Safety outcomes of tocilizumab and tofacitinib treatment for rheumatoid arthritis: Target trial emulation

Objectives

Biological disease-modifying antirheumatic drugs have been the primary treatment option for moderate to severe rheumatoid arthritis (RA) in Taiwan since 2010. Tocilizumab is an interleukin-6 receptor inhibitor, whereas tofacitinib is a Janus kinase inhibitor. The two medications were indicated to treat RA by direct and indirect inhibition of interleukin-6 cytokine. We compared the safety outcomes of tocilizumab and tofacitinib in patients with RA in real-world clinical settings, following the 7 key components of target trial emulation (TTE).

Methods

The data source was the Taiwan National Health Insurance Research Database. Patients with RA between 2010 and 2018 were eligible and assigned to either tocilizumab or tofacitinib based on their first prescription of these two medications. The index date was set as the first prescription date of either study medication. Propensity score stabilized weighting (PSSW) was used to balance the characteristics between the two medication groups. The incidences of safety outcomes were all-cause mortality, cancer, coronary heart disease, stroke, venous thrombosis events, tuberculosis, joint replacement events, and herpes zoster infection. The intention-to-treat (ITT) effect was commenced from the index date until the study outcomes, independently, 3 years, withdrawal, or December 31, 2021, whichever occurred first. For the per-protocol (PP) effect, patients were required to maintain the same medical group during the entire follow-up period.

Results

A total of 2125 patients with RA who were prescribed tocilizumab (n = 844) or tofacitinib (n = 1281) were included in this study. The mean follow-up duration was 2.78 years in the tocilizumab group and 2.83 years in the tofacitinib group. For ITT, the sample sizes were 721 and 1196 for the tocilizumab and tofacitinib, respectively, after PSSW. A substantially lower incidence rate of herpes zoster infection (per 100 patient-years) was observed in the tocilizumab group (3.67) than in the tofacitinib group (7.61), with a hazard ratio of 0.48 (95%CI =0.37–0.63; p < .0001). All-cause mortality, cancer, coronary heart disease, stroke, total hip replacement, and tuberculosis were similar between the two medication groups. For PP, the sample sizes were 619 and 1085 for the tocilizumab and tofacitinib, respectively, after PSSW. The results of the PP analysis were similar to those of the ITT analysis.

Conclusions

Tocilizumab and tofacitinib act along the same inflammatory pathway. A lower herpes zoster incident rate was observed in the tocilizumab group than in the tofacitinib group. The incidence rates of other safety concerns and mortality rates were comparable in both groups of patients with RA treated in real-world settings.