Explanation of Services

Transcription:

Scott Webb: The Department of Rheumatology and Memorial Health System offers expert treatment for patients with systemic autoimmune conditions, soft tissue, and musculoskeletal diseases. And I'm joined today by Dr. Jonathan Krant. He's gonna tell us what he does, explain his approach to care, and discuss the latest drug therapies that are benefiting his patients. This is Memorial Health Radio, a podcast from Memorial Health System. I'm Scott Webb. Doctor, thanks so much for your time today. We're gonna talk about what you do as a rheumatologist, what rheumatology is, latest in drug developments and all of that. But before we get there, just tell us a little bit about yourself and your approach to care.

Dr. Jonathan Krant: So I'm a product of an academic family in Boston, someone who always wanted to do exactly what my father did until in medical school I discovered this extraordinary experience of rheumatology. And that was because I had a mentor at Johns Hopkins, a woman named Mary Betty Stevens, who was a pioneer and she put her arm around me and said, describe something new and different when seeing patients in clinic. And wouldn't you know it, I had a patient who had no functioning thyroid, who had myotonic dystrophy, which is an inflammatory muscle disease, and a condition called Sjogren's syndrome.

And I presented that as unknown to the internal auditorium to a bunch of, internal medicine doctors. No one could figure this out. I presented it as an unknown and had the pleasure of actually making her diagnosis as a medical student, which made me a semi God in my own mind. Having said that, I knew that rheumatology was for me because what else allows you to put together remarkable clues about musculoskeletal disease, cardiovascular illness, kidney impairment, skin problems, hematologic abnormalities, you name the domain within our specialty, everything is impacted.

So to answer simply Rheumatology is one of those remarkably interesting cerebral specialties of medicine, allowing you to do injections, to do biopsies if you'd like to image things, which you couldn't imagine imaging as a kid growing up, what after all is the saciliot joint.

Scott Webb: Right? What is that even?

Dr. Jonathan Krant: And then to, a portion of the pelvis which can become inflamed and spondyloarthropathy. So it's a, great place to be and it's a place that I'm very comfortable in, and I've been doing this for 30 years and hopefully to do it a little bit longer.

Scott Webb: That's so awesome to hear. It's sort of a common thread in a lot of these that I do, that there's a family history, right? That there's a culture of being doctors and nurses and medicine and families and a lot of the guests that I have just have this calling and then they get to medical school and sometimes, as you say, you thought you were gonna do one thing and then you did something else and you found your calling in rheumatology. So what are the most common diseases you talked about? Just all the different things you do and see and different ways in which you help patients. So tell us about the common diseases and how you treat them and just generally how they affect patients?

Dr. Jonathan Krant: We within our field, certainly see a broad variety of diseases which range from the very simple things such as fibrmyalgia. Which may not sound simple, but actually is, tender spots fatigue, sleep disturbance, cognitive impairment. Generalized aches and pains in multiple joints, often associated with traumatic experiences in childhood and adulthood, which lead to significant what we call somatoform abnormalities. Two, crystal and arthritis, gout, pseudogout, and other forms of crystals which can precipitate and cause troubles.

And then the autoinflammatory and autoimmune diseases. We'll speak about the latter because that's what I'm most familiar with. And there are such diseases as ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, lupus, sjogren's syndrome, almost all of which are characterized by the presence of antibodies which are generated in reaction to an unknown stimulus, which can become pathogenic, that can actually cause damage to joints. That can cause damage to the lining of blood vessels. There's a lot of diseases would fall within that rubric.

And so one of the things that attracts me so much to this disease state or these diseases, is the development of novel therapies, which have very specific targeted benefit for patients with these problems and are somewhat selective in terms of their off target binding. So the world of rheumatology is just [inaudible] with new assets, monoclonal antibodies, Janus, kinase inhibitors, oral immunomodulators, much of which have come about since I trained. And then when I was at uc, San Francisco as a fellow, we had methotrexate.

We had Cytoxan and chlorambucil, which are alkylating agents in lupus. And now we have, at least in 2022, we had a an onslaught of new opportunity with the revelation that there's some new, very targeted therapies, especially for lupus nephritis and what's called ANCA associated vasculitis, which we called back in the day, Wagoner's, granulomatosis. Now granulomatous polyangiitis, microscopic polyangiitis diseases with wonderful long names. That appeals to me of course, but with very specific therapies that may help to keep people out of relapse and off steroids. And steroids in our business are not your friend, but we use them frequently.

