Janssen Pharmaceuticals and its development partner, Bayer, announced on 23 October 2016 results of two new real-world studies confirming the positive benefit-risk profile of rivaroxaban (Xarelto) in treating venous thromboembolism, and reducing the risk of recurrence.
One study showed that people with venous thromboembolism taking Xarelto for longer than three months had a lower risk of venous thromboembolism recurrence, without an increase in major bleeding, compared to those taking the medicine for only three months. The second was the first readout from Janssen’s Post-Marketing Safety Surveillance (PMSS) study in venous thromboembolism, which showed the rates and patterns of major bleeding in people taking Xarelto for venous thromboembolism in routine clinical practice were consistent with those reported in clinical trials. Results of both studies were presented at the American College of Chest Physicians (CHEST) Annual Meeting 2016.
Real-world study confirms benefit of extended use of Xarelto in venous thromboembolism
In nearly 5,000 people who were diagnosed with their first venous thromboembolism, researchers examined the long-term safety and effectiveness of Xarelto and found those who continued taking Xarelto for up to one year had significantly lower rates of venous thromboembolism recurrence at all measured time points, without an increased risk of major bleeding, compared to those who discontinued Xarelto after three months. Specifically:
- At three months, recurrent venous thromboembolism occurred in 0.57% of people in the continued cohort* and 1.19% in the discontinued cohort** (p<0.05). Major bleeding occurred in 0.51% and 0.72%, respectively (p>0.05).
- At six months, recurrent venous thromboembolism occurred in 1.07% of people in the continued cohort and 2.10% in the discontinued cohort (p<0.05). Major bleeding occurred in 0.79% and 0.72%, respectively (p>0.05).
- At 12 months, recurrent venous thromboembolism occurred in 1.45% of people in the continued cohort and 2.60% in the discontinued cohort (p<0.05). Major bleeding occurred in 1.06% and 1.13%, respectively (p>0.05).
Clinical guidelines recommend people diagnosed with venous thromboembolism be treated with an anticoagulant, such as rivaroxaban, for a minimum of three months when they are at the highest risk of experiencing a recurrence. However, the risk still remains after treatment ends and up to 10% of people will have a recurrent event within the first year.
“This study in a broad real-world setting affirms the ACCP guidelines for the extended treatment of an unprovoked venous thromboembolism,” said Scott Kaatz, lead study investigator and hospitalist, Henry Ford Hospital, Detroit, USA. “Extended treatment with rivaroxaban showed a decrease in recurrent venous thromboembolism without an increase in major bleeding and is consistent with a previous clinical trial.”
This study builds on findings from the phase 3 EINSTEIN clinical programme, which was used by regulatory authorities worldwide to approve Xarelto for the treatment of deep vein thrombosis and pulmonary embolism and reduction in the risk of recurrence of deep vein thrombosis and pulmonary embolism. The EINSTEIN-Extension study found continuing treatment with Xarelto for an additional six to 12 months beyond the initial treatment period resulted in significantly fewer venous thromboembolism recurrences (1.3%) versus placebo (7.1%), p<0.001. There was no difference in major bleeding between the two groups.
Study confirms safety profile of Xarelto in venous thromboembolism
Also presented were the first results from Janssen’s ongoing PMSS venous thromboembolism study, which follows people with deep vein thrombosis and pulmonary embolism in the USA taking Xarelto. Like Janssen’s PMSS study in non-valvular atrial fibrillation (NVAF), this retrospective, observational study evaluates major bleeding in these patients in a real-world, post-approval setting, using electronic health records from the US Department of Defense database.
The first data cut of 9,638 people with venous thromboembolism (5,426 with deep vein thrombosis; 4,212 with pulmonary embolism) showed:
- Of the 9,638 people taking Xarelto, 130 (1.3%) experienced a major bleeding event, translating into an incidence rate of 2.47 per 100 person-years, primarily in gastrointestinal sites.
- With deep vein thrombosis, major bleeding events in PMSS were observed in 74 people with deep vein thrombosis (1.4%), translating into an incidence rate of 2.74 per 100 person-years.
- With pulmonary embolism, major bleeding events in PMSS were observed in 56 people with PE (1.3%), translating into an incidence rate of 2.18 per 100 person-years.
- People who experienced major bleeding were typically older, female and had more comorbidities; fatal outcomes were rare.
“Post-marketing research is invaluable to physicians who are continually looking to understand how a medicine is performing in real-world settings in order to make informed treatment decisions for their patients,” said PMSS study investigator W Frank Peacock, associate chair and research director, Emergency Medicine, Baylor College of Medicine, Houston, USA. “We have been closely examining the use of rivaroxaban in daily clinical practice for more than three years in people with non-valvular atrial fibrillation, and are pleased to expand our work to those with venous thromboembolism.”
The PMSS study in venous thromboembolism was designed by Janssen in conjunction with the Department of Defense and Health ResearchTx LLC (HRTX), and in agreement with the US Food and Drug Administration (FDA), to proactively ascertain, analyse and report potential side effects with Xarelto use, including major bleeding events, associated risk factors and bleeding-related clinical outcomes in people with venous thromboembolism taking Xarelto. PMSS is a retrospective study with no comparator arm.