Intravenous Immune Globulin May Improve Dermatomyositis Symptoms in Adults

Intravenous immune globulin (IVIG) significantly improved symptoms of dermatomyositis compared to the placebo, according to investigators who recently published study results from the phase 3, double-blind, parallel-group, randomized, placebo-controlled ProDERM trial in the New England Journal of Medicine. However, investigators also observed that IVIG may put participants at risk for severe thromboembolism events.

“The percentage of patients who had a response of at least minimal improvement at week 16 was significantly higher among the patients who received IVIG than among those who received placebo,” wrote the study authors.

Dermatomyositis is an uncommon systemic autoimmune disorder characterized by chronic skin and muscle inflammation. Symptoms can manifest in the form of skin rashes and increased proximal muscle weakness.

Glucocorticoids are a typical first-line treatment, followed by immunosuppressants and IVIG as a second- or third-line therapy. Previous studies suggest IVIG could be an effective first-line; however, treatment with IVIG may also lead to severe thromboembolic adverse events (AEs).

The primary endpoint of this study was patients receiving a minimum of 20 on the Total Improvement Score (TIS) by week 16. Key secondary endpoints include moderate improvement, defined by a TIS of 40 or greater, major improvement (TIS of 60 or greater), and a score change on the Cutaneous Dermatomyositis Disease Area and Severity Index.

The phase 3 ProDERM trial looked at 95 patients aged 18 to 80 years with dermatomyositis. All patients included in the study had previously been treated with glucocorticoids or immunosuppressive drugs and did not demonstrate an effective response. Among participants, 47 were placed in the IVIG group and 48 in the placebo group.

At 16 weeks, 79% of the IVIG patients had a TIS of at least 20, whereas 44% of the placebo group reached this mark.

“The efficacy of IVIG with respect to the primary end point was observed among the patients across mild, moderate, and severe disease-activity categories,” study authors wrote.

Among secondary endpoints, 68% of patients in the IVIG group experienced moderate improvement compared to 23% of placebo patients. Major improvement according to TIS was 32% in the IVIG group, a 4-fold increase compared to placebo patients.

The most common AEs over the course of the trial include headache, experienced in 42% of participants in the IVIG group—19% of the IVIG group also experienced pyrexia, while 16% experienced nausea. Thromboembolism events were reported in 8 IVIG patients.

The trial was limited due to participant selection bias. Additionally, the primary endpoint was based on TIS, whose measurements can be interpreted differently. The threshold may have been too low. Finally, 3 placebo patients switched to the IVIG group in the middle of the study.

IVIG may function by inhibiting actions that can lead to the formation and deposition of membrane attack complex, which can destroy capillaries. Another theory is that IVIG can promote cytokine and chemokine down-regulation, which can effectively modify gene expression in these patients. However, the investigators noted they were unable to determine this relationship based on the data.

“The percentage of patients with dermatomyositis who had at least minimal improvement according to a composite score of disease activity was significantly greater with IVIG than with placebo; however, IVIG was associated with adverse infusion events and thromboembolism,” study authors wrote. “Larger and longer trials to determine the long-term effects and risks of IVIG in patients with dermatomyositis are warranted.”

Reference

Aggarwal, R., Charles-Schoeman, C., Schessl, J. et al. Trial of Intravenous Immune Globulin in Dermatomyositis. 2022. N Engl J Med 2022;387:1264-78. DOI: 10.1056/NEJMoa2117912