Five-Year Data Show Superiority of Upadacitinib to Adalimumab Treating Rheumatoid Arthritis

The safety profile of upadacitinib over 5 years was consistent with 3-year results while continuing to show a better clinical response compared to adalimumab in patient with rheumatoid arthritis (RA), according to the results of a study presented at the European Alliance of Associations for Rheumatology 2023 Congress. Investigators also reported that the radiographic progression was similar for through 192 weeks with both drugs.

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“[RA] can have a profound effect on the lives of patients. It's an autoimmune disease where the immune system mistakenly attacks healthy cells, causing inflammation and painful swelling, especially in the joints of the hands, wrists, and knees. This can make it tough for people to do their everyday tasks and activities,” Roy Fleischmann, MD, from the Metroplex Clinical Research Center in Dallas, Texas, said in an email to Pharmacy Times. “That's why it's crucial to treat-to-target so patients have a better chance of achieving and maintaining remission, which is when the disease activity is low or even absent. Ideally, our goal is to actively manage rheumatoid arthritis to effectively minimize symptoms, prevent further joint damage, and improve the overall quality of life for our patients.”

Upadacitinib is an oral reversible Janus kinase inhibitor for individuals with RA. In the SELECT-COMPARE (NCT02629159) study, upadacitinib 15 mg once daily demonstrated a better clinical response compared to adalimumab 40 mg every other week at 12 weeks.

Investigators of the initial phase 3 study found that the results were maintained 3 years later with an acceptable safety profile in the long-term extension study.

“SELECT-COMPARE is part of a larger trial program called SELECT that provides ongoing insights on the potential of upadacitinib as a treatment for different types of rheumatic diseases, including rheumatoid arthritis,” Fleischmann told Pharmacy Times. “The long-term findings from SELECT-COMPARE build on what we've seen in previous studies and the benefits of upadacitinib remain consistent even after 5 years of treatment.”

Patients in the study who were receiving background methotrexate were randomized 2:2:1 to either upadacitinib daily, a placebo, or adalimumab every other week. Investigators reported the rescue, placebo to upadacitinib, upadacitinib to adalimumab, or adalimumab to upadacitinib, was mandated for lack of response or failure to achieve Clinical Disease Activity Index low disease activity at week 26.

Lack of response qualified as less than a 20% improvement in tender or swollen joint counts at weeks 14, 18, or 22. At week 26, all individuals taking the placebo were switched to upadacitinib. Patients who completed the 48-week double-blind period could continue to receive open label upadacitinib or adalimumab in the long-term extension study for up to 10 years.

Efficacy assessments at 5 years were performed by the original randomized group for Clinical Disease Activity Index low disease activity and remission, and disease activity score for 28-joints C-reactive protein. The radiographic progressions were assessed at 192 weeks by treatment sequence.

Through the 5-year follow up, investigators included 1417 individuals who were exposed to upadacitinib and 579 to adalimumab. They found that upadacitinib was generally well tolerated, with similar rates of treatment-emergent adverse events (TEAEs) serious TEAEs, and TEAEs leading to discontinuation compared to adalimumab.

Rates of most AEs of special interest were similar between the 2 drugs, except for higher rates of herpes zoster, creatine phosphokinase elevation, lymphopenia, and hepatic disorder with upadacitinib.

Additionally, investigators found that in 651 and 327 patients randomized to upadacitinib and adalimumab, respectively, a greater proportion of individuals achieved Clinical Disease Activity Index low disease activity and remission, and DAS28(CPR) scores of 3.2 or less or 2.6 or less with upadacitinib. There were also similar proportions of patients treated with upadacitinib and adalimumab who had no radiographic progression.

“Patients in the SELECT-COMPARE long-term extension study can participate for up to 10 years. At the 5-year point, we’ve already treated over 1400 patients with upadacitinib and collected data from nearly 4500 patient years. This is a significant amount of information we have been able to gather and will continue to gather. With these ongoing insights, we will continue to better understand the long-term safety and efficacy effects of upadacitinib on people living with rheumatoid arthritis,” Fleischmann said in an interview with Pharmacy Times.

Reference

Fleischmann RM, Swierkot J, Penn S, Durez P, et al. Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: 5-year data from the SELECT-COMPARE study. RMD Open. 2022;8(1):e002012. doi:10.1136/rmdopen-2021-002012