Table 2.
Published case reports following discontinuation of eculizumab in 52 patients with aHUS (A) and patients with aHUS receiving a single eculizumab dose (B)
| (A) | |||||||
|---|---|---|---|---|---|---|---|
| Case report | Kidney status | Mutation | Time on eculizumab | Reason for discontinuationa | Time to new TMA | Event underlying new TMA | Length of follow-up if no new TMA |
| Cayci et al. [19] | Native | CFI | 3 weeks | Safety concern of long-term eculizumab | – | – | 4 months |
| Garjau et al. [20] | Native | MCP | 27 weeks | In ESRD, late eculizumab start | – | – | Not reported |
| Delmas et al. [23] | Native | CFH, CFI | Tapered after 18 months | Stable condition | – | – | 2 months |
| Gulleroglu et al. [25] | Native | MCP | 5 weeks | Normal neurological, renal, and haematological parameters | – | – | 9 months |
| Canigral et al. [26] | Native | None identified | 6 months | No mutation found | – | – | 6 months |
| Fakhouri et al. [28] | Native | 5 patients discontinued | 3 weeks to 19 months | No detectable CFH antibodies, haemodialysis | – | – | 5–13 months |
| De Sousa Amorim et al. [32] | Native | None identified, homozygous CFH and MCP risk haplotypes | 11 months | Absence of TMA | – | – | 12 months |
| Ardissino et al. [11, 17] | Native (n = 10) KTx (n = 1) | 11/16 CFI, CFH antibodies, MCP, CFHR3/1 deletion | Median 4.3 (range 0.5–14.4) months | Physician-led patient decision | – | – | Range 0.4–40 months |
| Pu and Sido [30] | NR | None identified | 12 weeks | Urinary infection | – | – | 12 months |
| Sheerin et al. [34] | NR | 11/14; none identified (n = 6), CFH, MCP, C3 | 1–34 weeks | No mutation identified (n = 4), still on dialysis at 4 months (n = 3), not aHUS (n = 2), MCP mutation (n = 1), non-compliance (n = 1) | – | – | Not reported, of patients with no identified mutations, 4 recovered, 2 are on dialysis, 2 patients died |
| Giordano et al. [21] | Native | CFH | 18 months | Stable condition | 45 days | No specific event reported (reduced platelet count and increased proteinuria) | – |
| Carr et al. [22] | Native | CFH | 9 months | Patient request | 6 months | Respiratory infection | – |
| Gilbert et al. [24] | Native | MCP | 9 weeks | Cisplatin discontinuation and tumour excision | 15 weeks | No specific event reported (elevated sC5b9 and renal biopsy results) | – |
| Ardissino et al. [11, 17] | Native | 5/16 CFH, CFI, CFHR3/1 deletion, CFH antibodies | Median 4.3 (range 0.5–14.4) months | Physician-led patient decision | Range 0.7–17.3 months | Not reported | – |
| Chaudhary et al. [27] | Native | Heterozygous for CFHR1-3, CFH point mutation | 9 months | Patient request | Not reported | Pregnancy | |
| Kourouklaris et al. [29] | Native | Not tested | ∼6 weeks | Patient request | 5 months | No specific event reported (worsening anaemia, increased LDH and creatinine) | – |
| Schalk et al. [33] | Native | CFH | 1 week (2 doses) | Assumed absence of effect | 2 months | Not reported | – |
| Alachkar et al. [18] | LD KTx | None identified | 8 months | Stable serum creatinine and normalization of laboratory and clinical parameters | 5 months | Pneumonia | – |
| Wetzels et al. [31] | NR | 3 patients CFH | 4–6 months | Stable disease | 3 months for one patient | Not reported | 11–17 months for two patients |
| Sheerin et al. [34] | NR | 3/14; none identified, CFH, MCP | 24–27 weeks | Still on dialysis at 4 months (n = 2) | 6–36 weeks | Haemolysis (n = 2) | – |
|
(B) | |||||||
| Case report | Kidney status | Mutation | Reason for discontinuationa | Time to new TMA | Complement amplifying condition | Outcome | |
| Mache et al. [35] | Native | No mutation identified | Improvement of renal function, platelet count normalization | 2 weeks | Unknown | Eculizumab reintroduced, hypervolemic hypertension required haemodialysis, eculizumab discontinued again after the patient reached ESRD. A subsequent TMA complication resulted in anuria | |
| Kose et al. (case 2) [37] | Native | CFH and CFI polymorphisms | Improvement of renal function, platelet count normalization | 2 months | Unknown | Patient progressed to ESRD | |
| Vilalta et al. [39] | Native | CFH | Normalization of renal function and haematological stabilization | 8 weeks | Unknown | No new TMA events over subsequent 2.5 years eculizumab treatment | |
| Nürnberger et al. [36] | DD KTx aged 30 and 37 years | CFH and CFHR1 deletion | Normalization of renal function and haemolysis markers | – | – | Stable renal graft function at 8 months (last reported follow-up) | |
| Larrea et al. and Zuber et al. [38, 40] | DD KTx | CFH risk polymorphism | Single dose was planned | 12 days | – | Eculizumab reintroduced | |
a
As reported in published case study. aHUS, atypical haemolytic uraemic syndrome; CF, complement factor; CFHR, complement factor H receptor; DD, deceased donor; ESRD, end-stage renal disease; KTx, kidney transplant; LDH, lactate dehydrogenase; LD, living donor; MCP, membrane cofactor protein; NR, not reported; TMA, thrombotic microangiopathy.