Evaluating the efficacy of upadacitinib in patients with moderate rheumatoid arthritis: a post-hoc analysis of the SELECT phase 3 trials

Lay Summary What does this mean for patients? Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with joint pain and stiffness and poor quality of life. When left untreated, the inflammation in the joint lining destroys the joints. Modern treatment focuses on treating many aspects of the disease, such as reducing pain, fatigue and joint destruction. For cost reasons, some health systems have had to restrict access to certain drug treatments to people with severe RA only; however, people with moderate disease could also benefit from these treatments. It is therefore important to know whether a modern effective therapy works in people who have moderately active RA. In this study, we looked at four previously performed large clinical trials of an oral therapy called upadacitinib (UPA) and selected only the patients with moderately active RA receiving UPA or placebo (dummy treatment). These studies showed significant improvements in disease symptoms with UPA after 3 months when compared with placebo, with improved function and less pain in those receiving UPA. Joint destruction, measured by an X-ray, was also significantly reduced after 6 months compared with placebo. This study supports the use of modern therapies for treating people with moderate RA, in addition to severe RA. Objectives Moderately active RA is associated with poor patient outcomes. Despite this, some health systems have restricted access to advanced therapies to those with severe RA. There is also limited evidence of the efficacy of advanced therapies in the moderately active RA population. This post-hoc analysis from four phase 3 trials explored the efficacy of upadacitinib (UPA) for moderately active RA. Methods Patients included in this analysis received UPA 15 mg once daily [monotherapy after switching from MTX or in combination with stable background conventional synthetic DMARDs (csDMARDs)] or placebo. Clinical, functional and radiographic outcomes were analysed separately for patients with moderate disease activity {28-joint count DAS using CRP [DAS28(CRP)] of >3.2 and <= 5.1} and severe disease activity [DAS28(CRP) >5.1]. Results Patients with moderate disease activity who received UPA 15 mg (combination or monotherapy) after an inadequate response to biologic DMARDs and/or csDMARDs were significantly more likely to achieve a 20% improvement in the ACR response criteria, low disease activity status [DAS28(CRP) <= 3.2] or clinical remission [DAS28(CRP) < 2.6] by week 12/14 vs placebo. Statistically significant improvements in patient-reported functioning and pain from baseline were observed for UPA 15 mg vs placebo at week 12/14. Radiographic progression was also significantly reduced at week 26 compared with placebo. Similar improvements were observed for severe disease. Conclusion This analysis provides support for the use of UPA for the treatment of patients with moderate RA.