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3.
Gastroenterol. hepatol. (Ed. impr.) ; 42(5): 339-347, mayo 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-183784

RESUMO

Los objetivos actuales del tratamiento en la enfermedad inflamatoria intestinal (EII), tanto en enfermedad de Crohn como en colitis ulcerosa, son alcanzar la remisión clínica, endoscópica e idealmente histológica, mejorando de esta manera la calidad de vida de estos pacientes. Las terapias actuales son efectivas en lograr estos objetivos, pero no existen guías claras respecto de la duración óptima del tratamiento de mantención. Esta revisión tiene por objetivo evaluar la evidencia actual respecto del retiro de la terapia con 5-aminosalicilatos, tiopurínicos y metotrexato. A su vez, buscamos determinar grupos específicos de pacientes que, encontrándose en remisión y en ausencia de factores de riesgo, pudieran suspender la terapia con el menor riesgo de recaída posible


The current goals of treatment in inflammatory bowel disease, both Crohn's disease and ulcerative colitis, are to achieve clinical, endoscopic and ideally histological remission and improve the quality of life of these patients. Current therapies are effective in achieving remission in most cases, but there is a lack of clear guidelines on their optimal duration. This review aims to evaluate the current evidence on the withdrawal of therapy with 5-aminosalicylates, thiopurines and methotrexate. We also aim to identify which specific group of patients, while in remission and in the absence of risk factors, may be able to discontinue therapy without a significant risk of relapse


Assuntos
Humanos , Doença Inflamatória Pélvica/tratamento farmacológico , Qualidade de Vida , Metotrexato/administração & dosagem , Azatioprina/administração & dosagem , Suspensão de Tratamento , Fatores de Risco , Terapia Biológica
4.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(3): 181-181, abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-181706

RESUMO

Antecedentes: La dermatitis atópica (DA) es una enfermedad inflamatoria crónica de la piel típicamente infantil cuyas formas graves pueden afectar intensamente la calidad de vida del paciente. Existen formas refractarias al tratamiento convencional en las que es preciso emplear inmunosupresores sistémicos como la azatioprina (AZA) para alcanzar un buen control de la enfermedad. Objetivo: Evaluar la eficacia y la tolerancia de la AZA en niños con DA grave. Pacientes y métodos: Se realizó una revisión retrospectiva de niños con DA grave tratados con AZA entre enero de 2007 y mayo de 2017. Resultados: Se revisaron 11 pacientes (6 varones, 5 mujeres) con una edad promedio de 13 años (rango 8-18 años). La edad media ± DE al inicio del tratamiento fue de 10,9 ± 2,2 años (IC 95% 8,6-13,1). La media de la dosis inicial de AZA fue de 1,8 ± 0,2 mg/kg/d. Evaluamos la respuesta al tratamiento de nuestros pacientes a las 4 semanas, entre la semana 12 y la 16, y a partir de los 6 meses. La media del tratamiento fue de 10,8 ± 5,7 meses. Dos pacientes tuvieron que suspender el tratamiento por efectos adversos. Siete de los 9 pacientes restantes presentaron un aclaramiento completo o casi completo de la DA a los 6 meses de tratamiento. Conclusión: En nuestra experiencia, la AZA es bien tolerada y puede ser considerada como una opción terapéutica en los niños con DA grave refractaria a tratamientos convencionales


Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that typically affects children. Severe forms may have a profound effect on patients’ quality of life. Some forms are resistant to conventional treatment and require the use of systemic immunosuppressants such as azathioprine (AZA) to adequately manage the disease. Objective: To evaluate the effectiveness and tolerance of AZA in children with severe AD. Patients and methods: We performed a retrospective study of children with severe AD treated with AZA between January 2007 and May 2017. Results: We reviewed the cases of 11 patients (6 boys and 5 girls) with a mean age of 13 years (range, 8-18 years). The mean (SD) age at start of treatment was 10.9 (2.2) years (95% CI 8.6-13.1). The mean initial dosage of AZA was 1.8 (0.2) mg/kg/d. We evaluated treatment response after 4 weeks, 12 to 16 weeks, and 6 months. Mean treatment duration was 10.8 (5.7) months. Treatment had to be suspended in 2 patients because of adverse effects. Seven of the 9 remaining patients presented complete or almost complete clearance of the AD after 6 months of treatment. Conclusion: In our experience, AZA is well tolerated and may be considered as a treatment option in children with severe AD resistant to conventional treatment


