scholarly journals A modified regimen of low-dose rituximab therapy for patients with refractory immune thrombocytopenia associated with systemic lupus erythematosus

2021 ◽  
Vol 12 ◽  
pp. 204062232110486
Author(s):  
Shuo Zhang ◽  
Nan Jiang ◽  
Li Wang ◽  
Li Zhang ◽  
Hua Chen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Intervention Study ◽  
Response Rate ◽  
Small Sample Size ◽  
Small Sample ◽  
Systemic Lupus ◽  
Refractory Itp

Background: Severe and refractory immune thrombocytopenia (ITP) affects the life expectancy of patients with systemic lupus erythematosus (SLE) and poses a challenge in their clinical management. This intervention study employed a small sample size to evaluate the efficacy and safety of a modified low-dose rituximab (RTX) regimen in patients with SLE-associated refractory ITP. Methods: Eight patients with severe SLE-associated refractory ITP were enrolled in this intervention study. They received an infusion of intravenous RTX (200 mg) on days 1 and 15. The dose of corticosteroids (prescribed previously) was gradually tapered, and immunosuppressants were withdrawn. Patients were followed up at 1, 3, 6, and 12 months; platelet counts, other laboratory indicators, and side effects were recorded. We used intention-to-treat analysis to calculate the response rate. Results: Seven participants (87.5%) completed the study. At 1 month, two patients (25.0%) achieved partial response (PR); the PR rate increased to 87.5% at 3 months. At 6 months, three patients (37.5%) achieved complete response (CR). However, the CR rate dropped to 25.0% at 12 months. The overall responses (ORs) were 25.0% (2/8), 87.5% (7/8), 75.0%(6/8), and 75.0%(6/8) at 1, 3, 6, and 12 months, respectively. Two patients developed a mild infusion reaction and one discontinued the study due to herpes zoster virus infection and an allergic reaction 2 weeks after the first dose of RTX. Conclusion: Modified low-dose RTX therapy (two infusions of 200 mg every 2 weeks) could be a promising new option for patients with SLE-associated refractory ITP with a satisfactory response rate.

scholarly journals Proinflammatory and autoimmunogenic gut microbiome in systemic lupus erythematosus

2019 ◽  
Author(s):  
Bei-di Chen ◽  
Xin-miao Jia ◽  
Jia-yue Xu ◽  
Li-dan Zhao ◽  
Jun-yi Ji ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Small Sample Size ◽  
Bacterial Species ◽  
Organ Damage ◽  
Small Sample ◽  
Oral Microbiome ◽  
Systemic Lupus ◽  
Microbial Composition

AbstractSystemic lupus erythematosus (SLE), characterized by chronic inflammation and multi-organ damage, has been suggested to associate with gut dysbiosis, but knowledge is limited from small sample size and 16s rRNA-based studies. To shed new light on the role of microbiota in SLE development, we analyzed the fecal metagenome of 117 treatment-naïve SLE patients and 115 sex- and age-matched healthy controls (HC) by deep-sequencing; in addition, 52 of the aforementioned patients have post-treatment fecal metagenome for comparison. We found significant differences in microbial composition and function between SLE and HC, revealing multiple plausible contributing bacterial species and metabolic pathways in SLE. In-depth SNP-based analysis revealed an oral-microbiome origin for two marker species, strengthening the importance of bacterial translocation in disease development. Lastly, we confirmed experimentally that peptides of SLE-enriched species mimicking autoantigens such as Sm and Fas could trigger autoimmune responses, suggesting a potential causal role of gut microbiota in SLE.

scholarly journals Propensity Score Methods in Rare Disease: A Demonstration Using Observational Data in Systemic Lupus Erythematosus

2020 ◽  
pp. jrheum.200254
Author(s):  
Ibrahim Almaghlouth ◽  
Eleanor Pullenayegum ◽  
Dafna D. Gladman ◽  
Murray B. Urowitz ◽  
Sindhu R. Johnson
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Propensity Score ◽  
Rare Disease ◽  
Lupus Erythematosus ◽  
Small Sample Size ◽  
Study Groups ◽  
Small Sample ◽  
Observational Research ◽  
Systemic Lupus ◽  
Real World Data

Observational studies allow researchers to understand the natural history of rheumatic conditions, risk factors for disease development, and factors affecting important disease-related outcomes, and to estimate treatment effect from real-world data. However, this design carries a risk of confounding bias. A propensity score (PS) is a balancing score that aims to minimize the difference between study groups and consequently potential confounding effects. The score can be applied in 1 of 4 methods in observational research: matching, stratification, adjustment, and inverse probability weighting. Systemic lupus erythematosus (SLE) is a rare disease characterized by a relatively small sample size and/or low event rates. In this article, we review the PS methods. We demonstrate application of the PS methods to achieve study group balance in a rare disease using an example of risk of infection in SLE patients with hypogammaglobulinemia.

GATA3 rs3824662 gene polymorphism as possible risk factor for systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2112-2119 ◽  
Author(s):  
Y M Mosaad ◽  
A Hammad ◽  
A A Elghzaly ◽  
Z M E Tawhid ◽  
E M Hammad ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Risk Factor ◽  
Lupus Erythematosus ◽  
Small Sample Size ◽  
Positive Association ◽  
Small Sample ◽  
Limiting Factor ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Genotype Frequencies

Background There is no report about the association between GATA3 rs3824662 polymorphism and systemic lupus erythematosus (SLE). Objective To investigate the possible role of GATA3 rs3824662 polymorphism as a susceptibility risk factor for either adult SLE (aSLE) or pediatric SLE (pSLE) and to evaluate its role in the development of lupus nephritis (LN) in pSLE. Methods Typing of GATA3 rs3824662 polymorphism was done using real-time polymerase chain reaction for three groups; 104 pSLE patients, 140 aSLE patients and 436 age- and sex-matched healthy controls. Results Non-significant differences were found between SLE patients and healthy controls for the allele and genotype frequencies of GATA3 rs3824662 ( p > 0.05). In pSLE; the AC genotype was associated with LN ( p = 0.04); the A allele and AC genotype were associated with persistent proteinuria ( p = 0.036 and 0.01, respectively) and both the A allele and AA genotype were associated with higher chronicity index ( p = 0.031 and 0.04, respectively). In aSLE; the C allele was associated with cellular cast ( p = 0.03) and thrombocytopenia ( p = 0.01). Logistic regression analysis revealed significant association between the AC+AA genotypes and the prediction of LN and renal active disease in pSLE ( p = 0.04 and 0.01, respectively). Conclusion GATA3 rs3824662 is not associated with susceptibility to SLE either in adult or in pediatric patients; however, in pSLE patients, the heterozygous AC genotype could be considered a risk factor for LN. At the same time, the AC and AA genotypes could be considered as predictors for LN and active renal disease. However, the small sample size is a limiting factor of the present study when interpreting the positive association.

scholarly journals POS0698 BIIB059 DEMONSTRATED A CONSISTENT THERAPEUTIC EFFECT ON SRI-4 RESPONSE ACROSS SUBGROUPS OF PARTICIPANTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN THE LILAC PHASE 2 STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 597-598
Author(s):  
R. Van Vollenhoven ◽  
R. Furie ◽  
K. Kalunian ◽  
S. Navarra ◽  
J. Romero-Diaz ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Response Rate ◽  
Small Sample ◽  
Statistical Testing ◽  
Type I ◽  
Phase 2 ◽  
Systemic Lupus ◽  
Research Support ◽  
Chemokine Production

Background:Type I interferons and other inflammatory mediators derived from plasmacytoid dendritic cells (pDCs) are implicated in systemic lupus erythematous (SLE) pathology. BIIB059 is a humanized monoclonal antibody that targets blood dendritic cell antigen 2 (BDCA2), a pDC-specific receptor. The binding of BIIB059 to BDCA2 leads to rapid internalization of BDCA2 from the surface of pDCs and subsequent inhibition of interferon, cytokine, and chemokine production. In Part A of the 2-part, phase 2 LILAC study (NCT02847598), BIIB059 significantly reduced SLE activity, as evidenced by reduced total active joint count (primary endpoint) and higher SLE Responder Index (SRI-4)1 response (a secondary endpoint) versus placebo.2Objectives:To evaluate SRI-4 response for BIIB059 versus placebo at Week 24 in SLE participant subgroups.Methods:Enrollment in LILAC Part A was open to adults fulfilling ≥ 4 of 11 revised 1997 ACR criteria for classification of SLE, with ≥ 4 tender and ≥ 4 swollen joints, active skin disease, and positive lupus antibodies. Participants were randomized to receive either BIIB059 450 mg or placebo subcutaneously every 4 weeks for 20 weeks (with an additional dose at Week 2). SRI-4 response at Week 24 was analyzed in subgroups, though analyses were limited by small sample sizes and were not powered for statistical testing.Results:In LILAC Part A, 64 and 56 participants were dosed with BIIB059 450 mg and placebo, respectively. At week 24, SRI-4 response rate was observed in favor of BIIB059 regardless of the baseline disease activity, such as SLEDAI-2K <10 versus ≥10, presence of BILAG-2004 grade A or B arthritis, oral corticosteroid usage, positivity for anti-ds DNA autoantibody and/or complement status, with point estimates for least-squares mean differences as well as corresponding 95% CIs consistently favoring BIIB059 (Figure 1). The incidence of adverse events in the overall study population was similar between the placebo and BIIB059 groups.2Conclusion:BIIB059 treatment was associated with greater SRI-4 response rate, consistent among different subgroups of baseline disease activity as measured by SLEDAI-2K and BILAG-2004, glucocorticoid dosage, and serology. These findings provide additional evidence of the potential benefit of BIIB059 for the treatment of patients with active SLE.References:[1]Furie RA, et al. Arthritis Rheum. 2009;61(9):1143-1151. 2. Furie RA, et al. Arthritis Rheumatol. 2020;72(suppl 10). Abstract 0935.Acknowledgements:This study was sponsored by Biogen (Cambridge, MA, USA). Writing and editorial support was provided by Excel Scientific Solutions (Fairfield, CT, USA); funding was provided by Biogen.Disclosure of Interests:Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biotest, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Arthrogen, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, UCB, Richard Furie Consultant of: Biogen, Grant/research support from: Biogen, Kenneth Kalunian Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Equillium, Genentech, Gilead, ILTOO, Janssen, Nektar, Roche, Viela, Grant/research support from: Lupus Research Alliance, Pfizer, Sanford Consortium, Sandra Navarra Speakers bureau: Astellas, Johnson & Johnson, Novartis, Pfizer, Consultant of: Biogen, Grant/research support from: Biogen, Juanita Romero-Diaz Consultant of: Biogen, Boehringer Ingelheim, Victoria Werth Consultant of: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Gilead, GlaxoSmithKline, Janssen, Kyowa Kirin, Resolve, Viela, Grant/research support from: Biogen, Celgene, Gilead, Janssen, Viela, XIAOBI HUANG Shareholder of: Biogen, Employee of: Biogen, HUA CARROLL Shareholder of: Biogen, Employee of: Biogen, Cristina Musselli Shareholder of: Biogen, Employee of: Biogen, Catherine Barbey Shareholder of: Biogen, Employee of: Biogen, NATHALIE FRANCHIMONT Shareholder of: Biogen, OMass Therapeutics, Employee of: Biogen

