Robert F. Spiera, MD: Mycophenolate Treatment Is Associated with Improved Outcomes in Trial of Lenabasum in Patients With Systemic Sclerosis

Rheumatology Network interviewed Robert F Spiera, MD, To discuss his ACR presentation entitled, ”Background Mycophenolate (MMF) Treatment Is Associated with Improved Outcomes in a Phase 3 Trial of Lenabasum in Diffuse Cutaneous Systemic Sclerosis (dcSSc).” Spiera is the Director of the Vasculitis and Scleroderma/Vasculitis Program at the Hospital for Special Surgery and Professor of Clinical Medicine at Weill Cornell Medical College. He explains more about mycophenolate, the study design, and the clinical significance of these results.

Below is a preview of our conversation:

Rheumatology Network: Can you give me a little bit of background on mycophenolate?

Robert F Spiera, MD: So mycophenolate is an immunosuppressive drug that we've been using in rheumatology for a long time and actually often using it off label. It was originally a drug that was of interest to the transplant world. But now, probably going back about 20 years, it emerged as a really important drug in the treatment of lupus nephritis. And it’s widely used in that context. In the past decade, it's been used more and more in systemic sclerosis scleroderma. Much of that experience has been based on descriptive series of retrospective experiences looking at how patients fared on mycophenolate. There's very little in the way of prospective trial experience with mycophenolate and really no double-blinded, randomized, placebo-controlled trials specifically looking at the efficacy of mycophenolate in scleroderma. Some of the organized experience we have with it, though, does come from clinical trials. So 1 trial was an interstitial lung disease trial, called scleroderma lung study, to where cyclophosphamide was compared to mycophenolate in the treatment of scleroderma-associated interstitial lung disease, with the thought being that mycophenolate is a safer alternative of cyclophosphamide. And in that double-blinded, randomized, controlled trial, patients treated with mycophenolate did as well as patients treated with cyclophosphamide. So it wasn't showing superiority, but it showed non-inferiority with what we thought was the safer medicine. The second robust clinical trial experienced with mycophenolate was in a trial that wasn't specifically designed to look at mycophenolate, but it was in the census trial that showed to be an effective therapy and preventing progression of scleroderma-associated interstitial lung disease. But in that trial, at the discretion of the investigators, patients were allowed to be on background mycophenolate or be on no background therapy, and then would get either [the medication] or placebo. And when they analyzed how patients did in the context of that trial, who were not on mycophenolate, some people were on mycophenolate and some on placebo, it was recognized that patients that had mycophenolate had less decline in their lung function than patients who were not on mycophenolate. So those were some of the background studies that led this to being a drug that's been interested in the treatment of systemic sclerosis, and actually really widely used by clinicians in many parts of the world.

RN: Does your team plan on doing any further research on this topic?

RS: We have a lot of analyses to do, both of this data and other data embedded in this very robust 365-patient trial. Whether there's any further development of, lenabasum, specifically, is really unclear treatment and did not reach its primary endpoint in this trial. On the other hand, there were some benefits seen, if you did certain post hoc analyses in which for example, patients were on their background immunosuppressive therapies for more than 2 years of the point that when lenabasum was added to their therapy, there seemed to be an advantage. Patients who were on no background immunosuppressive therapy, and then received lenabasum, seemed to do better than patients on no background immunosuppressive therapy that received placebo. But I really don't know whether further development of that will happen. I think that a lot will be learned from this database about the treatment of systemic sclerosis and its various manifestations in general.