RESUMO
OBJECTIVE: To assess the longitudinal production of anti-adalimumab antibody (AAA) and baseline risk factors for this antibody development in juvenile idiopathic arthritis (JIA) patients initiating adalimumab (ADA). METHOD: Thirty consecutive JIA patients under ADA therapy were prospectively followed. JIA clinical/laboratorial/treatment data and sera for ADA and AAA assays (ELISA and bridging ELISA) were obtained at baseline (BL), 2 months (2M), 3 months (3M), 6 months (6M), 12 months (12M), and 24 months (24M). Patients with therapy failure requiring ADA withdrawn had their sera evaluated at their last medical visit prior to biologic switch (blinded to ADA and AAA levels). RESULTS: AAA was absent at BL, first detected at 2M after ADA initiation in 2/30 (7%) patients with a significant increase at 3M (10/29 (34%), p = 0.013) and no major change in 6M (11/30 (37%)) and 12M (9/26 (35%)). Of note, at 3M, AAA levels correlated negatively with ADA levels (r = - 0.781, p = 0.0001). Analysis of BL predictors revealed a significantly higher risk of developing AAA in patients with female gender (OR 21; 95% CI 1.08-406.57; p = 0.044), ESR > 30 mm/1st hour (OR 5.44; 95% CI 1.04-28.53; p = 0.045), and leflunomide use (OR 9.33; 95% CI 1.51-57.66; p = 0.016). In contrast, concomitant use of methotrexate was protective for AAA appearance (OR 0.08; 95% CI 0.01-0.53; p = 0.009). After 12M of ADA, 60% of AAA-positive patients required drug switch for drug failure compared with 15% in AAA-negative group (p = 0.03). CONCLUSIONS: This study provides novel evidence of AAA production kinetics demonstrating a timely significant increase starting at 3M and stable throughout 24M. We also identified female gender, increased ESR, and leflunomide use as relevant risk factors for AAA production at BL, whereas methotrexate was protective. Early systematic monitoring of AAA at 3M may, therefore, guide drug switching in these patients.Key Points⢠Anti-adalimumab antibodies (AAA) production kinetics demonstrated a timely significant increase starting at 3M in juvenile idiopathic arthritis (JIA) patients under adalimumab therapy⢠Female gender, increased ESR, and leflunomide use were identified as relevant risk factors for AAA production in JIA, whereas methotrexate was protective.
Assuntos
Adalimumab/uso terapêutico , Anticorpos/metabolismo , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Substituição de Medicamentos , Leflunomida/uso terapêutico , Metotrexato/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Uveíte/tratamento farmacológico , Adalimumab/imunologia , Adolescente , Adulto , Formação de Anticorpos , Sedimentação Sanguínea , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Cinética , Masculino , Razão de Chances , Fatores de Proteção , Fatores de Risco , Fatores Sexuais , Inibidores do Fator de Necrose Tumoral/imunologia , Adulto JovemRESUMO
OBJECTIVES: To compare clinical and laboratorial features between childhood-onset systemic lupus erythematosus (cSLE) and adult SLE (aSLE) at concomitant diagnosis of immune thrombocytopenic purpura (ITP). METHODS: This study evaluated 56 cSLE and 73 aSLE patients regularly followed at Pediatric and Rheumatology Divisions of the same University hospital with ITP (platelets count <100,000/mm3 in the absence of other causes) at lupus onset. RESULTS: Median current age was 11.6 and 27.3 years in cSLE and aSLE, respectively. cSLE had a higher frequency of ITP compared to aSLE (17% vs. 4%, p < .0001) and the former group had more hemorrhagic manifestations (36% vs. 16%, p = .0143). Constitutional symptoms and reticuloendothelial manifestations (p < .05), as well as pericarditis (25% vs. 10%, p = .029) and central nervous system (CNS) involvement (30% vs. 14%, p = .029) were more common in cSLE. Conversely, in aSLE, ITP was solely associated with cutaneous and articular involvements (p < .05). Concerning treatment, intravenous methylprednisolone, intravenous immunoglobulin, blood transfusion and platelets transfusion were more frequently used in the cSLE population (p < .05). CONCLUSION: ITP at cSLE has distinct features compared to aSLE with a more severe presentation characterized by concomitant constitutional/reticuloendothelial manifestations, CNS involvement and hemorrhagic manifestation. These findings reinforce the need for a more aggressive treatment in this age group.
Assuntos
Lúpus Eritematoso Sistêmico/patologia , Púrpura Trombocitopênica Idiopática/patologia , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Metilprednisolona/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/imunologiaRESUMO
INTRODUCTION: The characteristic feature of Henoch-Schönlein purpura (HSP) is palpable purpura, however hemorrhagic vesicles and blisters have been rarely reported. CASE REPORTS: From January 1983 to December 2007, 5079 patients were followed in our Pediatric Rheumatology Unit, 232 (4.6%) of them with the diagnosis of HSP. Three female patients (1.3%) presented hemorrhagic vesicles and bullous lesions associated with palpable purpura. In one case the lesions were severe and widespread, and in another they preceded the typical purpuric lesions. In both cases, skin biopsy disclosed leukocytoclastic vasculitis with IgA and C3 deposits. Two patients healed with residual lesions: ulcers in one case and skin hyperpigmentation in two of them. DISCUSSION: Hemorrhagic vesicle-bullous lesions are rare in HSP. This manifestation may represent a more severe and prolonged disease course with scars or may precede typical skin lesions.