Characteristics of Patients Treated with JAK Inhibitors in Rheumatoid Arthritis before versus after VTE Risk Warnings

Abstract

Background: Baricitinib (BARI) or Tofacitinib (TOFA) were the first Janus Kinase Inhibitors (JAKi) to be marketed in rheumatoid arthritis (RA). Concerns regarding venous thromboembolism (VTE) risk have emerged during the past years. The aim of the study was to compare the baseline characteristics of patients initiating BARI or TOFA in RA before versus after European Medicine Agency (EMA)’s VTE warnings and to compare real-world persistence with these two drugs. Methods: In this multicentric cohort study, RA patients initiating BARI or TOFA were included from October 2017, date of BARI marketing authorization in France, to September 2020. Baseline characteristics regarding VTE risk were compared (before vs. after May 2019) by using pre-specified statistical tests. Comparison of persistence was assessed by using propensity-score methods. Results: 232 patients were included; 155 with BARI and 77 with TOFA. Baseline characteristics of patients regarding VTE risk factors were not statistically different when Janus Kinase inhibitor (JAKi) was initiated before vs. after EMA’s warnings although a trend towards a lower proportion of VTE history was observed. Five VTE events occurred, four with BARI, one with TOFA. Cumulative persistence rate at 2 years was similar between BARI and TOFA: HR 0.96; 95% Cl: 0.52 to 1.74; p = 0.89. Conclusions: Our study did not show a significant change in patients characteristics starting a JAKi after the EMA’s warnings, probably due to a lack of power. Though, the lower proportion of VTE history in patients after May 2019 suggests that rheumatologists have taken into account the potential VTE risk. These results need to be confirmed by further evidence.

Different biologics for biological-naïve patients with psoriatic arthritis: a systematic review and network meta-analysis

“…Concerning serious adverse events, McInnes et al (2021) and Reich et al (2022) reported the higher incidences of serious adverse events in patients receiving upadacitinib (30-mg dose) and adalimumab, respectively. According to European Medicine Agency (EMA) and US Food and Drug Administration (FDA) recent warnings, JAKi were associated with increased risks of major adverse cardiac events, cancer, venous thromboembolic events, severe infections, and death ( Kragstrup et al, 2022 ; Philippoteaux et al, 2022 ), and clinicians needs to carefully consider risk factors and assess corresponding risks of individual patients before use of JAKi. For the arthritis activity endpoint, skin endpoint, and drug retention, qualitative descriptions were provided since unsynthesizable data from the included studies.…”

Atopic Dermatitis in the Elderly Population

“…The Food and Drug Administration (FDA) labels for tofacitinib, upadacitinib, and abrocitinib indicate a higher frequency of serious infections especially in older adults, the FDA label for baricitinib states that no overall differences in the safety and efficacy of the drug were observed between older and younger adults. FDA labels for abrocitinib and upadacitinib also indicate a higher frequency of malignancy in elderly patients, and an increased risk of major cardiovascular events, and thrombosis in patients with rheumatoid arthritis ( 36 , 37 ). Based on data from the use of tofacitinib on rheumatoid arthritis, the European Medicines Agency (EMA) has recently raised concerns about the use of JAK inhibitors in patients older than 65 years and recommended caution in their use only when no suitable alternative treatment options are available ( 38 ).…”

Cardiovascular implications of inflammatory bowel disease: An updated review

“…The overall risk of VTE with vedolizumab is low[ 91 , 92 ]. Pooled safety analysis from Phase 2/3 studies on ustekinumab reported no significant difference in VTE risk in patients treated with ustekinumab compared to placebo (0.75/100 person years vs 0.34/100 person years, respectively)[ 93 - 95 ].…”

“…Janus kinase (JAK) inhibitors: A safety study done in patients older than 50 year with rheumatoid arthritis and more than one cardiovascular risk factor showed that VTE, DVT and PE was higher for tofacitinib when used in the dose of 10 mg twice daily[ 95 ]. Similar to these observations, in the OCTAVE open study, with a follow-up of 7 years, 10 mg tofacitinib group had 0.1% and 0.7% prevalence of DVT and PE, respectively [IR = 0.06 (95%CI: 0.00-0.31) and 0.28 (95%CI: 0.09-0.65)].…”