Melanie Cole (Host):  Welcome to Better Edge, a Northwestern Medicine Podcast for Physicians. I'm Melanie Cole, and I invite you to listen as we discuss lupus nephritis and the comprehensive care of lupus patients at Northwestern Medicine. Joining me in this panel is Dr. Mary Mahieu. She's an Assistant Professor of Medicine and Rheumatology at Northwestern Medicine and Dr. Shikha Wadhwani. She's an Assistant Professor of Medicine in Nephrology and Hypertension at Northwestern Medicine. Thank you both, doctors for joining us today. And Dr. Wadhwani, I'd like to start with you. You represent two specialties, both focused on treating lupus nephritis. Tell us about the combined clinic. Why is it relevant? What are some of the best benefits that you've found? How did this even come about?

Shikha Wadhwani, MD, MS (Guest): Great question. So, lupus is a complex relapsing remitting disease that often affects young patients, especially women who are often in their childbearing years and up to 50% of them at some point in their lifetime, will develop clinical signs of kidney involvement. A lot of these patients may just present with protein in the urine or microscopic hematuria. So, blood in the urine and have completely normal kidney function. And given the fact that nephritis in these lupus patients can come in different flavors, we have to have a kidney biopsy to diagnose them. So, we use the kidney biopsy to tailor our treatment plan that often includes high dose steroids and one or more immune modulating therapies. So, as you can imagine, it's pretty complex. And that's why we really wanted to develop a clinic that's specifically focused for these patients.

Mary A. Mahieu, MD (Guest): The other thing I would add is that as a rheumatologist treating systemic lupus, it's really important to be attuned to whether someone who's having a lot of other systemic activity is also developing renal activity because that can be silent. And the earlier we can recognize and treat renal lupus in our patients, the better the long-term prognosis is. Because kidney can really portend a worse prognosis for our patients long-term particularly if they develop damage or scarring in the kidney. So, really the largest benefit of having our clinic together is that we can provide a coordinated care for complex patients in real time, since patients aren't in a vacuum with just their kidney disease, they also have other symptoms going on too. And so, Dr. Wadhwani and I can work together to develop a treatment plan, to best address each of the symptoms that they're experiencing in every organ system.

Melanie Cole (Host): Dr. Mahieu, then tell us how the clinic works exactly. What makes it so unique? How do you work together? And is there sometimes a differing of decisions as we see this improved coordination of care and the opportunity to assess patients from many viewpoints? Tell us how that works for other providers.

Dr. Mahieu: So, Dr. Wadhwani and I, we have some dedicated time, twice a month, we've carved out some clinic time where we can actually see the patients together, in the same room at the same time. We tend to talk about the patients ahead of time outside the room, because we have different agendas usually for what we're going to cover in the visit. But then we examine the patients together. We get their history together. We review all the relevant labs with the patient in the room, and then we actually try to formulate a treatment plan with the patient, along with us, with their input as well.

Dr. Wadhwani: Yeah. And I would say that the fact that we see our patients at the same time is really what does make this clinic so unique. A lot of our patients are busy moms. They're raising a family, they're caring for elderly parents, and so it's difficult for them to make it down to Chicago, especially some of our patients who are coming from further away suburbs, Indiana, Wisconsin. So, the fact that they can see two specialists simultaneously is a huge time saver for them. And it also helps with compliance with their follow-up visits. We've also noticed that some of our patients that have difficulty adhering to treatment regimens, do better when both of us are in the room together and can provide them with each of our opinions.

And I guess going to the point about the differing opinions between Dr. Mahieu and I, we really haven't come across that. I think we both recognize the expertise the other person brings in, and we also really like to engage our patients. So, sometimes we'll have a couple of different treatment options and the three of us like to talk together and figure out what's best for that particular patient, because there really isn't a one size fits all treatment plan.

Dr. Mahieu: I would also just add to that, that model also makes us more efficient at it providing patient care. Sometimes when I see a patient on my own, I'll be suggesting a certain treatment, but then I say, well, let me talk to your nephrologist and I'll get back to you on what we discussed. And in this case, we can really make decisions about escalating or even deescalating treatment, starting to taper off prednisone, really without any delays for the patient.

