Jonathan Kay, MD; Allan Gibofsky, MD, JD

Disclosures

June 16, 2011

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Introduction

Jonathan Kay, MD: Hello. I'm Dr. Jonathan Kay, Professor of Medicine at the University of Massachusetts (UMass) Medical School and Director of Clinical Research in the Division of Rheumatology at UMass Memorial Medical Center, both in Worcester, Massachusetts. Welcome to this Medscape Peer-to-Peer from the European League Against Rheumatism (EULAR) 2011 Annual Scientific Congress in London, during which we will discuss highlights of systemic lupus erythematosus from the meeting. I'm here today with Dr. Allan Gibofsky, Professor of Medicine in Public Health at the Weill Cornell Medical College in New York and attending rheumatologist at the Hospital for Special Surgery also in New York. Welcome, Allan.

Allan Gibofsky, MD, JD: Thank you, Jon.

Dr. Kay: We're going to talk about several topics in lupus today, belimumab, interferon alpha, azathioprine in pregnancy, and the study of mycophenolate mofetil in lupus nephritis.

Dr. Gibofsky: Yes. In trying to select which abstracts are most important, one is always faced with a challenge -- which abstracts are thought to be most important by the abstract authors and which abstracts are thought to be most important by the audience? We saw a very intense interest in lupus here at the Congress, perhaps evidenced by the fact that the morning symposium on lupus was so oversubscribed that quite literally, no one could get into it, and so they were chasing the butterfly all around London to get a seat.

Belimumab

The areas that seem to be of most interest began with new therapies, and as you know in the past year the US Food and Drug Administration (FDA) approved a drug called belimumab for the treatment of a certain number of patients with lupus, certainly not for all patients with lupus, and we are still trying to tease out exactly which patients with lupus are the most appropriate.

Dr. Kay: This is quite exciting because it has been more than 50 years since the FDA has approved a drug for treatment of lupus. Belimumab has been quite effective in 2 studies, the BLISS [Belimumab in Subjects with Systemic Lupus Erythematous] 52 and the BLISS 76 studies, meeting the primary end points at 52 weeks, but in these studies there is a question as to whether it's applicable to African-American individuals who make up a significant proportion of the patients with lupus.

Dr. Gibofsky: Indeed, and the challenge of all of the presentations that were made today, the abstracts, and posters and oral presentations, was exactly how do you identify the most appropriate patient for this drug? It appears to be the case that the safety of the drug is acceptable, and so that is not as great a concern, but exactly which patient is going to benefit from the drug, which patient is going to have the most cost-effective reaction to it is what I think we're still trying to tease out.

Dr. Kay: Now patients with lupus present in protean ways. Some patients will present with serologic abnormalities and hematologic manifestations, such as a low platelet count and perhaps a photosensitive skin rash. Other patients will present with fulminant nephritis or central nervous system (CNS) changes and psychosis. Certainly, this drug hasn't been studied in lupus nephritis or CNS lupus, but of the patients with other forms of lupus, which are the most appropriate for using this drug?

Dr. Gibofsky: You are exactly right, Jon, that the patients who probably need the therapy the most are the ones in whom this therapy was not yet studied, yet we do have some tantalizing evidence, for example, that patients with extremely high serologic activity may be among those who would benefit from the drug. It's still an open question when you begin to subset and slice and dice by sex and by ethnic background which patients will be appropriate -- by ethnic background in particular, because we know that African-Americans do not seem to have as good a response to this drug as others. But certainly patients with high serology, seemingly almost irrespective of what ethnic background they fall into, are a class of patients that will benefit.

Mycophenolate Mofetil in Lupus Nephritis

Dr. Kay: Well, that's encouraging and will help us to determine which patients to try using golimumab on first. Patients with lupus nephritis are often presenting to rheumatologists and pose a significant therapeutic quandary. We use cyclophosphamide to treat this disease but it has issues related to sterility and risk for infection. Mycophenolate mofetil has gained currency and is often the drug of choice now in the treatment of lupus nephritis. The ALMS [Aspreva Lupus Management Study] is an interesting study and data continue to be presented from this trial.[1]

Dr. Gibofsky: Yes, and we saw here some data on the continued comparative safety of mycophenolate or "mighty Mo" as its proponents like to call it. We're going to continue to see the use of this drug rather than the cytotoxic or immunosuppressive agents as we've seen from the abstracts presented here, and it does appear that this agent is safer and at least as effective. The combination of a safer drug with comparable efficacy may very well be the choice that individuals make in terms of what to use and when to use it.

Azathioprine in Pregnancy

Dr. Kay: Lupus is a disease that affects many more women than men and as we discussed, immunosuppressive therapies can have potential toxicities. One of the areas in which immunosuppressive drugs is usually contraindicated is pregnancy but what about azathioprine?

Dr. Gibofsky: An interesting study[2] presented at this meeting looked at azathioprine compared with other therapies and what they found was that azathioprine was not less safe than some of the other therapies that are being used, giving comfort to the physicians who treat lupus about the continued ability to use azathioprine. Certainly when you treat a patient who is pregnant with any drug, even distilled water, you treat with a great degree of caution. But we are a little bit more reassured from the data presented here on azathioprine that it can be a choice in pregnancy after being discussed carefully with the patient.

A New Monoclonal Therapy

Dr. Kay: As we have new therapies such as golimumab, and epratuzumab is another drug under study, we think about other approaches to the treatment of lupus and the interferon alpha signature is a hallmark in many patients with lupus. A monoclonal antibody directed against interferon alpha is in development. What about the data presented about that?

Dr. Gibofsky: It was quite encouraging and the key there is that this monoclonal antibody, which is an IgG1 monoclonal antibody, does appear to significantly change and down-regulate the interferon alpha signature in many patients, not in all patients, but in a significant number of the patients that were tested. Now the caveat here is, to what extent does down-regulation of the interferon alpha signature result in clinical improvement of the disease? It's one thing to make a very notable laboratory observation; it's another to show that it translates into clinical practice. Obviously, it's also a challenge to avoid shutting off interferon alpha entirely, which could render the patient unable to fight certain kinds of viral infections and other infections.

We're going to see this work developed further to see to what extent does the change in signature correlate with clinical improvement in patients with lupus and to what extent does one have to change the signature without running into toxicity?

Dr. Kay: This is very encouraging because it's been a long time since we have had new drugs for lupus and now we have belimumab and epratuzumab and this monoclonal antibody to interferon alpha in development, and it looks as if the process of drug development in lupus is starting to take an exponential rise in its pace. I anticipate that at future meetings we will have additional data and look forward to your return to talk about this in Chicago at subsequent meetings.

Dr. Gibofsky: Thank you, Jon. I would be delighted.

Dr. Kay: Thank you very much for participating in this Medscape Peer-to-Peer discussion, and I look forward to seeing you again on Medscape.

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