Rate of aHUS relapse after eculizumab discontinuation in 4 previously published retrospective series from Europe and the United States and in Present Prospective Study
| . | n (%) . | |||||
|---|---|---|---|---|---|---|
| Ardissino et al11 (2014) . | Fakhouri et al12 (2016) . | Wijnsma et al13 (2017) . | Merrill et al17 (2017) . | Present study . | Total . | |
| Patients with complementgene screening | 16 | 38 | 18* | 13† | 55 | 140 |
| Adults | 8 | 29 | 14 | 13 | 36 | 100 |
| Children | 8 | 9 | 4 | 0 | 19 | 40 |
| Duration of follow-up‡ | NS | |||||
| Median | 13.1 mo | 22 mo | 239 d | 19.8 mo§ | ||
| Range | 0.4-40 | 5-43 | 0-1390 | 5.4-24 | ||
| Patients with no variant and no anti–factor H Ab | 5 | 16 | 4 | 8‖ | 23 | 56 |
| Relapse rate | 0 | 0 | 0 | 1 (13) | 1 (4) | 2 (3.5)¶ |
| Patients with rare variants (MAF <0.1%) | 7 | 21 | 13 | 5 | 28 | 74 |
| Relapse rate | 3 (43) | 12 (57) | 5 (38) | 2 (40) | 12 (43) | 34 (46) |
| Patients with rare pathogenic variant | 4 | 18 | 9 | 2 | 26 | 59 |
| Relapse rate | 3 (75) | 10 (56) | 3 (33) | 2 (100) | 10 (38) | 28 (47) |
| Patients with CFH rare variant | 2 | 11 | 7 | 2 | 6 | 28 |
| P/LP | 2 | 9 | 4 | 1 | 6 | 22 |
| VUS | 0 | 2 | 3 | 1 | 0 | 6 |
| Relapse rate | 2 (100) | 8 (72) | 4 (57) | 1 (50) | 3 (50) | 18 (64) |
| P/LP | 2 | 7 | 2 | 1 | 3 | 15 |
| VUS | 0 | 1 | 2 | 0 | 0 | 3 |
| Patients with MCP rare variant | 2 | 8 | 0 | 2 | 12 | 24 |
| P/LP | 1 | 7 | 1 | 12 | 21 | |
| VUS | 1 | 1 | 1 | 0 | 3 | |
| Relapse rate | 0 | 3 (37) | — | 0 | 6 (50) | 9 (37) |
| P/LP | 3 | 6 | 9 | |||
| VUS | 0 | 0 | 0 | |||
| Patients with CFI rare variant | 3 | 2 | 1 | 0 | 7 | 13 |
| P/LP | 1 | 2 | 0 | 6 | 9 | |
| VUS | 2 | 0 | 1 | 1 | 4 | |
| Relapse rate | 1 (33) | 0 | 0 | — | 2 (29) | 3 (23) |
| P/LP | 1 | 0 | 1 | 2 | ||
| VUS | 0 | 0 | 1 | 1 | ||
| Patients with C3 rare variant | 0 | 1 | 4 | 0 | 2 | 7 |
| P/LP | 0 | 4 | 2 | 6 | ||
| VUS | 1 | 0 | 0 | 1 | ||
| Relapse rate | 0 | 1 (25) | — | 0 | 1 (14) | |
| P/LP | 1 | 1 | ||||
| VUS | 0 | 0 | ||||
| Patients with CFB rare variant | 0 | 0 | 1 | 1 | 0 | 2 |
| P/LP | 1 | 0 | 1 | |||
| VUS | 0 | 1 | 1 | |||
| Relapse rate | — | — | 0 | 1 (100) | 1 (50) | |
| P/LP | 0 | 0 | ||||
| VUS | 1 | 1 | ||||
| Patients with anti–factor H Ab | 4# | 1 | 1 | 0 | 4 | 10 |
| Relapse rate | 2 (50) | 0 | 0 | 0 | 2 (20) | |
| . | n (%) . | |||||
|---|---|---|---|---|---|---|
| Ardissino et al11 (2014) . | Fakhouri et al12 (2016) . | Wijnsma et al13 (2017) . | Merrill et al17 (2017) . | Present study . | Total . | |
| Patients with complementgene screening | 16 | 38 | 18* | 13† | 55 | 140 |
| Adults | 8 | 29 | 14 | 13 | 36 | 100 |
| Children | 8 | 9 | 4 | 0 | 19 | 40 |
| Duration of follow-up‡ | NS | |||||
| Median | 13.1 mo | 22 mo | 239 d | 19.8 mo§ | ||
| Range | 0.4-40 | 5-43 | 0-1390 | 5.4-24 | ||
| Patients with no variant and no anti–factor H Ab | 5 | 16 | 4 | 8‖ | 23 | 56 |
| Relapse rate | 0 | 0 | 0 | 1 (13) | 1 (4) | 2 (3.5)¶ |
