Upadacitinib Use Increases Risk for Herpes Zoster in Patients with Rheumatoid Arthritis

By Adam Hochron, Staff Writer
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According to a pooled analysis study, patients with rheumatoid arthritis treated with upadacitinib are at greater risk of developing herpes zoster than those treated with methotrexate or in combination with adalimumab. 

In an article published in Annals of Rheumatic Diseases, the authors noted the general population has around a 30% risk of contracting herpes zoster. That risk, they said, is increased for people who have a weakened immune system or the elderly. For patients with rheumatoid arthritis, that risk is doubled. The authors looked at six phase 3 clinical trials in their research, including more than 5,300 patients. 

The incidence of herpes zoster per 100 patient-years (95% CI) was 0.8 (0.3-1.9) in the methotrexate monotherapy arm, 1.1 (0.5-1.9) in the methotrexate-adalimumab arm, 3.0 (2.6-3.5) in the upadacitinib 15 mg arm, and 5.3 (4.5-6.2) in the upadacitinib 30 mg arm. Just 0.3% of the cases of herpes zoster reported in the upadacitinib 15 mg arm were serious compared to 1.2% of cases in the 30 mg arm. 

In addition to looking at new cases of herpes zoster, the authors also evaluated recurrence for those treated with upadacitinib. For patients treated with the lower dose, 6.4% experienced a recurrence, compared with 9.3% of those treated with a higher dose after the first episode. In addition, one case of recurrence in the lower dose was more severe than the initial case. 

Risk factors for developing herpes zoster included prior history of herpes zoster and patients in and around Asia. Previous studies showed people in Asia have a higher rate of herpes zoster compared to other parts of the world. This is especially true in patients living in the Koreas and Japan treated with baricitinib, peficitinib, and tofacitinib, and Japanese people treated with upadacitinib. The authors said the reason for that connection is unknown. They cited potential explanations including genetic predisposition, differences in means of reporting, and “other cultural or medical factors.” 

While groups like EULAR and ACR recommend a live attenuated herpes zoster vaccine for high-risk patients and those with rheumatic diseases, including rheumatoid arthritis, the authors said their findings could not assess how effective the vaccine is for these patients. They noted that under 5% of patients studied had received the live virus vaccine at baseline. 

“Similar to herpes zoster reported with other JAK inhibitors, the majority of herpes zoster cases in upadacitinib-treated patients were non-serious and involved a single dermatome,” the authors said. “Furthermore, in contrast to previous studies with JAK inhibitors, we did not find an association between herpes zoster and concomitant use of glucocorticoids.” 


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