Results of the phase 2 SLEek trial, which will be presented at the European Congress of Rheumatology (EULAR) 2023, demonstrated that at week 24, patients with systemic lupus erythematosus (SLE) receiving upadacitinib treatment met the primary endpoint of the SLE Responder Index (SRI-4) and a steroid dose of ≤10 mg prednisone once daily.¹ The findings indicated significant reductions in both disease activity and glucocorticoid use.

Joan Merrill, MD

Credit: Lupus Foundation of America

"Lupus is an imbalance in the immune system caused by a diverse set of inherited and environmental factors," noted Joan Merrill, MD, Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Research Program. "To achieve sustainable progress with SLE, we need more treatment options for patients with this disease."

SLE is an autoimmune disease which causes widespread inflammation and tissue damage in affected organs, often resulting in symptoms such as fatigue, fever, pain and swelling in the joints, and skin rashes, and can impact the brain, kidneys, joints, lungs, and blood vessels. Disease activity, called flares, are unpredictable and came vary in severity.

The Trial

The randomized, placebo-controlled, parallel-group, multicenter SLEek trial evaluated upadacitinib 30 mg both alone and in combination with elsubrutinib 60 mg (ABBV-599 high dose) in adult patients with moderate-to-severe SLE who were receiving standard lupus therapies.

Investigators initially enrolled 341 patients who were randomized to receive once daily ABBV-599 high dose, ABBV-599 low dose (elsubrutinib 60 mg plus upadacitinib 15 mg), elsubrutinib 60 mg, upadacitinib 30 mg, or placebo.

An interim analysis was performed when 50% of patients either reached week 24 or withdrew from the study, at which point investigators discontinued both the ABBV-599 low dose and elsubrutinib 60 mg treatment arms due to lack of efficacy. Subsequently, 205 patients continued with treatment through week 48 (ABBV-599 high dose: n = 68; upadacitinib 30 mg: n = 62; and placebo: n = 75).

The Results

In addition to meeting the primary endpoint, patients treated with upadacitinib maintained greater improvements in SLE disease activity at week 48, as evaluated via the British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI), Lupus Low Disease Activity State (LLDAS), SRI-4, lupus flares, and time to first flare when compared with the placebo cohort. Patients in the upadacitinib monotherapy and ABBV-599 cohorts were able to achieve the primary endpoint of SRI-4 at rates of 54.8% and 48.5%, respectively, compared with 37.3% in the placebo group.

There were no new safety signals observed and adverse events were comparable among patients treated with upadacitinib alone and ABBV-599 high dose. The rate of treatment emergent adverse events (TEAEs) in the study were comparable across treatment arms, with 82.3% of patients in the upadacitinib monotherapy group experiencing events, 86.8% in the ABBV-599 group, and 78.7% in the placebo group.

Although no reports of venous thromboembolic events or malignancies were reported, serious adverse events were exhibited in 21.0% of patients receiving upadacitinib 30 mg, 10.3% in the ABBV-599 high dose group, and 17.3% of those receiving the placebo.

"There are limited treatment options for people living with SLE, leaving physicians challenged on how to effectively slow disease progression and limit potential organ damage in their patients," stated Roopal Thakkar, MD, senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "We are encouraged by these positive Phase 2 data and look forward to continuing to study upadacitinib for systemic lupus erythematosus in 2 Phase 3 trials as part of our ongoing clinical program."

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.}