RESUMEN
OBJECTIVE: The 48-week, phase 2 SLEek study (NCT03978520) evaluated the efficacy and safety of upadacitinib (JAK inhibitor) and elsubrutinib (BTK inhibitor) alone or in combination (ABBV-599) in adults with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients were randomized 1:1:1:1:1 to elsubrutinib 60 mg and upadacitinib 30 mg once daily (ABBV-599 high dose), elsubrutinib 60 mg and upadacitinib 15 mg once daily (ABBV-599 low dose), elsubrutinib 60 mg once daily (QD), upadacitinib 30 mg QD, or placebo QD. The primary endpoint was the proportion of patients achieving both Systemic Lupus Erythematosus Responder Index 4 (SRI-4) and glucocorticoid dose ≤10 mg QD at week 24. Additional assessments through week 48 included British Isles Lupus Assessment Group-Based Composite Lupus Assessment (BICLA) and Lupus Low Disease Activity State (LLDAS) responses, number of flares, time to first flare, and adverse events. RESULTS: The study enrolled 341 patients. The ABBV-599 low dose and elsubrutinib arms were discontinued after a planned interim analysis showed lack of efficacy (no safety concerns). More patients achieved the primary endpoint with upadacitinib (54.8%; P = 0.028) and ABBV-599 high dose (48.5%; P = 0.081) versus placebo (37.3%). SRI-4, BICLA, and LLDAS response rates were higher for both upadacitinib and ABBV-599 high dose versus placebo at weeks 24 and 48. Flares were reduced, and time to first flare through week 48 was substantially delayed with both upadacitinib and ABBV-599 high dose versus placebo. No new safety signals were observed beyond those previously reported for upadacitinib or elsubrutinib. CONCLUSION: Upadacitinib 30 mg alone or in combination with elsubrutinib (ABBV-599 high dose) demonstrated significant improvements in SLE disease activity and reduced flares and were well tolerated through 48 weeks.
RESUMEN
OBJECTIVE: The soluble triggering receptor expressed on myeloid cells (TREM-1)-like transcript 1 (sTLT-1) has a modulatory effect on the activation of TREM-1. We compared plasma sTLT-1 levels between patients with systemic lupus erythematosus (SLE) and healthy individuals and determined the association between sTLT-1 levels and clinical features and patient-reported outcomes (PROs) among patients with lupus. METHODS: An unmatched case-control study was conducted in 46 patients with SLE and 28 healthy subjects. sTLT-1 plasma levels were determined using enzyme-linked immunosorbent assay. Demographic factors, SLE manifestations, comorbidities, pharmacologic profile, disease activity (per SLAM-R), damage accrual, and PROs (as per Lupus Patient-Reported Outcome [LupusPRO]) were studied. RESULTS: Patients with SLE were found to have lower sTLT-1 levels compared with healthy individuals (9.0±7.2 vs. 18.6±22.3 pg/mL, p=0.008). Among patients with SLE, higher sTLT-1 levels were found in those taking corticosteroids (11.1±8.8 vs. 6.9±4.6 pg/mL, p=0.014). Significant correlations were found for the cognition (r=-0.442, p=0.027) and desires/goals (r=0.435, p=0.030) domains of LupusPRO. A tendency was observed between sTLT-1 levels and the SLAM-R (r=-0.278, p=0.064) and the lupus symptoms (r=-0.388, p=0.055) and physical health (r=-0.382, p=0.060) domains of LupusPRO. CONCLUSION: Compared with healthy individuals, sTLT-1 levels were significantly lower in patients with SLE. Among patients with SLE, correlations were observed for some domains of LupusPRO. Given that sTLT-1 has anti-inflammatory properties, the deficiency of this protein could play an important role in the pathogenesis of SLE.
RESUMEN
As a cutaneous variant of lupus erythematosus, discoid lupus erythematosus (DLE) is thought to have a good prognosis; however, the involvement of internal organs with a transition to systemic disease may occur. The progression from DLE to systemic lupus erythematosus has been reported in up to 28% of patients. This progression to systemic disease has been associated with a benign course. Herein, we report the case of a 31-year-old woman with a 10-year history of discoid lupus, now presenting with dyspnea and pleuritic chest pain of 1 month's duration. A significant drop in hemoglobin and hematocrit levels was observed in association with leukopenia, lymphopenia, a positive ANA, and hypocomplementemia. Chest radiography and computed tomography revealed bilateral infiltrates. An open lung biopsy confirmed the presence of intra-alveolar hemorrhage. Based on the results of the tests and analyses detailed herein, a diagnosis of pulmonary hemorrhage secondary to systemic lupus erythematosus was made. To our knowledge, pulmonary hemorrhage as the initial manifestation of the systemic involvement of discoid lupus has not been reported before.