Assuntos
Humanos , Criança , Adolescente , Dermatite Atópica/tratamento farmacológico , Azatioprina/administração & dosagem , Hospitais , Encaminhamento e Consulta/tendências
5.
J Coll Physicians Surg Pak ; 29(4): 379-380, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30925966

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune relapsing demyelinating disorder which often leads to severe disability typically targeting spinal cord, optic nerves, and brainstem. Around 75% of NMOSD patients have serum immunoglobulin-G (IgG) autoantibodies to the aquaporin-4 channel (AQP4-IgG). AQP4-IgG antibodies have a central role in new diagnostic criteria of NMOSD. These antibodies have a critical role in long-term management after the first attack. The prevalence of this disorder is lower than multiple sclerosis in European countries. However, NMO makes a substantial proportion of the demyelinating diseases of the central nervous system in countries like Pakistan, where it can be mistaken for multiple sclerosis. Accurate diagnosis is essential as some of the drugs for multiple sclerosis can potentially worsen NMOSD. We present a case of sequential optic neuritis with positive aquaporin 4 antibodies. We have discussed the history, examination findings, diagnostic workups, and treatment of the patient.


Assuntos
Aquaporina 4/sangue , Autoanticorpos/sangue , Neuromielite Óptica/diagnóstico , Neurite Óptica/diagnóstico , Adolescente , Azatioprina/administração & dosagem , Feminino , Humanos , Imunoglobulina G/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/terapia , Neurite Óptica/sangue , Neurite Óptica/terapia , Troca Plasmática/métodos , Prednisolona/administração & dosagem , Resultado do Tratamento
6.
Lupus ; 28(4): 565-568, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30862250

RESUMO

Organizing pneumonia is an inflammatory lung entity that presents with a huge variety of clinical, radiological and pathological patterns. Organizing pneumonia can be idiopathic or secondary to other diseases. Corticosteroid therapy is usually the first-line treatment showing clinical improvement in most cases. This report presents the case of a 56-year-old woman with systemic lupus erythematosus who was diagnosed with an organizing pneumonia and showed a poor response to steroid and azathioprine treatment. We considered the use of belimumab, which resulted in excellent clinical and radiological outcomes.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Bronquiolite Obliterante/tratamento farmacológico , Bronquiolite Obliterante/etiologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Anticorpos Antinucleares/sangue , Anticorpos Monoclonais Humanizados/administração & dosagem , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Bronquiolite Obliterante/sangue , Progressão da Doença , Tolerância a Medicamentos , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Leucocitose/sangue , Pulmão/diagnóstico por imagem , Pulmão/patologia , Lúpus Eritematoso Sistêmico/sangue , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Testes de Função Respiratória , Tomógrafos Computadorizados , Resultado do Tratamento
7.
Dig Dis Sci ; 64(6): 1612-1621, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30604371

RESUMO

BACKGROUND: The benefits of immunosuppressants for sustaining remission and preventing flares of IBD are well known. However, optimal timing for withdrawal has not been determined. AIMS: The objective of this study was to calculate the risk of relapse and predictors after withdrawal of azathioprine (AZA) monotherapy in patients who sustain deep remission. METHODS: This was a multicenter observational study of patients with IBD in remission whose immunosuppressant had been withdrawn. We recorded demographic variables, disease data, laboratory values, and the results of imaging tests performed at withdrawal and, in patients who relapsed, time to relapse and the efficacy of reintroducing the drug. RESULTS: Ninety-five patients were included (35 UC and 60 CD). The mean duration of AZA treatment was 87 and 77 months for UC and CD, respectively. Endoscopic remission was evaluated in 23 patients with UC and 35 with CD. After AZA withdrawal, 91% patients with UC and 67% with CD received high doses of salicylates. A total of 26 patients relapsed. The cumulative relapse rate at 5 years was 46% for CD and UC. AZA was reintroduced in 19 patients, of whom 14 responded. Predictors of relapse were corticosteroid dependence, early introduction of AZA (CD), and late introduction of AZA (UC). CONCLUSIONS: Almost half of the patients in whom AZA was withdrawn were in remission at 5 years. The candidates for withdrawal could be better identified based on corticosteroid dependence, previous surgery, timing of initiation, and indication for AZA.


