uric acid crystals, those are more likely to be found in MTP one joints and patellar tendons. However, when these lesions were found in other sites, large joints like knees or in the ankle, mid tarsal, talocurl, or in Achilles or quadriceps tendons, they were more likely to not be gout having other characteristics and some of these actually having calcium in them.

So this goes to what we've reported before that, Dex you the use of Dex in patients with gout or suspected gout is interesting, but again, it doesn't have great sensitivity or specificity that warrants its widespread use. Obviously, it's not widely available, but there are limitations to these scans. Speaking of ILD, it was studied in almost seven hundred patients with idiopathic inflammatory myositis, and a high percentage of these pay people, five hundred plus, had ILD. Who gets ILD with myositis? Well, in their cross sectional view, that if you had amyotrophic dermatomyositis, CADM, clinically amyopathic dermatomyositis, a high percentage, ninety three percent of those people had ILD, it's almost part of the syndrome.

It was seen less frequently in dermatomyositis, seventy four percent of patients, and fifty five percent of patients with dermatomyositis had ILD. ILD was greater in patients who had the antisynthetase antibody or the antisynthetase syndrome like JO-one and other antisynthetase antibodies, and also patients who have the MDA five. That is a good biomarker for the amyopathic dermatomyositis patients. Obviously, if you had both, the, MDA five and antisynthetase syndrome, had a much higher rate of ILD, but more importantly, a higher rate of mortality, thirty three percent versus about fifteen percent if you didn't have that. So we have a slew of reports this week on lupus.

Let's start with the nurses' health study. You know, they got like 8,000,000 nurses in this thing and they measure everything. God bless the nurses for all the hard work that they put out. And again, most of these reports I think are useful. I think this one is, on this particular report of almost eighty thousand women, in the study, they identified one hundred and ninety four incident cases of lupus.

And as you know, they do measure a lot of things including diet. And they looked at four specific diets, the DASH diet, popularized for its use not only in weight loss but also control hypertension, Mediterranean diets, anti inflammatory diets, and overall healthy diet. None of these were associated with a risk of getting lupus or protection against getting lupus. So those of you who were asked often by your patients, is it my diet doc? And when a case of lupus, it's not you know, doesn't seem to be that it's linked in some way.

Obviously, we should always strive for a healthier diet. It will certainly cut down on a lot of comorbidities associated with lupus, and that may be more important. The New England Journal had two good reports this week. One, a small little one of two patients treated with an anti CD38 monoclonal antibody, identifies plasma cells. Plasma cells are the ones that are making all the antibodies.

You can knock out B cells with an anti CD19, anti CD20 monoclonal antibody, and patients may or may not do better, but you're really not affecting immunoglobulin levels because there's tissue plasma cells that live forever. We don't know how long they live, but they live a really long time, and you can't deplete them all that well. And so the effects of rituximab and other B cell directed antibodies hasn't been quite as great as you'd like it to be. This particular, drug is called daratumumab. Daratumumab, proud of myself for saying that.

And it was given to two patients who noted clinical improvement, had depletion of plasma cells, reduced their type one interferon signatures, down regulated T cell transcripts. They clearly had a significant immunologic and clinical benefit. Again, the question is, will there be a downside to knocking out plasma cells? How long will your immunoglobulins be down? What's going to be the infectious risk that is attendant to that?

So, I think it's interesting, not sure where it's going to go. A Taiwan National Health Population Study compared lupus and non lupus patients undergoing hip surgery, hip replacement surgery, six fifty lupus, and the same number, actually six fifty patients overall, half having lupus, half not having lupus, And it shows that lupus did not increase the risk of prosthetic infections, especially early on, but late prosthetic infections were increased in, and actually, sorry, not prosthetic, it was late superficial wound infections were higher in lupus patients, eleven percent versus five percent hazard ratio two point four. So, had another report this week from JAMA, actually JAMA Dermatology, talking about drugs that induce lupus. Specifically, they looked at the, types of lupus that were being induced. And as you would imagine, systemic lupus was a minority, you know, it was like four percent.

Like like almost half of the cases were DLE and like thirty percent of patients were SCLE, I may have gotten those backwards. But the point is that most cases of drug induced lupus were really discoid or subacute cutaneous lupus. The leading candidates that they identified in this population based analysis was fexofenadine, Allegra, levothyroxine, metoclopramide, Reglan, metronidazole, Flagyl, terbinafine, which is Lamisil, and as you know, TNF inhibitors have been associated with the risk of drug induced lupus. Now, what's not on the list, actually it was appeared somewhere else in the paper are, the PPIs, the proton pump inhibitors, which have been linked with SCLE. So again, the spectrum of drug induced lupus seems to be evolving over time and you should be aware of that.

Our last report is about belimumab, and its use in lupus nephritis. This was a big presentation at ACR. I'm sure I talked about it about two or three months ago. Rich Furey presented the data. It was really impressive.

And I say that knowing that in the past, I've not been too kind to belimumab clinical trial results because I didn't think the magnitude of response or benefit was sufficient. I think the problem wasn't so much the magnitude as it is in doing trials in lupus. I think it's really difficult to do trials in lupus with a global lupus outcome like SLETE I and, you know, this, SRI-four and other things. I just don't think that those are good outcomes and the margins of benefit are too small to be meaningful, and then you're not left not knowing how to use the drug. The new trend is doing clinical trials in lupus specific diseases like lupus nephritis, lupus arthritis, lupus skin disease.

Why not hematologic lupus or CNS lupus? Well, we have a bevy of studies looking at lupus nephritis and belimumab looked very good at this particular report. This is a phase three trial, again, in New England Journal this week, four forty eight patients who have biopsy proven class three and four glomerulonephritis. They had to be ANA and double stranded DNA or double stranded DNA positive. They could have had a class five lesion in addition to their three and four lesion, And they showed they had two stringent definitions, a complete renal response and a PRP response.

At week fifty two, belimumab 43, where is it? 52, it was forty three percent versus thirty two percent in placebo. At week one hundred four or two years, again, the response was forty seven percent versus thirty five percent. Maybe more importantly, belimumab patients were less likely, half as likely to have a renal event or toxicity related to the kidney or proteinuria when they were treated with blimep versus those who were treated with placebo. I think this is a good turnaround.

Think it tells you that, oh, by the way, I left out an important point. These patients were sick enough for their nephritis that they had to get induction therapy. Hence, they were all being treated with Citoxan followed by azathioprine or mycophenolate, they were on standard of care throughout the study and belimumab was added on top of that. So the point being that patients who are sick with and you're worried about lupus with their lupus nephritis, it might not be unreasonable to add belimumab to your induction protocol or what you're going to continue them on going forward. I think a really important study.

I'll stop there, go to the website, check out our citations and more. We didn't get any calls this week on our back talk feature. You can find back talk on the daily email or on the website, click on it, you can ask a question, we'll feature it here on the website, on the on the weekly podcast. You can ask a question, present a short case. Again, short case, three lines, that's it.

And we'll discuss it here on the podcast. Take care of yourself. Oh, one more thing. ACR, big, virtual, what the heck? How are we gonna do it?

Room now. We're doing a lot of new things. It's gonna be really exciting. We are gearing up. You give us two hours, we will give you the ACR.

Think about it. We'll tell you about it as time goes on. Take care. Bye bye.