Lupus Science & Medicine最新文献

Introduction: SLE is a chronic autoimmune disease characterised by multisystem involvement and fluctuating clinical course, often leading to permanent organ damage. Childhood-onset SLE (cSLE) tends to be more aggressive with increased organ involvement compared with adult-onset SLE. Despite advances in treatment, there is a rising incidence of morbidity and chronic damage in cSLE patients. This study aims to evaluate the patterns of damage and identify risk factors associated with damage accrual in a cohort of cSLE patients.

Materials and methods: We conducted a retrospective cohort study of 120 patients meeting the Systemic Lupus International Collaborating Clinics 2012 criteria for cSLE, followed by the paediatric rheumatology clinic from 2004 to March 2023. After excluding 18 patients for monogenic lupus or inadequate follow-up, 102 patients were analysed. Damage accrual was assessed using the Paediatric Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (PedSDI) and associations between clinical, laboratory and demographic variables with damage accrual were evaluated using univariate and multivariate analyses.

Results: The mean age at diagnosis was 12.9 years, with a mean disease duration of 6.3 years. At the end of the study, 33.3% of patients had accrued damage (PedSDI≥1). The most frequently involved domains were growth failure (24%), renal (11.8%), neuropsychiatric (8.8%) and mucocutaneous (5.9%). Multivariate analysis revealed that higher median SLE Disease Activity Index-2000 scores, haemolytic anaemia and renal involvement were independent risk factors for damage accrual.

Conclusions: Our study confirms that higher median disease activity over time, haemolytic anaemia and renal disease are significant predictors of long-term damage in cSLE. Additionally, growth failure was the most frequently involved domain in PedSDI, followed by renal and neuropsychiatric domains. These findings underscore the importance of early and effective disease management and regular monitoring for these risk factors.

Objective: SLE affects multiple organs and is associated with increased mortality and organ damage. While treatment recommendations for non-renal SLE stratify by disease activity, no standard approach to measuring severity exists. This study aimed to estimate the prevalence and incidence of SLE in Sweden, quantify patients with moderate-to-severe disease using register-based algorithms and examine associations between disease severity and survival.

Methods: We identified adult SLE patients in the Swedish National Patient Register with at least two SLE-coded visits between July 2005 and December 2019. Annual incidence and point prevalence were calculated. SLE patients were matched 5:1 with non-SLE comparators. SLE disease severity was classified annually postdiagnosis using an adapted algorithm based on prescriptions and comorbidities. Survival between SLE patients by each severity level in the year following diagnosis was compared with matched comparators using Cox regression models.

Results: In total, 10 186 SLE patients were identified, including 5076 incident cases. The average incidence of adult SLE in Sweden between 2015 and 2019 was 4.1 cases per 100 000, with a 2019 prevalence of 93.8 per 100 000. In the first year postdiagnosis, 61% of SLE patients had moderate-to-severe disease, stabilising at approximately 45% after 3-4 years among patients still in follow-up. Across all severity levels, SLE patients had poorer survival than comparators. High severity in the year following diagnosis was independently associated with increased mortality risk compared with mild disease, regardless of age, sex or prescribed treatments.

Conclusions: Using national register data, the estimated prevalence of SLE in Sweden is higher than published figures from previous years. This is the first Swedish register-based study characterising SLE severity and its survival impact. Mortality risk is particularly increased in patients with moderate or severe SLE at diagnosis, underscoring the need for targeted strategies to improve outcomes for this group.

Objective: Negative self-perceptions of ageing are associated with decreased health-related quality of life (HRQoL) in older adults. We sought to characterise the association of self-perceptions of ageing, both positive and negative, with pain, depression and self-reported disability and frailty status in middle-aged and older adults with SLE.

Methods: We enrolled adults ≥50 years with validated SLE in a single-centre cross-sectional study. Sociodemographic characteristics and disease features were self-reported. Self-perceptions of ageing were assessed using awareness of age-related change (AARC). We assessed patient-reported outcomes, disability and frailty status using the Patient-Reported Outcomes Measurement Information System 29-Item Profile (PROMIS-29), Valued Life Activities and Fatigue, Resistance, Ambulation, Illness, Loss of Weight Scale. Associations between AARC gains (ie, positive self-perception of ageing) and losses (ie, negative self-perception of ageing) and pain interference, depression, disability and frailty status (frail ≥3/5 criteria) were assessed using linear or logistic regression and adjusted for age, race, ethnicity, and SLE disease activity and organ damage.

Results: Participants (n=80) were mostly female (95.0%) with mean age and SLE duration of 63.2 (SD=8.5) years and 23.1 (SD=14.5) years, respectively. Mean PROMIS-29 T-scores for pain interference and depression were 54.6 (SD=10.1) and 49.8 (SD=8.5), respectively; 29.9% were frail. After covariate adjustment, AARC losses, but not gains were significantly associated with pain interference (ß coefficient 0.94, 95% CI 0.33 to 1.54, p<0.01), depression (ß coefficient 0.67, 95% CI 0.04 to 1.30, p=0.04) and frailty (OR 2.09, 95% CI 1.30 to 3.37, p<0.01). After covariate adjustment, both AARC gains (ß coefficient -0.07, 95% CI -0.09 to -0.02, p<0.01) and losses (ß coefficient 0.08, 95% CI 0.03 to 0.12, p<0.01) were statistically significantly associated with disability.

