Why carry out this study? |
Although efgartigimod and ravulizumab are both approved for treating acetylcholine receptor auto-antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG), they have not been compared in a head-to-head study. |
To address this gap, this study conducted an indirect treatment comparison assessing the relative efficacy of efgartigimod versus ravulizumab in adults with AChR-Ab+ gMG. |
What was learned from the study? |
Efgartigimod was associated with a statistically significant improvement compared with ravulizumab in terms of Myasthenia Gravis Quality of Life 15-item-revised scale (MG-QoL15r). |
Findings were mixed for Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG), with efgartigimod showing a significant improvement over ravulizumab at week 4 and at time of best response, but not over 26 weeks. |
The results suggest that efgartigimod provides a faster and greater improvement over 26 weeks in quality of life than ravulizumab in adults with AChR-Ab+ gMG. |
Introduction
Methods
Overall Approach
Alignment of ADAPT Population to CHAMPION Population
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Only patients with AChR-Ab+ gMG were recruited in CHAMPION, therefore only ADAPT patients with AChR-Ab+ gMG were included in the analysis.
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In CHAMPION, patients diagnosed with gMG in the six months before randomization were excluded, while in ADAPT there were no restrictions on the time from diagnosis. Therefore, the ADAPT patients with a gMG diagnosis within 6 months of baseline were excluded.
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In CHAMPION, only patients with a baseline MG-ADL score ≥ 6 points were included. In ADAPT, the analogous threshold was 5 points. Therefore, ADAPT patients with a baseline MG-ADL score of 5 were excluded.
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The ADAPT study excluded patients with a thymectomy in the prior 3 months, while CHAMPION excluded patients with a thymectomy in the prior 6 months. Therefore, the ADAPT patients treated with a thymectomy between 3 and 6 months before baseline were excluded.
Outcomes
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The AUC of the reduction in disease symptoms (based on MG-ADL, QMG, and MG-QoL15r) over 26 weeks (primary analyses).
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The change from baseline versus placebo at week 4 and at time of best response over the 26-week study period selected as the time of the lowest average MG-ADL score for each treatment (4 weeks for efgartigimod and 26 weeks for ravulizumab) in MG-ADL, QMG, and MG-QoL15r.
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The proportion of cohort with ≥ 3, ≥ 4, or ≥ 5 points reduction in MG-ADL at the time of best response.
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The number needed to treat (NNT), defined as the number of patients that need to be treated to observe ≥ 3, ≥ 4, or ≥ 5 points reduction in MG-ADL at the time of best response.
Statistical Analysis
