Tofacitinib and Thromboembolic Risk Save

Mease and colleagues have reviewed the tofacitinib drug development and clinical trial data, finding the risk of venous (VTE) and arterial thromboembolism (ATE) to be low and augmented in patients with baseline cardiovascular abd VTE risk factors and those taking higher doses of tofacitinib (10 mg bid). 

While tofacitinib was originally FDA approved without a warning for VTE or ATE, a post-marketing safety study (Study A3921133) later reported an increased risk of pulmonary embolism (PE) and all-cause mortality in patients receiving tofacitinib 10 mg twice daily (compared to those receiving tumour necrosis factor inhibitors). This lead to adding a boxed warning for thrombotic risk in the tofacitinib safety label (that has also appeared among other JAK inhibitors). 

The current post-hoc analysis of the tofacitinib RA, PsO and PsA programmes, examines the risk of DVT, PE, VTE and ATE and is coupled with real world data from the CORRONA registry, IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database.

The drug development data included 12410 tofacitinib-treated patients (RA: n=7964; PsO: n=3663; PsA: n=783). The incidence rates (IRs (and 95% CI) for thromboembolic events for different disorders are shown below. Incidence rates are reported as events per 100 patient-years (PY) of exposure.

RA patients on tofacitinib 5 mg and 10 mg twice daily:

• DVT (0.17 (0.09–0.27) and 0.15 (0.09–0.22)
• PE (0.12 (0.06–0.22) and 0.13 (0.08–0.21)
• ATE (0.32 (0.22–0.46) and 0.38 (0.28–0.49)

Psoriasis patients on tofacitinib:

• DVT (0.06 (0.00–0.36) and 0.06 (0.02–0.15)
• PE (0.13 (0.02–0.47) and 0.09 (0.04–0.19)
• ATE (0.52 (0.22–1.02) and 0.22 (0.13–0.35).

Among PsA patients on tofacitinib:

• DVT (0.00 (0.00–0.28) and 0.13 (0.00–0.70)
• PE (0.08 (0.00–0.43) and 0.00 (0.00–0.46)
• ATE (0.31 (0.08–0.79) and 0.38 (0.08–1.11)

Overall, thrombotic risk was similar between tofacitinib doses and generally higher in patients with baseline cardiovascular or VTE risk factors.

Analysis of the CORRONA registry found similar numbers with no disproportionate reporting of DVT, PE or ATE in this database or the FAERS database.

These data suggest an overall low rate of VTE and ATE in RA, PsO and PsA patients, that is augmented in the face of VTE or cardiovascular risk factors or high dose tofacitinib (10 mgbid) use.