RESUMEN
OBJECTIVES: To evaluate the prevalence of late-onset neutropenia and its complications in patients treated with rituximab (RTX) for rheumatoid arthritis (RA) and other autoimmune diseases (AIDs) in a prospective registry. METHODS: The AutoImmunity and Rituximab registry is an independent 7-year prospective registry promoted by the French Society of Rheumatology. For each episode of neutropenia, data were validated by the clinician in charge of the patient. RESULTS: Among 2624 patients treated with RTX for refractory AIDs, and at least 1 follow-up visit (a total follow-up of 4179 patient-years in RA and 987 patient-years in AIDs), late-onset neutropenia was observed in 40 patients (25 RA (1.3% of patients with RA, 0.6/100 patient-years), and AIDs in 15 (2.3% of patients with AIDs, 1.5/100 patient-years)). 6 patients (15%) had neutrophils <500/mm(3), 8 (20%) had neutrophils between 500 and 1000/mm(3), and 26 (65%) had neutrophils between 1000 and 1500/mm(3). Neutropenia occurred after a median period of 4.5 (3-6.5) months after the last RTX infusion in patients with RA, and 5 (3-6.5) months in patients with AIDs. 5 patients (12.5%), 4 of them with neutrophils lower than 500/mm(3), developed a non-opportunistic serious infection and required antibiotics and granulocyte colony-stimulating factor injections, with a favourable outcome. After resolution of their RTX-related neutropenia, 19 patients (47.5%) were re-treated, and neutropenia reoccurred in 3 of them. CONCLUSIONS: Late-onset neutropenia might occur after RTX and may result in serious infections. Thus, monitoring of white cell count should be performed after RTX. However, in this large registry of patients with AIDs, the frequency of RTX-induced neutropenia was much lower than that previously reported in patients treated for blood malignancies or AIDs.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inmunosupresores/uso terapéutico , Polietilenglicoles/uso terapéutico , Piodermia Gangrenosa/tratamiento farmacológico , Artritis Reumatoide/complicaciones , Certolizumab Pegol , Femenino , Humanos , Piodermia Gangrenosa/etiología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Tuberculosis (TB) is associated with anti-tumor necrosis factor (anti-TNF) monoclonal antibody (mAb) therapy, but whether this association is drug-specific remains a concern. Our objective was to describe cases of TB associated with anti-TNF mAb therapy, identify risk factors, and estimate the incidence. METHODS: We conducted an incidence study and a case-control analysis to investigate the risk of newly diagnosed TB associated with the use of anti-TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti-TNF mAb therapy for any indication; for each case, 2 patients treated with anti-TNF agents served as control subjects. RESULTS: We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex- and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7-15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4-25.8] and SIR 29.3 [95% CI 20.3-42.4] versus SIR 1.8 [95% CI 0.7-4.3], respectively). In the case-control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6-69.0] and OR 17.1 [95% CI 3.6-80.6], respectively). Other risk factors were age, the first year of anti-TNF mAb treatment, and being born in an endemic area. CONCLUSION: The risk of TB is higher for patients receiving anti-TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.
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Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Factor de Necrosis Tumoral alfa/inmunología , Adalimumab , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Artritis Reumatoide/tratamiento farmacológico , Síndrome de Behçet/tratamiento farmacológico , Estudios de Casos y Controles , Colitis/tratamiento farmacológico , Etanercept , Femenino , Francia , Humanos , Inmunoglobulina G/efectos adversos , Inmunoglobulina G/uso terapéutico , Infliximab , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Espondiloartritis/tratamiento farmacológico , Resultado del Tratamiento , Tuberculosis/inducido químicamenteRESUMEN
OBJECTIVES: The use of biologicals such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. METHODS: Plasma profiles of 60 patients with RA (28 non-responders (as defined by the American College of Rheumatology 20% improvement criteria (ACR20)) negative and 32 responders (ACR70 positive) to infliximab) were studied by surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterisation was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by matrix assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS analysis. RESULTS: Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity>56%, specificity>77.5%). Moreover, combination of several biomarkers improved the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterised as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. CONCLUSIONS: Six plasma biomarkers are characterised, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders.
