Efficacy and Safety of Tofacitinib in Patients With COVID-19 Pneumonia

TOFA-COV-2 is a cohort study that is conducted in the three clinics of the Sechenov University (Moscow, Russia) in patients with moderately severe COVID-19 pneumonia. A diagnosis of COVID-19 associated pneumonia suspected clinically was confirmed by polymerase chain reaction (PCR) and/or chest CT. In patients with inconclusive or negative results of PCR on nasopharyngeal swab, SARS-CoV-2 induced pneumonia was defined as an acute respiratory infection with typical CT findings (4 or 5 on CO-RADS scale) and no other obvious aetiology.

In order to be included in this study, patients must have COVID-19 pneumonia involving at least 25% of lung tissue in combination with at least one of the following: (1) oxygen saturation at rest ≤93% on ambient air, (2) increased C-reactive protein (CRP ≥50 mg/L) and/or (3) fever (≥38.0°C) that persisted for at least two days despite treatment with nonsteroidal antiinflammatory drugs or paracetamol. Exclusion criteria for the administration of tofacitinib were coexistent infection other than COVID-19; requirement for invasive mechanical ventilation; estimated glomerular filtration rate calculated using CKD-EPI formula ≤30 ml/min/1.73 m2; elevated ALT and/or AST levels more than 3 times the upper limit of normal; chronic use of glucocorticoids or immunosuppressive agents; and administration of interleukin-6 inhibitors and/or high-dose glucocorticoids (≥250 mg prednisone equivalent intravenously) for the treatment of COVID-19.

All patients are divided into four groups depending on nadir levels of oxygen saturation and therapy: (1) patients with oxygen saturation ≤93% who received tofacitinib and SoC, (2) patients with oxygen saturation ≤93% who received only SoC, (3) patients with oxygen saturation >93% who received tofacitinib and SoC, (4) patients with oxygen saturation >93% who received only SoC. The aim of the study is to test the hypothesis that administration of tofacitinib could influence the risk of mechanical ventilation and/or death.

All patients provided written, informed consent for the off-label use of experimental medications, including tofacitinib, according to the provisional recommendations issued by the Russian Ministry of Health during the outbreak of infection.

Inclusion criteria

• SARS-CoV2 Infection diagnosed by PCR and/or typical lesions on CT-scan (4 or 5 on CO-RADS scale) in combination with at least one of the following:

• oxygen saturation at rest ≤93% on ambient air,
• AND/OR C-reactive protein ≥50 mg/L,
• AND/OR fever (≥38.0°C) that persisted for at least two days despite treatment with nonsteroidal antiinflammatory drugs or paracetamol
• Written Informed Consent

Exclusion criteria

• Age <18 years
• Coexistent infection other than COVID-19
• Requirement for invasive mechanical ventilation
• Estimated glomerular filtration rate calculated using CKD-EPI formula ≤30 ml/min/1.73 m2;
• Elevated ALT and/or AST levels more than 3 times the upper limit of normal
• Chronic use of glucocorticoids or immunosuppressive agents
• Administration of interleukin-6 inhibitors and/or high-dose glucocorticoids (≥250 mg prednisone equivalent intravenously) for the treatment of COVID-19