IVIg therapy gains the upper hand in ProDERM

Results of the phase III, placebo-controlled ProDERM trial reported at EULAR 2021 showed significant efficacy and acceptable safety for immunoglobulin therapy given intravenously (IVIg) to patients with dermatomyositis – a systemic autoimmune disease marked by progressive proximal muscle weakness and a distinctive skin rash.  

At week 16, the response rates were 78.7 percent and 43.8 percent (p=0.0008) for IVIg and placebo, respectively. “The effects of IVIg on the muscle and the skin were both highly statistically significant,” said study investigator Dr Rohit Aggarwal, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh in Pittsburgh, Pennsylvania, US.

The CDASI* score, a tool used to assess disease activity, was reduced by almost half at 16 weeks in those treated with IVIg. Improvement in MMT-8** scores, a set of 8 designated muscles tested unilaterally (range of 0–80 where 0=worst and 80=best), were also clinically and statistically significant in these patients. (EULAR 2021, abstract OP0008]

Results eagerly awaited

Session moderator Dr Hendrik Schulze-Koops from Ludwig Maximilian University of Munich in Munich, Germany, who is unaffiliated with the study, said ProDERM is a much-awaited trial. Admittedly, he said rheumatologists have been doing “what we have been doing, but we had no evidence for support.” He added that IVIg is listed among treatment options by the US Myositis Association despite the absence of controlled studies, as well as most immunosuppressive therapies used for this disease that is affecting both children and adults.

ProDERM included over 90 patients with dermatomyositis who were randomly assigned to 2 g/kg of IVIg or placebo given every 4 weeks. The mean age of the patients was 53 and 75 percent were women.

At 16 weeks, the mean Total Improvement Score (TIS) was more than doubled in those receiving IVIg vs placebo (48.4 vs 21.6). Patients who had not worsened while on IVIG treatment and those on placebo entered the open-label extension period of 24 weeks.

By 12 weeks, the mean TIS score in the IVIg group jumped to 54 vs 44.4 for those initially on placebo but had switched to IVIg.

At the end of the 24-week extension phase, the mean TIS scores were almost comparable between groups (55.4 for those on IVIg for 40 weeks vs 51.1 for those who started with placebo and then switched to IVIg).

Tolerable safety profile

The most common side effects reported were headache, pyrexia, and nausea, which were the same side effects reported for IVIg in other studies. Those were generally mild though, according to Aggarwal.

The rate of serious adverse events was only slightly higher for IVIg (5.8 percent vs 4.2 percent).

Potential new indication

The proprietary IVIg (Octagam 10%) used in ProDERM is approved in the US for the treatment of chronic immune thrombocytopenic purpura. Its manufacturer is set to file a supplemental new drug application with the US Food and Drug Administration for dermatomyositis. Earlier, the European Medicines Agency has greenlighted the agent for the same condition, Aggarwal shared.