Filgotinib shows dose-dependent risks for malignancy, mortality in older adults with RA
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Key takeaways:
- Filgotinib demonstrated “potential dose-dependent relationships” with herpes zoster, malignancies and all-cause mortality in older adults.
- Other treatment-emergent adverse events were stable over time.
A long-term safety analysis of filgotinib for moderate-to-severe rheumatoid arthritis demonstrated potential dose-dependent risks for herpes zoster, malignancies and all-cause mortality in patients aged 65 and older, according to data.
This latest analysis of the JAK inhibitor, published in Annals of the Rheumatic Diseases, follows results from the ORAL Surveillance study, which prompted “regulatory agencies to conduct an extensive safety review of all JAK inhibitors,” Gerd R. Burmester, MD, professor of medicine at Charité-Universitätsmedizin Berlin, in Germany, and colleagues wrote. The review led to an updated summary of product characteristics for JAK inhibitors, including filgotinib (Gilead Sciences/Galapagos NV).
“This states that filgotinib should only be used if no suitable treatment alternatives are available in patients who are 65 years of age or older, have a history of atherosclerotic [cardiovascular] disease,” the researchers wrote. “Following the results of the ORAL Surveillance study and subsequent filgotinib [summary of product characteristics] updates, a longer-term analysis of filgotinib safety data is warranted.”
To examine the long-term safety of filgotinib in moderate-to-severe RA, Burmester and colleagues integrated data from seven clinical trials, including two phase 2 and phase 3 long-term extension studies, with data as recent as May 6, 2022. Patients with RA included in the analysis (n = 3,691) received at least one dose of daily filgotinib, either 100 mg or 200 mg.
The frequencies of treatment-emergent adverse events (TEAEs) were calculated as exposure-adjusted incidence rates per 100 patient-years of exposure.
In the pooled group of patients on either dosage, filgotinib was taken for a median of 3.8 years, with a reported maximum of 8.3 years. According to the researchers, rates of most treatment-emergent adverse events were stable over time, including serious infections, malignancies, major adverse cardiovascular events (MACE) and venous thromboembolism (VTE).
However, the exposure-adjusted incidence rate of herpes zoster was lower among those receiving 100 mg filgotinib (1.1 per 100 patient-years of exposure) vs. 200 mg (1.5 per 100 patient-years of exposure).
For patients aged older than age 65 years, the researchers noted a lower incidence of herpes zoster and malignancies among those taking 100 mg filgotinib vs. 200 mg. The incidence of all-cause mortality was also numerically lower in the lower-dose group.
“Over a median of 3.8 and a maximum of 8.3 years of exposure, the safety and tolerability of filgotinib were similar following 100mg and 200mg dosing,” Burmester and colleagues wrote. “Rates of TEAEs of interest remained stable over time. In general, small differences in the rates of some TEAEs between filgotinib doses, which were observed in a previous analysis of these studies, were reduced or absent in the current analysis, including for serious infections, herpes zoster and all-cause mortality.
“In patients aged 65 years, the incidences of most TEAEs of interest were similar between the two doses,” they added. “Potential dose-dependent relationships for herpes zoster, malignancies and all-cause mortality were observed in patients aged 65 years, which cannot be excluded based on the current data set. This indicates the potential impact of age on the safety profile of filgotinib, and that some patients aged 65 years may benefit from the 100mg dose option. These analyses demonstrate that long-term filgotinib exposure was well tolerated in patients with moderate-to-severe active RA, with a stable rate of TEAEs over time.”
Perspective
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When discussing treatment options and the treat-to-target approach for rheumatoid arthritis with our patients, it is crucial to have real-world data to back up our recommendations, rather than relying solely on anecdotal evidence.
People aged 65 years and older have additional concerns about medications and health outcomes due to overarching health issues. If previous medications have been ineffective and we are considering starting Janus kinase inhibitors, studies like this one, which followed patients a maximum of more than 8 years, are important. Burmester and colleagues identified issues that were unique to the 65-plus age group and reported their findings. None of these findings were surprising, but having real-world evidence from research is crucial for making informed decisions about treatment options.
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