Legendre 2013.

Study characteristics
Methods	Study design: 2 single‐arm studies Country: multicentre (North America, Europe) Recruitment: not reported Intention to treat: yes Follow‐up: 26 week study period and optional extension period
Participants	Total number: study 1 (17); study 2 (20) Age range: ≥ 12 years Inclusion criteria Study 1: weight ≥ 40 kg; confirmed diagnosis of aHUS; evidence of haemolysis; evidence of kidney impairment; evidence of progressive TMA after 4 or more sessions of PE/PI in the prior week Study 2: Weight ≥ 40 kg; confirmed diagnosis of aHUS; evidence of haemolysis; evidence of kidney impairment; no decrease in the platelet count > 25% for at least 8 weeks before receipt of first dose of eculizumab and treated with PE/PI at least once every 2 weeks but no more than 3 times/week Exclusion criteria: ADAMTS13 activity at or below 5% in plasma; evidence of STEC infection; prior eculizumab exposure
Interventions	Intervention group Eculizumab therapy: 900 mg/week (IV) for 4 weeks, a dose of 1200 mg 1 week later, and a maintenance dose of 1200 mg every 2 weeks Control group Not applicable
Outcomes	Primary outcomes Study 1 Inhibition of complement‐mediated TMA, as indicated by a change in the platelet count and normalisation of haematologic values (normal platelet count and LDH level) sustained for at least 2 consecutive measurements over a period of at least 4 weeks Study 2 Inhibition of complement‐mediated TMA, as indicated by TMA event–free status for at least 12 weeks (no decrease in the platelet count of > 25%, no PE/PI, and no initiation of dialysis) and normalisation of haematologic values (normal platelet count and LDH level), sustained for at least 2 consecutive measurements over a period of at least 4 weeks Secondary outcomes Study 1 TMA event–free status Measures of kidney function Changes in HRQoL Pharmacokinetics and pharmacodynamics Safety and tolerability Study 2 Measures of kidney function Changes in HRQoL Pharmacokinetics and pharmacodynamics Safety and tolerability
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	Very little 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	Unclear risk	Participants in the first sub‐study were treated within 3 days, however those in the second sub‐study underwent an eight‐week observation period following recruitment and prior to initiation of treatment which may have increased the potential for lead time bias
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