Adding intravenous immunoglobulin (IVIG) to high-dose prednisone was associated with greater symptom improvement than prednisone alone in adults with newly diagnosed idiopathic inflammatory myopathies (IIMs), a small clinical trial showed.

Patients receiving add-on IVIG also responded more quickly, with 91% of those achieving at least moderate improvement by week 12 compared with 53% of those who received placebo. The IVIG group also achieved a moderate response in just 4 weeks compared with 12 weeks in the placebo group.

“The results of this randomized clinical trial may indicate that newly diagnosed patients with IIMs are substantially undertreated with prednisone monotherapy in the first months of their disease,” lead investigator Pinar Özkaynar, MD, Department of Neurology, Amsterdam University Medical Center, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, Netherlands, and colleagues wrote.

The study was published online on September 14 in JAMA Neurology.

Earlier, More Intensive Treatment?

IIMs are systemic immune-mediated inflammatory disorders that primarily affect skeletal muscles. High-dose glucocorticoids are the standard initial treatment, but improvement can be slow and limited.

IVIG is a purified preparation of immunoglobulin G derived from human plasma. It has a rapid immunomodulatory effect and has shown benefit in patients with refractory dermatomyositis. However, the potential benefit of adding IVIG to initial treatment in newly diagnosed IIMs was unclear.

The TIME IS MUSCLE trial was a double-blind, randomized, placebo-controlled study at a tertiary IIM referral center in Netherlands conducted between September 2021 and September 2025.

The trial included 44 adults (mean age, 58.7 years; 50% women) with newly diagnosed IIMs, including dermatomyositis, immune-mediated necrotizing myopathy, antisynthetase syndrome, and overlap or nonspecific myositis.

All participants had a disease duration of less than 12 months, symptoms for about 6 months, and at least three abnormal findings among six standardized measures of myositis activity. Most (71%) had myositis-specific antibodies, and 60% had extramuscular disease involvement.

Participants were randomly assigned to receive IVIG at 2.0 g/kg or placebo at weeks 0, 4, and 8. Both groups also received prednisone at 1 mg/kg/d, up to 80 mg/d, with a standard taper.

The primary outcome was the Total Improvement Score (TIS) at 12 weeks, a composite score ranging from 0 to 100 based on muscle strength, physician- and patient-rated disease activity, disability, extramuscular disease activity, and muscle enzyme levels. Major improvement was defined as a TIS ≥ 60, with moderate improvement classified as a score ≥ 40.

IVIG Boosts Early Improvement

Of the 44 patients who were randomly assigned to treatment or placebo, 23 vs 19 patients in the IVIG group vs the placebo group reached the primary endpoint.

Four patients in the placebo group and one in the add-on IVIG group stopped treatment early when their condition did not improve or worsened. All five subsequently received open-label IVIG rescue treatment.

By week 12, mean TIS was 60.0 vs 42.5 with IVIG vs placebo, a between-group difference of 17.5 points (P = .01).

At least moderate improvement was reported in 91% vs 53% of patients in the IVIG group vs the placebo group (P = .01). Nearly 70% vs 26% of IVIG-treated patients vs placebo showed major improvement (P = .005).

IVIG recipients also reported a significantly faster time to moderate improvement than placebo recipients (4 weeks vs 12 weeks; P = .005). Improvements were also seen across several individual measures, showing better muscle strength, lower disease activity, and less disability with IVIG.

Thromboembolic Concerns

Nine serious adverse events occurred, including five vs four with the IVIG vs placebo group. One IVIG-treated patient had an asymptomatic deep venous thrombosis, while another died suddenly after an open-label infusion. Although the cause of death was unclear, the investigators recommended monitoring for thromboembolic events and considering prophylactic anticoagulation.

The findings support a more intensive approach to initial IIM treatment, investigators wrote, although they noted the study’s small and heterogeneous sample.

Other limitations include the study’s single tertiary referral center and the fact that it was not designed to assess whether IVIG works differently across IIM subtypes. The investigators also noted that some of the treatment effect could reflect variability in patients’ responses to prednisone or an interaction between IVIG and prednisone.

Assessments at 6 and 12 months are planned to provide additional information on the durability of the response and longer-term safety, researchers noted.

Disclosure information for study authors is available in the original study publication.