Conclusions: Negative self-perception of ageing was independently associated with decreased HRQoL among middle-aged and older adults with SLE. Addressing negative self-perceptions of ageing may improve HRQoL in this population.

Objective: This study uses Mendelian randomisation (MR) to investigate the causal link between SLE and osteoporosis across different ethnic groups.

Methods: Genetic variants associated with SLE were identified from publicly available genome-wide association studies in European and East Asian populations. Two-sample MR (TSMR) analysis and meta-analysis with inverse variance weighting (IVW) assessed their effects on bone mineral density (BMD) and fracture risk. Multivariable MR (MVMR) analysis in East Asians adjusted for potential mediators, and two-step mediation analysis evaluated mediation effects of independent covariates.

Results: A meta-analysis of IVW results from TSMR in East Asian populations revealed a significant positive genetic association of SLE with osteoporosis (OR=1.023, CI 1.007 to 1.040, p<0.01). A similar, although weaker, association was observed in the European population (OR=1.001, CI 1.000 to 1.001, p<0.01). Furthermore, SLE was identified as a risk factor for reduced BMD in both East Asian (β=-0.0690, p<0.05) and European (β=-0.0109, p<0.05) populations, and for fracture risk in European (OR=1.002, p<0.05) populations, while no significant association was observed in the East Asian population (OR=1.010, p=0.705). MVMR analysis of East Asian data assessed mediation effects and found that the SLE-osteoporosis association was nullified after adjusting for cardiovascular disease and health status. Mediation analysis identified low-density lipoprotein cholesterol (LDL-C) and anti-inflammatory medication use as independent mediators, with mediation effects of 0.1170 and 0.0510, respectively. No significant heterogeneity or pleiotropy was detected.

Conclusions: SLE appears to be a causal risk factor for osteoporosis. LDL-C and anti-inflammatory medication use mediate this relationship, suggesting the importance of managing these factors in patients with SLE to reduce osteoporosis risk.

Objective: Pregnant patients with systemic lupus erythematosus (SLE) have 2-3 times higher risk of preterm delivery (PTD). Hydroxychloroquine (HCQ) is recommended during pregnancy and may reduce PTD risk. This study investigates whether early pregnancy HCQ-use reduces PTD risk in a diverse SLE cohort.

Methods: We included singleton pregnancies reaching ≥20 weeks' gestation (2011-2020) among patients with SLE aged 18-50 receiving care at Kaiser Permanente Northern California. HCQ exposure was defined as ≥2 prescriptions filled from 3 months before the last menstrual period through the first trimester. PTD was defined as delivery <37 weeks and continuously as gestational weeks for time-to-delivery analyses. Propensity scores (PS) based on demographics, comorbidities and medication use were calculated to address confounding. Risk ratios (RR) and HRs, including 95% CIs, were estimated using PS-adjusted Poisson regression with robust SEs and Cox regression, stratified by parity. To investigate effect modification, we stratified by prepregnancy comorbidities and pregnancy corticosteroid use.

Results: Among 399 pregnancies in 324 patients, 21% were preterm. The PS-adjusted RR was 1.08 (95% CI 0.52 to 2.23) and 0.88 (95% CI 0.50 to 1.57) for nulliparous and multiparous pregnancies exposed to HCQ, respectively. The PS-adjusted HRs were similar, and results remained consistent across analyses stratified by potential effect modifiers.

Conclusions: Although periconceptional HCQ-use was not associated with reduced PTD nor appreciably altered gestational age at delivery, we found no increased risks for these specific adverse outcomes. Consistent with other work, we found potentially protective associations in subsets stratified by parity. However, we had limited statistical power to test this.

Objectives: SLE associated with immune checkpoint inhibitors (ICIs) is rare, and a comprehensive profile of ICI-induced SLE remains poorly characterised. This study aimed to explore the potential association between ICIs and SLE and characterise clinical features.

Methods: We extracted adverse event reports of patients with cancer with SLE from the FAERS (US Food and Drug Administration Adverse Event Reporting System) database (Q1 2011-Q4 2024). A disproportionality analysis was conducted using the reporting OR (ROR) and the information component, with adjusted ROR calculated via logistic regression to control for confounders.

Results: 146 066 ICI-related adverse events cases from patients with cancer were identified. Among these, 209 (median (IQR) age 63 (55.3-71.7) years; 106 (51%) female) cases of SLEs were reported. Our analysis detected significant positive signals for SLE associated with ICIs overall, particularly for anti-programmed cell death protein 1 (PD-1) and anti-programmed death-ligand 1 therapy. Eight positive signals of SLEs were identified, predominantly cutaneous lupus and SLE. The risk of ICI-related SLEs was significantly higher in females than in males. However, age and chemotherapy were not significant risk factors for the incidence of ICI-related SLEs. The risk was higher with anti-PD-1 therapy compared with other ICI therapies. Patients with lung cancer, melanoma or breast cancer appeared to be at higher risk. Most patients experienced serious outcomes, with a mortality rate of 4.31% (nine cases).