Assuntos
Azatioprina/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Imunossupressores/administração & dosagem , Corticosteroides/administração & dosagem , Adulto , Idoso , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Recidiva , Indução de Remissão , Fatores de Risco , Espanha , Fatores de Tempo
8.
Med Hypotheses ; 122: 120-123, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30593393

RESUMO

Retroperitoneal fibrosis (RF) is part of a rare fibrosclerotic disorder. Oral steroids are the initial treatment. Steroid combination with other immunosupressants is used in refractory cases. Steroids refractoriness has been observed in chronic cases. Some cases of RF represent a manifestation of the IgG4 related disease (IgG4-RD) that is associated to a dramatic response to steroid therapy. It is uncertain if RF́s treatment response differs according to its association with IgG4-RD. We hypothesize that RF́s treatment response to steroids depends on the association with IgG4-RD, thus, we collected and compared clinical data from 10 RF cases; 6 male, mean age 50.6 (±16.15 SD) years. Mean FU was 28 (±25.7 SD) months. According to IgG4 levels, patients were categorized as idiopathic RF (IRF n = 5) or RF-IgG4-RD (n = 5). Therapy response was categorized as complete, partial, stable disease, recurrence or non-response. Nine cases received initial therapy with prednisone; complete response was achieved in 4 RF-IgG4 RD. The remaining 5 cases (1 RF-IgG4RD and 4 IRF) underwent a 2nd line therapy; 4 prednisone + tamoxifen and 1 prednisone + azathioprine. Prednisone + tamoxifen combination achieved complete response in 1 case (RF-IgG4RD), partial response in 1 IRF; in 1 IRF case, disease remained stable and 1 did not respond. The prednisone + azathioprine treatment achieved complete response. At follow-up all patients remained stable and no recurrence was registered. These observations suggest and support the hypothesis that response to steroid monotherapy depends on the association of RF with IgG4, suggesting that IRF cases might benefit from initial combination therapies instead of steroid monotherapy.


Assuntos
Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/imunologia , Fibrose Retroperitoneal/tratamento farmacológico , Fibrose Retroperitoneal/imunologia , Esteroides/uso terapêutico , Adulto , Idade de Início , Idoso , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Azatioprina/administração & dosagem , Feminino , Seguimentos , Humanos , Imunoglobulina G/imunologia , Doença Relacionada a Imunoglobulina G4/complicações , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Prospectivos , Fibrose Retroperitoneal/complicações , Estudos Retrospectivos , Tamoxifeno/administração & dosagem , Resultado do Tratamento
9.
Mod. rheumatol ; 29(1)2019.
Artigo em Inglês | BIGG | ID: biblio-1015359

RESUMO

The Japan Research Committee for Intractable Vasculitis has fully revised the clinical practice guidelines (CPG) for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) to improve and standardize the medical treatment of the disease in Japan. The previous CPG was published in a classical review style in Japanese in 2011 and 2014. We adopted the Grading of Recommendations Assessment, Development and Evaluation system for this revision, and various stakeholders, including patients, participated in it. The expected users of this CPG are AAV patients in Japan and their families and healthcare professionals, including both AAV specialists and non-specialists. We set clinical questions concerning the three important clinical topics of remission induction therapy, plasma exchange, remission maintenance therapy, and developed eight recommendation statements. For remission induction therapy for newly developed AAV, we weakly recommend glucocorticoid (GC) plus intravenous cyclophosphamide pulse (IVCY) or oral cyclophosphamide (POCY) rather than GC alone, and IVCY rather than POCY. We also weakly recommend CY rather than rituximab. In the case of AAV with severe renal impairment, we weakly recommend plasma exchange as a conjunction therapy. We weakly recommend azathioprine for remission maintenance therapy. The revised CPG has demonstrated evidence-based treatment recommendations for AAV.