Host: I find that wonderful. And with this increasingly complex treatment algorithms that are adding new options all the time to your armamentarium of available therapies, it's really great when subspecialties come together for the patient. So, Dr. Wadhwani along those lines, what's new in the treatment of lupus

Melanie Cole (Host): nephritis?

Host: What's  

Dr. Wadhwani: Yeah. You know, for many, many years we've had limited options for induction treatment of lupus nephritis, essentially just mycophenolate or cyclophosphamide plus high dose steroids. And we all know those come with significant adverse effects. And even with treatment, complete remission rates are less than 50% in most patients. And then we have disease heterogeneity, yet we have minimal options to personalize care. Unfortunately, many of the prior drug trials for lupus nephritis have failed to meet their primary endpoints. But the good news is that in the last few months we have had some positive trials. And there's a lot of excitement within the lupus nephritis world.

Dr. Mahieu: I'll just mention that belimumab or Benlysta, which was FDA approved for the treatment of systemic lupus, such as like joint pain, rashes, hematologic abnormalities, belimumab was approved actually almost exactly 10 years ago this month. And, patients with active lupus nephritis though, were excluded from those clinical trials. So, it's never really been used to treat patients with active nephritis until recently. The BLISS LN trial was published last year, that randomized about 450 patients with lupus nephritis to either receive belimumab or placebo while also getting background standard of care treatments. And more patients in the belimumab group reached the primary efficacy endpoint and were more likely to have complete renal remission than the placebo group. So, that ultimately led to the FDA approval of lupus nephritis at the end of 2020. And we're excited to start offering it to our patients too.

Dr. Wadhwani: Yeah, I agree. It was extremely exciting to see Benlysta or belimumab be FDA approved and then, just in January of this year, we actually had FDA approval for voclosporin in lupus nephritis. And that is an oral calcineurin inhibitor, similar to some drugs that people may be more familiar with, such as tacrolimus or cyclosporin with the exception that it doesn't need drug monitoring, due to some better pharmacodynamic predictability, and also has increased potency.

So, this drug actually had a successful phase two trial, the AURORA study. And now they just finished a phase three trial where patients were randomized either voclosporin or a placebo on a background of mycophenolate and corticosteroids. There was this required rapid steroid taper, which was a unique feature of this study. And the drug met the primary efficacy endpoint at 52 weeks and then was FDA approved, subsequently. So, we're excited to not only have one, but now two, new treatment options for our patients.

Host: What an exciting time to be in your field and along those lines, Dr. Mahieu, are there any trials or therapies for lupus or lupus nephritis that excites you on the horizon? Are there any game changers that you're looking forward to?

Dr. Mahieu: Well, so there's one really exciting therapy that's being investigated right now for lupus. Actually it's called mesenchymal STEM cell treatment. So, mesenchymal STEM cells are cells that are derived from human umbilical cords, and they actually possess pretty significant immunosuppressive properties with very little toxicity. There's been some studies in other autoimmune diseases like rheumatoid arthritis and some small studies in lupus patients actually showed about a 65 to 75% partial response and 30 to 45% complete response with little toxicity or side effects. So, some researchers at the Medical University of South Carolina are conducting a large multicenter randomized control trial to evaluate the efficacy and safety in lupus patients.

Northwestern is actually a site for this study, which is exciting. Patients with lupus nephritis are able to be included in the study if they still have active disease, despite at least three months of treatment with standard of care therapies. So, we're hoping to get some encouraging data out of this study over the next couple of years as it's being conducted. One other drug I would mention too, is anifrolumab. Anifrolumab is a monoclonal antibody that blocks type one interferon signaling, which is a key pathogenic mechanism in some patients with lupus. It's actually not yet FDA approved for either systemic lupus or lupus nephritis, but there's been two, phase three clinical trials, which showed some promise for systemic disease. And a trial in patients with lupus nephritis was recently completed, but we're still waiting for some of those results to be reported.

Dr. Wadhwani: Yeah, I'll also add, one of the drugs I'm excited about is obinutuzimab, which is currently being used to treat certain lymphomas. It's essentially a monoclonal antibody to CD-20, but it has greater B-cell depletion than a sister drug that we all know, rituximab. So, there was a phase two NOBILITY trial, which looked at obinutuzimab versus placebo on a background of standard of care, mycophenolate and steroids, and it showed some promising results.

So, now there's a phase three study ongoing, and we're looking forward to what those results will show. And then also we have a clinical trial here at Northwestern for patients with lupus nephritis, specifically for proliferative lupus nephritis, that's called the PAISLEY LN study and it's a phase two trial looking at a novel TYK-2 inhibitor, plus standard of care.

This is a selective tyrosine kinase inhibitor that was originally studied in patients with psoriasis and showed positive results. So, they decided to study it in lupus nephritis. The trial design is actually unique in that it has this open label run-in period where all patients first must receive three months of mycophenolate. And then following that, only the patients with persistent proteinuria over a gram and a half a day, so those patients who are essentially felt to not really respond to the mycophenolate would then move on to be randomized for the study drug and the patients who are responding to mycophenolate actually get to stay in the study on open-label mycophenolate. So I think the study design is really unique and we're happy to be able to offer that to our patients.

Host: How exciting. What an informative episode this is. So, Dr. Mahieu, in these unprecedented times, how has your clinic evolved care since the onset of COVID? What's changed and how will it change the way your clinic practices in the future?

Dr. Mahieu: Well, so like a lot of other practicing physicians, we had to quickly become comfortable with Telemedicine. So, we've adopted three way video calls if needed. We do three-way telephone calls. It's really been a positive experience for a lot of our patients. People who live outside of the city, some of our patients who come from Indiana or Wisconsin, we can kind of alternate, doing Telemedicine versus in-person visits, and still be able to pretty efficiently assess their disease activity, side effects of treatment, medication compliance, as needed.

Dr. Wadhwani: Another thing that we tried to make patients' lives easier is by having them get labs to monitor their disease activity closer to home. So, a lot of these patients, it's difficult for them to come all the way to Northwestern to do labs. And so we'll order them prior to their visits, especially if they're doing a Telemedicine visit, that way, it is useful for them. And we can make treatment decisions over the phone or by video without having them to come in person.

Host: In the future, do you think you're to keep with this technology since it is proving across the spectrum of the healthcare industry to be such a great thing? So, Dr. Mahieu, do you think you're going to keep using it? Do you see that you might?

Dr. Mahieu: You know, I think we will. I think particularly for the patients who are well controlled or we're just doing check-ins to make sure nothing's changed, refill medications. I think particularly for those patients, Telemedicine is going to be a great benefit for the future.

Host: I agree. So, I'd like to you each a chance for a final thought. Dr. Wadhwani, what else would you like providers to know about referral and your clinic at Northwestern Medicine? And when you want them to refer their patients?

Dr. Wadhwani: So, I think the main thing I would say is that patients with lupus nephritis can really present with normal kidney function and just have hematuria and proteinuria on a urine test. Others can have dramatic presentations with acute kidney injury, but that's probably less common. So, I would really love for all of our lupus patients to have regular urine tests done, so we're not missing these early opportunities to diagnose and treat the disease. And, we are more than willing to help out with these types of patients, even if they haven't had an official diagnosis of lupus. If there's suspected auto-immune disease, there are signs in the urine that the patient might have inflammation, we would love to get involved in that patient's care.

Host: And Dr. Mahieu, last word to you. What would you like other providers to know about the uniqueness of your clinic at Northwestern Medicine and why what you're doing is so exciting for these patients?

Mary A. Mahieu, MD (Guest): I just think that having this comprehensive model is just really an opportunity to drill down and get patients on the best path for treatment and getting their symptoms under control. We're really willing to see patients at any stage of their nephritis diagnosis, either brand new diagnosis, suspected, but not yet biopsy proven, patients who are struggling to reach remission with their current treatment or even people who are relapsing after years of being quiet. So, we're always happy to discuss individual cases with referring providers to help decide if our clinic's a good fit.

Patients or physicians wishing to make a referral, they can reach us by calling the rheumatology office here at Northwestern at 312-695-8628 is our office number and our coordinator, Julie Holly can take information and pass it along to us.

Host: Thank you both so much for joining us today and really sharing your incredible expertise. Thank you again. To refer your patient or for more information, you can visit our website at nm.org to get connected with one of our providers. And that concludes this episode of Better Edge, a Northwestern Medicine Podcast for Physicians. Please, always remember to download, subscribe, rate, and review this podcast and all the other Northwestern Medicine podcasts. Until next time, I'm Melanie Cole.