scholarly journals Epidemiology of disease-activity related ophthalmological manifestations in Systemic Lupus Erythematosus: A systematic review

Lupus ◽  
2021 ◽  
pp. 096120332110503
Author(s):  
Nitish Jawahar ◽  
Jessica K Walker ◽  
Philip I Murray ◽  
Caroline Gordon ◽  
John A Reynolds
Keyword(s):  
Systematic Review ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Retinal Vasculitis ◽  
Small Sample ◽  
Systemic Lupus ◽  
Ocular Manifestations ◽  
Ophthalmic Manifestations

Objective Ophthalmic complications in Systemic Lupus Erythematosus (SLE) are broad and can occur in up to a third of patients. The British Isles Lupus Assessment Group (BILAG) 2004 Index identifies 13 ocular manifestations of active SLE, as opposed to those related to previous disease activity and/or the consequences of therapy. We conducted a systematic review of published literature to determine the frequency of ophthalmic manifestations of active SLE. Methods A systematic literature search of Ovid MEDLINE and EMBASE from their respective inceptions to July 2020 was conducted to identify cohort, case–control and cross-sectional studies. Results 22 studies meeting eligibility criteria were included. Most studies featured small sample sizes and were judged to have a high risk of methodological bias. The number and quality of studies did not allow us to confidently estimate the incidence of the conditions. No studies reported epidemiological data for orbital inflammation/myositis/proptosis. The prevalence of each of the other ocular manifestations, with the exception of retinal vaso-occlusive disease, was consistently less than 5%. Retinal vasculitis, uveitis and isolated cotton wool spots tended to be associated with more active SLE disease. Conclusion The prevalence of eye disease due to SLE activity is uncommon, but clinicians should be aware that some conditions tend to be associated with more active systemic disease. Further studies to determine the incidence and risk factors for these ophthalmic manifestations are needed.

Associations between paraoxonase-1 and systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (13) ◽  
pp. 1571-1576
Author(s):  
S -C Bae ◽  
Y H Lee
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Confidence Interval ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Small Sample ◽  
Mean Difference ◽  
Paraoxonase 1 ◽  
Systemic Lupus ◽  
Standard Mean Difference ◽  
Meta Analyses

Objective The objective of this analysis was to explore associations between paraoxonase-1 levels, gene polymorphisms and systemic lupus erythematosus. Methods Meta-analyses of paraoxonase-1 levels and Q192R and L55M and polymorphisms in systemic lupus erythematosus were conducted. Results Nine articles were incorporated in our meta-analysis, which uncovered that the paraoxonase-1 level was decreased in systemic lupus erythematosus compared to control (standard mean difference = −1.626, 95% confidence interval = −2.829–−0.424, p = 0.008). Ethnicity-specific meta-analysis demonstrated a relation tendency between decreased paraoxonase-1 activity and lupus in Europeans (standard mean difference = −1.236, 95% confidence interval = −2.634–0.163, p = 0.083). Paraoxonase-1 activity was reduced in systemic lupus erythematosus in a single Arab and African population. Decreased paraoxonase-1 activity was found in a small sample of systemic lupus erythematosus patients (standard mean difference = −1.642, 95% confidence interval = −3.076–−0.247, p = 0.021). Ethnicity-specific analysis indicated a relationship between the paraoxonase-1 55 M allele in the Arab systemic lupus erythematosus population. However, a lack of association with systemic lupus erythematosus and the paraoxonase-1 192 R allele was observed. Conclusions Meta-analyses revealed reduced paraoxonase-1 activity in patients with systemic lupus erythematosus and found possible associations between systemic lupus erythematosus and paraoxonase-1 L55M polymorphism in a specific ethnic group.

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