In long-term data, upadacitinib/reflex continued to produce SLE responses when used alone and in combination with elsubrutinib

In a long-term extension (LTE) study, Upadacitinib (Upadacitinib) monotherapy and Upadacitinib/els Ubrutinib combination therapy continued to be well tolerated and improved disease activity, glucocorticoid doses, and flares in patients with systemic lupus erythematosus (SLE) through 104 weeks.

SLE is a chronic autoimmune disease. Despite some advanced treatment options, treatment of SLE remains challenging. The response to any individual treatment is known to vary between patients, and an individual patient's response may change over time. Remission or low disease activity is a recognized therapeutic goal, but there are substantial barriers to achieving long-term remission, including the heterogeneity and volatility of immune diseases, limited treatment options, and the lack of validated predictive or prognostic biomarkers.

The one-year LTE study (NCT04451772) follows the 48-week Phase 2 SLEek study (NCT03978520), which evaluated the JAK1 inhibitor upadatinib alone or in combination with the BTK inhibitor elsubrutinib in adults with moderately to severely active SLE. The previous main study found that at week 24, 54.8% (P=0.028) of patients in the upapatinib monotherapy group and 48.5% (P=0.081) of patients in the upadacitib/elsubrutinib HD combination therapy group achieved systemic lupus erythematosus remission index 4 (SRI-4) and a glucocorticoid dose of ≤10 mg. The primary endpoint of QD was 37.3% compared with 37.3% of patients in the placebo group. LTE evaluated safety and effectiveness for an additional 56 weeks.

The LTE included patients from the SLEek study who were randomized to receive either upadacitinib 30 mg once daily (QD) or upadacitinib 30 mg/elsubrutinib 60 mg QD (upatinib/elsubrutinib) and continued their assigned treatment during the LTE. In LTE, patients who initially received placebo were switched to upadacitinib/elsubrutinib, and a total of 127 patients were included in the analysis. Researchers assessed SRI-4, the British Isles Lupus Assessment Group-based Combined Lupus Assessment (LLDAS), changes from baseline in glucocorticoid dose, and flare events and adverse events (AEs) at week 104.

Accepted from week 48 to week 104Efficacy responses to upapatinib/elsubrutinib were maintained or increased in the upatinib, upadapatinib/elsubrutinib, and placebo groups (Week 104: SRI-4: 82.1%, 85.4%, and 61.3%; BICLA: 69.2%, 78.0%, and 54.8%; LLDAS: 60.0%, 78.0%, 34.4%).

Of note, daily glucocorticoid doses decreased in all treatment groups from Week 0 to Week 104. The mean daily glucocorticoid doses at baseline were 5.9 mg, 6.1 mg, and 8.3 mg in the upatinib 30 mg, upatinib/elsubrutinib, and placebo groups, which decreased to 0.4 mg, 0.3 mg, and 0.6 mg, respectively, at Week 104. .

In addition, the overall flare rate from Weeks 0 to 48 remained unchanged in the upadacitinib 30 mg arm compared with Weeks 48 to 104 (1.38 vs 1.45 episodes/PY), compared with 1.18 vs 0.62 episodes/PY in the upadacitinib/elsubrutinib arm (1.18 vs 0.62 episodes/PY) and placebo (2.54 vs 1.45 episodes/PY). 1.56 episodes/PY) decreased. In terms of safety, the findings were similar to those in the SLEek pilot study, although researchers believed there was 1 abscess limb adverse event related to the study drug.

The long-term extension of the Phase 2, multicenter, double-blind, SLEek study demonstrated sustained or improved efficacy across multiple endpoints and no new safety findings in upadacitinib 30 mg monotherapy or upadacitinib/elsubrutinib HD combination therapy for up to 104 weeks. Entering the 56-week LTE study, patients who switched from placebo to upactinib/elsubrutinib HD experienced improvements in SLE disease activity and reduced daily glucocorticoid doses in all treatment groups at Week 104, with patients in the upadapatinib monotherapy and upadapatinib/elsubrutinib HD groups achieving lower mean glucocorticoid doses at week 104. The corticosteroid dose in the placebo group was reduced to the same level as in LTE patients starting active treatment.

Reference materials:https://www.hcplive.com/view/upadacitinib-alone-with-elsubrutinib-continue-to-yield-sle-responses-lte