Immune-mediated lung injury plays a pivotal role in severe interstitial pnemumonia related to SARS-CoV2 infection. Tofacitinib, a JAK1/3-Inhibitor, could mitigate alveolar inflammation by blocking IL-6 signal. The aim of this prospective single cohort open study is to test the hypotesis that early administration of tofacitinib in patients with symptomatic pneumonia could reduce pulmonary flogosis, preventing function deterioration and the need of mechanical ventilation and/or admission in intensive care units.
Interstitial Pneumonia is the main complication of SARS-CoV2 infection. Immune system
hyperactivation, leading to alveolar inflammation, is the main mechanism in determining lung
damage. Evidence are accumulating about the pivotal role played by IL-6 in this disease.
Preliminary evidence, indeed, point out the efficacy of an IL-6 receptor inhibitor in
improving clinical conditions in a proportion of rapidly deteriorating patients. Our
hypotesis is that a precocious inhibition of IL-6 signal, by the administration of
tofacitinib (JAK 1/3 Inhibitor), could hinder the progression to more severe grades of lung
inflammation leading to pulmonary function deterioration. In a prospective single cohort open
study, 50 patients admitted in Hospital due to SARS-CoV 2 symptomatic interstitial pneumonia,
but not requiring mechanical ventilation, will be enrolled. Tofacitinb will be administered
every day for 14 days, starting within 24 h from the admission. The primary outcome is to
evaluate the effect of this drug on the rate of patients who will need mechanical
ventilation. Safety in this population will also be actively monitored.
Drug: Tofacitinib
Tofacitinib 10mg twice a day will be administered within 24h from hospital admission for 14 days
Inclusion Criteria:
- SARS-CoV2 Infection diagnosed by rt-PCR
- Rx or CT-scan confirmed interstitial pneumonia
- Hospital admission from less than 24h
- Written Informed Consent
Exclusion Criteria:
- Age <18 ys or >65
- Patients in mechanical ventilation at time of admission
- Severe Hearth failure (NYHA 3 or 4)
- Severe History of Chronic Ischemic Hearth Disease, defined as history of Major Adverse
Cardiovascular Event and/or recent (one year) revascularization.
- History of recurrent Deep Venous Thrombosis and Pulmonary Embolism
- Active Bacterial or Fungal Infection
- Hematological cancer
- Metastatic or intractable cancer
- Pre-existent neurodegenerative disease
- Severe Hepatic Impairment
- Severe Renal Failure (Creatinine Clearance <30ml/h)
- Active Herpes zoster infection
- Severe anemia (Hb<9g/dl)
- Lymphocyte count below 750/mcl
- Neutrophil count below 1000/mcl
- Platelet count below 50000/mcl
- Pregnancy or Lactation
- Inability to give informed consent (severe transitory or permanent mental impairment,
incapacitation)
Ospedali Riuniti di Ancona
Ancona, Marche, Italy
Investigator: Armando Gabrielli, Prof
Contact: +390712206104
a.gabrielli@staff.univpm.it
Investigator: