A comprehensive five-year study has affirmed the long-term efficacy and safety of upadacitinib (UPA) in treating rheumatoid arthritis (RA). The SELECT-NEXT trial, a phase III long-term extension (LTE) study published in The Journal of Rheumatology, reveals promising results for patients with inadequate responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).
Clinical outcomes improved or were maintained over the study duration. . Notably, 51% and 43% of patients achieved Clinical Disease Activity Index remission among those initially randomized to UPA 15 mg QD and UPA 30 mg QD, respectively. Furthermore, 75% and 66% of patients achieved a Disease Activity Score in 28 joints based on C-reactive protein <2.6 among those in the UPA 15 mg QD and UPA 30 mg QD groups, respectively. The proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria responses increased steadily from week 60 to the five-year mark, regardless of initial randomization. TEAEs, including those of special interest, were consistent with earlier analyses and other SELECT studies. Malignancies (excluding nonmelanoma skin cancer), major adverse cardiovascular events, and venous thromboembolic events were reported infrequently.
Upadacitinib is a selective Janus kinase (JAK) inhibitor, primarily targeting JAK1 over JAK2, JAK3, and TYK2. By inhibiting these intracellular enzymes, Upadacitinib disrupts the JAK-STAT signaling pathway, preventing the phosphorylation and activation of signal transducers and activators of transcription (STATs). This interference reduces gene expression linked to inflammation, thereby mitigating the inflammatory effects crucial in immune-mediated inflammatory diseases (IMIDs).
Upadacitinib has consistently shown robust clinical response rates, including remission, across diverse patient populations—whether methotrexate-naïve, methotrexate-failure, or biologic failure. In a head-to-head randomized clinical trial, upadacitinib plus methotrexate outperformed adalimumab plus methotrexate in patients with an inadequate response to methotrexate. Furthermore, upadacitinib proved superior to abatacept in patients with rheumatoid arthritis who had previously failed other biologic treatments. The safety profile of upadacitinib aligns with those observed with biological therapies and other JAK inhibitors, demonstrating consistent safety outcomes.
The SELECT-NEXT trial underscores a favorable five-year benefit-risk profile for upadacitinib in the treatment of rheumatoid arthritis. These findings reinforce upadacitinib as a viable long-term treatment option for RA patients with an inadequate response to conventional therapies. As the medical community continues to seek effective and safe long-term treatments for RA, upadacitinib stands out as a promising option, offering sustained clinical benefits and manageable safety risks over an extended period.
Reference
- Burmester GR, Van den Bosch F, Tesser J, Shmagel A, Liu Y, Khan N, Camp HS, Kivitz A. Upadacitinib in Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs: Efficacy and Safety Through 5 Years (SELECT-NEXT). J Rheumatol. 2024 Jul 1;51(7):663-672.
- Sanmartí R, Corominas H. Upadacitinib for Patients with Rheumatoid Arthritis: A Comprehensive Review. J Clin Med. 2023 Feb 21;12(5):1734.
- Padda IS, Bhatt R, Patel P, Parmar M. Upadacitinib. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Aug 7]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK572088/