MACE, malignancy risks similar for upadacitinib, adalimumab in rheumatoid arthritis
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Key takeaways:
- The risks for major adverse cardiac events and malignancy, excluding non-melanoma skin cancer, are similar between patients with RA receiving upadacitinib and adalimumab.
- The researchers found an increased risk for major adverse cardiac events and malignancy, excluding non-melanoma skin cancer, in higher-risk patients with RA.
Although major adverse cardiac events, malignancy and venous thromboembolism are more frequent in at-risk patients with rheumatoid arthritis, rates are similar between those receiving upadacitinib vs. adalimumab, according to data.
“The publication of ORAL Surveillance and the subsequent review of the safety of all JAK inhibitors by the FDA and European Medicines Agency prompted this review of upadacitinib with respect to the occurrence of major adverse cardiac events (MACE), malignancies and venous thromboembolism (VTE) in comparison to a TNF inhibitor and methotrexate,” Roy Fleischmann, MD, MACR, of the University of Texas Southwestern Medical Center, and lead author of the study, told Healio. “We looked at age as a factor as well as most of the CV risk factors explored in ORAL Surveillance.”
To investigate the safety profile of upadacitinib (Rinvoq, AbbVie) in patients with RA, Fleischmann and colleagues pooled data from six phase 3 trials in which patients received upadacitinib, adalimumab (Humira, AbbVie) or methotrexate. All analyzed studies originated from the SELECT RA program. Each study investigated upadacitinib as either a monotherapy or as part of a combination strategy.
Across all studies, patients received either upadacitinib 15 mg once per day — with or without conventional synthetic disease modifying antirheumatic drugs — or adalimumab 40 mg biweekly alongside methotrexate, or methotrexate alone. A subset of patients aged 50 years and older, and with one or more CV risk factor, were identified as having higher CV risk. The researchers analyzed higher-risk patients from the head-to-head SELECT-COMPARE study of upadacitinib 15mg vs. adalimumab in parallel.
Safety events of consideration included malignancies other than non-melanoma skin cancer (NMSC), NMSC, MACE, VTE, serious infections and herpes zoster infections. The researchers included data for events that occurred after the first dose but within 30 days of the final dose of upadacitinib, and 70 days following adalimumab. Among patients who passed away, events were considered even if they happened after the cutoff period.
The analysis included 3,209 patients who received upadacitinib, 579 who received adalimumab and 314 who received methotrexate monotherapy. According to the researchers, MACE, malignancies other than NMSC and VTE were more common among the higher-risk patients, compared with the overall population. However, these events were “generally similar across treatment groups,” the researchers wrote.
Meanwhile, serious infections — in the higher-risk cohort — as well as herpes zoster infections and NMSC — in the overall population — were more common in patients who received upadacitinib vs. adalimumab or methotrexate.
“Older patients — those older than 65 years — have more of these events in the population of increased risk, as shown in ORAL Surveillance, compared with patients younger than age 65 years,” Fleischmann said. “However, the IR of these events was similar with upadacitinib compared to the TNF inhibitor and methotrexate.”
Perspective
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The use of Janus kinase inhibitors has increased since their debut in 2012. Not only are they quick to provide patients relief, but the convenience of the oral form has led to increased adherence and reduced patient burden.
We know our patients with rheumatoid arthritis have an increased risk for cardiovascular events, and recent data have raised questions about the safety of upadacitinib (Rinvoq, AbbVie), with studies suggesting a potential increased risk for major adverse cardiovascular events with its use. The study by Fleischmann and colleagues examined the potential risk in this RA population.
Like other JAK inhibitors, upadacitinib carries certain safety concerns, such as increased risks for herpes zoster and non-melanoma skin cancer. Fleischmann was able to show comparable but not higher CV risk between upadacitinib, TNF-inhibitor therapy and methotrexate monotherapy.
It is important for health care professionals to carefully assess any patient for underlying infections, as well as understand the significance of careful patient selection and ongoing CV monitoring when considering upadacitinib in patients with RA and increased CV risk.
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