Transcription:
Studies Show Promise for Systemic Lupus Erythematosus

Melanie Cole (Host):  Welcome. This is Better Edge, a Northwestern Medicine podcast for physicians. I’m Melanie Cole and today we’re discussing the Northwestern Medicine Lupus Program. Joining me is this panel discussion are Dr. Rosalind Ramsey-Goldman. She is the Salovey Arthritis Research Society Research Professor and a Professor of Medicine in the Division of Rheumatology at Northwestern Medicine. And Dr. Mary Mahieu. She’s an Assistant Professor of Medicine in the Division of Rheumatology at Northwestern Medicine. Doctors, I’m so glad to have you join us today. Dr. Ramsey-Goldman, since there’s currently no cure for lupus, tell us what the Northwestern Medicine Lupus Program is doing to help advance the understanding and treatment of this condition.

Rosalind Ramsey-Goldman (Guest):  The Northwestern Medicine Lupus Program aims to improve care for patients with lupus by improving clinical outcomes and developing and testing new treatment strategies and we are working towards a cure for this disease. We have four objectives to try to achieve our aims. And that includes providing outstanding care for lupus, this complex disease that requires coordinating care across specialties such as working with the nephrologists who treat lupus kidney disease and with the maternal fetal medicine specialists who treat high risk pregnant patients.

We are developing this clinical research program to improve those outcomes and the quality of life for patients who have lupus. And some of our discoveries are leading to decreasing the risk for complications seen in lupus such as heart attacks, strokes or bone fractures. And we are also assessing fatigue which impacts daily life and we’re studying different strategies to minimize this problem.

We collaborate with basic scientists who uncover mechanisms that cause lupus and an example of teamwork uniquely at Northwestern is working on lupus fog or why a patient might have difficulty thinking. And then we want to figure out how to fix that. And lastly, we are training the next generation of clinicians and scientists to carry this work forward so that we get earlier and more accurate diagnoses. We want better treatments with less side effects and we are as mentioned earlier, we’re working towards a cure for this disease.

Host:  Dr. Mahieu, what are some of the genetic risk factors of lupus and is there any way to predict who may be more susceptible to this disease and thereby being able to come up with the best treatments for that patient?

Dr. Mahieu:  So, the genetics of lupus are actually very complex. Comparing to a disease like cystic fibrosis where a mutation in one gene leads to the disease; in lupus, it’s actually the cumulative effect of multiple genes that usually is necessary to increase a person’s risk for disease development. Equally important to the genetics, are the superimposed environmental influences that a person might be exposed to. So, for example, well-described environmental factors include ultraviolet light exposure, certain infections, cigarette smoking, and even exposure to certain medications. Women are also much more likely to develop lupus than men so there are also hormonal influences that add to the susceptibility to develop lupus as well.

Host:  Dr. Mahieu, what are some of the current advances we should know about? What’s going on in the field?

Dr. Mahieu:  So, novel therapies for the treatment of lupus really are an unmet need. Any patient with lupus a rheumatologist will tell you that. As a reference point, in 2011, belimumab was the first drug approved by the FDA for the treatment of lupus in almost 50 years. At Northwestern, we participated in some of the early development trials that eventually led to that FDA approval. Now in 2019, we’re pleased to see promising results from three different phase III trials for lupus kidney disease and also one for non-kidney disease. So, one of those trials was for belimumab for lupus renal disease which showed positive results. Previously, belimumab was only studied for non-renal lupus. In addition, there’s a later generation version of a medication that’s used by our transplant colleagues for maintaining kidney transplants. It’s called voclosporin that has reported positive results as well.

These studies are very exciting because kidney disease is one of the most common and severe manifestations of lupus. So, it’s always exciting to have more treatment options to offer our patients. Another exciting trial or I guess two trials that came out in 2019, were phase III trials of a medicine called anifrolumab that had promising results. So, one of those studies called TULIP-2 showed lower lupus disease activity compared to placebo in patients who received anifrolumab and specifically patients anifrolumab had improvement in lupus skin disease and also required less corticosteroids. So, definitely some advances sort of on the threshold of having more options for us to offer our lupus patients in the future.

Dr. Ramsey-Goldman:  These are just the studies that have been presented at our national meetings and there are many others which are showing very promising results in the earlier phases of drug development. So, this is finally taking off in terms of the potential of having lots of new treatments for lupus patients in this new decade.

Host:  What an exciting time to be in your field. Dr. Ramsey-Goldman, what are some of the most innovative technologies supporting your work?

Dr. Ramsey-Goldman:  We work in a discipline called medical informatics which studies large amounts of data to identify patterns of disease. So, at Northwestern, we’re examining data using two different strategies. One is called supervised or rules learning and the other is unsupervised or computer driven learning and this helps identify patients who have lupus or might be a risk for developing lupus. And then these studies are then going to help us study the genetics of lupus where we can then look at mechanisms or pathways that cause lupus or how a patient might respond or have a side effect to a particular treatment.

So, this medical informatics from the clinical side gets merged with the genetic findings and these challenges that are facing researchers worldwide, is being investigated at Northwestern as part of a national network called E-MERGE and this network has taken on lupus as a way to try to address these questions to further our understanding of the role of genetics in lupus.