| Patients with rare variants (MAF <0.1%) | 7 | 21 | 13 | 5 | 28 | 74 |
| Relapse rate | 3 (43) | 12 (57) | 5 (38) | 2 (40) | 12 (43) | 34 (46) |
| Patients with rare pathogenic variant | 4 | 18 | 9 | 2 | 26 | 59 |
| Relapse rate | 3 (75) | 10 (56) | 3 (33) | 2 (100) | 10 (38) | 28 (47) |
| Patients with CFH rare variant | 2 | 11 | 7 | 2 | 6 | 28 |
| P/LP | 2 | 9 | 4 | 1 | 6 | 22 |
| VUS | 0 | 2 | 3 | 1 | 0 | 6 |
| Relapse rate | 2 (100) | 8 (72) | 4 (57) | 1 (50) | 3 (50) | 18 (64) |
| P/LP | 2 | 7 | 2 | 1 | 3 | 15 |
| VUS | 0 | 1 | 2 | 0 | 0 | 3 |
| Patients with MCP rare variant | 2 | 8 | 0 | 2 | 12 | 24 |
| P/LP | 1 | 7 | 1 | 12 | 21 | |
| VUS | 1 | 1 | 1 | 0 | 3 | |
| Relapse rate | 0 | 3 (37) | — | 0 | 6 (50) | 9 (37) |
| P/LP | 3 | 6 | 9 | |||
| VUS | 0 | 0 | 0 | |||
| Patients with CFI rare variant | 3 | 2 | 1 | 0 | 7 | 13 |
| P/LP | 1 | 2 | 0 | 6 | 9 | |
| VUS | 2 | 0 | 1 | 1 | 4 | |
| Relapse rate | 1 (33) | 0 | 0 | — | 2 (29) | 3 (23) |
| P/LP | 1 | 0 | 1 | 2 | ||
| VUS | 0 | 0 | 1 | 1 | ||
| Patients with C3 rare variant | 0 | 1 | 4 | 0 | 2 | 7 |
| P/LP | 0 | 4 | 2 | 6 | ||
| VUS | 1 | 0 | 0 | 1 | ||
| Relapse rate | 0 | 1 (25) | — | 0 | 1 (14) | |
| P/LP | 1 | 1 | ||||
| VUS | 0 | 0 | ||||
| Patients with CFB rare variant | 0 | 0 | 1 | 1 | 0 | 2 |
| P/LP | 1 | 0 | 1 | |||
| VUS | 0 | 1 | 1 | |||
| Relapse rate | — | — | 0 | 1 (100) | 1 (50) | |
| P/LP | 0 | 0 | ||||
| VUS | 1 | 1 | ||||
| Patients with anti–factor H Ab | 4# | 1 | 1 | 0 | 4 | 10 |
| Relapse rate | 2 (50) | 0 | 0 | 0 | 2 (20) | |
Complement gene variants were classified as pathogenic, likely pathogenic, or of unknown significance according to recommendations published by Richards et al.23
Ab, antibody; MAF, minor allele frequency; NS, not specified; P/LP, pathogenic/likely pathogenic; VUS, variant of unknown significance.
Including 4 renal transplant recipients.
The study included 6 patients with HUS and coexisting diseases/conditions: liver transplantation (n = 1), quinine use (n = 1), possible scleroderma (n = 1), inflammatory bowel disease (n = 1), and polymyositis-scleroderma overlap (n = 1). Two additional patients had malignant hypertension, including 1 with TMA attributed to accelerated primary hypertension. The 3 HUS relapses after eculizumab discontinuation occurred in the settings of active inflammatory bowel disease (n = 1), malignant hypertension with nonadherence to antihypertensive treatment (n = 1), and liver transplantation with medication nonadherence (n = 1).
Time to relapse or last follow-up.
Mean.
Two patients had heterozygous ADAMTS13 variants (1 relapsed), and another had heterozygous DGKe variant.
The 2 HUS relapses after eculizumab discontinuation in patients without identified rare variants occurred in the settings of liver transplantation with medication nonadherence (n = 1) and late discovery of complete ADAMTS13 deficiency (n = 1).
One patient with anti–factor H antibodies carried CFH gene variant. Titer of the autoantibodies was not specified.