Assuntos
Humanos , Azatioprina/administração & dosagem , Azatioprina/uso terapêutico , Plasmaferese/métodos , Ciclofosfamida/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Quimioterapia de Manutenção , Rituximab/uso terapêutico
11.
Curr Gastroenterol Rep ; 20(11): 53, 2018 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-30267281

RESUMO

PURPOSE OF REVIEW: The increased use of biologic agents over the past two decades has led to a reappraisal of the role of the immunomodulators (thiopurines and methotrexate) in the treatment of inflammatory bowel disease. The purpose of this review is to summarize recent data on the use of thiopurines and methotrexate either as monotherapy or as part of combination therapy with biologic agents. RECENT FINDINGS: Recent studies have addressed the need for concomitant immunomodulatory therapy in treatment-naïve patients starting anti-TNF-α therapy, the appropriate dose of the immunomodulator in this setting, the minimum duration of combination therapy, and the possible mechanisms by which immunomodulators enhance the effectiveness of anti-TNF-α agents. Little is known about the role of immunomodulators in combination with agents belonging to other classes of biologic therapies. Recent studies have shown that methotrexate is not effective in inducing or maintaining remission in ulcerative colitis. Finally, several studies have broadened our understanding of the infection and malignancy risks of the immunomodulators. Immunomodulators continue to have a place in the treatment of inflammatory bowel disease. However, with the ever-increasing list of biologic agents, properly positioning the immunomodulators within the overall therapeutic scheme is a complicated task. In order to optimize outcomes, each patient requires an individualized approach, which takes into account risks, benefits, cost, alternatives, and patient preferences.


Assuntos
Fármacos Gastrointestinais/administração & dosagem , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Metotrexato/administração & dosagem , Purinas/administração & dosagem , Compostos de Enxofre/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Azatioprina/administração & dosagem , Fatores Biológicos/administração & dosagem , Fatores Biológicos/uso terapêutico , Quimioterapia Combinada , Fármacos Gastrointestinais/uso terapêutico , Humanos , Fatores Imunológicos/administração & dosagem , Mercaptopurina/administração & dosagem , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Purinas/uso terapêutico , Compostos de Enxofre/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores
12.
Medicine (Baltimore) ; 97(34): e11814, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30142769

RESUMO

Azathioprine (AZA) 2 to 2.5 mg/kg/d is recommended for European patients with Crohn disease (CD), but several Asian studies reported that low dose of AZA was also effective to treat CD. To confirm those observations, we perform this prospective observational study to compare the efficacy and safety of low and standard doses of AZA in the treatment of active CD.This was a prospective, open-labeled observational study. Two hundred twenty-six active CD patients were divided into 2 groups and treated with AZA 1.5 or 2.0 mg/kg/d respectively, combined with steroid therapy. Patients were followed up for 96 weeks. The complete remission (CR) rate, response rate, relapse rate, and adverse effect rate were assessed at weeks 24, 48, and 96 by intention-to-treat (ITT) analysis.Azathioprine 1.5 mg/kg/d showed no significant difference compared with AZA 2 mg/kg/d in CR rate, response rate and relapse rate by ITT analysis at week 24, 48, or 96 (all P > .05). Their adverse effect rates had no significant difference either (P > .05). Up to 21.7% (49/226) of the patients reported adverse events and 69.4% (34/49) of them were myelosuppresion.Azathioprine 1.5 mg/kg/d combined with steroids is as effective as AZA 2.0 mg/kg/d to induce remission of active CD in the first 6 months, and to maintain remission of inactive CD in the first 2 years, without increasing the recurrence of active CD after clinical remission. The most common adverse effect is myelosuppression.


