Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Abstract

Objective: To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups.

Methods: Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed.

Results: Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension.

Interpretation: Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

Figure 1

Patient disposition through January 2019. In total, 117 patients were enrolled in the OLE; 56 had received eculizumab and 61 had received placebo during REGAIN. At OLE study end, 30 patients in total had discontinued (23.2% of the eculizumab/eculizumab group [13/56] and 27.9% of the placebo/eculizumab group [17/61]), and 87 patients had completed the study (76.8% of the eculizumab/eculizumab group [43/56] and 72.1% of the placebo/eculizumab group [44/61]). OLE = open‐label extension. Figure reproduced with permission from Vissing J, Jacob S, Fujita KP, et al. ‘Minimal symptom expression’ in patients with acetylcholine receptor antibody‐positive refractory generalized myasthenia gravis treated with eculizumab. J Neurol 2020. (https://creativecommons.org/licenses/by/4.0/).

Figure 2

Changes in (A) MG‐ADL mean total score and (B) QMG mean total score from REGAIN baseline to OLE week 130. Patient numbers were not the same for each assessment. BL = baseline; CI = confidence interval; MG‐ADL = myasthenia gravis activities of daily living profile; OLE = open‐label extension; QMG = quantitative myasthenia gravis scale.

Figure 3

Changes in (A) MG‐ADL LS mean total score and (B) QMG LS mean total score from open‐label baseline to week 130. ^‡ P ≤ 0.001 compared with open‐label extension baseline, repeated‐measures analysis. Patient numbers were not the same for each assessment. Stable scores in the eculizumab/eculizumab group are evidence of maintained improvement achieved during eculizumab treatment in REGAIN in these patients. BL = baseline; CI = confidence interval; LS = least‐squares; MG‐ADL = myasthenia gravis activities of daily living profile; QMG = quantitative myasthenia gravis scale.

Figure 4

Correlations between MG‐ADL and QMG total scores (A) for changes from eculizumab baseline to last OLE assessment and (B) at last OLE assessment. Pearson’s correlation coefficients (R) were calculated for each treatment group. Each regression line was determined by a simple linear regression model of (A) change in MG‐ADL total score from REGAIN baseline to last OLE assessment against change in QMG total score from eculizumab baseline to last OLE assessment or (B) MG‐ADL total score at last OLE assessment as the response variable against QMG total score at last OLE assessment as the predictor variable for respective treatment groups, and its 95% confidence band was determined by the pointwise 95% confidence band. MG‐ADL = myasthenia gravis activities of daily living profile; OLE = open‐label extension; QMG = quantitative myasthenia gravis scale.

Figure 5

Changes in MG‐ADL mean domain scores from REGAIN baseline to OLE week 130 for (A) ocular, (B) bulbar, (C) respiratory, and (D) limb domains. Patient numbers were not the same for each assessment. Data are from patients with abnormal domain scores at REGAIN baseline only. BL = baseline; CI = confidence interval; MG‐ADL = myasthenia gravis activities of daily living profile; OLE = open‐label extension.

Figure 6

Changes in MG‐ADL LS mean domain scores from open‐label baseline to week 130 for (A) ocular, (B) bulbar, (C) respiratory, and (D) limb domains. *P ≤ 0.05, ^† P ≤ 0.01, ^‡ P ≤ 0.001 compared with open‐label baseline, repeated‐measures analysis. Patient numbers were not the same for each assessment. Stable scores in the eculizumab/eculizumab group are evidence of maintained improvement achieved during eculizumab treatment in REGAIN in these patients. Data are from patients with abnormal domain scores at REGAIN baseline only. BL = baseline; CI = confidence interval; LS = least‐squares; MG‐ADL = myasthenia gravis activities of daily living profile.

Figure 7

Changes in QMG mean domain scores from REGAIN baseline to OLE week 130 for (A) ocular, (B) bulbar, (C) respiratory, and (D) gross motor domains. Patient numbers were not the same for each assessment. Data are from patients with abnormal domain scores at REGAIN baseline only. BL = baseline; CI = confidence interval; OLE = open‐label extension; QMG = quantitative myasthenia gravis scale.

Figure 8

Changes in QMG LS mean domain scores from open‐label baseline to week 130 for (A) ocular, (B) bulbar, (C) respiratory, and (D) gross motor domains. *P ≤ 0.05, ^† P ≤ 0.01, ^‡ P ≤ 0.001 compared with open‐label baseline, repeated‐measures analysis. Patient numbers were not the same for each assessment. Stable scores in the eculizumab/eculizumab group are evidence of maintained improvement achieved during eculizumab treatment in REGAIN in these patients. Data are from patients with abnormal domain scores at REGAIN baseline only. BL = baseline; CI = confidence interval; LS = least‐squares; QMG = quantitative myasthenia gravis scale.