More Than Half of RA Patients Achieve Remission After Upadacitinib 15 mg

A new study demonstrated the benefit of upadacitinib for rheumatoid arthritis (RA), more than half reaching remission on upadacitinib for 15 mg.¹

The trial was an extension of the study, SELECT-NEXT, which randomized patients to daily doses of upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 12 weeks, on top of staying on stable conventional synthetic disease-modifying antirheumatic drugs.² SELECT-NEXT found upadacitinib 15 mg or 30 mg for patients with severe or moderate RA demonstrated significant improvements in clinical signs and symptoms. At week, ACR20 was met by 64% of patients on upadacitinib 15 mg, 66% on upadacitinib 30 mg, and 36% on placebo.

The extension study, led by Gerd R. Burmester, MD, sought to assess the 5-year efficacy and safety of upadacitinib in RA.¹ Like the precursor study, the team once again found upadacitinib at 15 mg and 30 mg was a favorable treatment option for RA patients. Participants who were originally on placebo switched to either upadacitinib 15 mg or upadacitinib 30 mg. The patients who were already randomized to upadacitinib continued with the same dose.

Throughout the study, participants were unaware which treatment group they were in. The blinding maintained until participants needed to switch from the higher upadacitinib dose to the lower one due to the approval of the upadacitinib 15 mg by regulatory authorities. The earliest switch occurred at week 169.

Despite the lack of blinding in the later portion of the study, the team continued assessing efficacy and treatment-emergent adverse events (TEAEs) through 5 years.

In total, 611 (95%) randomized patients participated in the long-term extension study. Less than half (44%) discontinued the study during the 5 years; for 16%, it was due to adverse events.

Investigators saw clinical outcomes improved or were maintained at 5 years, with 51% and 43% of patients on upadacitinib 15 mg and 30 mg, respectively, achieving Clinical Disease Activity Index remission. Furthermore, 75% of patients on upadacitinib 15 mg and 66% on upadacitinib 30 mg achieved 28-joint Disease Activity Score-C-reactive protein < 2.6.

Additionally, the number of patients achieving ≥ 20/50/70% improvement in the American College of Rheumatology criteria responses rose from week 60 through the 5 years. Participants had similar remission rates regardless of being initially randomized to upadacitinib or placebo.

The team also saw TEAEs were consistent with the SELECT-NEXT study. Commonly reported adverse events were malignancies—excluding non-melanoma skin cancer—cardiovascular events, and venous thromboembolic events. Investigators did not observe any new safety concerns.

“The 5-year benefit–risk profile for upadacitinib in RA remains favorable,” investigators concluded.

References

1. ^{Burmester, G, Van den Bosch, F, Tesser, J. Upadacitinib in Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs: Efficacy and Safety Through 5 Years (SELECT-NEXT). The Journal of Rheumatology. April 2024. jrheum.2023-1062; DOI: https://doi.org/10.3899/jrheum.2023-1062.}
2. ^{Burmester GR, Kremer JM, Van den Bosch F, et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391(10139):2503-2512. doi:10.1016/S0140-6736(18)31115-2}