Abstract
Introduction Primary immune thrombocytopenia (ITP) is an autoimmune condition marked by low platelet counts due to antibody-mediated platelet destruction and impaired production. Pathogenic IgG autoantibodies play a central role in its pathogenesis, often leading to chronic or relapsing disease. The neonatal Fc receptor (FcRn) extends the half-life of IgG by protecting it from degradation; antagonizing FcRn accelerates IgG clearance, including autoantibodies, offering a targeted therapeutic strategy. Several FcRn inhibitors (namely efgartigimod, rozanolixizumab, and batoclimab) have shown promising results in clinical trials, but to date, no meta-analysis has synthesized randomized trial data to evaluate their efficacy and safety in ITP.
Methods We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials evaluating FcRn antagonists in adult patients with ITP. Comprehensive searches of PubMed, Embase, Cochrane CENTRAL, ClinicalTrials.gov, and WHO-ICTRP were performed through August 2, 2025.
Efficacy was measured using the International Working Group (IWG) platelet response criteria, with response being defined as a platelet count of ≥30 × 10⁹/L with at least a twofold increase from baseline, no bleeding, and confirmation across at least two consecutive visits. Data were pooled using a Mantel–Haenszel random-effects model. Safety was evaluated based on the incidence of serious treatment-emergent adverse events (TEAEs), using an inverse-variance random-effects model. Heterogeneity was assessed using the DerSimonian–Laird method. Risk of bias was assessed using the RoB 2 tool.
Results Of 169 records identified, 78 duplicates were removed. After screening 91 titles and abstracts and reviewing five full-text articles, four publications reporting five eligible trials were included: three efgartigimod studies (ADVANCE-SC, ADVANCE-IV, and Newland 2020), and two rozanolixizumab studies (TP0003 and TP0006). The Newland 2020 trial included two dose arms (5 mg/kg and 10 mg/kg), with its placebo group appropriately split.
A total of 439 patients were included, with 290 receiving an FcRn antagonist and 149 receiving placebo. Only two patients (0.5%), both in the 5 mg/kg arm of Newland 2020, had newly diagnosed ITP (≤3 months), while all others had persistent (3–12 months) or chronic (>12 months) disease. The IWG platelet response was achieved in 104 of 290 FcRn-treated patients compared to 27 of 149 in the placebo group, yielding a pooled risk ratio (RR) of 1.92 (95% CI: 1.32–2.80; P = 0.0006), with no observed heterogeneity (I² = 0%). Subgroup analyses showed that efgartigimod, evaluated across four trial arms, was associated with an RR of 1.87 (95% CI: 1.26–2.76; P = 0.002), while the two rozanolixizumab studies produced a pooled RR of 2.87 (95% CI: 0.69–11.91; P = 0.15), though estimates were imprecise due to wide confidence intervals. Serious TEAEs were reported in 29 of 290 FcRn-treated patients and 19 of 149 placebo-treated patients, corresponding to a pooled RR of 0.75 (95% CI: 0.43–1.30; P = 0.30), again with no observed heterogeneity (I² = 0%).
Conclusion FcRn antagonists nearly doubled the likelihood of achieving an IWG platelet response in adults with persistent or chronic ITP, without an associated increase in serious adverse events. This effect was primarily driven by efgartigimod, while evidence for rozanolixizumab remains inconclusive due to limited data and imprecision. Despite the small number of short-duration trials and modest sample sizes, the consistency of treatment effect and favorable safety profile support FcRn blockade as a promising and generally well-tolerated treatment option. Larger, longer-term studies are needed to confirm the durability of response and better characterize the long-term safety profile.
