The first multinational, phase 3, placebo-controlled trial conducted with intravenous immunoglobulin therapy (IVIg) for dermatomyositis has confirmed significant efficacy and acceptable safety, according to data presented at the opening plenary abstract session of the annual European Congress of Rheumatology.
At the week 16 evaluation of the trial, called ProDERM, the response rates were 78.7% and 43.8% (P = .0008) for active therapy and placebo, respectively, reported Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh.
ProDERM is a “much-awaited study,” according to session moderator Hendrik Schulze-Koops, MD, PhD, of the division of rheumatology and clinical immunology at Ludwig Maximilian University of Munich (Germany). He was not involved in the study.
“We all have been doing what we have been doing,” Dr. Schulze-Koops said, referring to the use of IVIg for the control of dermatomyositis, “but we had no evidence for support.”
This statement could apply not only to IVIg, which has long been listed among treatment options by the Myositis Association despite the absence of controlled studies, but also to most immunosuppressive therapies and other options used for this challenging disease.
The proprietary IVIg employed in this study, Octagam 10%, has been approved in the United States for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer, Octagam, plans to file a supplemental new drug application with the Food and Drug Administration for the treatment of dermatomyositis. The agent is already approved for dermatomyositis by the European Medicines Agency, according to Dr. Aggarwal.
Multiple response criteria favor IVIg
In the trial, 95 patients with dermatomyositis were randomized to 2 g/kg of IVIg (Octagam 10%) or placebo administered every 4 weeks. In a subsequent open-label extension study in which patients on placebo were switched to active therapy, the same every-4-week treatment schedule was used. The patients’ mean age was 53; 75% were women, and 92% were White.
The primary endpoint was at least minimal improvement on 2016 ACR/EULAR (American College of Rheumatology/European Alliance of Associations for Rheumatology) myositis response criteria, defined as a 20-point or greater gain in the Total Improvement Score (TIS) and no clinical worsening at two consecutive visits. But IVIg also provided a large relative benefit over placebo using more rigorous definitions of improvement. For moderate improvement, defined as at least a 40-point TIS improvement, there was a 45.2% relative advantage for IVIg over placebo (68.1% vs. 22.9%; P < .0001). For major improvement, defined as at least a 60-point TIS improvement, the relative advantage was 23.6% (31.9% vs. 8.3%; P < .0062).
At 16 weeks, the mean TIS score was more than twice as high in those receiving IVIg than in those randomized to placebo (48.4 vs. 21.6). At that point, an open-label extension was initiated. Those in the IVIg group were permitted to remain on therapy for an additional 24 weeks if they had not worsened in the blinded phase.
The mean TIS score in the IVIg group continued to rise during the extension phase. By 12 weeks in this phase, it reached 54.0. Over the same period, mean TIS scores climbed steeply among the placebo-treated patients who had switched to active therapy, reaching 44.4.
At the end of 24 weeks of the extension trial, when patients initiated on IVIg had been on active therapy for 40 weeks, the mean TIS score advantage of starting on IVIg rather than placebo was relatively modest (55.4 vs. 51.1).