Scott Webb: Yeah, a lot of big words. And thankfully we have experts like yourself who know what all these big words mean and can do. As you're doing today, translate this into sort of lay speak for the rest of us. So let's talk about some of the evolving initiatives in drug development. You talked about therapies there and avoiding some certain things that are just no friends to rheumatology. But generally speaking, where are things at and what's got you excited in terms of the development for drugs as it relates to all these diseases?

Dr. Jonathan Krant: Well, this is something that I spend a lot of my time obsessing over because in our business there's so many side effects of therapy. As one good example. Back in the day, we gave a drug called Cyclophosphamide or Cytoxan, or by intravenous infusion to patients with vasculitis, a form of inflammation of blood vessels that can extend to major organs, lung, liver, kidney, brain, heart, amongst other organ systems. And Cytoxan for young people with lupus was a bad idea.

We didn't know it at that time, at least not as we do now, but that was a molecule that could cause malignancy. And in young people, that's terrible. It can cause irreversible infertility. And we of course don't want to do that. And so we are looking for options and opportunity and as things got along in the past couple of decades, we've now turned to a molecule called Rituximab as an inducing agent. Terms borrowed from our oncology colleagues because we often find ourselves trying to bring about remission and then maintain it.

So induction is the bringing about phase and remission is that phase in which we're trying to get people off the drugs they don't need on a maintenance regimen that's not toxic. And there are a couple of new additions to that regimen in the last year. Especially for the, what are called ANCA associated vasculinities, and then what all that means is that it's a series of blood tests which help to define the disease state. Then you have lupus, and lupus has been around forever. There are a lot of folks who have had lupus over the years, and one of the dreaded complications of this autoimmune disease is lupus nephritis.

And what effectively happens that the body loses self tolerance. It decides to go after unknown proteins, where stimulated immune response, and that translates into attack on things like the blood vessels, the brain, the kidney, the lung. And in lupus, that's the quintessential autoimmune, pathologic disease. And we have new antibodies that are actually attacking this process by some remarkable immunologic mechanisms. We have Treg, T regulatory cells, T-cells, these are lymphocytes cells which circulate to become antibody secreting. And if we can abort that process, we can diminish the disease state.

We have CAR T, which is a very interesting new, chimeric antigen receptor therapy, which the oncologists have brought forward. We're now borrowing to see if we can use it in severe autoimmune disease like lupus. So there's some very specific kinds of therapies that have evolved in the last year that are now becoming state of care or standard of care. And for us in rheumatology, this is extraordinary time where clinical research, which we conducted on an outpatient basis for the most, meets patient care at the bedside, and I teach full-time.

I've got residents and medical students where we have put our clinical research activities on hold, in the Covid era because people weren't coming in to get their scheduled assessments. But having said that, it's a very rich time to be engaged in autoimmunity, and that's perhaps the most compelling component of rheumatology to me, is all these autoimmune and autoinflammatory diseases. The latter representing those diseases which don't have specific antigen or protein induced, reactive arthritis just to come out of the clear blue sky.

And there's so many things happening in some other diseases. I mentioned gout earlier as a crystal in arthritis. We have a new therapy from Horizon Biosciences, called Krystexxa, a drug that's been around for a long time. It's an IV infusion every two weeks, and it's taking people with severe tophaceous gout, with kidney involvement to being completely symptom free within a couple of infusion. That's mind blowing, especially when you work in an area as I do, there's so much polyarticular, gout and kidney disease.

So to summarize, this is a time of great intellectual development. Drugs are coming forward that we never had before cause we never knew the mechanisms. And that brings us, I think, if you will, to the issues of cost because a lot of these drugs are absolutely mind-blowingly expensive.

Scott Webb: Yeah, you did say mind blowing. And before we get to cost, just wanted to just discuss a little bit about any safety concerns, whether it's interactions with things or just overall safety concerns. e even though these things are mind blowing and do sound like they're becoming the standard of care in many cases, is there anything that we need to know about the safety or efficacy of some of them?