Conclusion: This first pharmacovigilance study identified a significant association between ICI use and SLEs, suggesting ICIs may constitute a novel class of drug-induced SLE triggers. Personalised long-term safety monitoring for ICIs is warranted for high-risk patients (eg, females, anti-PD-1 recipients).

Background: SLE complicated with thrombotic thrombocytopenic purpura (SLE-TTP) is a rare but potentially fatal condition. Current studies regarding SLE-TTP are limited to case reports and literature reviews. This study presents a cohort of patients with SLE-TTP and aims to investigate their clinical characteristics and treatment outcomes, as well as to explore the efficacy of rituximab (RTX) maintenance therapy (RMT) for relapse prevention and long-term disease control.

Methods: Patients with SLE-TTP were retrospectively identified in an SLE cohort. Baseline characteristics, acute-phase treatment responses and long-term outcomes were collected. All patients received RTX-containing induction therapy during the acute phase of TTP. Maintenance therapy was categorised as RMT (regular RTX infusions) or non-RMT (conventional immunosuppressants and/or biologics) regimens. TTP relapse, lupus low disease activity state (LLDAS) and infection rates were compared between groups.

Results: Of 33 patients with SLE-TTP, 31 (94%) achieved clinical remission following RTX-containing induction therapy, while 2 died during the acute phase. Fourteen patients (45%) received RMT, and 17 (55%) received non-RMT regimens. During a median follow-up of 22.9 months, TTP relapse occurred in seven (23%) patients: one (7%) in the RMT group and six (35%) in the non-RMT group. Kaplan-Meier analysis revealed significantly longer relapse-free survival with RMT (log-rank p=0.027). All patients receiving RMT achieved LLDAS, compared with 59% of patients in the non-RMT group. Infection rates were comparable between the two groups.

Conclusions: RTX-containing induction regimens resulted in high rates of clinical remission in patients with SLE-TTP. RMT was associated with a significantly reduced risk of TTP relapse and superior long-term control of SLE disease activity, without an excess risk of severe infection. These findings support RMT as a potential option for long-term management of SLE-TTP.

Objective: Breastfeeding prevalence and challenges among women of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is under-researched especially in the Middle East-North Africa region. This study aimed to assess breastfeeding initiation, duration and predictors of early discontinuation (<6 months post partum) among Egyptian mothers with SLE or RA.

Methods: This multicentre retrospective cohort study included 320 pregnancies: 62 SLE (105 pregnancies), 71 RA (110 pregnancies) and 59 healthy mothers (105 pregnancies). Data on pregnancy history, breastfeeding intent, initiation, duration and weaning reasons were collected.

Results: Exclusive breastfeeding was lowest in SLE (29.9%) vs RA (50.6%) and controls (60%, p<0.001). Continuation beyond 6 months was significantly lower in SLE (36.2%) and RA (33.6%) vs controls (81%, p<0.001). Postpartum depression independently predicted discontinuation in SLE (adjusted OR (aOR)=0.06, 95% CI 0.01 to 0.6) and RA (aOR=0.34, 95% CI 0.13 to 0.9). Multivariable generalised estimating equation confirmed SLE reduced breastfeeding odds versus controls (aOR=0.41, p=0.040).

Conclusion: Breastfeeding is significantly less prevalent among Egyptian mothers with SLE and RA when compared with control group. Targeted educational programme and support may help improve breastfeeding rates in SLE/RA mothers.

Objective: SLE is a complex, heterogenous autoimmune disease. SLE researchers do not always collect the same data, making comparative studies difficult. We aimed to ascertain what variables SLE clinical researchers commonly collect for SLE research. Our ultimate goal is to generate a minimal core dataset for future SLE studies.

Methods: In 2020, we designed and distributed a questionnaire to members of the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) as well as additional active research centres in China. Our survey included 26 questions about the types of data that are routinely collected for research. Variables collected by ≥75% of participating respondents were used as a threshold for inclusion.

Results: 18 of 36 invited respondents replied (8 from USA/Canada, 5 from China and 5 from Europe). Many key variables in the domains of sociodemographics, SLE specific, comorbidities, baseline haematology/biochemistry/immunology and treatment data were collected by ≥75% respondents including the 1997 American College of Rheumatology (ACR) Classification Criteria (83%), SLE Disease Activity Index-2000 (82%), current treatment (100%), drug name, dose, frequency and start date (75-100%) and complement C3/4 (94%). A range of other items was collected by 50-<75% of respondents including SLICC 2012 Criteria (67%), SLICC/ACR Damage Index (68%) and Short Form Health Survey-36 (53%). Less than 50% of respondents collect certain items including European Alliance of Associations for Rheumatology/ACR 2019 criteria (33%), British Isles Lupus Assessment Group scores (12%) and pneumococcal vaccine status (39%).

Conclusions: The frequency with which an initial set of variables is collected in SLE cohorts globally was identified and can form the basis from which to develop a core minimum dataset for SLE. Further refinement and common definitions will be needed to finalise a minimal core dataset suitable for widespread use.