Vikas Majithia, MD, on Advances in Therapies for SLE

Dr Majithia discusses how therapeutics have advanced for the treatment of systemic lupus erythematosus.

Vikas Majithia, MD, is chair of the Division of Rheumatology and senior associate consultant in the Department of Medicine at Mayo Clinic Florida.

TRANSCRIPT:

Gastroenterology Learning Network:  Welcome to another podcast from the Rheumatology & Arthritis Learning Network. I'm your moderator Rebecca Mashaw. Today we're joined by Dr. Vikas Majithia, chair of the Division of Rheumatology and senior associate consultant in the Department of Medicine at Mayo Clinic Florida in Jacksonville.

He's going to give us an overview on systemic lupus erythematosus and some recent advances in medical therapy and patient care that seem to hold great promise. Thanks for joining us today, Dr. Majithia.

Dr. Vikas Majithia:  Thank you, Rebecca.

GLN:  To start off, can you give us a quick overview of our current understanding of lupus?

Dr. Vikas:  SLE is a very heterogenous autoimmune disease where it impacts and affects a variety of systems, but most commonly women in young age, between 20 and 40 years of age, then to develop skin and joint manifestations with inflammatory autoimmune abnormalities, and typically leading to arthritis or rashes.

However, it also affects internally a number of organs, especially in African-American women, where it intends to cause kidney disease in an earlier stage than the other ethnicities.

It tends to have somewhat milder to moderate manifestations without any organ involvements, but concomitantly also has a variety of organ involvements, particularly kidneys, but also others, including heart, lung, and brain.

GLN:  What are the primary unmet needs for patients with SLE?

Dr. Vikas:  In case of lupus patients, we have had a number of opportunities for treatment, but yet there seems to be a lack of significant advancement until recently in therapy of SLE.

We have been using glucocorticoids, hydroxychloroquine, and other antimalarials for years, for decades, with a fair amount of response, yet there seems to be a lack of presence of biologic agents in this field at this point.

There are a number of manifestations which do not respond to these commonly used agents. The next set of agents are disease-modifying agents we use from other disorders such as methotrexate, azathioprine, and most recently, mycophenolate. They all have helped to improve the outcomes in these patients yet none of them work well on each and every patient. Most of them do not get these diseases to remission.

Hence, we end up using more significantly stronger therapies like cyclophosphamide in a number of these patients, which tend to have a number of other side effects. There has been somewhat of an advancement in the last 10 years. We had a new drug which was approved for management of SLE and it has shown promise.

Yet there are a number of patients where none of these therapeutic options are getting them to remission and helping us reduce the dose of corticosteroids. In a number of cases, they are not tolerated by the patients. Lastly, they don't always work and these patients continue to have disease activity, organ damage, and the worst-case scenarios, even death.

GLN:  We now have a newly approved drug, anifrolumab, trade name Saphnelo. How does this drug add to that armamentarium? How does it affect the control of lupus?

Dr. Vikas:  As I mentioned, there is a significant need for further therapies, and anifrolumab or Saphnelo fits into that advancement.

It is type 1 interferon receptor antagonist, and it has just been approved for treatment of patients with moderate to severe SLE who are receiving standard of care therapy, i.e., antimalarials or one of these other immunosuppressive agents I already mentioned, and possibly steroids.

What it does is it blocks the activity of type 1 interferons, which includes interferon-alpha, beta, and kappa. Typically these are cytokines which they are known seem to play a role in pathogenesis of patients with SLE, they're elevated.

There are a number of mutations in their signaling pathways, which have been linked to disease susceptibility suggesting significant role of these type 1 interferons in lupus pathogenesis and disease activity.

This agent goes ahead and blocks these interferons, and ultimately what we are looking at is working towards decreasing the activity of immune system and leading on to improvement in clinical disease for lupus patients.

GLN:  Are there particular patients for whom this is the best therapy, or are there indications where this would not be as effective?

Dr. Vikas:  Again, a great question. This particular agent was studied with and has been approved for any patient who has lupus with moderate to severe disease activity.

However, the ones which we do not know how it will work are the patients with severe active lupus kidney disease or lupus nephritis and neuropsychiatric SLE. Those were the patients where it was not studied and it's not necessarily the agent to be used, at least at this time.

What we also found was overall, it led to improvement in disease activity across the spectrum of lupus, but it was particularly useful in patients who have skin disease and joint disease. A lot of that has to do with the kind of patients who are enrolled in the clinical trials, but it clearly shows a significant benefit in these patients.

I suspect—and there is also evidence of a trend towards improvement in other organ-active disease activity with this particular agent—I think it is a great advancement and one of the other tools in our armamentarium to continue the fight against lupus and getting improved outcomes in these patients.

GLN:  Would this be a good therapy for a patient who has not developed lupus nephritis but is at risk of developing that complication?

Dr. Vikas:  That could be a difficult question to answer at this time. But again, in my clinical practice, if a patient has moderate to severe disease activity, they are at a higher risk of developing lupus nephritis. And if we can get them to remission or if we can get their disease under control at the very least, the risk of progression to lupus nephritis does go significantly down. I think this would fit just well in that pathway, but we do not have evidence to support that as of yet.

GLN:  Are there ongoing studies to try this with different types of patients?

Dr. Vikas:  Absolutely. Anifrolumab has ongoing, some of the observation studies to look for a continued performance in the real world, and then additional organ-based therapy, particularly in lupus kidney disease is being planned or being continued.

One additional benefit I want to point out in this particular medication is decrease in the steroid dose. What we see is overall outcomes of patients who have lupus once they undergo treatment and improve is based on how long and how much steroids these patients take. The goal for lupus therapy also is to decrease the number of our amount of steroids these patients take, and hopefully get them completely off of it if it's possible.

All the trials which were done with this agent, it clearly showed a benefit in decreasing the overall steroid dose and duration that these patients were taking steroids, which I think would be a tremendous benefit for these lupus patients and improve their outcome.

GLN:  Going back to those unmet needs, what would you like to see in the future in terms of new therapies? What's your wish list look like?

Dr. Vikas:  First, in this particular agent, I would like to see, how does it perform in patients with more severe disease activity. I would also like to see, for all lupus patients, ability to get them to remission with well-tolerated therapies with minimal side effects, which at this point is lacking.

I would also foresee use of these therapies, especially something like anifrolumab, which is relatively safe, in combination with other agents beyond standard of care therapy.

That's another benefit for the anifrolumab. When we look at the side effect profile, there is not a significant bad side effect signal that we can see on these. I believe what I would like to see is that these patients are getting well-tolerated effective therapies which we ultimately can get them to remission and then are able to stop it very similar to what oncologists do.

GLN:  I think that's the ultimate dream for every rheumatologist for a variety of these anti-inflammatory diseases and particularly steroid-free remission.

Dr. Vikas:  Absolutely. That is very, very correct.

GLN:  Thank you for your time today. This is very interesting, and we will look forward to see what new observational studies and post-marketing studies come along, what they have to say about how this drug works in the real world, but it does sound like it has significant promise.

Dr. Vikas:  I think it's a significant advancement, and we hope that it will improve the lives of these lupus patients.

Rebecca:  Wonderful. Thank you so much.