The use of efgartigimod in adult patients with primary immune thrombocytopenia (ITP) results in higher platelet response with no increase in serious adverse events (AEs), reports a meta-analysis of phase III randomized controlled trials (RCTs).
Furthermore, “[i]ntravenous (IV) administration demonstrates consistent efficacy across trials whereas efficacy of subcutaneous formulation remains limited due to single trial evidence,” said first study author Dr Mehak Dang from JSS Medical College, Mysore, India.
Three phase III RCTs, involving a total of 249 patients receiving efgartigimod and 127 on placebo, met the eligibility criteria. Two studies assessed the IV formulation, and one assessed the subcutaneous (SC) formulation. ITP was newly diagnosed in two patients, while the rest had persistent of chronic ITP. [EHA 2026, abstract PS2453]
The meta-analysis revealed a significant improvement in International Working Group (IWG) platelet response among patients treated with efgartigimod (relative risk [RR], 1.84, 95 percent confidence interval [CI], 1.26‒2.70; p=0.002; I2, 7 percent).
However, overall IWG complete response was not statistically significant (RR, 2.87, 95 percent CI, 0.93‒8.88; p=0.07; I2, 58 percent).
Administration route
Regarding the route of drug administration, the exploratory analysis showed greater efficacy for IWG response with IV formulation (RR, 2.27, 95 percent CI, 1.39‒3.71; p=0.001; I2, 0 percent). In comparison, the SC formulation did not reach statistical significance (RR, 1.42, 95 percent CI, 0.83‒2.44; p=0.20).
The IV formulation also demonstrated a significant improvement in IWG complete response (RR, 5.64, 95 percent CI, 2.10‒15.17; p=0.0006; I2, 0 percent), but this was hardly the case for the SC formulation which showed no substantial benefit (RR, 0.89, 95 percent CI, 0.39‒2.03; p=0.79).
With regard to safety, the incidence of any treatment-emergent (TE) AEs and serious TEAEs did not significantly differ between the treatment groups (RR, 0.67, 95 percent CI, 0.37‒1.21; p=0.19; I2, 0 percent).
“[O]ur study supports neonatal FC receptor (FcRn) inhibitors as an effective and well tolerated treatment strategy in ITP and highlights the need of larger studies to comprehensively define the optimal administration strategies,” Dang said.
Systematic search
Dang and colleagues performed a systematic search of Embase, PubMed, and the Cochrane Library to identify studies comparing efgartigimod with placebo in patients with ITP from database inception to November 2025. They then conducted a systematic review and meta-analysis following the recommendations of the Cochrane Handbook for Systematic Reviews and PRISMA guidelines.
The authors assessed the clinical effectiveness of efgartigimod (primary outcome) using the IWG platelet response criteria: complete response was defined as any platelet count of at least 100 × 109/L, while response refereed to any platelet count between 30 and 100 x 109/L and at least doubling of the baseline count. They also assessed safety (secondary outcome) relative to placebo, including serious TEAEs and any TEAEs, such as headache, hypertension, petechiae, and purpura.
Statistical analyses were performed using Review Manager version 5.4.1, with a random-effects model and 95 percent CIs. The I2 statistic was used to assess heterogeneity.
“Immunoglobulin G (IgG) autoantibodies are central to pathophysiology of ITP, promoting platelet clearance through Fc receptor dependent pathways. FcRn protects the IgG from degradation, thereby prolonging the circulation of autoantibodies,” wrote Dang and colleagues.
“Efgartigimod is an FcRn inhibitor which competitively inhibits IgG-FcRn interactions, thus accelerates lysosomal degradation of IgG resulting in a reduction in circulating IgG levels,” they added.