Effective Sample Size (ESS)
Ethical Approval
Results
Study Populations and Matching
Characteristic | ADAPTa | CHAMPION | ||||
---|---|---|---|---|---|---|
Total (n = 111) | Efgartigimod (n = 55) | Placebo (n = 56) | Total (n = 175) | Ravulizumab (n = 86) | Placebo (n = 89) | |
Mean (SD) | ||||||
Age at enrolment, years | 47.3 (15.8) | 45.0 (15.5) | 49.7 (15.7) | 55.6 (15.1) | 58 (13.8) | 53.3 (16.1) |
Age at diagnosis, years | 37.6 (18.0) | 35.2 (17.8) | 39.9 (18.1) | 46.1 (18.9) | 48.6 (18.5) | 43.7 (19) |
Years from diagnosis to randomization | 9.8 (8.4) | 9.8 (8.6) | 9.8 (8.3) | 9.9 (9.3) | 9.8 (9.7) | 10 (8.9) |
Baseline clinical disease activity | ||||||
MG-ADL score | 9.2 (2.1) | 9.5 (2.2) | 8.8 (2.0) | 9.0 (2.5) | 9.1 (2.6) | 8.9 (2.3) |
QMG score | 15.8 (4.8) | 16.3 (5.2) | 15.3 (4.3) | 14.7 (5.2) | 14.8 (5.2) | 14.5 (5.3) |
MG-QoL15r score | 16.8 (5.5) | 16.4 (5.8) | 17.2 (5.2) | – | – | – |
Count (%) | ||||||
Woman | 75 (67.6) | 40 (72.7) | 35 (62.5) | 89 (50.9) | 44 (51.2) | 45 (50.6) |
Race/ethnicity | ||||||
Asian | 10 (9.0) | 6 (10.9) | 4 (7.1) | 31 (17.7) | 15 (17.4) | 16 (18.0) |
African/American | 2 (1.8) | 0 (0.00) | 2 (3.6) | 6 (3.4) | 2 (2.3) | 4 (4.5) |
White | 95 (85.6) | 46 (83.6) | 49 (87.5) | 128 (73.1) | 67 (77.9) | 61 (68.5) |
Other | 3 (2.7) | 3 (5.4) | 0 (0.00) | 3 (1.7) | 0 (0.0) | 3 (3.4) |
Not reported | 1 (0.9) | 0 (0.00) | 1 (1.8) | 7 (4.0) | 2 (2.3) | 5 (5.6) |
Current/previous treatments | ||||||
Prior thymectomy | 62 (55.9) | 36 (65.5) | 26 (46.4) | – | – | – |
Glucocorticoids | 84 (75.7) | 39 (70.9) | 45 (80.4) | 121 (69) | 56 (65) | 65 (73) |
Other NSID | 66 (59.5) | 33 (60.0) | 33 (58.9) | 119 (68) | 56 (65) | 63 (71) |
MGFA clinical class | ||||||
Class I | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Class II | 43 (38.7) | 20 (36.3) | 23 (41.1) | 78 (44.6) | 39 (45.3) | 39 (43.8) |
Class III | 63 (56.8) | 33 (60.0) | 30 (53.6) | 86 (49.1) | 41 (47.7) | 45 (50.6) |
Class IV | 5 (4.5) | 2 (3.6) | 3 (5.4) | 11 (6.3) | 6 (7.0) | 5 (5.6) |
Overall Findings
AUC for MG-ADL, QMG and MG-QoL15r
AUC | ||||||
---|---|---|---|---|---|---|
MG-ADL | QMG | MG-QoL15r | ||||
n | Mean (95% CI) | n | Mean (95% CI) | n | Mean (95% CI) | |
Adjusted results estimated using reweighted data from the ADAPT study | ||||||
Efgartigimod | 55 | – 62.2 (– 86.8, – 37.7)*** | 55 | – 73.8 (– 107.4, – 40.3)*** | 55 | – 121.9 (– 166.6, – 77.2)*** |
Placebo | 56 | – 22.0 (– 46.8, 2.9) | 54 | – 14.0 (– 48.4, 20.3) | 56 | – 31.3 (– 76.4, 13.8) |
Efgartigimod vs. placebo | 111 | – 40.3 (– 62.5, – 18.0)** | 109 | – 59.8 (– 91.0, – 28.5)** | 111 | – 90.6 (– 130.5, – 50.8)*** |
Results estimated from the CHAMPION study | ||||||
Ravulizumab | 86 | – 73.3 (– 90.8, – 55.3)*** | 86 | – 70.9 (– 93.0, – 49.0)*** | 86 | – 84.6 (– 116.8, – 53.6)*** |
Placebo | 89 | – 41.8 (– 59, – 23.5)*** | 89 | – 24.8 (– 47.6, – 3.4)* | 89 | – 46.6 (– 77.6, – 15.2)** |
Ravulizumab vs. placebo | 175 | – 31.6 (– 56.7, – 6.4)*** | 175 | – 46.1 (– 77.2, – 14.9)*** | 175 | – 38.0 (– 69.4, – 6.6)* |
MAIC results anchored on above comparisons with placebo | ||||||
