Table 1

Clinical experience with JAK2 inhibitors in COVID-19

Study ID noBrief title of the studyPromoter/SponsorStatus (first posted)Patient’s condition/inclusion criteriaNo of patientsStudy typeStudy phaseCentersIntervention/drugsPrimary outcome measuresReference
June 2020 (published)COVID-19-induced (mild to severe) pneumonia4Cases reportPilot studyMonocentricBaricitinib
  • Clinical variables and evolution of the COVID-19 disease

  • Laboratory analysis (blood counts, inflammatory markers/IL-6 serum levels, viral load)

Stebbing et al117
NCT04438629Evaluation of Immune Response in COVID-19 Patients (IMMUNOVID)Azienda Ospedaliera Universitaria Integrata Verona (sponsor) and Pederzoli Hospital of Peschiera, ItalyMarch–June 2020 (published), recruitingCOVID-19-induced pneumonia88 (20 on baricitinib)Observational, longitudinal, prospectiveBicentricBaricitinib, 4 mg two times per day 2 days, 4 mg/day 7 days
  • Evolution of the COVID-19 disease

  • Laboratory analysis

    • COVID-19 associated immune disorder (time frame: 24 hours) : circulating cell subsets by flow cytometry

    • COVID-19 associated inflammation (time frame: 48 hours): plasma levels of different solubles factors

    • Oxygenation (time frame: 24 hours)

Bronte et al118
NCT04358614Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical ImpactHospital of Prato, Italycompleted (published October 2020)COVID-19 moderate pneumonia12 patients in the pilot study
191 (113 on baricitinib) in the second phase
Observational, longitudinal, retrospectivePhase 2
Phase 3
Multicentric (seven in Italy)Baricitinib 4 mg/d and antiviral therapy (lopinavir/ritonavir) for 2 weeks vs
SOC (hydroxychloroquine and lopinavir/ritonavir) for 2 weeks
Mortality rateCantini et al120
NCT04401579Adaptive COVID-19 Treatment Trial 2US National Institute of Allergy and Infectious DiseasesCompleted (published March 2021)COVID-19 hospitalized patients1033 (515 on baricitinib)Interventional, randomized, double-blind, placebo-controlledPhase 3Multicentric (67 international centers)Remdesivir plus baricitinib 4 mg/d, up to 2 weeks vs
Remdesivir plus placebo
Time to recoveryKalil et al121
NCT04421027A Study of Baricitinib (LY3009104) in Participants With COVID-19 (COV-BARRIER)Eli Lilly and CompanyCompleted (published August 2021)O2-dependent COVID-19 patients with risk indicators of aggravation1585Interventional, randomized, double-blind, placebo-controlledPhase 3MulticentricBaricitinib 4 mg/d and SOC for 2 weeks vs
Placebo and SOC for 2 weeks
  • Death rate or

  • Requirement of Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation including ECMO (Time frame: 28 days)

Marconi et al124
NCT04469114Tofacitinib in Hospitalized Patients With COVID-19 Pneumonia (STOP-COVID)Hospital Israelita Albert Einstein, Brazil (sponsor)Completed (published)COVID-19 hospitalized patients with pneumonia289Interventional, randomized, double-blind, parallel-design, placebo-controlledPhase 3Multicentric (15 in Brazil)Tofacitinib, 10 mg Twice daily up to 14 days vs
Placebo
Death or respiratory failure until Day 28Guimaraes et al131
Hammersmith Hospital, London, UKJune 2020 (published)HSCT for CML
Diabetes
Male
1Case reportMonocentricTocilizumab 8 mg/kg (two doses, no effect)
Ruxolitinib 5 mg Twice daily 3 days,
10 mg Twice daily 8 days, 5 mg Twice daily 10days
Case report (severe disease)Innes et al142
Aachen University Hospital, Aachen, GermanyMay 2020 (published)MF
high-risk for COVID-19 (arterial hypertension, obesity, hyperuricemia, chronic kidney disease)
Male
1Case reportMonocentricRuxolitinib, 10 mg BD (patient on drug before COVID-19)Case report (mild disease)Koschmieder et al143
No 47 (Italian Agency for Drug (AIFA) and Istituto Spallanzani)
No 17 104 (RUXO-COVID (institutional ethic committee in Florence)
RUXO-COVIDAzienda Ospedaliera-Universitaria Careggi, Florence, ItalyApril-May 2020 (inclusions)
August 2020 (published)
Severe COVID-19 (no mechanical ventilation at diagnosis)34Observational, prospectiveMonocentricRuxolitinib (compassionate use), 5 mg Twice daily 1–2 days, 10 mg Twice daily 1–2 days,
  • Clinical variables and evolution of the COVID-19 disease

