Phase 2 Trial Reaches Primary Endpoint for Upadacitinib Treatment in Active SLE

Results of a phase 2 trial reported upadacitinib (RINVOQ, 30 mg), given either alone or as a part of combination with a Bruton's Tyrosine Kinase inhibitor (elsubrutinib, 60 mg), was able to improve responses in adult patients with moderate-to-severe systemic lupus erythematosus (SLE). The study met its primary endpoint of the SLE Responder Index (SRI-4) with a steroid dose of ≤ 10 mg prednisone once daily at week 24 in the upadacitinib cohort, according to a press release from AbbVie.¹

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SLE, a complex autoimmune disorder, impacts the musculoskeletal system, kidneys, skin, and other organs, and often results in impaired function, joint pain, and fatigue.

The phase 2 M19-130 (SLEek) trial (NCT03978520) enrolled and categorized 341 patients into 5 experimental treatment groups: upadacitinib and placebo combination therapy; elsubrutinib and placebo combination therapy, 2 different doses of upadacitinib combined with elsubrutinib treatment, and placebo only. The primary outcome, SRI-4, was defined as a ≥ 4-point reduction in the SLE Disease Activity Index 2000 score (SLEDAI-2K) without worsening of the patient’s overall condition or without development of significant disease activity in new organ systems.

Secondary outcomes included the achievement of British Isles Lupus Assessment Group (BILAG) Based Combined Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), changes in steroid burden from baseline, and number of flares.

Eligible patients had a clinical diagnosis of SLE, a SLEDAI-2K ≥ 6 despite background therapy, a Physician’s Global Assessment (PhGA) ≥ 1 during the screening period, and were required to be on background treatment with antimalarials, prednisone or its equivalent, azathioprine, mycophenolate, leflunomide, cyclosporine, tacrolimus, and/or methotrexate.

Adverse events in the upadacitinib 30 mg cohort were consistent with the known safety profile of the drug, a selective and reversible Janus kinase (JAK) inhibitor, with no new safety signals identified. Similar results were demonstrated in those receiving upadacitinib and elsubrutinib combination therapy (ABBV-599). Common adverse reactions of upadacitinib treatment include upper respiratory tract infections, shingles, herpes simplex virus infection, fever, headache, nausea, and allergic reactions. Upadacitinib and elsubrutinib are not approved for the treatment of SLE and their safety and efficacy have yet to be analyzed by regulatory authorities.

"Systemic lupus erythematosus is a very unpredictable life-long condition and the way it affects a patient can change over time. Therefore, there is a critical need for additional treatment options," wrote Roopal Thakkar, MD, senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "With a quarter-century of experience and commitment to the treatment of rheumatic diseases, our focus remains on areas of high unmet need like systemic lupus erythematosus, and we look forward to further evaluation of the potential benefits that upadacitinib could bring to patients."

Upadacitinib is currently being studied for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, axial spondyloarthritis, and Crohn’s disease, among others. AbbVie is advancing its clinical program of upadacitinib in patients with SLE to phase 3 based on these promising results.

References

1. ^{AbbVie. (2023, March 23). AbbVie advances upadacitinib (RINVOQ®) to phase 3 clinical trials in systemic lupus erythematosus. PR Newswire: press release distribution, targeting, monitoring and marketing. Retrieved March 23, 2023, from https://www.prnewswire.com/news-releases/abbvie-advances-upadacitinib-rinvoq-to-phase-3-clinical-trials-in-systemic-lupus-erythematosus-301779254.html}