Meta-analysis of efficacy and safety of belimumab in the treatment of childhood-onset systemic lupus erythematosus / 中国药房

OBJECTIVE To evaluate the efficacy and safety of belimumab in the treatment childhood-onset systemic lupus erythematosus （cSLE）， and to provide evidence-based references for clinical medication. METHODS Randomized controlled trials （RCTs） about belimumab or belimumab combined with hormone or belimumab combined with hormone and traditional drugs （test group） compared with placebo or hormone or traditional drugs or traditional drugs combined with hormone （control group） were collected by computer searching CNKI， Wanfang data， VIP， SinoMed， PubMed， Embase， Web of Science and the Cochrane Library； the search deadline was from the establishment of the databases to April 9th， 2023. After screening the literature and extracting the data， the quality of the included literature was evaluated by using the bias risk assessment tool recommended by Cochrane system evaluation manual 5.1.0； meta-analysis and sensitivity analysis were conducted by using RevMan 5.4 software. RESULTS A total of 510 children were included in 7 RCTs. Results of the meta-analysis showed that the clinically effective rate of test group was significantly better than the control group [OR＝6.16， 95%CI （2.23， 17.00）， P＝0.000 4]. There were no statistically significant differences in SLE disease activity index （SLEDAI） [MD＝－1.73， 95%CI （－3.50， 0.05）， P＝0.06]， the incidence of adverse drug reactions [OR＝0.72， 95%CI （0.43， 1.19）， P＝0.02]， complement C3 levels [MD＝0.12， 95%CI （－0.06， 0.30）， P＝0.18]， complement C4 levels [MD＝0.08，95%CI （－0.07，0.24）， P＝0.30] or the response rate of SLE responder index 4 [OR＝1.52， 95%CI （0.94，2.44）， P＝0.09] between 2 groups. The results of sensitivity analysis showed that when SLEDAI， the complement C3 levels and complement C4 levels were used as indicators， the results obtained in this study were robust. CONCLUSIONS The efficacy of belimumab in the treatment of cSLE is good， and its safety is comparable to the basic treatment.

Clinical characteristics and follow-up study of 210 children with systemic lupus erythematosus / 中华实用儿科临床杂志

Objective:To evaluate the systemic involvement, outcome and other disease characteristics of children with systemic lupus erythematosus (cSLE), and to explore the prognostic factors.Methods:cSLE treated in Beijing Children′s Hospital, Capital Medical University from January 1, 2016 to December 31, 2017 were enrolled in this study.Medical records including clinical manifestations and evaluation of affected systems, autoantibodies, treatment adjustment, and follow-up were collected and analyzed retrospectively.SPSS 21.0 was used for statistical analysis and mapping.The prognostic factors were studied by the Cox proportional risk regression model.Results:A total of 210 children were included, including 37 males and 173 females, with a male to female ratio of 1.0∶4.7.The average age of onset was (121.39±30.44) months.There were 167 (79.5%) patients with skin and mucous membrane damage, 137(65.2%) patients with blood system damage, 129(61.4%) patients with digestive system damage, 123(58.6%) patients with kidney damage, 119(56.7%) patients with skeletal and musculoskeletal system damage, 71(33.8%) patients with nervous system damage, 68(32.4%) patients with heart damage, and 60(28.6%) patients with respiratory system damage.The 90.95%(191/210) of the children enrolled presented moderate or high disease activity at the first visit.The effective rate was 76.92% (150/195) after 1-month follow-up and 96.95% (159/164) after 1-year follow-up.A high level of compliment C 3 was a protective factor for disease remission.The glucocorticoid level was declined to 5 mg or less in 42 children, and the median time was 40.5 (36.0, 42.0) months.Young onset age and no renal damage were protective factors for glucocorticoid reduction. Conclusions:cSLE tends to occur in female children with multiple involved systems and severe conditions.After reasonable treatment and follow-up, the disease can be alleviated or improved in one year.A high level of complement C 3 at the beginning of disease is conducive to rapid remission of the disease, and the young age of onset and no renal damage is conducive to rapid glucocorticoid reduction.

Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onsetlupus nephritis

Abstract Background: Urinary parameters, anti-dsDNA antibodies and complement tests were explored in patients with childhood-Systemic Lupus Erythematosus (cSLE) early-onset lupus nephritis (ELN) from a large multicenter cohort study. Methods: Clinical and laboratory features of cSLE cases with kidney involvement at presentation, were reviewed. Disease activity parameters including SLEDAI-2 K scores and major organ involvement at onset and follow up, with accrued damage scored by SLICC-DI, during last follow up, were compared with those without kidney involvement. Autoantibodies, renal function and complement tests were determined by standard methods. Subjects were grouped by presence or absence of ELN. Results: Out of the 846 subjects enrolled, mean age 11.6 (SD 3.6) years; 427 (50.5%) had ELN. There was no significant difference in the ELN proportion, according to onset age, but ELN frequency was significantly higher in non-Caucasians (p = 0.03). Hematuria, pyuria, urine casts, 24-h proteinuria and arterial hypertension at baseline, all had significant association with ELN outcome (p < 0.001). With a similar follow up time, there were significantly higher SLICC-DI damage scores during last follow up visit (p = 0.004) and also higher death rates (p < 0.0001) in those with ELN. Low C3 (chi-square test, p = 0.01), but not C3 levels associated significantly with ELN. High anti-dsDNA antibody levels were associated with ELN (p < 0.0001), but anti-Sm, anti-RNP, anti-Ro, anti-La antibodies were not associated. Low C4, C4 levels, low CH50 and CH50 values had no significant association. High erythrocyte sedimentation rate (ESR) was associated with the absence of ELN (p = 0.02). Conclusion: The frequency of ELN was 50%, resulting in higher morbidity and mortality compared to those without ELN. The urinary parameters, positive anti-dsDNA and low C3 are reliable for discriminating ELN.(AU)

Initial digital vasculitis in a large multicenter cohort of childhood-onset systemic lupus erythematosus / Vasculite digital inicial em uma grande coorte multicêntrica de pacientes com lúpus eritematoso sistêmico de início na infância

Abstract Objectives: To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a large population. Methods: Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in São Paulo State, Brazil. Results: DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p = 0.008), discoid rash (16% vs. 4%, p = 0.017), photosensitivity (76% vs. 45%, p = 0.002) and other cutaneous vasculitides (80% vs. 19%, p < 0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p = 0.003), fever (32% vs. 56%, p = 0.020) and hepatomegaly (4% vs. 23%, p = 0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p > 0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p = 0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p = 0.014) was significantly lower in the DV group. Conclusion: Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients.

Resumo Objetivos: Avaliar a vasculite digital (VD) clínica como uma manifestação inicial do lúpus eritematoso sistêmico de início na infância (LESi) em uma grande população. Métodos: Estudo transversal multicêntrico que incluiu 852 pacientes com LESi (critérios do ACR), acompanhados em dez centros de reumatologia pediátrica do Estado de São Paulo. Resultados: Observou-se VD em 25/852 (3%) pacientes com LESi. Diagnosticaram-se hemorragia periungueal em 12 (48%), infarto periungueal em sete (28%), úlcera de ponta de dígito em quatro (16%), nódulos dolorosos em um (4%) e gangrena em um (4%). Um desfecho ruim, com reabsorção digital, ocorreu em cinco (20%) pacientes. A comparação entre pacientes com e sem VD revelou maior frequência de erupção malar (80% vs. 53%, p = 0,008), erupção discoide (16% vs. 4%, p = 0,017), fotossensibilidade (76% vs. 45% p = 0,002) e outras vasculites cutâneas (80% vs. 19%, p < 0,0001), enquanto a frequência de características constitucionais totais (32% vs. 61%, p = 0,003), febre (32% vs. 56% p = 0,020) e hepatomegalia (4% vs. 23%, p = 0,026) foram menores nesses pacientes. A frequência do gênero feminino, o envolvimento grave de múltiplos órgãos, perfil de autoanticorpos e baixo complemento foram semelhantes nos dois grupos (p > 0,05). A mediana no Sledai-2 K, exclusive o descritor de VD, foi significativamente menor nos pacientes com VD em comparação com aqueles sem essa manifestação [10 (0 a 28) vs. 14 (0 a 58), p = 0,004]. Não foram observadas vasculite visceral nem morte nessa coorte de pacientes com LESi. A frequência de uso de ciclofosfamida (0% vs. 18%, p = 0,014) foi significativamente menor no grupo VD. Conclusão: Este grande estudo multicêntrico identificou a VD clínica como uma rara manifestação inicial do LESi ativo, associada a doença multissistêmica leve, apesar da ocorrência de reabsorção digital em alguns desses pacientes.

