EFFICACY AND SAFETY OF ELSUBRUTINIB AND UPADACITINIB COMBINATION AND UPADACITINIB MONOTHERAPY FOR THE TREATMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS THROUGH 104 WEEKS
Bibliographic record
Abstract
O007 / #176 Topic:AS24 - SLE-Treatment ABSTRACT CONCURRENT SESSION 01: FINDINGS FROM LUPUS CLINICAL TRIALS 22-05-2025 1:40 PM - 2:40 PM Background/Purpose ABBV-599 (a combination of a selective Bruton’s tyrosine kinase inhibitor, elsubrutinib [ELS], and a selective Janus kinase inhibitor, upadacitinib [UPA]) targets a spectrum of signaling pathways associated with SLE, which may extend the immunologic effects of either alone. In the phase 2 SLEek study ( NCT03978520 ), patients with moderately to severely active SLE were randomized 1:1:1:1:1 to receive once daily ABBV-599 high dose (HD; ELS 60 mg + UPA 30 mg), ABBV-599 low dose (LD; ELS 60 mg + UPA 15 mg), ELS 60 mg, UPA 30 mg, or placebo (PBO). After a planned interim analysis, the ABBV-599 LD and ELS 60 mg groups were discontinued due to lack of efficacy. Through 48 weeks, treatment with ABBV-599 HD or UPA 30 mg resulted in significant improvements in SLE disease activity and flares compared with PBO. Here, we report results from the SLEek long-term extension (LTE) study ( NCT04451772 ) through 104 weeks. Methods In the LTE study, patients continued their original randomized treatment from the SLEek study except for the PBO group, who were rerandomized 1:1 to ABBV-599 HD or ABBV-599 LD at week 48. This analysis included the continued groups: ABBV-599 HD, UPA 30 mg, and PBO to ABBV-599 HD. Efficacy measures included SLE Responder Index (SRI-4), BILAG–based Combined Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), mean glucocorticoid dose, and flares. Treatment-emergent adverse events (TEAEs) were summarized using the Medical Dictionary for Regulatory Activities v26.0. Efficacy (as observed) and safety were assessed through 104 weeks. Results The LTE included 127 patients (ABBV-599 HD, n = 45; UPA 30 mg, n = 47; PBO to ABBV-599 HD, n = 35). Baseline characteristics were balanced across groups. The proportion of patients achieving SRI-4 increased from weeks 48 through 104 to 85.4% (95% CI, 74.5–96.2), 82.1% (95% CI, 70.0–94.1), and 61.3% (95% CI, 44.1–78.4) in the ABBV-599 HD, UPA 30 mg, and PBO to ABBV-599 HD groups, respectively (Figure 1). Other secondary endpoints (BICLA and LLDAS) were either maintained or improved through week 104 in the ABBV-599 HD and UPA 30 mg groups and improved from weeks 48 through 104 in the PBO to ABBV-599 HD group. In all 3 groups, patients were nearly glucocorticoid free by week 104. TEAEs occurred in 75.6%, 66.0%, and 85.7% of patients in the ABBV-599 HD, UPA 30 mg, and PBO to ABBV-599 HD groups, respectively (Table). No cases of venous thromboembolism or major adverse cardiovascular events occurred. Figure 1. Key Efficacy Endpoints Through Week 104 of Achievement of (A) SRI-4, (B) BICLA, (C) LLDAS, and (D) Change From Baseline in Daily Glucocorticoid Dose Table. Treatment-Emergent Adverse Events From Weeks 48 Through 104 Conclusions In patients with moderately to severely active SLE, ABBV-599 HD or UPA 30 mg resulted in maintenance or further improvement in lowered disease activity, flare reduction, and decreased glucocorticoid use through 104 weeks of treatment. Patients who switched from PBO to ABBV-599 HD at week 48 improved in all measures through week 104. No new safety signals were identified.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".