Filgotinib, a JAK inhibitor used to treat rheumatoid arthritis (RA), appears to carry a substantially lower risk of herpes zoster (shingles) compared with four other JAK inhibitors in its class. The finding comes from a real-world analysis of nearly 1,100 treatment courses across five different JAK inhibitors, offering patients and doctors new information about safety differences among these widely prescribed arthritis drugs.

What Are JAK Inhibitors and Why Does Shingles Risk Matter?

JAK inhibitors are a class of biologic drugs that work by blocking specific proteins in the immune system to reduce inflammation and slow joint damage in rheumatoid arthritis. While these medications are highly effective at controlling disease, they also suppress immune function, which can increase the risk of infections like herpes zoster, the virus that causes shingles. Understanding which JAK inhibitor carries the lowest infection risk helps doctors and patients make more informed treatment decisions.

Researchers from nine hospitals in Japan conducted a retrospective analysis of the ANSWER cohort, examining data from 765 patients who received 1,096 different JAK inhibitor treatment courses. The study compared five JAK inhibitors: tofacitinib, baricitinib, peficitinib, upadacitinib, and filgotinib. Participants had a mean age between 62.6 and 65.7 years, were predominantly women, and were followed for an average of 18.2 months.

Which JAK Inhibitor Had the Lowest Shingles Risk?

The differences in shingles incidence across the five drugs were striking. During the follow-up period, shingles occurred in 88 of the 1,096 treatment courses. When researchers calculated the annual incidence rates per 100 person-years of treatment, filgotinib stood out with the lowest risk:

• Filgotinib: 1.73 cases per 100 person-years of treatment
• Peficitinib: 3.79 cases per 100 person-years of treatment
• Tofacitinib: 5.84 cases per 100 person-years of treatment
• Baricitinib: 6.21 cases per 100 person-years of treatment
• Upadacitinib: 7.38 cases per 100 person-years of treatment

When researchers compared filgotinib directly against tofacitinib (the reference drug), filgotinib showed a significantly lower hazard ratio of 0.11, meaning patients on filgotinib had roughly one-tenth the risk of shingles compared with those on tofacitinib. Filgotinib also showed significantly lower risk compared with baricitinib and upadacitinib.

Patient-specific factors such as age, sex, use of other arthritis medications like methotrexate or glucocorticoids, prior biologic drug use, or a history of shingles did not significantly affect shingles risk across the different JAK inhibitors.

How Should Patients and Doctors Use This Information?

While the findings are encouraging for filgotinib, researchers emphasized caution in interpreting the results. The study was observational rather than a randomized controlled trial, meaning it captured real-world data but cannot prove that filgotinib directly causes lower shingles risk. Additionally, the number of shingles cases was relatively limited, and differences in vaccine availability and the timing of when each drug was introduced in Japan may have influenced the results.

"A lower observed incidence of HZ was noted among filgotinib users compared with some of the other JAKi. However, given the limited number of events and the observational nature of this study, these findings should be interpreted cautiously," the researchers stated.

Study Authors, ANSWER Cohort Research Team

The researchers called for larger, longer-term studies to confirm these findings and understand the biological mechanisms behind filgotinib's apparent protective effect. Such research could help clarify whether the difference is due to how filgotinib selectively targets certain JAK proteins compared with the other drugs in the class.

Steps to Consider When Choosing a JAK Inhibitor for RA

• Discuss infection risk with your rheumatologist: Ask about the shingles risk profile of any JAK inhibitor your doctor recommends, and mention if you have a personal or family history of shingles or other infections.
• Review your vaccination status: Ensure you are up to date on the shingles vaccine (Shingrix) before starting any JAK inhibitor, as vaccination can reduce your risk even while on these immunosuppressive drugs.
• Monitor for early symptoms: Learn to recognize the early signs of shingles, such as burning pain, tingling, or a rash in a band-like pattern on one side of your body, and report them to your doctor immediately if they occur.
• Consider your overall health profile: Work with your rheumatologist to weigh the shingles risk against the drug's effectiveness for your specific type of arthritis and any other health conditions you may have.

For patients with rheumatoid arthritis already taking a JAK inhibitor, this study does not suggest switching medications without consulting a doctor. Instead, it provides additional safety data that can inform future treatment decisions, particularly for patients who are starting JAK inhibitor therapy for the first time or who have experienced shingles in the past.

The findings underscore an important principle in modern arthritis care: not all drugs in the same class are identical in their safety profiles. As JAK inhibitors continue to be refined and new versions are developed, real-world studies like this one help ensure that patients receive the most effective and safest treatment possible for their condition.