Jonathan Kay, MD: Hello. I am Jonathan Kay, Professor of Medicine and Director of Clinical Research in the Division of Rheumatology at UMass Memorial Medical Center in Worcester, Massachusetts. Welcome to this Medscape peer-to-peer discussion.
I am in Washington, DC, at the American College of Rheumatology and Association of Rheumatology Health Professionals (ACR/ARHP) 2012 Annual Scientific Meeting. Joining me is Ronald Van Vollenhoven, Professor of Therapeutic Medicine at the Karolinska Institute and Chief of the Clinical Trials Unit in the Department of Rheumatology at Karolinska University Hospital in Stockholm, Sweden. Welcome, Ron.
Ronald Van Vollenhoven, MD, PhD: Thank you.
Dr. Kay: Today we are going to discuss belimumab. Belimumab was approved in the United States more than a year ago, and the BLISS-76 data and BLISS-52 data were presented at the ACR and EULAR (European League Against Rheumatism) meetings over the past 2 years. You were very instrumental in these trials and presented these data as well as a combined analysis of the 2 trials. Where do we stand nowadays with belimumab?
Dr. Van Vollenhoven: It is a great story and a bit of a roller coaster ride. First there was disappointment, because before belimumab, many other trials had failed. Then there was excitement when belimumab succeeded in 2 very large phase 3 clinical trials.[1] It was then approved by the regulators, the US Food and Drug Administration and the European Medicines Agency. It is now an approved treatment, one of the first for lupus in a very long time, and certainly the first biologic agent to get approval. That was very exciting. But then people started asking, "Which patient is the right patient for this treatment?" It turned out that it wasn't so easy to answer that question.
Earlier this year, we published an analysis[2] in which we actually identified some characteristics of patients as being good predictors for having a reasonably good chance of benefiting from belimumab: high disease activity, low complement (which is an indication of immune activation), and anti-DNA antibodies. Also, a patient who is on corticosteroids and cannot be tapered off. Those are indications that belimumab may be a good idea, and they are included in the label in European countries.
Of course, there is still a bit of a learning curve, and rheumatologists by nature will ask, "Should we use it? Are there any risks?" Safety data from trials don't always tell you the whole story, so it was very nice to see, here at the ACR meeting, that there is now a report of 7 years of follow-up on a large group of patients -- 1700 patients -- who were treated in these trials and allowed to continue with belimumab treatment.[3] It is presented by Dr. Merrill from Oklahoma. She shows that the safety profile actually holds up very nicely over the 7 years of follow-up. There are no new safety signals, nothing that pops up and makes you worry. Of course, there are always some risks associated with a biomodulator, something that affects the immune system. But so far, it looks rather benign and supports clinical decision-making if you feel that the patient is appropriate.
Dr. Kay: In your clinical experience, you have had over a dozen patients whom you have treated with belimumab.
Dr. Van Vollenhoven: Yes. At the Karolinska Hospital, we now have a group of 14 patients and they have been treated for variable lengths of time. Some of them started about a year ago, so we are getting a feel for it as clinicians deciding whether this is the right patient. I have to tell you honestly that some of these patients have done very well. For some patients, we do believe that it is an important treatment. You learn as you go, and sometimes it takes a little bit longer before you feel comfortable with the treatment, but I think that we have something here that is at least a boost for lupus treatment that makes a difference for some patients. We will learn more in the future.
Dr. Kay: Yesterday I was talking to my friend and colleague, Neal Birnbaum, who practices rheumatology in San Francisco. He was telling me about a patient that he just started on belimumab who had anti-double-stranded DNA antibodies at a titer level of over 4000 IU/mL. After 1 or 2 treatments, her anti-double-stranded DNA antibody level went down to 300 IU/mL. The drug seems to be very effective in that patient. I just started my first patient on belimumab last week, so I look forward to seeing how it goes.
Dr. Van Vollenhoven: It will be great to see, and these are important observations. Even if it is just 1 patient, you get a feel that there is something really happening when you use this treatment. It may not benefit everybody, but it does benefit some.
This is an intravenous therapy, which I think is a disadvantage. It would be advantageous if the drug could be administered subcutaneously, and that is being developed. At this ACR meeting, there was a report of the first trial with a subcutaneous form of belimumab, something that may become a reality in the future.