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Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Apolipoproteína A-I/sangre , Artritis Reumatoide/tratamiento farmacológico , Factor Plaquetario 4/sangre , Adulto , Anciano , Artritis Reumatoide/sangre , Biomarcadores/sangre , Monitoreo de Drogas/métodos , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Pronóstico , Proteómica/métodos , Sensibilidad y Especificidad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine whether joint destruction, indication for, and response to infliximab in rheumatoid arthritis are associated with the shared epitope (SE) or selected cytokine gene polymorphisms (interleukin (IL) 1B, IL1-RN, and tumour necrosis alpha). METHODS: In a large rheumatoid arthritis population of 930 patients from the same area (Rhône-Alpes, France), patients with (n = 198) or without infliximab treatment (n = 732) were compared according to their genetic status. Clinical, biological, and radiological data were collected. Typing for SE status and cytokine polymorphisms was carried out using enzyme linked oligosorbent assay. Statistical analysis was by chi(2) testing and calculation of odds ratios (OR). RESULTS: A dose relation was observed between the number of SE copies and joint damage in the whole rheumatoid population (OR, 1 v 0 SE copy = 2.38 (95% confidence interval, 1.77 to 3.19), p<0.001; OR 2 v 0 SE copy = 3.92 (2.65 to 5.80), p<0.001. The SE effect increased with disease duration but was not significant before two years. Selection for infliximab treatment (n = 198) was associated with increased disease activity, joint damage, and the presence of the SE with a dose effect. In all, 66.2% patients achieved an ACR20 improvement. No clinical or genetic factors were able to predict the clinical response to infliximab. CONCLUSIONS: This post-marketing study in a large cohort of rheumatoid arthritis patients indicates a linkage between rheumatoid arthritis severity, selection for treatment with infliximab, and the presence and dose of the SE.
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Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Epítopos/genética , Adulto , Edad de Inicio , Anciano , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Citocinas/genética , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Selección de Paciente , Polimorfismo Genético , Vigilancia de Productos Comercializados , Pronóstico , Índice de Severidad de la Enfermedad , Resultado del TratamientoAsunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Erupciones por Medicamentos/etiología , Inmunoglobulina G/efectos adversos , Lupus Eritematoso Discoide/inducido químicamente , Crioglobulinemia/inducido químicamente , Etanercept , Femenino , Humanos , Persona de Mediana Edad , Receptores del Factor de Necrosis TumoralRESUMEN
Functional disability and quality of life were evaluated using the Functional Independence Measure and the Reintegration to Normal Living Index, respectively, in 57 subjects (15 men and 42 women) with a mean disease duration of 15 years. Scores on both these nonspecific scales correlated with those obtained using instruments specifically designed for rheumatoid arthritis (ARA index, Lee index) and with a number of clinical parameters including patient age, disease duration and number of affected joints. Functional ability was correlated with quality of life in this study and in others performed using other evaluation tools. Nonspecific assessment scales are useful for comparing function and quality of life in various diseases.
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Actividades Cotidianas , Artritis Reumatoide/fisiopatología , Calidad de Vida , Adulto , Anciano , Análisis de Varianza , Artritis Reumatoide/rehabilitación , Evaluación de la Discapacidad , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perfil de Impacto de EnfermedadRESUMEN
The authors report a case of thrombotic thrombocytopenic purpura (TTP) which revealed a hitherto unrecognized ankylosing spondylitis. After a 4-year follow-up, the spondylitis is still progressing in its axial and/or peripheral form, and TTP has not relapsed. TTP is usually primary, but numerous forms consecutive to various diseases, and notably autoimmune diseases, have been reported. The TTP-ankylosing spondylitis association is extremely rare: analysis of the literature yielded only one case. The authors discuss the hypothesis of a common triggering factor.
