Background/Purpose: Achievement of treat-to-target measures Lupus Low Disease Activity State (LLDAS) and Definition of Remission in SLE (DORIS) has been associated with improved outcomes and quality of life in patients with systemic lupus erythematosus (SLE).1,2 Upadacitinib (UPA), an oral, selective JAK inhibitor, reduced SLE disease activity in the phase 2, randomized, double-blind SLEek study (NCT03978520) of adults with moderately to severely active SLE.3 In this post hoc analysis of SLEek, we evaluate the achievement of LLDAS and DORIS with upadacitinib (UPA) monotherapy (30 mg) vs placebo (PBO).

Methods: LLDAS was defined as meeting a clinical SLE Disease Activity Index 2000 (SLEDAI-2K) score ≤ 4, absence of SLE disease activity in major organ systems, no new disease activity, by clinical criteria including SLE Disease Activity Index 2000 (SLEDAI-2K) score ≤ 4, no major organ activity, a Physician Global Assessment (PhGA) score ≤ 1, glucocorticoid (GC) dose ≤ 7.5 mg/day, and stable maintenance doses of standard immune-modulating drugs. In this analysis, DORIS was defined as meeting a clinical SLEDAI-2K score of 0, PhGA score < 0.5, GC ≤ 5 mg/day, and stable maintenance doses of standard immune-modulating drugs but with stricter criteria. Data were reported based on nonresponder imputation incorporating multiple imputation for missing data due to COVID-19. Between-group differences were adjusted using the Cochran-Mantel-Haenszel test and Cox proportional hazard model; adjustments were made for SLEDAI-2K score at screening ( < 10 or ≥ 10), baseline GC dose ( < 10 mg or ≥ 10 mg), baseline immunosuppressant use (yes or no), and baseline IFN score (high, low, or not applicable). No multiplicity adjustments were applied; all P values are nominal.

Results: Data were included from 137 patients (UPA 30 mg, n = 62; PBO, n = 75; female: 96.4%, White: 56.2%). Rates of achievement of LLDAS and DORIS, respectively, with UPA vs PBO at week 48 were 50.0% vs 24.0% (P < 0.001) and 19.4% vs 9.3% (P = 0.063). Median time to first achievement of LLDAS was shorter with UPA vs PBO (20.4 vs 39.9 weeks; HR [95% CI]: 2.0 [1.2, 3.2]; P = 0.005); median time to DORIS could not be estimated due to < 50% of patients achieving DORIS at any time point (Figure 1). Cumulative % of time spent in LLDAS and DORIS was greater with UPA vs PBO; LLDAS: LS mean [95% CI]: 28.9% [19.8, 38.1] vs 12.5% [4.6, 20.5]; P = 0.001; DORIS: 9.1% [3.4, 14.7] vs 3.0% [−1.9, 8.0]; P = 0.051. Higher proportions of patients were in LLDAS or DORIS for various cumulative proportions of time with UPA vs PBO, and the proportions of patients who sustained LLDAS or DORIS for ≥ 3, ≥ 5, and ≥ 6 consecutive monthly visits were higher with UPA vs PBO (P < 0.05 for all; Figure 2).

Conclusion: Patients with SLE who received UPA achieved higher rates of LLDAS and DORIS, had a shorter time to first LLDAS, spent more cumulative time in LLDAS and DORIS, and experienced more consecutive visits in these states versus PBO. These data support the potential benefit of UPA in achieving stringent SLE treat-to-target measures.

DORIS, Definition of Remission in SLE; LLDAS, Lupus Low Disease Activity State; NE, not estimable; PBO, placebo; SLE, systemic lupus erythematosus; UPA, upadacitinib.

Horizontal dashed lines are located at 50% on the y-axis.

Vertical dashed lines represent the median time to first response for each treatment group.

aThe median time to reach DORIS could not be estimated due to < 50% of participants reaching DORIS at any time point for either treatment group.

DORIS, Definition of Remission in SLE; LLDAS, Lupus Low Disease Activity State; PBO, placebo; SLE, systemic lupus erythematosus; UPA, upadacitinib.

*P < .05; ** P < .01; *** P < .001 vs placebo.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/achievement-of-treat-to-target-measures-with-upadacitinib-in-patients-with-systemic-lupus-erythematosus-phase-2-randomized-sleek-clinical-trial-results/