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

Childhood-onset systemic lupus erythematosus (cSLE) exhibits an aggressive clinical phenotype and severe complications. This could be due to a pro-inflammatory cytokine milieu. Therefore, we determined plasma levels of Th1 (IL-2, IFN-γ, TNF), Th2 (IL-4), Th17 (IL-17A, IL-6), and Treg (IL-10) cytokines in a cohort of cSLE patients and healthy controls, and we evaluated the association between these cytokines and disease activity. We conducted a cross-sectional study with 51 cSLE patients from two pediatric rheumatology services. Ten cSLE patients participated in a longitudinal follow-up study. Blood samples were collected from the same patient during active and inactive disease. Disease activity was evaluated according to SLE Disease Activity Index 2000 (SLEDAI-2K). Cytokines levels were measured by cytometric bead array technique. cSLE patients had higher IL-6 (P<0.001) and IL-10 (P<0.001) levels than healthy controls. Patients with active disease had higher IL-6 and IL-10 levels than patients with inactive disease (P=0.001 and P=0.014, respectively) and the control group (both P<0.001). IL-6 (P=0.022), IL-10 (P=0.013), and IL-17A (P=0.041) levels were significantly higher during active than inactive disease. Linear regression analysis revealed IL-6 (P=0.002, 95%CI=0.006-0.025) and IL-10 (P=0.01 95%CI=0.021-0.150) as independent factors for increased SLEDAI-2K. IL-6, IL-10, and IL-17A are candidate biomarkers for disease activity in cSLE patients. This is the first longitudinal study to support their pivotal role in the pathogenesis of the disease.

Alcohol, smoking and illicit drug use in pediatric systemic lupus erythematosus patients / Uso de álcool, tabaco e drogas ilícitas por pacientes com lúpus eritematoso sistêmico pediátrico

Abstract Objective To evaluate alcohol, smoking and/or illicit drug use, and history of bullying in adolescent childhood-onset systemic lupus erythematosus and healthy controls. Methods 174 adolescents with pediatric rheumatic diseases were selected. All of the 34 childhood-onset systemic lupus erythematosus patients and 35 healthy controls participated in this study. A cross-sectional study included demographic/anthropometric data and puberty markers assessments; structured questionnaire and CRAFFT screening interview. Results McNemar tests indicated an excellent test–retest reliability of the structured questionnaire (p = 1.0). The median current age was similar between childhood-onset systemic lupus erythematosus patients and controls [15 (12–18) vs. 15 (12–18) years, p = 0.563]. The median of menarche age was significantly higher in childhood-onset systemic lupus erythematosus patients compared to controls [12 (10–15) vs. 11.5 (9–15) years, p = 0.041], particularly in those that lupus had occurred before first menstruation [13 (12–15) vs. 11.5(9–15) years, p = 0.007]. The other puberty marker and sexual function parameters were similar in both groups (p > 0.05). Alcohol use was similar in both childhood-onset systemic lupus erythematosus patients and controls (38% vs. 46%, p = 0.628). A trend of lower frequency of CRAFFT score ≥2 (high risk for substance abuse/dependence) was evidenced in childhood-onset systemic lupus erythematosus patients compared to controls (0% vs. 15%, p = 0.053). Bullying was reported similarly for the two groups (43% vs. 44%, p = 0.950). Further analysis in lupus patients regarding alcohol/smoking/illicit drug use showed no differences in demographic data, puberty markers, history of bullying, sexual function, contraceptive use, disease activity/damage scores, clinical/laboratorial features and treatments (p > 0.05). Conclusion This study showed high frequencies of early alcohol use in lupus adolescents and healthy controls, despite of a possible low risk for substance abuse/dependence in childhood-onset systemic lupus erythematosus patients.

