Table 4.
Patient characteristics and outcomes following discontinuation of eculizumab in clinical studies for 12 patients experiencing new TMA events (A) and following modification of eculizumab dosing (B) in clinical studies
| (A) | ||||||
|---|---|---|---|---|---|---|
| Age at initial eculizumab treatment (years) | Kidney status | Mutation | Reason for discontinuation | Time to new TMA (weeks) | Restarted eculizumab? | Outcome |
| <1 | Native | CFH | Did not enter extension | 14 | Yes | Not available |
| 1 | Native | CFH | Physician choice | 8 | Yes | Renal, haematological and cardiac improvement |
| 4 | Native | CFH | Did not enter extension | 9 | Yes | Not available |
| 7 | Native | CFI | Did not enter extension | 77 | Yes | Not available |
| 15 | Native | CFH | Did not enter extension | 11 | Yes | Renal and haematological improvement |
| 18 | Native | No mutation identified | Physician choice | 4 (2 complications) | Yes | ESRD and haemodialysis |
| 21 | Native | MCP | Did not enter extension | 84 and 153 (2 complications) | Yes | Not available |
| 34 | Native | CFH | Physician choice | 14 | Yes | Not available |
| 29 | Native | No mutation identified | Meningococcal meningitis | 5 | No | Progression to ESRD, haemodialysis |
| 80 | Native | No mutation identified | Lack of efficacy | 127 | No | Managed with PE and maintained elevated serum creatinine and low platelets |
| 22 | KTx | No mutation identified | Physician choice | <52 (2 complications) | Yes | Renal and haematological improvement |
| 31 | KTx | No mutation identified | Lack of renal improvement | 4 | No | ESRD |
| (B) | ||||||
|---|---|---|---|---|---|---|
| Age at initial treatment (years) | Kidney status | Mutation | Modification of dosinga | Restarted standard eculizumab dosing regimen? | Outcome | |
| 30 | KTx | C3 | 1200 mg: | No | Sepsis, renal impairment, gastrointestinal bleeding and other complications leading to death due to multi-organ failure | |
| Every 3 weeks for 6 weeks | ||||||
| Single doses after a further 6, 13 and 17 weeks | ||||||
| 43 | KTx | CFI | 1200 mg: | No | Progressed to ESRD, haemodialysis initiated and eculizumab discontinued | |
| Once a month for 1 month | ||||||
| Every 2 weeks for 8 weeks | ||||||
| Once a week for 5 weeks (due to adverse event of renal impairment) | ||||||
| Every 2 weeks for 12 weeks | ||||||
| Every 3 weeks for 3 weeks | ||||||
a
Recommended dosing for adult patients with atypical haemolytic uraemic syndrome is 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, then 1200 mg every 2 weeks thereafter. CF, complement factor; ESRD, end-stage renal disease; KTx, kidney transplant; MCP, membrane cofactor protein; PE, plasma exchange; TMA, thrombotic microangiopathy.