Dr. Jonathan Krant: Absolutely just about all drugs have safety constraints and in the pharmaceutical jargon, we use the term pharmaco vigilance. That is the ability to look at drugs that have been commercially approved, look backward at their use, and see whether or not there's a safety signal that's emergent. One great example of this was the drug Vioxx, which you may remember from a few years ago.

Scott Webb: I I do. Yeah.

Dr. Jonathan Krant: A pox 2 drug, which was utilized for both RA and osteoarthritis pain. People loved this, especially at the higher doses, so we went from 25 to 50 milligrams and suddenly patients were developing heart attacks, and Merck actually paid a terrible price for this because they were found to be, withholding information about potential toxicity, which should have been available now. And what that has meant for the FDA has been increased vigilance about the potential for toxicity from medications that we use routinely. A good example of that is the drug Xeljans and the class that it occupies, the Janus kinase inhibitors.

These are oral small molecules used to treat a variety of diseases, and Xeljanz was compared to Emeril. The TNF antagonist used again for a variety of indications in autoimmunity. Sure enough turns out that Xeljans was not safer, and had some toxicity, especially if you're over 50 and you were a smoker and had a history of clotting abnormalities because those things can be accentuated. And sudden death was also recorded. So now we have black box warnings on all the drugs that we use. We worry about using medications, first line, second line, third line.

Often because of the constraints imposed by the safety concerns and the safety is really in my book, given the variety of drugs we have to use, the most important component. And so the FDA is all about safety and to a lesser extent, efficacy these days because of the numbers of drugs that we have to use and the simplest of simple drugs, non-steroidals, you worry about GI bleeding and kidney risk. In the case of steroids, our favorite drugs to use, they're also a double-edged sword because steroids can cause weight gain, cataract formation, diabetes risk, hypertension, and by all means osteoporosis with fracture risk.

And so we're always thinking about what is the consequence of using the medications we do. And we inform our patients all the time about safety, and that's a very big deal.

Scott Webb: Yeah, it is a big deal. And you prefaced there, , just a second ago about cost, let's finish up there. I'd love it if you told me that all of these amazing mind blowing drug therapies, was all covered by insurance. So if you need it, it's covered. It's all good. I have a feeling, doctor, that's not what you're gonna say.

Dr. Jonathan Krant: You're taking me down the yellow brick road, but there's no oz at the end of it. The ability to make drugs available for orphan indication, less than 200,000 patients a year described who might be eligible for a drug that's approved out of phase two and out of these big registrational trials requiring thousands of patients in multiple sites is exciting. However, the costs are often not associated or translated to the patient. CAR-T, Treg or T-REG, , these forms of therapy are costing a million dollars a year. How does the indemnity plan cover that? Well, not comfortably, and there's manufacturer's discounts, copay assistance, foundational support for our patients.

We tap into all of them. We ask the drug makers to do everything in their power to mitigate cost because a lot of the drugs that we use have sticker about $50,000 a year, which may not sound like a lot when you're talking about a million dollar drug, which is used in the rarest of rare conditions for patients with refractory disease. That said, who can afford a $50,000 a year drug? And what if it's given to 3% of the country's population that has a disease like RA? So this is a big problem for us. We don't have an answer to it.

We need a combination of mitigation of costs for the manufacturers foundational support and Indemnity coverage for those folks who otherwise you're paying out of pocket and never can afford the cost of these molecules. And this has become a very, very big deal, especially in some of the other diseases that I don't treat routinely. Diabetes requiring insulin. Biden just came out to talk about this specifically. So how do we mitigate cost? How do we go forward with drug development? Understanding that these things are expensive and their societal priorities becomes a very important discussion for rheumatologists.

Scott Webb: Yeah. And we hope that podcasts like this, that we can talk about these things. Put these things out there, educate folks about what rheumatologists do and the different diseases and how they're being treated, and gold standards, and then ultimately keep these conversations going about how can we mitigate these costs to make them more, cost effective for folks who need them, who would benefit so much from them. So, really educational for me today, doctor, and I'm sure listeners as well. Thanks so much. You stay well.

Dr. Jonathan Krant: My pleasure and you as well, take care.

Scott Webb: And for more information, go to MHsystem.org/rheumatology. and please remember to subscribe, rate, and review this podcast and all the other Memorial Health System podcast as well. If you found this one helpful, please do share it on your socials and thanks for listening to Memorial Health Radio, a podcast for Memorial Health System. I'm Scott Webb. Stay well.