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1.
Arthritis Rheumatol ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31237427

RESUMO

OBJECTIVE: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as first biologic drug in a large series of patients with refractory uveitis due to Behçet's disease (BD) for 1-year period. METHODS: Open-label multicenter study of IFX or ADA-treated patients with BD-uveitis refractory to conventional non-biologic treatment. IFX or ADA were chosen as first biologic treatment based on physician and patient agreement. Dosing schedule was: IFX: 3-5 mg/kg i.v. at 0, 2 and 6 weeks and every 4-8 weeks thereafter, and ADA: 40 mg/s.c./every other week without loading dose. Comparison between patients treated with IFX and patients treated with ADA was performed. RESULTS: 177 patients (316 affected eyes) were included. IFX was used in 103 and ADA in 74 cases. No significant differences at baseline were observed between IFX vs ADA groups regarding main demographic features, previous therapy and ocular severity. After one year of therapy, we observed an improvement in all ocular parameters in both groups. However, ADA therapy yielded better outcome in some parameters that in some cases yielded statistically significant differences: anterior chamber inflammation (78.18% in IFX-treated vs 92.31%in ADA-treated; p=0.06), vitritis (78.95% vs 93.33%; p=0.04), retinal vasculitis (97% vs 95%; p=0.28), macular thickness (264.89±59.74 vs 250.62±36.85; p=0.15), best-corrected visual acuity (0.67±0.34 vs 0.81±0.26; p=0.001), and drug retention (84.95% vs 95.24%; p=0.042). CONCLUSION: Although IFX and ADA yields efficacy refractory BD uveitis, ADA appears to be associated with better outcome than IFX after one-year follow-up. This article is protected by copyright. All rights reserved.

2.
Am J Ophthalmol ; 200: 85-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30660771

RESUMO

PURPOSE: Cystoid macular edema (CME) is a leading cause of blindness. This study assessed the efficacy and safety of tocilizumab (TCZ) in refractory CME. DESIGN: Retrospective case series. METHODS: Patients with CME secondary to noninfectious uveitis who had inadequate response to corticosteroids and at least 1 conventional immunosuppressive drug, and in most cases to other biological agents, were studied. CME was defined as central retinal thickness greater than 300 µm. The primary outcome measure was macular thickness. Intraocular inflammation, best-corrected visual acuity (BCVA), and corticosteroid-sparing effect were also analyzed. RESULTS: A total of 25 patients (mean ± standard deviation age 33.6 ± 18.9 years; 17 women) with CME were assessed. Underlying diseases associated with uveitis-related CME are juvenile idiopathic arthritis (n = 9), Behçet disease (n = 7), birdshot retinochoroidopathy (n = 4), idiopathic (n = 4), and sarcoidosis (n = 1). The ocular patterns were panuveitis (n = 9), anterior uveitis (n = 7), posterior uveitis (n = 5), and intermediate uveitis (n = 4). Most patients had CME in both eyes (n = 24). TCZ was used in monotherapy (n = 11) or combined with conventional immunosuppressive drugs. Regardless of the underlying disease, compared to baseline, a statistically significant improvement in macular thickness (415.7 ± 177.2 vs 259.1 ± 499.5 µm; P = .00009) and BCVA (0.39 ± 0.31 vs 0.54 ± 0.33; P = .0002) was obtained, allowing us to reduce the daily dose of prednisone (15.9 ± 13.6 mg/day vs 3.1 ± 2.3 mg/day; P = .002) after 12 months of therapy. Remission was achieved in 14 patients. Only minor side effects were observed after a mean follow-up of 12.7 ± 8.34 months. CONCLUSION: Macular thickness is reduced following administration of TCZ in refractory uveitis-related CME.

3.
Ophthalmology ; 125(9): 1444-1451, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29602570

RESUMO

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

4.
Rheumatology (Oxford) ; 57(5): 856-864, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29471416

RESUMO

Objective: To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behçet's disease (BD). Methods: Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results: We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion: TCZ could be a therapeutic option in patients with BD and refractory uveitis.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome de Behçet/complicações , Receptores de Interleucina-6/antagonistas & inibidores , Uveíte/tratamento farmacológico , Adolescente , Adulto , Idoso , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Uveíte/diagnóstico , Uveíte/etiologia , Adulto Jovem
5.
Med. clín (Ed. impr.) ; 148(9): 394-400, mayo 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-162678

RESUMO

Introducción: El síndrome antifosfolípido (SAF) es un trastorno inmunitario adquirido, definido por la presencia de trombosis (arterial y/o venosa) y/o morbilidad del embarazo junto con la presencia de anticuerpos antifosfolipídicos (aFL) positivos. Existe una relación clara entre los aFL y algunas manifestaciones no incluidas en los criterios clínicos, entre ellas, las hematológicas. Objetivos: a) estudiar la probabilidad de desarrollar SAF clínico en pacientes con aFL positivos y trombocitopenia; b) identificar posibles factores de riesgo para trombosis, y c) estudiar la asociación entre trombocitopenia y aFL. Métodos: Estudio retrospectivo de 138 pacientes con aFL positivos sin cumplir criterios clínicos de SAF. Se definió trombocitopenia como una cifra de plaquetas≤100.000/μl. Se excluyeron los pacientes con otras causas de trombocitopenia. Resultados: Diecisiete de los 138 (12%) pacientes incluidos en el estudio presentaban trombocitopenia. La cifra media de plaquetas fue de 60.000/μl. El riesgo para desarrollar trombocitopenia fue mayor en los pacientes fumadores (OR 2,8; p=0,044), en aquellos con anticoagulante lúpico (OR 13,5; p<0,001) y en los que tenían una mayor carga de aFL (OR 50,8; p<0,001). Tras un seguimiento medio de 146±60,3 meses, 5 pacientes con trombocitopenia (29,4%) desarrollaron trombosis. Conclusiones: En nuestra serie, la incidencia de trombocitopenia es del 12%. Los pacientes con aFL positivos que desarrollan trombocitopenia tienen un riesgo potencial de desarrollar trombosis. El tabaco podría ser un factor de riesgo para trombocitopenia. La carga de autoanticuerpos es un factor de riesgo para el desarrollo de trombocitopenia (AU)