  • Laboratory analysis (immunophenotyping of peripheral blood cells, intra-cellular and serum cytokines levels)

Vannucchi et al144
Schwarzwald–Baar–Klinikum Villingen-Schwenningen, GermanyMarch-April 2020 (inclusions), June 2020 (published)Severe COVID-19105 consecutive patients,
14 patients on ruxolitinib
Retrospective, observational (multidisciplinary board decision on specific medical treatment)pilote case seriesMonocentricRuxolitinib, 7.5 mg Twice daily 1–7 days to 15 mg Twice dailyCISLa Rosee et al145
NCT04338958Ruxolitinib in COVID-19 Patients With Defined Hyperinflammation (RuxCoFlam)University of Jena, Germany (Sponsor)Completed (published)COVID-19 patients with hyperinflammation (COVID-19 Inflammation Score (CIS) ≥10/16)193Interventional, single arm (open), non-randomizedPhase 2MulticentricRuxolitinib, 10 mg Twice daily to 20 mg Twice dailyImprovement in CISLa Rosee et al145
NCT04337359 (expanded access for ruxolitinib)Ruxolitinib Managed Access Program for Patients Diagnosed With Severe/Very Severe COVID-19 IllnessPoliclinico S.Marco Gruppo San Donato University and Research Hospital, Zingonia, Bergamo, ItalyMarch–April 2020 (inclusions), November 2020 (published)Severe COVID-19 (no mechanical ventilation at diagnosis)75 (32 on ruxolitinib, 43 as control)Interventional, non-randomizedMonocentricRuxolitinib, 5 mg Twice daily 7 days, 5 mg/d 3 days
+
Methyl-prednisolone 1 mg/kg/day IV 3 days, 0.5 mg/kg/day 5 days, then oral prednisone tapered over 2 weeks
Evolution of the COVID-19 diseaseD'Alessio et al146
February 2020 (included), July 2020 (published)Severe COVID-1941 (20 on ruxolitinib, 21 as control)Interventional, prospective, single-blind, randomized and controlledPhase 2Multicentric (three in China)Ruxolitinib, 5 mg Twice daily and standard-of-care (SOC) vs
Placebo (C vitamin, 100 mg Twice daily) and SOC
Time to clinical improvementCao et al147
trial register no. 81 April 2020 (Italian COVID-19 Ethical Committee)
NCT04361903
Ruxolitinib for the Treatment of ARDS in Patients With COVID-19 Infection
(COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study)
August 2020 (published)COVID-19-related ARDS18Observational, retrospectiveMulticentric (three in Italy)Ruxolitinib, 20 mg Twice daily 2 days and de-escalation to 5 mg Twice dailyDegree of respiratory impairementCapochiani et al148
MPN-COVIDEuropean Leukemia NetworkMPNs175Observational, retrospectiveMulticentric, in 38 European centers (France, Germany, Italy, Poland, Spain and the UK)
  • Mortality

  • Sub-analysis of the effect of therapy

Barbui et al151
Royal Berkshire Hospital NHS Foundation Trust, Reading, UKCOVID-19 with secondary haemophagocytic lymphohistiocytosis (sHLH)
Patients with medical history of lymphoma
2Cases reportMonocentricRuxolitinib
+
Tocilizumab
Case report (severe diseases)Portsmore et al153
NCT04362137Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)Novartis PharmaceuticalsCompletedCOVID-19-related cytokine storm432Interventional, randomized, double-blind, placebo-controlledPhase 3MulticentricRuxolitinib, 5 mg Twice daily vs
Placebo
  • Death rate

  • Development of respiratory failure [requiring mechanical ventilation)

  • Requirement for ICU

NCT04377620Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)Incyte CorporationTerminatedCOVID-19-associated ARDS
AND intubation and mechanical ventilation
211Interventional, randomized, double-blind, placebo-controlledPhase 3MulticentricRuxolitinib, 5 mg or 15 mg, Twice daily and SOC vs
Placebo and SOC
Death rate
NCT04402866TD-0903 for ALI Associated With COVID-19Theravance Biopharma (sponsor)completed (published)Oxygen-requiring patients with COVID-19-associated:
  • ALI

  • Lung inflammation

235Randomized, double-blind, parallel-group trial, placebo-controlledPhase 2Multicentric (the UK, Moldova and Ukrain)Nezulcitinib (ascending-dose cohorts from 1 to 10 mg/day) for up to 7 days vs
Placebo
No of respiratory failure-free days (Baseline through Day 28)Singh et al157
  • ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation; JAK, Janus kinases; MF, myelofibrosis.