scholarly journals O17 Effectiveness of rituximab in the treatment of neuro-psychiatric SLE: results from the British Isles Lupus Assessment Group Biologics Register

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Trixy David ◽  
Ryan Malcolm Hum ◽  
Emily Sutton ◽  
Benjamin Parker ◽  
Eoghan McCarthy ◽  
...  
Keyword(s):  
Nervous System ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Large Scale ◽  
Oral Steroid ◽  
British Isles ◽  
Prednisolone Dose ◽  
Steroid Dose ◽  
Baseline Characteristics ◽  
Biologics Register

Abstract Background/Aims  Neuro-psychiatric (NP) involvement in systemic lupus erythematosus (SLE) can occur in 56.3% cases. Rituximab (RTX) has been demonstrated to be safe and efficacious in the treatment of refractory SLE although there is limited evidence for its use in NP-SLE. We aim to describe the baseline characteristics and short-term effectiveness of RTX in patients treated for NP-SLE within the British Isles Lupus Assessment Group Biologics Register (BILAG-BR). Methods  Patients with active NP involvement; scoring BILAG A or B and/or on SLEDAI-2K were included. Baseline characteristics, disease activity and oral steroid dose pre and 5 - 9 months post-treatment were analysed. Paired Wilcoxon-Signed-Ranked Test was used to determine changes in disease activity scores and steroid dose. Results  We identified 74 patients of whom 61 (82%) were female and 48 (74%) Caucasian. Median age [interquartile range (IQR)] was 45.5 years [37 - 58] and disease duration 11.5 years [7 - 18.8]. 68 patients had active disease on BILAG (A = 34, B = 34) with 6 scoring on SLEDAI-2K only. The majority (n = 71/74, 96%) had at least one other organ involved. Central nervous system (CNS) disease occurred in 45/65 (69%) cases, 12/65 (18%) had peripheral nervous system (PNS) disease and 8/65 (12%) CNS/PNS overlap. Anti-Ro was the commonest identified antibody (n = 26/57, 46%) and 42 of 59 (71%) patients had a raised anti-dsDNA and/or low complement. The majority (n = 64/74, 86%) were taking glucocorticoids and median prednisolone dose was 15mg [IQR 10 - 20]. Pre and post-RTX BILAG, total SLEDAI-2K and oral steroid dose were available in 50, 57 and 27 patients respectively. Following RTX, patients with NP BILAG A or B reduced from 50 to 11 (p < 0.0001). 4 of the 6 patients with NP-SLE on SLEDAI-2K alone, improved. Total median SLEDAI-2K score reduced from 12 [IQR 14 - 18] to 2 [IQR 0 - 4] (p < 0.0001). Median steroid dose reduced from 15mg [IQR 11.3 - 25] to 10mg [IQR 6.9 - 18.8] (p = 0.009). For 53 patients, active CNS, PNS and overlap disease reduced from 37 (70%) to 6 (11%), 10 (19%) to 3 (6%) and 6 (11%) to 4 (8%) respectively. In 9 patients treated with concomitant CYC, none had persistent NP disease. In contrast, 11 of 41 patients who had RTX alone had persistent NP disease. Conclusion  RTX use is associated with improvement in NP-SLE with reduction in oral steroid dose. Concomitant CYC may enhance the level of improvement seen with RTX. Large scale studies are therefore warranted to establish the effectiveness of RTX alone or in combination with CYC in the treatment of NP-SLE. Disclosure  T. David: None. R. Hum: None. E. Sutton: None. B. Parker: None. E. McCarthy: None. I. Bruce: None.

scholarly journals Effect of Disease Activity on Organ Damage Progression in Systemic Lupus Erythematosus: University of Toronto Lupus Clinic Cohort

2020 ◽  
Vol 48 (1) ◽  
pp. 67-73
Author(s):  
Murray B. Urowitz ◽  
Dafna D. Gladman ◽  
Dominique Ibañez ◽  
Jiandong Su ◽  
Sara Mursleen ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Organ Damage ◽  
Systemic Lupus ◽  
University Of Toronto ◽  
Start Date ◽  
Steroid Dose ◽  
Subgroup Analyses ◽  
Study Population ◽  
Year 2000

Objective.To examine the role of disease activity on organ damage over 5 years in patients with active systemic lupus erythematosus (SLE) despite standard of care.Methods.This analysis of the University of Toronto Lupus Clinic cohort assessed organ damage [measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] in patients with active SLE [SLE Disease Activity Index 2000 (SLEDAI-2K) ≥ 6], using Cox proportional time-independent hazard models. Subgroup analyses were conducted in patients with SLEDAI-2K 6 or 7, 8 or 9, and ≥ 10 at baseline, and in the overall study population by steroid dose at study entry (< 7.5 vs ≥ 7.5 mg/day).Results.Among the overall study population (n = 649), SDI progression was observed in 209 (32.2%) patients over the 5-year follow-up period. Mean SDI change in patients with a score > 0 was generally consistent across all SLEDAI-2K subgroups. Multivariable analyses identified age at study start (HR 1.03, P < 0.0001), steroid dose (HR 2.03, P < 0.0001), immunosuppressants (HR 1.44, P = 0.021), and SLEDAI-2K (subgroup analyses HR 1.64–2.03, P = 0.0017 to < 0.0001) as the greatest risk factors for SDI progression, while a study start date after the year 2000 had a protective effect on SDI progression compared with a start date prior to the year 2000 (HR 0.65, P = 0.0004).Conclusion.Patients within the higher SLEDAI-2K subgroups at study entry or receiving high doses of steroids were more likely to have organ damage progression.

scholarly journals British isles lupus assessment group 2004 index is valid for assessment of disease activity in systemic lupus erythematosus