Resumo Objetivo Avaliar o uso de álcool, tabaco e/ou drogas ilícitas e a história de bullying entre adolescentes com lúpus eritematoso sistêmico pediátrico (LES-i) e controles saudáveis. Métodos Selecionaram-se 174 adolescentes com doenças reumatológicas pediátricas. Todos os 34 pacientes com LES-i e 35 controles saudáveis participaram deste estudo. Um estudo transversal incluiu avaliações de dados demográficos/antropométricos e marcadores da puberdade, um questionário estruturado e a entrevista de triagem Crafft. Resultados Testes de McNemar indicaram uma excelente confiabilidade teste-reteste do questionário estruturado (p = 1,0). A idade média atual foi semelhante entre pacientes com LES-i e controles [15 (12 a 18) vs. 15 (12 a 18) anos, p = 0,563]. A mediana da idade na menarca foi significativamente maior em pacientes com LES-i em comparação com os controles [12 (10 a 15) vs. 11,5 (9 a 15) anos, p = 0,041], particularmente naquelas em quem o lúpus ocorreu antes da primeira menstruação [13 (12 a 15) vs. 11,5 (9 a 15) anos, p = 0,007]. Os outros marcadores da puberdade e parâmetros de função sexual foram similares nos dois grupos (p > 0,05). O uso de álcool foi semelhante entre pacientes com LES-i e controles (38% vs. 46%, p = 0,628). Evidenciou-se uma tendência de menor frequência de pontuação ≥ 2 no Crafft (alto risco para uso abusivo/dependência de substâncias) em pacientes com LES-i em comparação com os controles (0% vs. 15%, p = 0,053). O bullying foi relatado em frequência semelhante nos dois grupos (43% vs. 44%, p = 0,950). Uma análise mais aprofundada em relação ao uso de álcool/tabaco/drogas ilícitas em pacientes com lúpus não mostrou diferenças nos dados demográficos, marcadores da puberdade, história de bullying, função sexual, uso de anticoncepcionais, escores de atividade/danos da doença, características clínicas/laboratoriais e tratamentos (p > 0,05). Conclusão Este estudo mostrou uma alta frequência de uso precoce de álcool em adolescentes com lúpus e controles saudáveis, apesar de um possível baixo risco para uso abusivo/dependência de substâncias em pacientes com LES-i.

Serum interleukin-17 levels are associated with nephritis in childhood-onset systemic lupus erythematosus

OBJECTIVES: To determine the serum interleukin-17 (IL-17) levels in childhood-onset systemic lupus erythematosus patients and to evaluate the association between IL-17 and clinical manifestations, disease activity, laboratory findings and treatment. METHODS: We included 67 consecutive childhood-onset systemic lupus erythematosus patients [61 women; median age 18 years (range 11-31)], 55 first-degree relatives [50 women; median age 40 years (range 29-52)] and 47 age- and sex-matched healthy controls [42 women; median age 19 years (range 6-30)]. The childhood-onset systemic lupus erythematosus patients were assessed for clinical and laboratory systemic lupus erythematosus manifestations, disease activity [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index] and current drug use. Serum IL-17 levels were measured by an enzyme-linked immunosorbent assay using commercial kits. RESULTS: The median serum IL-17 level was 36.3 (range 17.36-105.92) pg/mL in childhood-onset systemic lupus erythematosus patients and 29.47 (15.16-62.17) pg/mL in healthy controls (p=0.009). We observed an association between serum IL-17 levels and active nephritis (p=0.01) and migraines (p=0.03). Serum IL-17 levels were not associated with disease activity (p=0.32), cumulative damage (p=0.34), or medication use (p=0.63). CONCLUSION: IL-17 is increased in childhood-onset systemic lupus erythematosus and may play a role in the pathogenesis of neuropsychiatric and renal manifestations. Longitudinal studies are necessary to determine the role of IL-17 in childhood-onset systemic lupus erythematosus. .