Intravenous Immunoglobulin Add-On in Newly Diagnosed Idiopathic Inflammatory Myopathies

Importance Preliminary evidence suggests that intravenous immune globulin (IVIG) may be valuable as an add-on treatment in newly diagnosed idiopathic inflammatory myopathies (IIMs), but a randomized clinical trial is warranted. Objective To determine whether 3 cycles of add-on IVIG lead to superior improvement, with acceptable safety, in patients with newly diagnosed IIMs treated with high-dose prednisone (1 mg/kg/d; maximum 80 mg/d). Design, Setting, and Participants This was a double-blind, randomized, placebo-controlled clinical trial conducted at a tertiary referral center for IIM between September 2021 and September 2025, with the primary end point at week 12. Adult patients with newly diagnosed IIMs, without (or with limited) prior immunosuppressive treatment, were assessed for inclusion; of 94 assessed, 50 were excluded or declined participation. Intervention All patients initiated treatment with standard of care high-dose prednisone and were assigned in a 1:1 ratio to receive add-on IVIG (2.0 g/kg body weight) or placebo at 0, 4, and 8 weeks Main Outcomes and Measures The primary outcome was the Total Improvement Score (TIS) at 12 weeks: a weighted composite score from 6 measures reflecting change in myositis activity over time. Secondary outcomes included moderate (TIS ≥40) and major (TIS ≥60; post hoc analysis) improvement, time to reach improvement, and safety outcomes. Results Of 44 adult patients with newly diagnosed IIMs included, 42 reached a primary end point (mean [SD] age, 58.7 [15.2] years; 21 [50%] female); 23 received IVIG and 19 received placebo. The mean TIS at 12 weeks was 60.0 (95% CI, 52.6-67.4) in the IVIG group and 42.5 (95% CI, 30.6-54.4) in the placebo group ( P = .01). Moderate and major improvement were achieved in 21 participants in the IVIG group (91%; 95% CI, 79-100) vs 10 in placebo (53%; 95% CI, 28-78; P = .01) and 16 in the IVIG group (70%; 95% CI, 49-90) vs 5 in placebo (26%; 95% CI, 5-48; P = .005), respectively. The median time to moderate response was 4 (95% CI, 4-8) weeks in the IVIG group and 12 (95% CI, 4-12) weeks in the placebo group ( P = .005). One asymptomatic deep venous thrombosis was found in the IVIG group. Conclusions and Relevance Adult patients with newly diagnosed IIMs treated with IVIG in addition to standard high-dose prednisone showed greater and faster improvement compared to patients who received standard high-dose prednisone. Trial Registration EudraCT Identifier: EUCTR2020-001710-37-NL