0640: Impact of Clinically Important Improvements in Patient-Reported Outcomes on Disease Activity in Patients With Systemic Lupus Erythematosus Treated With Upadacitinib or Placebo: Results From the Phase 2 SLEek Study

Background/Purpose: This analysis evaluated associations between clinically important improvements in patient-reported outcomes (PROs) and reduced disease activity from the phase 2 SLEek trial evaluating upadacitinib (UPA) vs placebo (PBO) in patients with systemic lupus erythematosus (SLE).

Methods: Data are reported for patients in SLEek who received UPA 30 mg monotherapy or PBO for 48 weeks. Assessments included achievement of British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA), Systemic Lupus Erythematosus Responder Index 4 (SRI-4), and Lupus Low Disease Activity State (LLDAS) responses among patients who reported or did not report minimum clinically important differences (MCID) in PROs at weeks 24 and 48. MCIDs were defined as: ≥ 4-point increase in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (in patients with FACIT-Fatigue ≤ 48 at baseline), ≥ 2.5-point increase in 36-Item Short-Form Health Survey Physical and Mental Component Summary scores, (SF-36 PCS and MCS scores; in patients with SF-36 PCS and MCS scores ≤ 97.5 at baseline), and ≥ 1-point reduction from baseline in Patient’s Assessment of Pain Numerical Rating Scale (NRS). Between-group differences and P values were estimated using Cochran-Mantel-Haenszel test, adjusted for baseline corticosteroid dose, Systemic Lupus Erythematosus Disease Activity Index 2000 score at screening, baseline interferon score, and baseline immunosuppressant use.

Results: 137 patients were included in the analysis (UPA 30 mg, n = 62; placebo, n = 75); 90% were female and most were White. Mean baseline FACIT-Fatigue, SF-36 PCS, SF-36 MCS, and Pain NRS scores were 29.3, 40.3, 42.4, and 5.3 (PBO); and 27.1, 38.2, 43.7, and 7.1 (UPA). Among patients who reported changes ≥ MCID for fatigue, physical or mental function, or pain at week 48, a higher proportion achieved SRI-4, BICLA, and LLDAS responses with UPA vs PBO (P < .05 for most; Figure 1). Similar trends were observed at week 24 (Figure 1). SRI-4, BICLA, and LLDAS responses at weeks 24 and 48 were lower among patients who did not report clinically meaningful improvements in PROs; however, a higher proportion of these patients achieved SRI-4, BICLA, and LLDAS responses with UPA vs PBO. Of patients who received UPA and reported changes ≥ MCID for FACIT-Fatigue at week 48, over 80% achieved SRI-4 and BICLA responses, and approximately three-quarters achieved LLDAS (Figure 1A). In patients who received UPA and reported clinically meaningful changes in SF-36 PCS or MCS scores or Pain NRS at week 48, over 80% achieved BICLA, and SRI-4 and LLDAS were achieved by approximately three-quarters of patients who reported changes ≥ MCID for SF-36 PCS scores (Figure 1B) and approximately two-thirds of patients who reported changes ≥ MCID for SF-36 MCS scores (Figure 1C) and Pain NRS (Figure 1D).

Conclusion: Patients who reported changes ≥ MCID in PROs for fatigue, physical and mental function, and pain generally demonstrated higher SRI-4, BICLA, and LLDAS responses than those who did not. These findings demonstrate the strong association of PRO improvements with disease activity improvements in SLE and highlight the potential multifaceted benefits of UPA for patients with SLE.