Fakhouri 2016.

Study characteristics
Methods	Study design: single‐arm study Country: multicentre (North America, Europe) Recruitment: not reported Intention to treat: yes Follow‐up: 26 weeks with optional 2‐year extension period
Participants	Total number: 41 Age range: ≥18 years Inclusion criteria: ≥ 18 years; diagnosis of aHUS; platelet count < 150 x 103/µL; Hb ≤ lower limit of normal range; LDH ≥ 1.5 times the upper limit of normal range; SCr ≥ the upper limit of normal range at screening; vaccinated against Neisseria meningitides Exclusion criteria: ADAMTS13 activity ≤ 5% in plasma; evidence of STEC infection; prior eculizumab exposure
Interventions	Intervention group Eculizumab therapy: 900 mg once a week for 4 weeks, 1,200 mg at week 5, and then 1,200 mg every 2 weeks. The dosing regimen was designed to ensure that ≥ 95% of patients had complete and sustained terminal complement inhibition (including at times of increased complement activity, e.g. infection or surgery) and to provide peak concentrations (50 to 700 μg/mL) within the target range Control group Not applicable
Outcomes	Primary outcomes Complete TMA response: defined as haematologic normalisation (platelet count ≥ 150 x109/µL and LDH < upper limit of normal range) and preservation of kidney function (SCr < 25% increase from baseline), confirmed by 2 or more consecutive measurements obtained 4 or more weeks apart Secondary outcomes Modified complete TMA response TMA event‐free status TMA intervention rate Hematologic normalisation Improvements in hematologic parameters and kidney function measures Change in HRQoL
Notes	Study sponsored by Alexian Pharmaceuticals, the manufacturer of eculizumab
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	All subjects treated with eculizumab. Given the rarity of the condition it is likely that all eligible participants encountered during the recruitment period were recruited, but this is not specifically reported. There is no reporting of how participants were selected for the study. Eligibility criteria clearly described.
Allocation concealment (selection bias)	High risk	Not randomised
Blinding of participants and personnel (performance bias) All outcomes	High risk	Not blinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Little or no missing outcome data
Selective reporting (reporting bias)	Low risk	All expected outcomes published
Other bias	Low risk	See below for single‐arm study bias assessment
Lead time bias / immortal time bias	Low risk	The time between recruitment and initiation of therapy was minimal (maximum seven days)
Confounding by indication	Low risk	Given the rarity of the condition participants at all stages of the disease were included with similar prognostic factors as compared with other studies
Misclassification bias / information bias	Low risk	Clear dosing regimen and outcome reporting
Bias from natural recovery / regression to the mean	Low risk	Given the severe nature of the condition and historical data it is unlikely that there was no significant bias from natural recovery observed
Bias due to adjunctive therapies	Low risk	The need for plasma therapy (the main adjunctive therapy) was well described