At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia. The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.
Cytokine storm syndrome (CSS) is caused by the excessive release of cytokines during an
exaggerated immune response. CSS can be triggered by infections or therapeutic interventions,
being more severe depending on the degree and duration of immune activation. CSS is as a
significant on-target side-effect of chimeric antigen receptor (CAR) T-cell therapies, which
have been subject to assessment for the treatment of haematological malignancies. Tocilizumab
(intravenous, IV) is indicated for the treatment of chimeric antigen receptor CAR T
cell-induced severe or life-threatening CSS.
Based on the experience with tocilizumab in the CSS, and that some patients infected with
SARS-CoV-2 can develop CSS, leading to potentially fatal damage to lung tissue, the drug is
being investigated in China and Italy, and clinical trials are being conducted/planned in
these and several other countries. Real-word experience with tocilizumab IV have shown that
in a substantial proportion of COVID-19 patients with severe pneumonia, fever returned to
normal and respiratory function based on oxygen intake and lung opacities improved
remarkably. Laboratory parameters such as C-reactive protein (CRP) that seem to be increased
in patients infected decreased significantly with tocilizumab, and lymphocytes levels also
returned to normal.
All these findings have led the Spanish Agency for Medicine and Health Products (AEMPS) to
initiate the controlled distribution of tocilizumab IV, in light of the increased interest on
the anti-cytokine therapy targeting IL-6 in COVID-19 infected patients. Therefore,
tocilizumab might be among the therapeutic armamentarium for preventing the fatal
consequences of acute respiratory and multi organ failure in around 20% of the COVID-19
infected patients.
The aim of the present study is to evaluate the effectiveness and safety of IV tocilizumab in
patients with COVID-19 severe pneumonia who are currently hospitalized or admitted to ICU.
This large real-world cohort provides a unique opportunity to study a potential medicine
during the current emergency situation, and support the findings from the Roche-sponsored
Phase III study that is planned to start in early April.
Drug: Tocilizumab
Treatment with Tocilizumab
Inclusion Criteria:
- Provide oral informed consent to participate in this study.
- At least 18 years of age.
- Diagnosed with COVID-19 pneumonia by RT-PCR.
- Have received the first dose of tocilizumab a maximum of two days before the inclusion
or is candidate for tocilizumab treatment
- Hospitalized or admitted to ICU
Exclusion Criteria:
- The patient has any other medical condition or is receiving concomitant medication
that could, in the opinion of the investigator, compromise the patient's safety or
collected data
- Known severe allergic reactions to tocilizumab or other monoclonal antibodies
- Active acute and severe infections, including tuberculosis infection
- Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
Hospital Universitario de Cabueñes
Gijón, Asturias, Spain
Hospital Universitari de Bellvitge
L'Hospitalet De Llobregat, Barcelona, Spain
Hospital Sant Joan de Déu de Manresa
Manresa, Barcelona, Spain
Hospital de Mataró
Mataró, Barcelona, Spain
Hospital Universitario de Galdakao
Galdakao, Bizkaia, Spain
Hospital Universitario Marqués Valdecilla
Santander, Cantabria, Spain
Hospital Público General del Tomelloso
Tomelloso, Ciudad Real, Spain
Hospital Jerez de la Frontera
Jerez De La Frontera, Cádiz, Spain
Hospital Universitari Son Espases
Palma De Mallorca, Islas Baleares, Spain
Hospital Universitario Fundación Alcorcón
Alcorcón, Madrid, Spain
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, Spain
Hospital Universitario de Getafe
Getafe, Madrid, Spain
Hospital Rey Juan Carlos
Móstoles, Madrid, Spain
Hospital Universitario Rey Juan Carlos
Móstoles, Madrid, Spain
Hospital Universitario Infanta Sofía
San Sebastián De Los Reyes, Madrid, Spain
Complejo Hospitalario de Navarra
Pamplona, Navarra, Spain
Hospital Nuestra Señora del Prado
Talavera De La Reina, Toledo, Spain
Complejo Hospitalario Universitario de Albacete
Albacete, Spain
Hospital Infanta Cristina
Badajoz, Spain
Hospital Clínic i Provincial Barcelona
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Universitario de Burgos
Burgos, Spain
Hospital Universitario Dr. Josep Trueta
Gerona, Spain
Hospital Universitario Clínico San Cecilio
Granada, Spain
Hospital Universitario Virgen de las Nieves
Granada, Spain
Hospital General Universitario Gregorio Marañón
Madrid, Spain
Hospital Universitario Fundación Jiménez Díaz
Madrid, Spain
Hospital Universitario HM Sanchinarro
Madrid, Spain
Hospital Universitario Infanta Leonor
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
Murcia, Spain
Hospital Regional Universitario de Málaga
Málaga, Spain
Complexo Hospitalario Universitario de Ourense
Orense, Spain
Hospital Universitario Salamanca
Salamanca, Spain
Hospital Universitario Virgen de la Macarena
Sevilla, Spain
Hospital Universitario Virgen del Rocío
Sevilla, Spain
Hospital Virgen de la Salud
Toledo, Spain
Hospital Clinico Universitario de Valencia
Valencia, Spain
Hospital Universitari i Poliectenic La Fe
Valencia, Spain
Hospital Universitario Dr. Peset
Valencia, Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Spain
Hospital Universitario Miguel Servet
Zaragoza, Spain
Jose Antonio Pérez Molina, Principal Investigator
Hospital Universitario Ramón y Cajal