Comparison of risks of cancer, infection, and MACEs associated with JAK inhibitor and TNF inhibitor treatment: a multicentre cohort study.

ABSTRACT

OBJECTIVES: The objective of this study was to compare the incidence rates (IRs) of infectious diseases, major adverse cardiovascular events (MACEs), and malignancies in RA patients treated with tofacitinib, baricitinib or a TNF inhibitor. METHODS: We retrospectively analysed the cases of 499 RA patients treated with tofacitinib (n = 192), baricitinib (n = 104), or a TNF inhibitor (n = 203). We determined the IRs of infectious diseases and the standardized incidence ratio (SIR) of malignancies and investigated factors related to infectious diseases. After adjusting the clinical characteristic imbalance by propensity score weighting, we compared the incidence of adverse events between the Janus kinase (JAK)-inhibitor and TNF-inhibitor groups. RESULTS: The observational period was 959.7 patient-years (PY), and the median observational period was 1.3 years. The IRs within the JAK-inhibitor treatment group were serious infectious diseases other than herpes zoster (HZ), 8.36/100 PY; HZ, 13.00/100 PY. Multivariable Cox regression analyses revealed independent risk factors the glucocorticoid dose in serious infectious diseases other than HZ, and older age in HZ. Two MACEs and 11 malignancies were identified in JAK-inhibitor-treated patients. The overall malignancy SIR was (non-significantly) higher than that of the general population (1.61/100 PY, 95% CI 0.80, 2.88). The IR of HZ in the JAK-inhibitor-treated group was significantly higher than the TNF-inhibitor-treated group, but there were no significant differences in the IRs of other adverse events between the JAK-inhibitor-treated group and the TNF-inhibitor-treated group, or between the treatment groups of the two JAK inhibitors. CONCLUSIONS: The infectious disease IR in RA was comparable between tofacitinib and baricitinib, but the IR for HZ in these treatment groups was high compared with that in the TNF inhibitor treatment group. The malignancy rate in the JAK-inhibitor-treated group was high but not significantly different from that of the general population or that of the TNF-inhibitor-treated group.