Assuntos
Azatioprina/administração & dosagem , Doença de Crohn/tratamento farmacológico , Imunossupressores/administração & dosagem , Adulto , Azatioprina/efeitos adversos , Feminino , Seguimentos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento
13.
Molecules ; 23(7)2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30018218

RESUMO

Thiopurines (TP) represent an important therapeutic tool for the treatment of inflammatory bowel diseases (IBD) in the current situation of rising incidence and health care costs. The results of multiple clinical studies aimed at finding correlations between levels of TP metabolites and response of IBD patients to the treatment are, however, often controversial due to variability in analytical and sample preparation procedures among these studies. In this work, therefore, an updated analytical and sample preparation procedure for therapeutic drug monitoring (TDM) of TP metabolites in blood samples obtained from patients with IBD was proposed to establish a unified protocol. An advanced analytical method based on ion-exchange liquid chromatography hyphenated with tandem mass spectrometry (IEC-ESI-MS/MS) was used for the determination of the profiles of 12 individual TP metabolites in the particular steps of sample preparation procedure including blood collection, red blood cells (RBC) isolation, lysis, and storage. Favorable performance parameters of the IEC-ESI-MS/MS method (LLOQs 1⁻10 nmol/L, accuracy 95⁻105%, intra-day and inter-day precision < 10%, selectivity demonstrated via no sample matrix interferences) and acceptable stability (peak area fluctuations < 15%) of clinical samples under the proposed sample preparation conditions {(i) EDTA anticoagulant tube for the blood collection; (ii) 4 °C and 4 h between the sample collection and RBC isolation; (iii) phosphate-buffered saline for RBC washing and re-suspendation; (iv) -20 °C for RBC lysis and short-term storage; (v) 50 mmol/L phosphate buffer, pH 7.4, 10 mmol/L DTT as a stabilizing medium for TPN in RBC lysates} demonstrated the suitability of such protocol for a well-defined and reliable routine use in studies on thiopurines TDM.


Assuntos
Azatioprina , Monitoramento de Medicamentos/métodos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mercaptopurina , Tioguanina , Adulto , Azatioprina/administração & dosagem , Azatioprina/farmacocinética , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Mercaptopurina/administração & dosagem , Mercaptopurina/farmacocinética , Pessoa de Meia-Idade , Tioguanina/administração & dosagem , Tioguanina/farmacocinética
15.
BMJ Case Rep ; 20182018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29848539

RESUMO

Sarcoidosis is a multisystem disease of unknown aetiology with pulmonary involvement in most patients. Uveitis is common and often characteristic. We report a case of ocular sarcoidosis with grossly atypical contiguous optic neuropathy and choroiditis and describe the diagnostic challenges in this highly unusual presentation. High-dose systemic corticosteroid and immunosuppressive treatment was required for sustained control of intraocular inflammation.


Assuntos
Oftalmopatias/diagnóstico , Sarcoidose/diagnóstico , Corticosteroides/administração & dosagem , Azatioprina/administração & dosagem , Corioidite/diagnóstico , Corioidite/tratamento farmacológico , Diagnóstico Diferencial , Esquema de Medicação , Quimioterapia Combinada , Oftalmopatias/tratamento farmacológico , Feminino , Humanos , Imunossupressores/administração & dosagem , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/tratamento farmacológico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisolona/administração & dosagem , Sarcoidose/tratamento farmacológico , Tomografia de Coerência Óptica , Uveíte/diagnóstico , Uveíte/tratamento farmacológico
16.
J Gastroenterol Hepatol ; 33(11): 1834-1838, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29664147

RESUMO

BACKGROUND AND AIM: Nonadherence is a risk factor of disease worsening in inflammatory bowel disease (IBD). We analyzed the frequency, predictors, and clinical outcomes of patients with IBD who are lost to follow-up in outpatient clinics. METHODS: Medical records of 784 IBD patients visiting our IBD clinic between January 2010 and December 2015 were reviewed retrospectively. Overall, 285 newly diagnosed IBD patients who were followed up for at least 12 months were included in the analysis. RESULTS: For 285 IBD patients (161 ulcerative colitis and 124 Crohn's disease), the mean disease duration was 66.3 ± 34.0 months (7-137 months). Forty-two patients (14.7%; 27 ulcerative colitis and 15 Crohn's disease) were lost to follow-up. On multivariate regression analysis, travel time to clinic (odds ratio, 2.37; 95% confidence interval, 1.63-3.45; P = 0.01) and C-reactive protein levels at diagnosis (odds ratio, 0.63; 95% confidence interval, 0.43-0.68; P = 0.01) were significantly associated with follow-up loss. Among the 42 patients lost to follow-up, 36 (85.7%) revisited the clinic. The cause of revisit was disease flare-up in 22 patients (61.1%). Step-up treatment was needed in 15 patients (41.7%). Steroid was introduced in 14 patients (38.9%). Azathioprine and an antitumor necrosis factor agent were newly prescribed in three patients (8.3%) and one patient (2.8%), respectively. CONCLUSIONS: Follow-up loss rate for IBD patients in remission state was 14.7%, and the predictors were far from hospital and low C-reactive protein levels. Because most of follow-up loss patients experienced flare-up, clinicians need to try to encourage patients to keep their adherence.


