Efficacy and Safety of Tocilizumab for Acute Chest Syndrome Treatment in Patients with Sickle Cell Disease

Inclusion Criteria:

1. SCD patient of all genotypes (SS, SC, S/β0 and S/β+)

2. Age ≥ 2 years old

3. Hospitalized for ACS, defined by the WHO as the association of fever and/or acuterespiratory symptoms with a new pulmonary infiltrate on chest imaging, (X-ray, lungultrasound, or CT scan)

4. Requiring supplemental oxygen ≥ 2 L/min for SpO2 ≥ 95% or non-invasive respiratorysupport (high flow nasal oxygen or continuous positive airway pressure or bilevelnon-invasive ventilation) or invasive mechanical ventilation or ECMO, for less than 48 hours

5. Negative pregnancy test for girls or women of childbearing age

6. Freely given, informed and written consent of patient or legal representatives

7. Affiliation to the social security (or health insurance)

8. Effective contraception up to 3 months after the administration of treatment (tocilizumab or placebo)

Exclusion Criteria:

1. Impossibility to perform tocilizumab/placebo injection within the first 48 hours ofsupplemental oxygen and/or respiratory support (as defined in inclusion criterian°4). If exchange transfusion is indicated at inclusion, it has to be performedbefore the injection of tocilizumab/placebo.

2. Known hypersensitivity to tocilizumab or its excipients

3. Known active current severe bacterial, viral, fungal, mycobacterial, or otherinfections (including but not limited to tuberculosis and atypical mycobacterialdisease, hepatitis B and C, and herpes zoster)

4. Immunization with a live/attenuated vaccine within the last 4 weeks

5. Immunomodulatory therapy, anti-rejection therapy, cell depleting therapies andinvestigational agents within the last 3 months

6. History of severe allergic or anaphylactic reactions to human, humanized, or murinemonoclonal antibodies

7. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chroniculcerative lower gastrointestinal disease such as Crohn's disease, ulcerativecolitis, or other symptomatic lower gastrointestinal conditions that mightpredispose a patient to perforations

8. Evidence of malignant disease or malignancies diagnosed within the last 3 years

9. Pregnancy or breastfeeding

10. Imminent and inevitable progression towards death in the opinion of the investigator

11. Absolute neutrophil count < 1.0 G/L or platelets < 50 G/L

12. ALT or AST > 5-fold the upper limit of normal

13. Glomerular Filtration rate (GFR) < 60 mL/min/1,73 m²

14. Current enrolment in another interventional research concerning a medicinal productfor human use