Compared with placebo, intravenous immune globulin (IVIG) significantly improved symptoms in patients with active dermatomyositis, researchers report, but was associated with adverse events, including thromboembolism.
In the 16-week trial, 95 patients with active dermatomyositis were randomized to IVIG 2 g/kg or placebo every 4 weeks. Those receiving placebo and those on active therapy without confirmed clinical deterioration could enter an open-label extension phase for another 24 weeks. The primary end point was based on a Total Improvement Score (TIS; range, 1–100, higher scores better) reflecting the change in a core set of 6 measures of myositis activity over time.
Results showed: “At 16 weeks, 79% of the patients in the IVIG group (37 of 47) and 44% of those in the placebo group (21 of 48) had a TIS of at least 20 (difference, 35 percentage points; 95% confidence interval, 17 to 53; P <0.001). The results with respect to the secondary end points, including at least moderate improvement and major improvement, were generally in the same direction as the results of the primary end-point analysis, except for the change in creatine kinase level (an individual core measure of the TIS), which did not differ meaningfully between the two groups. Over 40 weeks, 282 treatment-related adverse events occurred in the IVIG group, including headache (in 42% of patients), pyrexia (in 19%), and nausea (in 16%). A total of 9 serious adverse events that were considered to be related to IVIG occurred, including 6 thromboembolic events.”
Editorial: “In regard to future trials, 44% of the patients receiving placebo in the current trial met the primary end point of a response, defined as a [TIS] of at least 20, which indicates at least minimal improvement,” an editorialist writes. “Most of the core components of the TIS are subjective. Because of the high percentage of patients who had a response with placebo, large numbers of patients will be needed in future trials to show a significant difference between trial groups, or the primary end point would need to be set higher (e.g., a TIS of ≥40). The challenge of determining the appropriate sample size is compounded by the subtypes of dermatomyositis that are defined according to the presence of specific antibodies. It is fortunate that the difference in outcomes between the two trial groups was large enough to detect a benefit from IVIG. Finally, the TIS is probably an appropriate measure of disease activity in patients with typical dermatomyositis and in those with no or minimal muscle weakness, in whom rash and other extramuscular manifestations are present. However, it may not be as useful in patients with rash without muscle weakness (amyopathic dermatomyositis) or in those with immune-mediated necrotizing myositis who have no rash or other extramuscular manifestations. The FDA is currently mandating the use of this scoring system as the primary outcome measure in most trials involving patients with myositis, but one size may not fit all.”