Background/Purpose: Clinical and immunological manifestations of systemic lupus erythematosus (SLE) vary widely across patients, complicating diagnosis and treatment (1,2). Upadacitinib (UPA), an oral selective JAK inhibitor, significantly reduced disease activity compared with placebo (PBO) in the phase 2 SLEek trial of adult patients with moderately to severely active SLE (3). In this analysis, we evaluate potential differences in treatment responses to UPA vs PBO associated with baseline patient characteristics.

Methods: SLEek was a phase 2, randomized, double-blind, PBO-controlled trial (NCT03978520) (3). This post hoc analysis included participants who were randomized to receive once-daily UPA 30 mg or PBO for 48 weeks. We report the proportions of trial participants in each group who met the composite measures of disease improvement, Lupus Low Disease Activity State (LLDAS) and/or British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA). Participants were stratified into subgroups by sex, age, race, region, body mass index, medication use, clinical markers, and medical history. Missing data were handled with nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19. Between-group differences and 95% CIs were estimated according to the Cochran-Mantel-Haenszel test adjusted for baseline corticosteroid use (≤10 mg or >10 mg), Systemic Lupus Erythematosus Disease Activity Index 2000 score at screening (< 10 or ≥10), baseline interferon score (high, low, or not applicable), and baseline immunosuppressant use (yes or no). Analyses were exploratory, and the reported data are descriptive.

Results: A total of 137 participants (UPA 30 mg, n = 62; PBO, n = 75) were included. Most participants were White (56.2%) and female (96.4%). As previously published, at week 48, 31 participants (50.0%) treated with UPA 30 mg and 18 (24.0%) treated with PBO achieved LLDAS; 33 participants (53.2%) treated with UPA 30 mg and 19 (25.3%) treated with PBO achieved BICLA (3). A numerically higher proportion of participants in most baseline characteristic subgroups treated with UPA 30 mg vs PBO achieved LLDAS and/or BICLA (Table), with treatment differences (estimated by the Cochran-Mantel-Haenszel test) consistent with potential benefits of UPA 30 mg across most subgroups (Figure).

Conclusion: After 48 weeks of treatment, participants with SLE treated with UPA30 mg were more likely than those receiving PBO to achieve LLDAS and/or BICLA across various baseline demographics and clinical characteristics; however, the interpretation of data in this study is limited by sample size. These findings, if corroborated in further studies, may support the potential benefit of UPA in a broad spectrum of patients with SLE despite the heterogeneity of the disorder.

anti-dsDNA, anti–double-stranded DNA; BICLA, British Isles Lupus Assessment Group-Based Composite Lupus Assessment; BMI, body mass index; LLDAS, Lupus Low Disease Activity State; NA, not applicable; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.

aPercentage of responders with available data on LLDAS or BICLA.

anti-dsDNA, anti–double-stranded DNA; BICLA, British Isles Lupus Assessment Group-Based Composite Lupus Assessment; BMI, body mass index; LLDAS, Lupus Low Disease Activity State; NA, not applicable; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000.

Response rate differences and 95% CIs were estimated according to the Cochran-Mantel-Haenszel test adjusted for baseline corticosteroid use (≤10 mg or >10 mg), Systemic Lupus Erythematosus Disease Activity Index 2000 score at screening ( < 10 or ≥10), baseline interferon score (high, low, or not applicable), and baseline immunosuppressant use (yes or no).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-across-baseline-characteristic-subgroups-in-patients-with-systemic-lupus-erythematosus-treated-with-upadacitinib-results-from-sleek-a-phase-2-randomized/