SLEek Trial Demonstrates Significant Improvements for Patients With SLE Receiving Upadacitinib

In an interview with HCPLive Rheumatology, Joan Merrill, MD, discusses the results of the phase 2 SLEek trial, which will be presented at the European Congress of Rheumatology (EULAR) 2023. Data demonstrated that at week 24 and 48, patients with systemic lupus erythematosus (SLE) receiving upadacitinib experienced significant reductions in both disease activity and glucocorticoid use.¹

“The motivation behind this trial was driven by the challenges faced in conducting lupus clinical trials,” Merrill explained. “Lupus is a complex disease with heterogeneous pathology and clinical features, making it difficult to design effective trials. To overcome these challenges, our team aimed to ensure that the patients enrolled in the trial had active and reversible disease.”

To accomplish this, clinicians had to carefully assess and select qualified patients. By enrolling patients with active disease, they aimed to minimize the placebo response rates, which have historically been high in lupus trials. They also wanted to evaluate the efficacy of the drug while tapering down background medications, typically steroids, to assess its potential in reducing the reliance on such medications.

The results of the study are clinically significant as they provide a proof of concept for the mechanism of action. Upadacitinib, a Janus kinase (JAK) inhibitor, demonstrated efficacy as a monotherapy approach, while combination therapy showed potential advantages as well, albeit without statistical significance. This implies that upadacitinib alone could be a clinically significant treatment option for lupus patients.

It is important to acknowledge the potential limitations of the study. As the data is still being analyzed and ongoing research on biomarkers may provide further insights into patient selection and optimal dosing, the incorporation of biomarker data and continued research may enhance the understanding of how to optimize these therapies.

“The JAK inhibitor showed promise as a potential treatment option, and ongoing research will contribute to further refining its use in lupus patients,” Merrill concluded. “The field of lupus research is making strides, and it is encouraging to see this drug tested in light of the knowledge gained over the years.”

This transcript was edited for clarity.

References

1. ^{J T Merrill, Y Tanaka, D D’cruz, K Vila, et al. Efficacy and Safety of ABBV-599 High Dose (Elsubrutinib 60 mg and Upadacitinib 30 mg) and Upadacitinib Monotherapy for the Treatment of Systemic Lupus Erythematosus: A Phase 2, Double-Blind, Placebo-Controlled Trial. Paper presented at: European Congress of Rheumatology (EULAR) 2023. Milan, Italy. May 31 – June 3, 2023.}