Tofacitinib is safe according to real-world data analysis

Tofacitinib, a Janus kinase (JAK)1/3 inhibitor had a safety profile similar to that of biologics. Rheumatoid arthritis (RA) patients starting with tofacitinib or biological disease-modifying anti-rheumatic drugs (bDMARDs) had similar rates of cardiovascular events and serious infections. These are the main findings obtained after a prospective 5-year cohort study of >8,600 RA patients enrolled in a US national registry.

This is the first comparative real-world data study assessing long-term safety of tofacitinib which is an important consideration given the cardiovascular safety of anti-TNF agents. Dr Joel Kremer (Albany Medical College, New York, USA) et al. evaluated 5-year adverse event incidence rates in patients starting tofacitinib versus bDMARDs using cohorts from the US Corrona RA registry, during November 2012, the month when tofacitinib received US marketing approval, through December 2017 [1].

Data were obtained from RA patients in the registry who were treated with either tofacitinib (n=1,544) or biologics (n=7,083). The safety assessment focused on the combined rate of major adverse cardiovascular events (MACE), including myocardial infarction, stroke or transient ischaemic and fatal events; the incidence of serious infection events; herpes zoster (HZ) regardless of severity; and venous thromboembolism (VTE).

The results showed that patients treated with tofacitinib had slightly more than double the rate of HZ events (adjusted HR 2.12; 95% CI 1.22-3.66), compared with patients on biologics, a finding consistent with prior reports that found tofacitinib treatment to be linked with an almost 3-fold increased rate of HZ when compared with placebo-treated patients [2]. “None of the HZ activations identified in the registry patients on tofacitinib were rated as “serious,” said Dr Kremer. Patients treated with tofacitinib had a 42% lower rate of MACE, compared with patients who received a bDMARD, although the difference was not statistically significant. Both subgroups had virtually identical rates of all serious infections. VTE analysis showed a rate of 0.19/100 patient-years with tofacitinib treatment, and 0.33/100 patient-years with other biologicals, a difference that was not statistically significant. “It is an important finding because of prior concerns raised about VTE in patients taking tofacitinib or another JAK inhibitor,” said Dr Kremer. Adjusted analysis of VTE is expected within another couple of years. Comparison of the rates of pulmonary embolism and deep vein thrombosis were each not statistically different between the two treatment subgroups. These findings are very reassuring for the long-term use of this JAK inhibitor -and possibly the JAK class in general- in the real-world setting. Obviously, further studies are needed.

1. Kremer JM et al. Abstract OP0028. EULAR 2019
2. Winthrop KL, et al. Arthritis Rheumatol. 2014 Oct;66(10):2675-84.

Posted on 4 September 201931 January 2024