Finally, we also have a different way of looking at genetics partnering again, with someone in the basic sciences at Northwestern, Dr. Deborah Winter and what she does is study functional genomics or that looks at how genes might work at the cellular or tissue level. This approach gives us insight into what is going on that is wrong with the immune system that’s causing disruption in the way an organ is not functioning properly when someone has lupus.

Dr. Mahieu:  I’ll also add that one of the problems that we’re working on at Northwestern too is trying to better understand what lupus patients refer to as brain fog or the cognitive impairment that we see in some of our lupus patients. One of our basic scientists Dr. Carla Kooda [00:08:15] is working on a project where she has found that a type of brain cell called microglia may be important in mediating nervous system problems in a mouse model with lupus. So, we’re working to get cerebrospinal fluid samples from some of our lupus patients to see if we can confirm that the microglia cells are also important in human lupus as well.

Host:  Well then Dr. Mahieu, tell us a little bit about the Northwestern Medicine Lupus Program. What makes it stand apart? What’s unique about this program?

Dr. Mahieu:  From a clinical care perspective, we provide consultative services to help with the diagnosis and management of lupus. We are equipped to kind of coordinate care across a variety of specialties. Since it’s a multisystem disease, multiple specialists are generally involved in the care of complicated lupus patients. For example, we have a multidisciplinary care clinic where a patient with renal lupus can come to Northwestern and meet with myself and one of our nephrology colleagues Dr. Shikha Wadhwani who has a special interest in glomerular nephritis. The patient can meet with both of us during the same appointment to kind of get both of our input on the best way to be managing their disease.

We also have access to cutting edge treatments and clinical trials. For example, we’re involved in a study of mesenchymal stem cells or stem cells that come from placenta. Those are able to be given without any chemotherapeutic agents and we’re assessing how the lupus responds to the treatment and also monitoring for side effects. We’re entering our second of four years of enrollment and are actively looking for patients to enroll now.

Dr. Ramsey-Goldman:  I would like to add that about several other unique studies that we’re doing here. We have the only funded study by NIH to study two types of educational interventions to improve fatigue in patients with lupus. Fatigue has a negative impact on the quality of life, and this is present in the vast majority of lupus patients. And so, we are very privileged to be able to offer this option for our patients and this too is in the second year of four years of enrollment. So, we would be actively looking for patients for this study also.

We’ve mentioned these two clinical trials but we’re always looking for additional trials that might be of benefit to our patients. And finally, I’d like to add one other unique aspect of our program which involves our community engagement project where we are working towards eliminating health disparities in lupus. Dr. Mahieu mentioned that this primarily occurs – this disease primarily occurs in women of childbearing years and usually it affects women of color more severely and more often. We have developed teaching modules which are culturally and linguistically appropriate in our partnership work with community leaders and the goals are to improve lupus awareness, help individuals seek treatment for lupus and the current educational product, it’s currently under development, is to design teaching modules regarding participation in clinical trials for communities that are currently underrepresented in these studies but they do need to be – these individuals do need to be studied to see if these new therapeutics work in all individuals or just some individuals with lupus.

Host:  Well thank for that answer and before we wrap up, Dr. Ramsey-Goldman, what would you like other providers to know about the diagnosis and treatment for lupus and when you feel it’s important for them to refer to the specialists at Northwestern Medicine?

Dr. Ramsey-Goldman:  Lupus can be very difficult to diagnose. So, we welcome consultations as the experienced lupus clinicians to assess if lupus is indeed the diagnosis. It’s just as important to say if somebody has the diagnosis as well as if they don’t have the diagnosis so they don’t get treated for something they may not have. We also as part of our consultative service recommend treatment and one of our specialties is how to manage reproductive health including preparing for, during and after pregnancy because the goal would be to have a healthy mom and a healthy baby.

And from our research standpoint, we have new treatments that we can offer as part of our research program. Having this complex disease like lupus is difficult and partnering with these community leaders helps us to address the range of needs of lupus patients which go beyond medications but all of the other services and needs that they may require to lead a healthy life.

Host:  Dr. Mahieu, last word to you. What would you like other providers to know about the lupus program at Northwestern Medicine and your multidisciplinary approach?

Dr. Mahieu:  At Northwestern, we really do see a high volume of lupus patients and it can be a complicated disease to diagnose. We are always happy to take a look at a patient and help decide if that’s the true diagnosis and if so, what the treatment options are going forward and particularly in complicated cases. Because we have world class experts in areas like pulmonology, GI, hematology, who also have an interest in lupus patients and autoimmune conditions. It really is a good resource for patients to come here and be able to meet with a variety of specialists who can be on top of the best treatment approach for their condition. I think it’s an exciting time to be a physician who treats patients with lupus with some of the upcoming advances in treatment that we’re hoping will be approved in the coming years and we’re also happy to offer clinical trial enrollment to patients that fit the criteria that are looking for other options for treatment of their lupus as well.

Host:  Thank you doctors, so much for joining us and sharing your incredible expertise and the many interesting trials that you’ve got going on at the lupus program at Northwestern Medicine. And that wraps up this episode of Better Edge, a Northwestern Medicine podcast for physicians. To refer your patient or for more information on the latest advances in medicine, please visit our website at www.nm.org to get connected with one of our providers. Please also remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. For more health tips and updates follow us on your social channels. I’m Melanie Cole.