medwireNews: Individuals with rheumatoid arthritis (RA) receiving the oral Janus kinase (JAK) inhibitor upadacitinib have higher rates of herpes zoster than those being treated with methotrexate alone or in combination with adalimumab, research shows.
People with a history of prior herpes zoster and those from Asia are at particularly high risk, report Kevin Winthrop (Oregon Health & Science University, Portland, USA) and co-authors in the Annals of the Rheumatic Diseases.
Their study included data from six phase 3 clinical trials, in which 3209 participants received upadacitinib 15 mg once daily alone or in combination with other therapies, 1204 received upadacitinib 30 mg once daily, 579 received methotrexate plus adalimumab, and 314 received methotrexate monotherapy.
During 12 to 48 weeks of treatment plus 30 days of post-treatment follow-up (70 days for adalimumab), the incidence of herpes zoster was 3.0 cases per 100 person–years with upadacitinib 15 mg, 5.3 cases per 100 person–years with upadacitinib 30 mg, 1.1 cases per 100 person–years with methotrexate plus adalimumab, and 0.8 cases per 100 person–years with methotrexate monotherapy.
The researchers found that the rate of herpes zoster was generally constant over time “suggesting that there is not a ‘high-risk period’ shortly after starting therapy, as has been observed for serious bacterial infections in RA,” they write.
They say this also implies “that it is ‘never too late’ to vaccinate” against herpes zoster during upadacitinib treatment, even though “[f]urther research is required to determine the value of [herpes zoster] vaccination in patients with RA receiving JAK inhibitors, particularly with the recently approved subunit vaccine (Shingrix).”
In line with studies of other JAK inhibitors, the majority (74%) of herpes zoster cases in the upadacitinib groups involved a single dermatome and were considered to be not serious.
Multivariate analyses among upadacitinib-treated patients revealed that a history of herpes zoster was associated with a significant 3.28- to 3.42-fold increased risk for herpes zoster depending on the upadacitinib dose.
In addition, people from Asia had a significant 3.24- to 3.80-fold increased risk relative to those from Europe.
There was no significant association between herpes zoster risk and concomitant glucocorticoid and/or methotrexate use. However, people who received upadacitinib 15 mg, but not 30 mg, had a significantly increased risk if they were female (hazard ratio [HR]=1.51 vs male), from North America (HR=1.47 vs Europe), or aged 65 years and older (HR=2.23 vs <50 years).
Winthrop and team say it is not clear why these variables were only significant risk factors for herpes zoster with the lower upadacitinib dose, and therefore urge caution when drawing conclusions.
They remark that their study “provides further support for the need for continued vigilance and monitoring for signs of [herpes zoster] in patients receiving [upadacitinib], particularly in Asian populations and those with a history of [herpes zoster].
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Ann Rheum Dis 2021; doi:10.1136/annrheumdis-2021-220822