Rheumatology Director, Yale Lupus Program

Fotios Koumpouras, MD, FACR

 You touched on the brand-new drug anifrolumab. It’s another breakthrough in lupus, developed for SLE [systemic lupus erythematosus]. In the mid-1990s, they found that interferons were highly expressed in SLE, and particularly in the pathogenesis…

 Maybe so. But the trials had showed efficacy in both high and low responders, but maybe we’ll get there later.

 Yeah, it’s interesting. But it means you need to inhibit it a little—that’s all, right? There’s only so much you can get with interferon-alpha blocker probably.

 But it’s so new, we don’t know yet, right?

 Right. But that drug was developed out of genome-wide studies and that showed multiple SNPs, or single-nucleotide polymorphisms, in genes that encoded for the expression of interferon alpha. It’s this idea of rational drug design that’s being applied to SLE, that had been applied to other rheumatic diseases. We’re finally here, where we’re going to be at the breakthrough with new therapies.

 I’m very curious because it’s been approved in the United States for a number of months. Are you now—I mean 

 in the plural, so rheumatologists practicing in the United States—gaining experience with anifrolumab? Is it available?

 We are. It’s becoming available in the community setting. Most academic centers are getting it on their formulary. I have patients on the medication, and I’m doing a clinical trial incorporating that medication with Joan Merrill. We’re starting pick up, and it’s still too early to know how important this may be in the treatment of lupus and when it should be employed in SLE. As you know, the study showed an effect that was fairly rapid, so that there was a divergence of the treatment curves at 2 or 3 months, from what I recall. There was a particular improvement in skin disease with lupus. This might be an agent that 1 may try for rapid amelioration of skin manifestation of lupus.

 Interesting. There are also data that in the skin, interferon is upregulated. If you do a molecular analysis, you can see that.

 That stands to reason. But I’m also still intrigued by how lupus may be several pathophysiologies. In some people you have the high interferon signature or the low interferon signature, going back to belimumab you have patients for whom B-cell activity is very high, and they have all these other antibodies. Other patients might have lupus, but they may have only antinuclear antibodies and not the other ones. There could be a difference also. It might be that in the future, which is what I hope, we’ll do these analyses, immunological analyses, and it will tell us this patient should be treated with anifrolumab, this patient should be treated with belimumab, this patient will do best with a conventional therapy. That’s also possible. We might be able to start doing it that way. We’re not there yet by a long shot, but I want it for the future.

 Right, and there may be cycles of therapy. They may want to treat patients with anti-interferon therapy followed by B-cell therapy or combinations, particularly if there’s severe disease, and we’ll learn how to use them in combination to get our patients better. But it’s an exciting breakthrough.

 Interesting. I was involved in a combination trial with—I don’t know if you knew about this—the combination of belimumab with rituximab. That’s quite strange because rituximab is not approved for lupus. It’s used off-label, but it’s not approved. Then there’s a trial. There were several trials where these were combined with the idea that you could get some sort of a synergy. It’s a very interesting scientific concept, and it could work. The patients in the trials did well, but it was not so clear that the combination gave an added benefit. That’s still a little unclear. Some parameters said they did, but others said that it was the same. It will be very interesting to see it.

 You showed this data in an abstract at the American College of Rheumatology, am I right?

 I was a coauthor, so there were others who showed it.

 Right. After 52 weeks, though, you had stopped therapy, so of course lupus will flare. One wondered why these were not continued.

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The rationale for using a newer monoclonal antibody therapy, anifrolumab, to manage patients with systemic lupus erythematosus.

Fotios Koumpouras, MD, FACR

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