Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
Study Assessing an Algorithm-based Strategy of Eculizumab Discontinuation in Children and Adults With aHUS
Atypical hemolytic syndrome (aHUS) is a severe renal disease affecting children and adults.
 It is characterized by the occlusion of intrarenal vessels due to the presence of
 platelet/fibrin thrombi, and leads to end-stage renal disease in up to 2/3 of patients. The
 discovery of complement alternative pathway as a major risk factor for aHUS has led to the
 design of a disease-specific treatment, the anti-C5 monoclonal antibody, eculizumab.
 Complement inhibition using eculizumab has clearly improved the renal outcome of aHUS
 patients with a dramatic decrease in the risk of end-stage renal disease. However, the
 optimal duration of eculizumab therapy is still debated. The present study aims to assess the
 feasibility and safety of the discontinuation of eculizumab treatment in children and adults
 with aHUS.
A visit (physical examination; blood pressure measurement) will be performed every month for
 3 months, and every 3 months for 21 months.

 Blood (serum creatinine, platelet count, hemoglobin, LDH, haptoglobin) and urine
 (proteinuria/creatininuria ratio and microscopic hematuria) tests will be performed every 2
 weeks from inclusion to M6 and subsequently every month starting M7 Urine dipstick (for
 albuminuria and microscopic hematuria) will be performed by the patients at home at least
 twice a week.

 Markers of complement activation and biomarkers of endothelial cells activation and immune
 cells activation will be assessed at baseline, M1, M3, M6, M9, M12, M18 and M24.
Inclusion Criteria:

 1. Children and adults under eculizumab treatment for aHUS (initial episode or relapse)
 defined by at least two of the following: thrombocytopenia (platelet count < 150 G/L),
 mechanical hemolytical anaemia (Hb < 10 g:dl, LDH > upper limit of normal,
 undetectable haptoglobin, presence of schizocytes on blood smear), acute kidney injury
 (serum creatinine and/or proteinuria/creatininuria > upper limit of normal for age or
 an increase > 15% compared to baseline levels )

 2. Patients not requiring dialysis.

 3. Adults: HUS remission and normal or stabilized renal function under eculizumab
 treatment since at least 6 months (3 months in patients with MCP mutations)

 4. Children: age > 3 years at eculizumab withdrawal; HUS remission and normal renal
 function under eculizumab treatment since at least 3 months in children with isolated
 MCP mutation, at least 6 months in children with complement mutation other than MCP.

 Exclusion Criteria:

 1. Patients on dialysis.

 2. Women treated with eculizumab starting or planning a pregnancy. Pregnancy including
 the post-partum period is high-risk periods for the occurrence of aHUS.

 3. Patients who did not give informed consent.

 4. Patients under protection of a judicial authority

 Patients can be enrolled in the study within ten weeks after Eculizumab stop.