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Upadacitinib in rheumatoid arthritis: progress and challenges
Qiaofen Wang1,2, Long Zhong3, Yujing Fu1,2
1Department of Medicine, Hainan Medical University, Haikou, China.
Frontiers in Pharmacology
|April 2, 2026
Summary
Upadacitinib (UPA) offers significant relief for rheumatoid arthritis (RA) patients, demonstrating superior efficacy and sustained benefits over other treatments. While effective, ongoing monitoring for side effects and cost remain key considerations for its widespread use.
Area of Science:
- Rheumatology
- Immunology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint destruction and inflammation, with increasing global prevalence.
- Current treatments like csDMARDs and bDMARDs have limitations including side effects, cost, and variable patient response.
- Upadacitinib (UPA), a selective JAK1 inhibitor, offers a targeted approach to RA management.
Purpose of the Study:
- To evaluate the efficacy and safety of Upadacitinib (UPA) in rheumatoid arthritis (RA) patients.
- To compare UPA's performance against established treatments like adalimumab and tofacitinib.
- To assess real-world effectiveness and identify areas for future research and application.
Main Methods:
- Analysis of clinical trial data, including the SELECT-COMPARE study, comparing UPA with adalimumab.
- Review of real-world evidence from the CLOSE-UP observational study assessing patient outcomes.
- Comparative analysis of UPA's JAK1 selectivity against pan-JAK inhibitors.
Main Results:
- UPA demonstrated superior ACR 20, 50, and 70 responses compared to adalimumab at 12 weeks.
- Sustained efficacy of UPA observed for over 5 years in clinical trials.
- Real-world data showed significant DAS28-CRP remission rates at 6 months, supporting UPA's effectiveness.
Conclusions:
- Upadacitinib (UPA) provides a valuable oral treatment option for RA, showing robust efficacy and symptom relief.
- Potential for reduced off-target effects due to JAK1 selectivity, though safety monitoring for herpes zoster and cardiovascular events is crucial.
- Addressing cost barriers and further research into refractory RA and other inflammatory conditions are essential for optimizing patient outcomes.
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