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Púrpura Trombocitopénica Trombótica/etiología , Espondilitis Anquilosante/complicaciones , Adulto , Femenino , Humanos , Factores de TiempoRESUMEN
Bone mineral density (BMD) was measured in 128 normal postmenopausal women at different skeletal sites: lumbar spine and proximal femur, using dual-energy X-ray absorptiometry (DXA), and the cancellous and cortical envelopes of the distal third of radius and tibia, using precise low-dose quantitative computed tomography (QCT). Multivariate analysis included chronological age, ages related to menstrual history (menopause and menarche) and anthropometric factors, e.g. height and weight, as independent predictive variables. Weight is a much-studied predictor of bone density. At sites of high bone turnover, i.e. cancellous envelope, the effect of weight appeared overshadowed by estrogen-related parameters: age-past-menopause was the first predictor of BMD in the cancellous compartment of radius and in Ward's triangle, and the number of reproductive years was the strongest predictor of BMD in the cancellous compartment of tibia and in the spine (L2-4). This suggests that in addition to menopause, the length of menstrual life should be considered as an explanation for the variations in current bone mass in postmenopausal women. At the cortical level of radius, the effect of chronological age was predominant. At the cortical level of tibia, height and weight were the best predictors of BMD. We conclude that the influence of parameters related to menstrual history is predominant in sites with mainly cancellous tissue and that anthropometric factors constitute the best predictors of BMD in the cortical sites of weight-bearing bones.
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Envejecimiento/fisiología , Antropometría/métodos , Densidad Ósea , Menarquia/fisiología , Absorciometría de Fotón , Estudios Transversales , Femenino , Fémur/metabolismo , Humanos , Radio (Anatomía)/metabolismo , Análisis de Regresión , Reproducción , Columna Vertebral/metabolismo , Factores de TiempoRESUMEN
The efficacy of the biphosphonate etidronate has recently been demonstrated versus the vertebral fracture rate in fractured involuted osteoporosis in the literature. However, it would appear that the increase in bone mass (measured from the calcium density) may alone account for these results. The authors undertook a histomorphometrie study in 20 patients with a group mean age of 55 years presenting recent vertebral fracture in the context of osteoporosis, in order to assess the cell changes which may affect bone quality. This factor remains the only one which can account for the reduced number of fractures. The patients received treatment with phosphorus (1,500 mg/d) for 3 days followed by etidronate (400 mg/d) for 14 days every 90 days. A permanent daily intake of 50 mg of calcium and 400 IU of vitamin D was also administered. Each patient underwent bone biopsy of the iliac wing before and after one year of treatment (4 cycles). No change in the bone mass or architectural parameters was observed. However, general slowing of the bone remodeling was found, affecting the natality and activity of the osteoforming and osteoresorbing cells. However, this remodeling which is traditionally uncoupled in osteoporosis was once more coupled. This results in a slowing of bone loss, ageing of the bone present and no change in the architecture. Thus, the diphosphonates appear to have a beneficial effect on the quality of bone rather than on its quantity. This represents a novel approach to the treatment of osteoporosis.
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Huesos/patología , Ácido Etidrónico/uso terapéutico , Fracturas Espontáneas/etiología , Osteoporosis/patología , Traumatismos Vertebrales/etiología , Anciano , Biopsia , Esquema de Medicación , Ácido Etidrónico/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/tratamiento farmacológicoRESUMEN
The generalized use of phosphocalcic biological assays makes the discovery of sporadic primary hyperparathyroidism increasingly common. In 1989-1990, first-intention surgery was performed in 26 female patients. In all cases, an exploratory cervicotomy under cervical peridural anesthesia allowed discovering and treating a parathyroid lesion: adenoma, asymmetric or symmetric hyperplasia, cancer. We discuss: the circumstances of the clinical diagnosis and the biological criteria, the timeliness of preoperative radiological assessment, the surgical strategy advocated. In more than 90% of all cases, a cervicotomy for the exploration of all areas of parathyroid migration should allow curing primary hyperparathyroidism.