Dr. Kay: I have heard that with subcutaneous administration of B cell-directed therapy, for some reason the drug sticks around a little bit longer and you have more persistent lowering of B cells than with the intravenous route.
Dr. Van Vollenhoven: I am no expert on the pharmacokinetics of this, but as you know, belimumab does not deplete B cells nearly to the extent that we have seen with some other agents. With belimumab treatment, you see some lowering of B-cell numbers, but still well within the range in which you would think that there is no real safety issue. Of course, that has to be followed longitudinally, but I think that at this point, it looks like a safe therapy.
Dr. Kay: So, subcutaneous belimumab may actually be a real advantage -- more convenient for patients -- and might increase the use of this medication.
Dr. Van Vollenhoven: Yes.
Dr. Kay: It will be very interesting to see where this medication goes over the next year or two, and I look forward to talking more with you about the advances in lupus and belimumab next spring in Madrid.
Dr. Van Vollenhoven: Thank you. Me, too.
Dr. Kay: Thanks very much, Ron, and thank you all for joining us. I look forward to seeing you again on Medscape.
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COMMENTARY
Belimumab Revisited: How Has It Performed?
Jonathan Kay, MD; Ronald F. Van Vollenhoven, MD, PhD
DisclosuresDecember 13, 2012
Jonathan Kay, MD: Hello. I am Jonathan Kay, Professor of Medicine and Director of Clinical Research in the Division of Rheumatology at UMass Memorial Medical Center in Worcester, Massachusetts. Welcome to this Medscape peer-to-peer discussion.
I am in Washington, DC, at the American College of Rheumatology and Association of Rheumatology Health Professionals (ACR/ARHP) 2012 Annual Scientific Meeting. Joining me is Ronald Van Vollenhoven, Professor of Therapeutic Medicine at the Karolinska Institute and Chief of the Clinical Trials Unit in the Department of Rheumatology at Karolinska University Hospital in Stockholm, Sweden. Welcome, Ron.
Ronald Van Vollenhoven, MD, PhD: Thank you.
Dr. Kay: Today we are going to discuss belimumab. Belimumab was approved in the United States more than a year ago, and the BLISS-76 data and BLISS-52 data were presented at the ACR and EULAR (European League Against Rheumatism) meetings over the past 2 years. You were very instrumental in these trials and presented these data as well as a combined analysis of the 2 trials. Where do we stand nowadays with belimumab?
Dr. Van Vollenhoven: It is a great story and a bit of a roller coaster ride. First there was disappointment, because before belimumab, many other trials had failed. Then there was excitement when belimumab succeeded in 2 very large phase 3 clinical trials.[1] It was then approved by the regulators, the US Food and Drug Administration and the European Medicines Agency. It is now an approved treatment, one of the first for lupus in a very long time, and certainly the first biologic agent to get approval. That was very exciting. But then people started asking, "Which patient is the right patient for this treatment?" It turned out that it wasn't so easy to answer that question.
Earlier this year, we published an analysis[2] in which we actually identified some characteristics of patients as being good predictors for having a reasonably good chance of benefiting from belimumab: high disease activity, low complement (which is an indication of immune activation), and anti-DNA antibodies. Also, a patient who is on corticosteroids and cannot be tapered off. Those are indications that belimumab may be a good idea, and they are included in the label in European countries.
Of course, there is still a bit of a learning curve, and rheumatologists by nature will ask, "Should we use it? Are there any risks?" Safety data from trials don't always tell you the whole story, so it was very nice to see, here at the ACR meeting, that there is now a report of 7 years of follow-up on a large group of patients -- 1700 patients -- who were treated in these trials and allowed to continue with belimumab treatment.[3] It is presented by Dr. Merrill from Oklahoma. She shows that the safety profile actually holds up very nicely over the 7 years of follow-up. There are no new safety signals, nothing that pops up and makes you worry. Of course, there are always some risks associated with a biomodulator, something that affects the immune system. But so far, it looks rather benign and supports clinical decision-making if you feel that the patient is appropriate.
Dr. Kay: In your clinical experience, you have had over a dozen patients whom you have treated with belimumab.