2007 ◽  
Vol 56 (12) ◽  
pp. 4113-4119 ◽  
Author(s):  
Chee-Seng Yee ◽  
Vernon Farewell ◽  
David A. Isenberg ◽  
Anisur Rahman ◽  
Lee-Suan Teh ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
British Isles ◽  
Systemic Lupus ◽  
Assessment Of Disease Activity

scholarly journals Distinct patterns of disease activity over time in patients with active SLE revealed using latent class trajectory models

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
John A. Reynolds ◽  
Jennifer Prattley ◽  
Nophar Geifman ◽  
Mark Lunt ◽  
Caroline Gordon ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Trial Design ◽  
Drug Exposure ◽  
Latent Class ◽  
Clinical Trial Design ◽  
Steroid Dose ◽  
Trajectory Models ◽  
Over Time

Abstract Background Systemic lupus erythematosus (SLE) is a heterogeneous systemic autoimmune condition for which there are limited licensed therapies. Clinical trial design is challenging in SLE due at least in part to imperfect outcome measures. Improved understanding of how disease activity changes over time could inform future trial design. The aim of this study was to determine whether distinct trajectories of disease activity over time occur in patients with active SLE within a clinical trial setting and to identify factors associated with these trajectories. Methods Latent class trajectory models were fitted to a clinical trial dataset of a monoclonal antibody targeting CD22 (Epratuzumab) in patients with active SLE using the numerical BILAG-2004 score (nBILAG). The baseline characteristics of patients in each class and changes in prednisolone over time were identified. Exploratory PK-PD modelling was used to examine cumulative drug exposure in relation to latent class membership. Results Five trajectories of disease activity were identified, with 3 principal classes: non-responders (NR), slow responders (SR) and rapid-responders (RR). In both the SR and RR groups, significant changes in disease activity were evident within the first 90 days of the trial. The SR and RR patients had significantly higher baseline disease activity, exposure to epratuzumab and activity in specific BILAG domains, whilst NR had lower steroid use at baseline and less change in steroid dose early in the trial. Conclusions Longitudinal nBILAG scores reveal different trajectories of disease activity and may offer advantages over fixed endpoints. Corticosteroid use however remains an important confounder in lupus trials and can influence early response. Changes in disease activity and steroid dose early in the trial were associated with the overall disease activity trajectory, supporting the feasibility of performing adaptive trial designs in SLE.

THU0273 DISEASE ACTIVITY IS IMPORTANT RISK FACTORS FOR MATERNAL AND FETAL OUTCOMES DURING PREGNANCY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 363-363
Author(s):  
J. W. Kim ◽  
J. Y. Jung ◽  
H. A. Kim ◽  
C. H. Suh
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Logistic Regression ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Pregnancy Outcomes ◽  
Odds Ratio ◽  
Systemic Lupus ◽  
Steroid Dose ◽  
Adverse Pregnancy

Background:Systemic lupus erythematosus (SLE) primarily affects women of childbearing age and disease activity frequently increase during pregnancy. Patient with SLE still have markedly higher risk for obstetric complications, despite discussing reproductive planning with physicians and choosing a suitable time for pregnancy.Objectives:This study aimed to examine the frequency and risk factors of complications occurring during pregnancy for women with SLE and compare with the general obstetric population.Methods:The medical records of patients with SLE and age-matched controls at Ajou University Hospital between January 1999 and June 2019 were collected and retrospectively analyzed. Clinical features and pregnancy complications for all pregnancy-related admissions for women with and without SLE were compared. Multivariate logistic regression analysis was performed to obtain the predictor of maternal and fetal adverse outcomes.Results:During this period, we analyzed 163 pregnancies in patients with SLE and 596 pregnancies in general population. Of these, except for body mass index (BMI), no other significant differences regarding demographic characteristics were noted between the groups. Lupus patients delivered significantly earlier(37 weeks + 0 days vs. 37 weeks + 6 days, p<0.001) and experienced more stillbirth (odds ratio (OR) 12.8), pre-eclampsia (OR 4.2), preterm labor (OR 2.6), emergency cesarean section (OR 2.5) and intrauterine growth retardation (odds ratio: 2.4) than age-matched controls. Using logistic regression, thrombocytopenia, low complement levels, high proteinuria, anti-ds DNA antibody positivity and high SLE Disease Activity Index (SLEDAI) were associated with maternal and fetal complications, whereas high cumulative steroid dose after SLE onset, high median steroid dose during pregnancy and history of cyclophosphamide treatment were only correlated with maternal complications. The area under the curve for SLEDAI score of adverse pregnancy outcome was 0.726 (95% CI 0.65-0.81) and cumulative steroid dose after SLE onset and median steroid dose during pregnancy for maternal outcome were 0.658 (95% confidence interval (CI) 0.55-0.76) and 0.750 (95% CI 0.65-0.85). The optimal cut-off value for SLEDAI was 4 and cumulative and median steroid dose were 2750mg and 6mg, respectively.Conclusion:Pregnant women with SLE have a higher risk of adverse pregnancy outcomes. Pregnancies should be delayed until disease activity is well controls (SLEDAI<4) for longer than 6 months.References:[1]L-W Kwok, LS Tam, TY Zhu, et al., Predictors of maternal and fetal outcomes in pregnancies of patients with systemic lupus erythematosus. Lupus 2010;20:781-791[2]E Sugawara, M Kato, Y Fugieda, et al., Pregnancy outcomes in women with rheumatic disease: a real-world observational study in Japan. Lupus 2019;28:1407-1416[3]M Clowse, M Jamison, E Myers, et al., A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol 2008;199:127.e1-127.e6Disclosure of Interests:None declared

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