Sarilumab is an anti-interleukin-6 human monoclonal antibody, such as tocilizumab, which is administered subcutaneously every two weeks for the treatment of moderate to severe active rheumatoid arthritis in adult patients. Despite the effectiveness reported for tocilizumab in the recently published experiences, the need to rapidly find alternative therapies to manage the complications of Covid-19 infection remains extremely high. The lack of clinical experience on the usage of sarilumab in such patients prevents the possibility of adopting early access programs for using commercially available sarilumab (prefilled syringe) packs in patients with severe Covid-19 pneumonia. The present study is aimed to generate a rapid, still robustly documented, evidence on the potential clinical efficacy and tolerability of a further IL-6R antagonist in Covid-19 pneumonia.
In February 2020, the emergence of the COVID-19 epidemic in Italy and, especially, in
Lombardy, with a potential fatal outcome in a significant proportion of cases, determined the
need for adopting new therapeutic approached based on the few data available in literature.
Although there are no clinical data available in COVID-19 patients concomitantly treated with
Sarilumab subcutaneously (SC) nor intravenously (IV), there is scientific rationale that
supports the exploration of sarilumab to treat pulmonary complications related to
Covid-195-6. By inhibiting interleukin-6 (IL-6)signaling, sarilumab may potentially interrupt
cytokine-mediated pulmonary injury precipitated by infection with SARS-CoV-2 and thereby
ameliorate severity and/or reduce mortality among patients presenting with Covid-19 pneumonia
when administered in conjunction with antiviral therapy. given the apparent dose/dose
pharmacokinetic/ pharmacodynamic (PK/PD) equivalence of 400 mg of tocilizumab to 400 mg of
sarilumab, we propose a dose escalation protocol by which the first 5 included patients will
be treated with a dosage of 200 mg of sarilumab IV as 1st dose, followed by clinical
reassessment after 12 hours and in case of no major adverse events and lack of improvement in
respiratory function and / or persistence of fever and persistently high inflammatory markers
re-administration of 200 mg intravenous (IV) of sarilumab. If no patients showed unfavorable
safety signals, and no clear improvement is detected in >50% of the initially treated five
patients after 96 hours since last administration, the dosage will be increase to sarilumab
400 mg IV as first and second dose in the remaining patients.
Drug: Sarilumab Prefilled Syringe
Sarilumab administration must be associated with an antiviral treatment as defined by the treatment protocol suggested by the SIMET Experts group 4 and AIFA recommendations: chloroquine 500 mg 1 tablet twice daily or hydroxychloroquine 400 mg 1 tablet twice daily in the first day and then 200 mg 1 tablet twice daily.
Other Name: Sarilumab
Inclusion Criteria:
- Age ≥ 18 years and < 85 years.
- Documented (chest X-Ray or TC scan), severe (BCRSS ≥3 and <4) interstitial pneumonia
with respiratory failure (requiring supplemental oxygen) with positive Covid-19 swab
testing.
- Worsening of respiratory exchanges such as to require ventilation with Venturi mask
>31% (6L/minute).
- Increased levels of D-dimer (> 1500 ng/mL) or D-dimer progressively increasing (over 3
consecutive measurements) and reaching ≥ 1000 ng/mL.
- Signed informed consent.
Exclusion Criteria:
- Age < 18 years or ≥ 85 years.
- AST / ALT > 5x Upper normal limit.
- Neutrophil count lower than 500 cells / mL.
- Platelet count lower than 50,000 cells / mL.
- Documented sepsis due to infections other than Covid-19.
Divisione Clinicizzata di Malattie Infettive, ASST FBF-Sacco
Milano, MI, Italy
Massimo Galli, Professor, Principal Investigator
University of Milan