(241) Comparative effectiveness and economic evaluation of immunomodulatory therapies in generalized myasthenia gravis

Background: : Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder characterized by potentially life-threatening muscle weakness. In recent years, multiple novel immunomodulatory therapies have been approved or are under review in the United States based on trials demonstrating improved outcomes versus placebo. In the absence of head-to-head trials, comparing the effectiveness and costs of these treatments is essential to support informed treatment and coverage decisions.

Objective: : To evaluate the relative clinical benefits and costs per improved outcome (CPIO) of efgartigimod, ravulizumab, rozanolixizumab, zilucoplan, inebilizumab, and nipocalimab for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) gMG.

Methods: : A network meta-analysis (NMA) was conducted using data from placebo-controlled trials of efgartigimod IV (ADAPT), rozanolixizumab (MycarinG), ravulizumab (CHAMPION-MG), zilucoplan (RAISE), inebilizumab (MINT), and nipocalimab (VIVACITY-MG3) in patients with anti-AChR Ab+ gMG. Where feasible, trials were included in NMAs evaluating ≥3- and ≥5-point improvements in Myasthenia Gravis–Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. NMA results were used to estimate the number needed to treat (NNT) vs. placebo and relative to the therapy with the lowest NNT. CPIO (2025 USD) was calculated based on efficacy outcomes and treatment-specific drug and administration costs, using real-world weight distributions of gMG patients.

Results: : Efgartigimod IV had the lowest NNT vs. placebo across three endpoints. For a ≥3-point QMG reduction, its NNT was 2.18, significantly lower than inebilizumab (4.69), nipocalimab (5.13), ravulizumab (4.42), and zilucoplan (3.98) (all p< 0.05). For ≥5-point QMG reduction, efgartigimod IV had an NNT of 1.88, significantly lower than zilucoplan (4.85). For a ≥5-point MG-ADL reduction, it had the lowest NNT (1.94), outperforming ravulizumab (4.68) and zilucoplan (4.78) (p < 0.05). Rozanolixizumab had the lowest NNT vs. placebo ≥3-point MG-ADL reduction, though the differences were not significant compared to other treatments. Efgartigimod IV also had the lowest CPIO vs. placebo across all outcomes, with significantly lower costs than all comparators for QMG outcomes and all except rozanolixizumab for MG-ADL outcomes.

Conclusions: : All therapies demonstrated benefit; however, efgartigimod IV showed the lowest NNTs and lowest CPIO compared to ravulizumab, rozanolixizumab, zilucoplan, inebilizumab and nipocalimab for anti-AChR Ab+ gMG.

Sponsorship:: argenx, Inc.