Table 2

Summary of results from biomarker analyses

Biomarker evaluatedKey results
Tier 1
 CRP

  • No association with VTE events in any treatment arm at baseline or month 12

 D-dimer

  • Higher month 12 levels were prospectively associated with a greater risk of a subsequent VTE event with tofacitinib 5 mg or 10 mg two times per day (HR 4.676, p=1.61e–04; and HR 1.922, p=1.54e–03; respectively)

  • Treatment specificity of effects could not be established

 TPO

  • Higher month 12 levels were prospectively associated with a greater risk of a subsequent VTE event in the tofacitinib 10 mg two times per day arm (HR 1.752, p=0.008)

  • Treatment specificity of effects could not be established

Tier 2
 Factor VIII, TAT, TFPI, PAI-1, protein C, AT, apoCIII and leptin

  • No clinically meaningful differences across treatment arms

Tiers 3 and 4
 Proteomic assays (276 markers)

  • Tier 3: No clinically meaningful differences across treatment arms

  • Tier 4: Two markers with no known relationship to VTE (ANG and TNFSF13B) showed significant associations with PE events in the tofacitinib 10 mg two times per day arm

  • Treatment specificity of effects could not be established for either analyte

Genetic biomarkers
 Factor V Leiden R506Q, prothrombin (factor II) G20210A and JAK2 V617F mutations

  • Factor V Leiden and prothrombin risk alleles, individually or combined, were associated with an increased incidence of VTE events but did not explain increased risk in the tofacitinib arms (ie, removal of all risk allele carriers did not attenuate the treatment effect on VTE)

  • No VTE cases or matched controls had the JAK2 V617F activating mutation

Antibody biomarkers
 ACA IgG, ACA IgM, anti-β2GP1 IgG and anti-β2GP1 IgM

  • No statistical differences were observed between treatment arms or between VTE cases and matched controls

  • ACA, anticardiolipin antibody; ANG, angiogenin; apoCIII, apolipoprotein C-III; AT, antithrombin; CRP, C-reactive-protein; JAK2, Janus kinase 2; PAI-1, plasminogen activator inhibitor-1; PE, pulmonary embolism; TAT, thrombin-antithrombin complex; TFPI, tissue factor pathway inhibitor; TNFi, tumour necrosis factor inhibitor; TNFSF13B, tumour necrosis factor ligand superfamily member 13B; TPO, thrombopoietin; VTE, venous thromboembolism; β2GP1, beta-2-glycoprotein 1.