Herpes Zoster with JAK Inhibitors Save

JAK inhibitors (JAKi) are approved for several immune-mediated inflammatory diseases and carry a higher than usual risk of herpes zoster (HZ) in certain conditions like rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and ulcerative colitis (UC). A recent review a higher HZ risk with JAKi therapy shows the HZ-risk in RA and UC to be higher than PsA when treated with usual doses of TOFA, especially those given higher TOFA doses or concomitant glucocorticoids

This systematic review examined HZ risk in RA, PsA, AS and UC patients treated with (tofacitinib (TOFA), baricitinib (BARI) or upadacitinib (UPA). The primary outcomes were HZ incidence rate (/100 patient-years) or/and cumulative incidence of HZ.

Data were derived from 53 clinical trials and 25 real world studies. Clinical trial showed a HZ-incidence of:

• TOFA-treated RA (2.2–7.1/100 patient-years)
• TOFA treated UC (1.3–7.6/100 patient-years)
• TOFA-treated PsA (1.7/100 patient-years)
• TOFA in UC (rates with high dose 10 mg bid = 3.2–7.6/100 patient-years vs. usual dose 5 mg/twice daily = 1.3–2.3/100 patient-years).
• Limited data on HZ-risk in JAKi-treated AS and UPA-treated patients

Real world study results:

• HZ-incidence between TOFA and BARI (2 studies)

Concomitant glucocorticoid use in RA increased the HZ-risk.

HZ rates in the general population are 0.3–0.5/100 person-years (PY), and may be greater (>1.1./100 PY inthe elderly (> 80 years).

These studies show a marked (4 - >10 fold) risk of HZ when using JAKi, especially in RA and UC or with very high doses of JAKi. 

Preventive measures, including HZ subunit vaccination, and careful selection of JAKi-eligible are essential.  Reasons for lowre rates of HZ in PsA studies is uncertain.