Eculizumab versus placebo or alternative treatment for children and adults aHUS

Patient or population: children and adults with aHUS

Settings: inpatient

Intervention: eculizumab

Comparison: placebo or alternative treatment

Death

N/A

100 (4 single‐arm studies)

⊕⊝⊝⊝
very low

All 100 patients were alive at 26 weeks. There was 1 death in the 37 patients who were subsequently followed up over 2 years

Requirement for KRT

N/A

100 (4 single‐arm studies)

⊕⊝⊝⊝
very low

37/100 were undergoing dialysis at initiation of eculizumab therapy. Of these patients, 11 (30%) continued to require regular dialysis after 26 weeks of treatment representing a 70% reduction in dialysis requirement. At 2 years, 3/37 patients included within the secondary study remained dialysis‐dependent compared with 7 at baseline (57% reduction)

Disease remission

N/A

100 (4 single‐arm studies)

⊕⊝⊝⊝
very low

60/100 patients treated with eculizumab achieved complete TMA response after 26 weeks of treatment. Median time to complete TMA response was 56 ‐ 60 days. In a cohort of patients followed up for 2 years, 65% maintained complete TMA response at this time point

Change in eGFR

N/A

88 (3 single‐arm studies)

⊕⊝⊝⊝
very low

In patients treated with eculizumab, mean change in eGFR over 26 weeks was 33 ± 34 mL/min/1.73 m². At 2 years, eGFR had improved by ≥ 15 mL/min/1.73 m² in 37 patients (49%)

HRQoL

N/A

100 (4 single‐arm studies)

⊕⊝⊝⊝
very low

In 49 patients aged ≥ 12 years treated with eculizumab, 67% demonstrated a clinically significant improvement in EQ‐5D score. In 22 paediatric patients treated with eculizumab the mean improvement in FACIT‐F score was 19.7 (improvement of > 4.7 considered clinically meaningful)

Adverse events

N/A

100 (4 single‐arm studies)

⊕⊝⊝⊝
very low

Adverse events occurred in 100% of patients treated with eculizumab. Serious adverse events occurred in 37% of patients. The most commonly reported events included diarrhoea (23%), fever (21%), headache (19%), upper respiratory tract infection (19%), cough (17%) and urinary tract infection (10%)

Meningococcal infection

N/A

100 (4 single‐arm studies)

⊕⊝⊝⊝
very low

Meningococcal infection occurred in 2 patients (2%) treated with eculizumab

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; N/A: not applicable; KRT: Kidney replacement therapy; TMA: Thrombotic microangiopathy; eGFR: Estimated glomerular filtration rate; HRQoL: health‐related quality of life; FACIT‐F: Functional assessment of chronic illness therapy ‐ fatigue.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Ravulizumab versus placebo or alternative treatment for adults with aHUS

Patient or population: adults with aHUS

Settings: inpatient

Intervention: ravulizumab

Comparison: placebo or alternative treatment

Death

N/A

58 (1 single‐arm study)

⊕⊝⊝⊝
very low

Four deaths occurred, including one in a patient ultimately excluded based on eligibility criteria but who had received one dose of ravulizumab. No deaths were considered treatment‐related by the study investigators

Requirement for KRT

N/A

56 (1 single‐arm study)

⊕⊝⊝⊝
very low

29/56 were undergoing dialysis at initiation of ravulizumab therapy. Of these patients, 12 (41%) continued to require regular dialysis after 26 weeks of treatment representing a 59% reduction in dialysis requirement

Disease remission

N/A

56 (1 single‐arm study)

⊕⊝⊝⊝
very low

30/56 patients treated with ravulizumab achieved complete TMA response after 26 weeks of treatment. Median time to complete TMA response was 86 days

Change in eGFR

N/A

56 (1 single‐arm study)

⊕⊝⊝⊝
very low

In patients treated with ravulizumab, mean change in eGFR over 26 weeks was 35 ± 35 mL/min/1.73 m²

HRQoL

N/A

44 (1 single‐arm study)

⊕⊝⊝⊝
very low

A clinically meaningful improvement in FACIT‐F score (≥ 3‐point increase) was observed in 84% of patients treated with ravulizumab

Adverse events

N/A

58 (1 single‐arm study)

⊕⊝⊝⊝
very low

Adverse events occurred in 100% of patients treated with ravulizumab. Serious adverse events occurred in 52% of patients. The most commonly reported events included headache (36%), diarrhoea (31%), vomiting (26), hypertension (22%), nausea (22%) and urinary tract infection (17%)

Meningococcal infection

N/A

58 (1 single‐arm study)

⊕⊝⊝⊝
very low

No patients treated with ravulizumab developed meningococcal infection

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio; N/A: not applicable; KRT: Kidney replacement therapy; TMA: Thrombotic microangiopathy; eGFR: Estimated glomerular filtration rate; HRQoL: Health‐related quality of life; FACIT‐F: Functional assessment of chronic illness therapy ‐ fatigue.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.