Introduction: The antiphospholipid syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis (arterial and/or venous) and/or pregnancy morbidity along with the presence of positive antiphospholipid antibodies (aPL). There is a clear relationship between aPL and some events not included in the clinical criteria, including haematologic. Objectives: a) to study the probability of developing clinical APS in patients with positive aPL and thrombopenia; b) to identify potential risk factors for thrombosis, and c) to study the association between thrombocytopenia and aPL. Methods: A retrospective study of 138 patients with positive aPL without fulfilling clinical criteria for APS. Thrombocytopenia was defined as a platelet count≤100,000/μl. Patients with other causes of thrombocytopenia were excluded. Results: Seventeen of the 138 (12%) patients in the study had thrombocytopenia. The mean platelet count was 60,000/μl. The risk of developing thrombocytopenia was higher in smokers (OR 2.8; P=.044), in those with lupus anticoagulant (OR 13.5; P<.001) and those with higher burden of aPL (OR 50.8; P<.001). After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis. Conclusions: In our series, the incidence of thrombocytopenia is 12%. aPL-positive patients who develop thrombocytopenia have a potential risk of developing thrombosis. Tobacco could be a risk factor for thrombocytopenia. Autoantibodies load is a risk factor for the development of thrombocytopenia (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Trombocitopenia/complicações , Trombose/epidemiologia , Síndrome Antifosfolipídica/epidemiologia , Fatores de Risco , Anticorpos Antifosfolipídeos/isolamento & purificação , Autoanticorpos/análise , Fumar/efeitos adversos , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , Comorbidade , Inibidor de Coagulação do Lúpus/isolamento & purificação
6.
Med Clin (Barc) ; 148(9): 394-400, 2017 May 10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28153433

RESUMO

INTRODUCTION: The antiphospholipid syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis (arterial and/or venous) and/or pregnancy morbidity along with the presence of positive antiphospholipid antibodies (aPL). There is a clear relationship between aPL and some events not included in the clinical criteria, including haematologic. OBJECTIVES: a) to study the probability of developing clinical APS in patients with positive aPL and thrombopenia; b) to identify potential risk factors for thrombosis, and c) to study the association between thrombocytopenia and aPL. METHODS: A retrospective study of 138 patients with positive aPL without fulfilling clinical criteria for APS. Thrombocytopenia was defined as a platelet count≤100,000/µl. Patients with other causes of thrombocytopenia were excluded. RESULTS: Seventeen of the 138 (12%) patients in the study had thrombocytopenia. The mean platelet count was 60,000/µl. The risk of developing thrombocytopenia was higher in smokers (OR 2.8; P=.044), in those with lupus anticoagulant (OR 13.5; P<.001) and those with higher burden of aPL (OR 50.8; P<.001). After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis. CONCLUSIONS: In our series, the incidence of thrombocytopenia is 12%. aPL-positive patients who develop thrombocytopenia have a potential risk of developing thrombosis. Tobacco could be a risk factor for thrombocytopenia. Autoantibodies load is a risk factor for the development of thrombocytopenia.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Trombocitopenia/complicações , Trombose/etiologia , Adolescente , Adulto , Idoso , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/imunologia , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/diagnóstico , Trombose/diagnóstico , Adulto Jovem
7.
Ocul Immunol Inflamm ; 25(5): 604-609, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27726475

RESUMO

PURPOSE: To evaluate tocilizumab (TCZ) efficacy in severe and refractory birdshot chorioretinopathy (BSCR). METHODS: Assessment of BSCR patients refractory to conventional immunosuppressive and anti-TNF-α drugs who underwent TCZ therapy. RESULTS: Two HLA-A29 positive patients (man/37 years and woman/38 years; four affected eyes) with BSCR were studied. They had a chronic bilateral posterior uveitis. Patient 1 had been treated with intraocular and oral corticosteroids, cyclosporine A, and infliximab whereas Patient 2 received intravenous methylprednisolone pulses, cyclosporine A, azathioprine, and adalimumab. At TCZ onset they had macular edema (four eyes); visual acuity (VA) impairment (four eyes); vitritis (one eye); and diffuse angiographic signs of vasculitis (periphlebitis) (two eyes). Improvement of VA and OCT was observed following TCZ therapy in both patients. After a follow-up of 18 months (Patient 1) and 10 months (Patient 2), respectively, a corticosteroid sparing effect without any adverse effects was achieved in both cases. CONCLUSIONS: TCZ was effective in two patients with BSCR refractory to anti-TNF-α agents.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Coriorretinite/tratamento farmacológico , Edema Macular/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Adulto , Coriorretinite/diagnóstico , Coriorretinite/fisiopatologia , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Edema Macular/diagnóstico , Edema Macular/fisiopatologia , Masculino , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Acuidade Visual/fisiologia
8.
Arthritis Rheumatol ; 69(3): 668-675, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27696756

RESUMO

OBJECTIVE: To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. RESULTS: We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 µm to 259.1 ± 39.5 µm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient. CONCLUSION: TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Juvenil/complicações , Receptores de Interleucina-6/antagonistas & inibidores , Uveíte/tratamento farmacológico , Uveíte/etiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
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