Early administration of tofacitinib in COVID‐19 pneumonitis: An open randomised controlled trial

Abstract

Background Controversies on sub‐populations most sensitive to therapy and the best timing of starting the treatment still surround the use of immunomodulatory drugs in COVID‐19. Objectives We designed a multicentre open‐label randomised controlled trial to test the effect of prompt adding of tofacitinib to standard therapy for hospitalised patients affected by mild/moderate COVID‐19 pneumonitis. Methods Patients admitted to three Italian hospitals affected by COVID‐19 pneumonitis not requiring mechanical ventilation were randomised to receive standard treatment alone or tofacitinib (10 mg/bid) for 2 weeks, starting within the first 24 h from admission. Results A total of 116 patients were randomised; 49 in the experimental arm completed the 14‐day treatment period, 9 discontinued tofacitinib as the disease worsened and were included in the analysis, and 1 died of respiratory failure. All 58 control patients completed the study. Clinical and demographic characteristics were similar between the study groups. In the tofacitinib group, 9/58 (15.5%) patients progressed to noninvasive ventilation (CPAP) to maintain SO2 > 93%, invasive mechanical ventilation or death by day 14 was 15.5%, significantly less than in the control group (20/58, 34.4%, RR 0,45, RRR −55%, NNT 5; p = .018). No differences in severe adverse effect incidence had been observed across the groups. Conclusion High‐dose tofacitinib therapy in patients with COVID pneumonitis is safe and may prevent deterioration to respiratory failure.

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review

“…EULAR, in its recent update, has suggested using tofacitinib in combination with glucocorticoids as immunomodulatory therapy among critically ill or severe COVID-19 patients requiring oxygen therapy for reduced disease progression and mortality (Alunno et al, 2022). Similar findings have been reported by multiple observational studies and randomized controlled trials, suggesting the use of tofacitinib alone or in combination with dexamethasone to improve survival odds in severe and critical COVID-19 patients (Singh P. K. et al, 2021;Hayek et al, 2021;Panda et al, 2021;Shrestha et al, 2021;Ferrarini et al, 2022;Kodali et al, 2022;Murugesan et al, 2022). Based on available evidence, tofacitinib is a valid therapeutic option for COVID-19; however, more studies are needed compared to clinical trials, as the results are reported mainly from case studies.…”

Extended-Release Tofacitinib Therapy for a MDA5 Antibody-Positive Amyopathic Dermatomyositis Patient with Early-Stage Interstitial Lung Disease

“… 24 Prescribing high-dose Tof as a twice-daily 10 mg immediate-release formulation in patients with COVID-2019 pneumonia can prevent deterioration to respiratory failure. 25 …”

Determinants of COVID-19 Disease Severity–Lessons from Primary and Secondary Immune Disorders including Cancer

“…STAT1 alterations are no exception, potentially posing a life-threatening situation, resulting in bone marrow failure and poor outcomes [91,111]. This bone marrow failure phenotype [90,[112][113][114] seems particularly relevant due to the possibility of targeting the JAK/STAT pathway in COVID-19 [115].…”