Efgartigimod vs. ravulizumab | 141 | – 8.7 (– 36.1, 18.8) | 141 | – 13.7 (– 50.3, 22.9) | 141 | – 52.6 (– 103.0, – 2.3)* |
Change from Baseline at Week 4 for MG-ADL, QMG and MG-QoL15r
Change from baseline | ||||||
---|---|---|---|---|---|---|
MG-ADL | QMG | MG-QoL15r | ||||
N | Mean (95% CI) | N | Mean (95% CI) | N | Mean (95% CI) | |
Adjusted results estimated using reweighted data from the ADAPT study | ||||||
Week 4 (time of best response) | ||||||
Efgartigimod | 53 | – 4.3 (– 5.3, – 3.3)*** | 52 | – 5.6 (– 7.1, – 4.2)*** | 53 | – 7.6 (– 9.4, – 5.8)*** |
Placebo | 55 | – 1.3 (– 2.3, – 0.3)** | 53 | – 0.7 (– 2.1, 0.7) | 55 | – 2.0 (– 3.8, – 0.2) |
Efgartigimod vs. placebo | 108 | – 3.0 (– 4.0, – 2.0)*** | 105 | – 5.0 (– 6.6, – 3.4)*** | 108 | – 5.6 (– 7.6, – 3.6)*** |
Results estimated from the CHAMPION study | ||||||
Week 4 | ||||||
Ravulizumab | 84 | – 2.6 (– 3.2, – 1.9)*** | 79 | – 2.6 (– 3.4, – 1.7)*** | 85 | – 3.2 (– 4.5, – 2.0)*** |
Placebo | 84 | – 1.5 (– 2.1, – 0.8)*** | 76 | – 0.8 (– 1.6, 0.0) | 85 | – 1.6 (– 2.8, – 0.3)** |
Ravulizumab vs. placebo | 168 | – 1.1 (– 2.0, – 0.2)* | 155 | – 1.8 (– 3.0, – 0.6)** | 170 | – 1.6 (– 3.4, 0.2) |
Week 26 (time of best response) | ||||||
Ravulizumab | 78 | – 3.1 (– 3.8, – 2.3)*** | 76 | – 2.8 (– 3.7, – 1.9)*** | 78 | – 3.3 (– 4.7, – 1.9)*** |
Placebo | 82 | – 1.4 (– 2.1, – 0.7)*** | 78 | – 0.8 (– 1.7, 0.1) | 82 | – 1.6 (– 3.0, – 0.3)* |
Ravulizumab vs. placebo | 160 | – 1.6 (– 2.6, – 0.7)** | 154 | – 2.0 (– 3.2, – 0.8)** | 160 | – 1.7 (– 3.4, 0.1) |
MAIC results anchored on above comparisons with placebo | ||||||
Efgartigimod vs. ravulizumab at week 4 | 137 | – 1.9 (– 3.3, – 0.5)** | 131 | – 3.2 (– 5.2, – 1.2)** | 138 | – 4.0 (– 6.6, – 1.4)** |
Efgartigimod vs. ravulizumab at time of best response | 131 | – 1.4 (– 2.8, 0.0)* | 128 | – 3.0 (– 5.0, – 1.0)** | 131 | – 3.9 (– 6.5, – 1.3)** |
Change from Baseline at Time of Best Response for MG-ADL, QMG and MG-QoL15r
Minimum Point Improvements in MG-ADL from Baseline
N | Proportion (95% CI) of patients with minimum points improvement in MG-ADL from baseline at time of best response | |||
---|---|---|---|---|
3 points | 4 points | 5 points | ||
Adjusted results estimated using reweighted data from the ADAPT study | ||||
Efgartigimod | 53 | 0.752 (0.633, 0.871)*** | 0.681 (0.553, 0.809)*** | 0.610 (0.476, 0.744)*** |
Placebo | 55 | 0.374 (0.241, 0.507)*** | 0.253 (0.133, 0.374)*** | 0.145 (0.048, 0.243)** |
Efgartigimod vs. placebo | 108 | 0.378 (0.200, 0.556)*** | 0.428 (0.252, 0.604)*** | 0.465 (0.296, 0.634)*** |
Results estimated from the CHAMPION study | ||||
Ravulizumab | 78 | 0.567 (0.456, 0.678)*** | 0.425 (0.314, 0.536)*** | 0.316 (0.211, 0.421)*** |
Placebo | 82 | 0.341 (0.236, 0.446)*** | 0.247 (0.151, 0.343)*** | 0.150 (0.071, 0.229)** |
Ravulizumab vs. placebo | 160 | 0.226 (0.073, 0.379)** | 0.178 (0.031, 0.325)* | 0.166 (0.035, 0.297)* |
MAIC results anchored on above comparisons with placebo | ||||
Efgartigimod vs. Ravulizumab | 131 | 0.152 (– 0.085, 0.388) | 0.250 (0.019, 0.480)* | 0.299 (0.085, 0.513)** |