Risk-Benefit Analysis of Novel Treatments for Patients with Generalized Myasthenia Gravis

Abstract

Introduction: This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG).

Methods: Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a ≥ 3- or ≥ 5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA.

Results: Efgartigimod IV had the lowest NNT versus placebo for achieving a ≥ 3- and ≥ 5-point reduction in QMG, as well as a ≥ 5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a ≥ 3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors.

Conclusions: FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit-risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+ gMG.

Keywords: Eculizumab; Efficacy; Efgartigimod; Generalized myasthenia gravis; Network meta-analysis; Ravulizumab; Risk–benefit analysis; Rozanolixizumab; Safety; Zilucoplan.

Fig. 1

NNT estimates by treatment versus placebo and incremental NNT in the primary analysis. CrI credible interval, EFG IV efgartigimod intravenous, MG-ADL Myasthenia Gravis Activities of Daily Living, NNT number needed to treat, QMG Quantitative Myasthenia Gravis, RAV ravulizumab, ROZ rozanolixizumab, ZIL zilucoplan. *p < 0.05 based on the 95% CrI versus the treatment with the lowest NNT

Fig. 2

NNH estimates by treatment in the primary analysis. AE adverse event, EFG IV efgartigimod intravenous, NNT number needed to harm, RAV ravulizumab, ROZ rozanolixizumab, ZIL zilucoplan. ^aNasopharyngitis was not observed/reported for RAV. ^bNNH is not measurable, as the rates of AEs are the same or very similar between treatment and placebo arms. ^cNNH quantifies the number of patients needed to be treated for one additional person to experience an AE compared to placebo. Negative values indicate fewer AEs with treatment compared to placebo. For positive NNH, higher values indicate more favorable outcomes

Fig. 3

CPIO by treatment versus placebo and incremental CPIO in the primary analysis. CPIO cost per improved outcome, EFG IV efgartigimod intravenous, MG-ADL Myasthenia Gravis Activities of Daily Living, QMG Quantitative Myasthenia Gravis, RAV ravulizumab, ROZ rozanolixizumab, ZIL zilucoplan. *p < 0.05 versus efgartigimod IV, which was the treatment with the lowest CPIO

Fig. 4

NNT estimates by treatment versus placebo and incremental NNT in the sensitivity analysis. CrI credible interval, ECU eculizumab, EFG IV efgartigimod intravenous, EFG SC efgartigimod PH20 subcutaneous, MG-ADL Myasthenia Gravis Activities of Daily Living, NNT number needed to treat, QMG Quantitative Myasthenia Gravis, SC subcutaneous, RAV ravulizumab, ROZ rozanolixizumab, ZIL zilucoplan. *p < 0.05 based on 95% CrI versus the treatment with the lowest NNT

Fig. 5

NNH estimates by treatment in the sensitivity analysis. AE adverse event, ECU eculizumab, EFG IV efgartigimod intravenous, EFG SC efgartigimod PH20 subcutaneous, MG-ADL Myasthenia Gravis Activities of Daily Living, NNT number needed to harm, RAV ravulizumab, ROZ rozanolixizumab, ZIL zilucoplan ^aNasopharyngitis was not observed/reported for RAV and EFG SC; upper respiratory tract infection was not observed/reported for EFG SC; treatment-emergent AEs were not reported for ECU. ^bNNH is not measurable as the rates of AEs are the same or very similar between treatment and placebo arms. ^cNNH quantifies the number of patients needed to be treated for one additional person to experience an AE compared to placebo. Negative values indicate fewer AEs with treatment compared to placebo. For positive NNH, higher values indicate more favorable outcomes

Fig. 6

CPIO by treatment and incremental CPIO in the sensitivity analysis. CPIO cost per improved outcome, ECU eculizumab, EFG IV efgartigimod intravenous, EFG SC efgartigimod PH20 subcutaneous, MG-ADL Myasthenia Gravis Activities of Daily Living, NNT number needed to treat, QMG Quantitative Myasthenia Gravis, RAV ravulizumab, ROZ rozanolixizumab, ZIL zilucoplan. *p < 0.05 versus efgartigimod IV, which was the treatment with the lowest CPIO