A new study finds upadacitinib and baricitinib carry higher reactivation rates than tofacitinib, underscoring need for HBV screening and prophylaxis.
Rheumatoid arthritis patients treated with Janus kinase inhibitors face a clinically meaningful risk of hepatitis B virus (HBV) reactivation, according to a new retrospective study published in Rheumatology.
The findings raise concerns about the safety of these increasingly prescribed targeted agents, particularly in regions where HBV prevalence remains high.
The research team at National Taiwan University Hospital analysed the outcomes of 374 RA patients treated between 2015 and 2023, who had baseline HBV status available.
Of these, 35 were HBsAg-positive and 339 had resolved HBV infection (HBsAg-negative but anti-HBc–positive).
Patients received either TNF inhibitors, rituximab, or one of three JAK inhibitors: tofacitinib, baricitinib, or upadacitinib.
Results showed that among patients with resolved HBV infection, the risk of reactivation varied considerably by treatment. TNF inhibitors carried the lowest risk, at just 0.9% (2.8 per 1000 person-years).
Rituximab, long recognised as a high-risk therapy for HBV reactivation, showed a 3.2% risk (15.1 per 1000 person-years).
JAK inhibitors overall had a similar risk at 2.9% (10.3 per 1000 person-years), but important differences emerged between individual agents.
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Upadacitinib was associated with the highest risk, 6.5% (42.8 per 1000 person-years), followed by baricitinib at 4.7% (19.2 per 1000 person-years). Tofacitinib, by contrast, carried a relatively low risk of 1.0% (2.7 per 1000 person-years).
The situation was more striking among patients who were HBsAg-positive. Half of those receiving JAK inhibitors experienced a hepatitis flare, a rate that the authors describe as “emphasising the importance of vigilant monitoring and prophylaxis.”
The study fills an important evidence gap. While the risk of HBV reactivation is well established with rituximab and certain biologics, less has been known about targeted synthetic DMARDs such as JAK inhibitors, which have only more recently entered widespread use.
“Our findings reveal a non-negligible risk of HBV reactivation among RA patients receiving JAKi therapy, particularly with the more JAK1-selective JAKi,” the authors concluded.
“Larger registry or prospective studies are needed to validate these findings.”
