Upadacitinib’s risk-benefit profile in rheumatoid arthritis ‘favorable’ through 5 years
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Key takeaways:
- The initial clinical outcomes of upadacitinib for RA “improved or were maintained” through 5 years.
- Major adverse cardiovascular events and venous thromboembolisms were infrequent.
The risk-benefit profile of upadacitinib for rheumatoid arthritis “remains favorable” through 5 years, according to data published in The Journal of Rheumatology.
In a long-term extension of the phase 3 SELECT-NEXT study, major adverse cardiovascular events, venous thromboembolisms and malignancies, other than non-melanoma skin cancer, “were reported infrequently” among those who received the drug, Gerd R. Burmester, MD, a professor of medicine at Charité-Universitätsmedizin Berlin, in Germany, and colleagues wrote.
“The Janus kinase inhibitors, upadacitinib, tofacitinib, baricitinib and filgotinib, are [targeted synthetic DMARDs] that have demonstrated efficacy for the treatment of RA, with acceptable safety profiles,” they added. “However, it is recommended that they are used with caution in patients who have an increased risk of major adverse cardiovascular event[s] (MACE). It is important to evaluate long-term safety data for JAK inhibitors, particularly events with typically low incidence.”
In the initial trial, patients with RA were randomly assigned to receive either 15 mg or 30 mg of upadacitinib (Rinvoq, AbbVie) once daily, or placebo, for 12 weeks. Included participants must have had an inadequate response to conventional synthetic DMARDs. After 12 weeks, 92% of participants (n = 611) entered the long-term extension study, and those on placebo were randomly assigned to one of the treatment arms.
Participants remained blinded “until a protocol amendment due to the approval of the upadacitinib 15 mg dose for RA, after which all patients received open-label upadacitinib 15 mg,” the researchers wrote.
Overall, 44% of participants in the long-term extension study discontinued the drug by 5 years; 16% of those participants cited adverse events. The initial clinical outcomes “improved or were maintained” through 5 years, with similar results regardless of initial drug assignment, according to the researchers. From week 60 through 5 years, there were increasing proportions of patients achieving ACR20, ACR50 and ACR70 criteria responses.
A total of 29 malignancy events were recorded, most of which “were serious” and led to discontinuation, the researchers wrote. Major adverse cardiovascular events occurred at rates of 0 to 0.9 per 100 patient -years, while venous thromboembolism rates ranged from 0.3 to 0.5 per 100 patient-years.
“Upadacitinib continued to improve clinical outcomes in patients with RA who were csDMARDs-IR through 5 years,” Burmester and colleagues wrote. “Moreover, no new safety findings were identified during the LTE. Results remained consistent with earlier analyses of SELECT-NEXT. Overall, the long-term benefit–risk profile for upadacitinib in RA remains favorable.”
Perspective
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This is an informative study that highlights the importance of continual research on patient outcomes and safety data, and will be useful for physicians when prescribing upadacitinib — or choosing not to prescribe due to comorbidities.
As a nurse who has taken care of patients with rheumatoid arthritis for nearly 20 years, it is important and very useful to have and share information with patients who are reluctant to start treatment due to fear of unknown outcomes. This study faced some challenges because of the COVID-19 pandemic during the last 2 years of the study, however it shows favorable results.
Data for the treatment of patients with moderate-to-severe RA, despite treatment with conventional synthetic DMARDs, found upadacitinib to be efficacious across multiple disease activity measures, including achievement of low disease activity and remission through 5 years, with no new safety signals. The study also found that treatment with upadacitinib continued to improve clinical outcomes in patients with RA who had an inadequate response to conventional synthetic DMARDs through the 5 years.
It's great to have data that supports the long-term benefit/risk profile for upadacitinib in RA.
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