乌鸦传媒

Treatment with intravenous immunoglobulins (IVIG) for dermatomyositis was effective in a pivotal phase III randomized trial, a researcher reported.

At week 16, 78.72% of patients receiving IVIG were considered responders versus 43.75% among those given placebo, which represented a difference of 34.97% (95% CI 16.70-53.24, P=0.0008). "This was a highly significant difference," said Rohit Aggarwal, MD, co-director of the Myositis Center at the University of Pittsburgh, during a plenary abstract session at the European League Against Rheumatism (EULAR) virtual congress.

"Dermatomyositis is a rare, chronic autoimmune disease characterized by progressive proximal muscle weakness and a characteristic skin rash," he explained. Current therapeutic options include corticosteroids, other immunosuppressants, and IVIG. However, none of these therapies have been evaluated in phase III studies.

To address this gap, Aggarwal and colleagues conducted the international Progress in Dermatomyositis (ProDERM) trial, which included 95 patients with definite or probable dermatomyositis according to the .

During the first 16-week double-blind phase of the trial, patients were randomized to IVIG (Octagam 10%) 2 g/kg every 4 weeks or placebo. The primary endpoint was response at week 16, with response being defined according to the 2016 American College of Rheumatology/EULAR myositis response criteria of a minimal improvement in total improvement score of at least 20 points.

The double-blind phase was followed by a 24-week open-label period in which all patients received infusions of 2 g/kg, with the exception that at week 28 patients who were stable could have the dose reduced to 1 g/kg every 4 weeks. Those who showed clinical worsening at two consecutive visits between weeks 8 and 16 were switched to the alternate treatment arm.

At baseline, patients had active disease, and were either on standard immunosuppressive therapy or had previously failed or been intolerant to standard treatment. Participants also were required to have a manual muscle testing-8 score below 142/150. All had symmetrical proximal muscle weakness and the typical dermatomyositis skin rash.

Patients' median age was 53, three-quarters were women, and more than 90% were Caucasian; 95% completed the first phase of the trial and 72% completed the extension phase.

Secondary endpoints included the proportion of patients with a moderate or major improvement at week 16. Moderate improvement was defined as an increase in the total improvement score of at least 40 points, while major improvement was an increase of 60 points or more.

At week 16, moderate improvements were observed in 68.1% of the IVIG group compared with 22.9% of the placebo group, for a 45.2% difference (P<0.0001). Major improvements were seen in 31.9% versus 8.3%, for a difference of 23.6% (P=0.0062). Both of these comparisons were highly statistically significant, Aggarwal said.

After the switch to open-label treatment at week 24, patients formerly on placebo showed dramatic improvements and ultimately had almost the same response rate. By week 40, response rates were 71.1% in the IVIG group and 69.6% in the placebo/IVIG group.

The investigators also directly compared total improvement scores between the IVIG and placebo/IVIG groups at three specific time points:

• Week 16: 48.4 vs 21.6
• Week 28: 54 vs 44.4
• Week 40: 55.4 vs 51.1

With regard to safety, two-thirds of patients reported any adverse event, with the most common being mild headache, pyrexia, and nausea. During the first 16 weeks, three patients in the IVIG group had five serious adverse events, while two patients in the placebo group had four serious adverse events. The most common serious adverse events were thromboembolic, such as pulmonary embolism and deep venous thrombosis.

"This first large placebo-controlled phase III randomized clinical trial of IVIG treatment in patients with dermatomyositis clearly confirmed the efficacy, safety, and tolerability of Octagam 10% in patients with dermatomyositis," Aggarwal said.

"Based on the results of this study, Octagam 10% was approved for the treatment of dermatomyositis in Europe. In the U.S.A., the FDA is currently reviewing the submission," he noted.

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