Infection, Malignancy Incidence Rates Associated With JAK vs TNF Inhibitors Assessed in RA

Incidence rates of infection and malignancy were mostly comparable among patients with RA receiving treatment with JAK vs TNF inhibitors.

In patients with rheumatoid arthritis (RA), the overall infection and malignancy rates associated with treatment with Janus kinase (JAK) inhibitors were not significantly higher than those in the general population and patients who received treatment with tumor necrosis factor (TNF) inhibitors; however, the incidence rate of herpes zoster was elevated with JAK vs TNF inhibitors. Results of the study were published in Rheumatology.

Researchers retrospectively evaluated the medical records of patients with RA who received treatment with JAK or TNF inhibitors at participating hospitals in Japan between 2013 and 2020.  The JAK inhibitors included tofacitinib and baricitinib, and TNF inhibitors were adalimumab and etanercept.

Patients were followed-up for the development of severe infections, cancer, and major adverse cardiovascular events (MACE).

A total of 499 patients were enrolled in the study – 296 received treatment with with JAK inhibitors and 203 with TNF inhibitors. The total observation period was 961.9 patient-years and the median follow-up time was 1.3 years. Among patients who received treatment with JAK inhibitors, the incidence rate of serious infections was 8.36 per 100 patient-years. In the TNF cohort, the incidence rate of infections was significantly lower, at 4.07 per 100 patient-years. The most common infection in both groups was pneumonia; discontinuation due to infection was reported by 11 participants who received JAK inhibitors and 5 who received TNF inhibitors.

[T]­hus clinicians should pay close attention to RA patients’ background factors when the use of tofacitinib or baricitinib is being considered for the treatment of RA.

The incidence of herpes zoster was substantially elevated in the JAK inhibitor group compared with the TNF inhibitor group (13.0 vs 1.47 per 100 patient-years). In the JAK inhibitor group, herpes zoster developed more frequently in those receiving tofacitinib vs baricitinib (13.37 vs 11.63 per 100 patient-years). In multivariable regression models, independent predictors of herpes zoster infection included patient age of 65 years and older and the use of glucocorticoids.

In the JAK inhibitor group vs general population, the overall malignancy standardized incidence ratio (IR) was elevated, though the difference was not significant (1.61 per 100 patient-years; 95% CI, 0.80-2.88). The rate of MACEs and other adverse events did not differ significantly between the drug groups or between each drug group and the general population.

Results from this study identified an elevated rate of herpes zoster as the primary adverse outcome of JAK vs TNF inhibitor treatment.

Study limitations included the small study cohort and short follow-up period, which may have failed to capture all long-term adverse events.

“[C]linicians should pay close attention to patients’ [with RA] background factors when the use of tofacitinib or baricitinib is being considered for the treatment of RA,” the researchers concluded.


Uchida T, Iwamoto N, Fukui S, et al. Comparison of risks of cancer, infection, and MACEs associated with JAK inhibitor and TNF inhibitor treatment: a multicenter cohort study. Rheumatology (Oxford). Published online February 16, 2023. doi:10.1093/rheumatology/kead079