Dr. Van Vollenhoven: Yes. At the Karolinska Hospital, we now have a group of 14 patients and they have been treated for variable lengths of time. Some of them started about a year ago, so we are getting a feel for it as clinicians deciding whether this is the right patient. I have to tell you honestly that some of these patients have done very well. For some patients, we do believe that it is an important treatment. You learn as you go, and sometimes it takes a little bit longer before you feel comfortable with the treatment, but I think that we have something here that is at least a boost for lupus treatment that makes a difference for some patients. We will learn more in the future.
Dr. Kay: Yesterday I was talking to my friend and colleague, Neal Birnbaum, who practices rheumatology in San Francisco. He was telling me about a patient that he just started on belimumab who had anti-double-stranded DNA antibodies at a titer level of over 4000 IU/mL. After 1 or 2 treatments, her anti-double-stranded DNA antibody level went down to 300 IU/mL. The drug seems to be very effective in that patient. I just started my first patient on belimumab last week, so I look forward to seeing how it goes.
Dr. Van Vollenhoven: It will be great to see, and these are important observations. Even if it is just 1 patient, you get a feel that there is something really happening when you use this treatment. It may not benefit everybody, but it does benefit some.
This is an intravenous therapy, which I think is a disadvantage. It would be advantageous if the drug could be administered subcutaneously, and that is being developed. At this ACR meeting, there was a report of the first trial with a subcutaneous form of belimumab, something that may become a reality in the future.
Dr. Kay: I have heard that with subcutaneous administration of B cell-directed therapy, for some reason the drug sticks around a little bit longer and you have more persistent lowering of B cells than with the intravenous route.
Dr. Van Vollenhoven: I am no expert on the pharmacokinetics of this, but as you know, belimumab does not deplete B cells nearly to the extent that we have seen with some other agents. With belimumab treatment, you see some lowering of B-cell numbers, but still well within the range in which you would think that there is no real safety issue. Of course, that has to be followed longitudinally, but I think that at this point, it looks like a safe therapy.
Dr. Kay: So, subcutaneous belimumab may actually be a real advantage -- more convenient for patients -- and might increase the use of this medication.
Dr. Van Vollenhoven: Yes.
Dr. Kay: It will be very interesting to see where this medication goes over the next year or two, and I look forward to talking more with you about the advances in lupus and belimumab next spring in Madrid.
Dr. Van Vollenhoven: Thank you. Me, too.
Dr. Kay: Thanks very much, Ron, and thank you all for joining us. I look forward to seeing you again on Medscape.
Medscape Rheumatology © 2012 WebMD, LLC
Cite this: Belimumab Revisited: How Has It Performed? - Medscape - Dec 13, 2012.
Tables
References
Authors and Disclosures
Authors and Disclosures
Interviewer
Jonathan Kay, MD
Professor of Medicine, University of Massachusetts Medical School; Director of Clinical Research, Division of Rheumatology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts
Disclosure: Jonathan Kay, MD, has disclosed the following relevant financial relationships:
Served as an advisor or consultant for: Array BioPharma Inc.; Bristol-Myers Squibb Company; Centocor, Inc.; Roche; UCB Pharma, Inc.; Genentech, Inc., Pfizer Inc.; Eisai Inc.; Covidien
Received research grant from: Roche; sanofi-aventis
Interviewee
Ronald F. Van Vollenhoven, MD, PhD
Professor; Chief, Clinical Trials Unit, Rheumatology, Karolinska Institute, Stockholm, Sweden
Disclosure: Ronald F. Van Vollenhoven, MD, PhD, has disclosed the following relevant financial relationships: Served as a speaker or a member of a speakers bureau for: Abbott Laboratories; Bristol-Myers Squibb Company; GlaxoSmithKline; Merck Sharp & Dohme Corp.; Pfizer Inc.; Roche; UCB Pharma, Inc.
Received a research grant from: Abbott Laboratories; Bristol-Myers Squibb Company; GlaxoSmithKline; Merck Sharp & Dohme Corp.; Pfizer Inc.; Roche; UCB Pharma, Inc.
Received income in an amount equal or greater than $250 from: Abbott Laboratories; Bristol-Myers Squibb Company; GlaxoSmithKline; Merck Sharp & Dohme Corp.; Pfizer Inc.; Roche; UCB Pharma, Inc.