Assuntos
Doenças Inflamatórias Intestinais , Perda de Seguimento , Cooperação do Paciente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Azatioprina/administração & dosagem , Biomarcadores/sangue , Proteína C-Reativa , Feminino , Seguimentos , Previsões , Glucocorticoides/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Exacerbação dos Sintomas , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
17.
Curr Gastroenterol Rep ; 20(5): 18, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29623442

RESUMO

PURPOSE OF REVIEW: Therapeutic drug monitoring (TDM) has emerged as a useful tool to optimize the use of drug therapies in adults with inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC), especially during the use of biological therapies, for which the pharmacokinetics and pharmacodynamics are highly variable among patients. Fewer data exist in children. This review examines the current literature on TDM in pediatric IBD. RECENT FINDINGS: Drug clearance is affected by a number of patient and disease factors. For thiopurines, adjusting dosing by monitoring 6-thioguanine (6TGN) and 6-methylmercaptopurine ((6MMP) levels is demonstrated to maximize response and minimize toxicity, while monitoring metabolite levels when treating with anti-tumor necrosis factor (anti-TNF) remain controversial. While in adults the use of TDM in the setting of loss of response to anti-TNF therapy is established, in children, only a small number of studies exist, but these too have encouraging results. There are however, conflicting data regarding the optimal timing of TDM, comparing "reactive" monitoring and "proactive" monitoring. No such data exist in pediatrics. TDM is cost-effective, and dose reduction may represent a safety benefit. There are limited adult data for use of TDM for the newer biologics, vedolizumab and ustekinumab, but early results suggest similarly promising utility. The use of TDM in pediatric IBD is increasing in clinical practice, with similar efficacy to adults demonstrated in children with loss of response to anti-TNF therapy. More prospective studies are needed in children to examine proactive monitoring and utility of TDM with newer biologics.


Assuntos
Produtos Biológicos/sangue , Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/sangue , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Azatioprina/administração & dosagem , Azatioprina/sangue , Azatioprina/uso terapêutico , Produtos Biológicos/administração & dosagem , Produtos Biológicos/uso terapêutico , Criança , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Humanos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/administração & dosagem , Ustekinumab/sangue , Ustekinumab/uso terapêutico
18.
Dig Liver Dis ; 50(7): 682-688, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29525182

RESUMO

AIMS: To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. METHODS: A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. RESULTS: Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance. 64/89 (72%) had Crohn's disease, 38 (43%) were males, median age at switch was 40y (range 17-78), median IBD duration 6y (0-29). Median follow-up was 1.9y (0-5). Reasons for switching to co-therapy included fatigue (37%), hepatotoxicity (23%), nausea (23%), arthralgia (10%), headache (12%) and hypersensitivity reaction (4%). Overall, 66 (74%) patients remained on co-therapy until most recent review and achieved a clinical response. High rates of overcoming intolerance (62-100%) occurred with co-therapy for all reasons above, although fatigue was less amenable to switching than non-fatigue indications (62% vs 91%, p = <0.001). Of 34 patients not escalated to biologics with endoscopic data, 15 were in remission (44%) at most recent review. CONCLUSION: Low-dose thiopurine combined with allopurinol appears safe and effective in overcoming intolerances to thiopurine monotherapy in many cases.


Assuntos
Alopurinol/administração & dosagem , Azatioprina/administração & dosagem , Imunossupressores/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adolescente , Adulto , Idoso , Alopurinol/efeitos adversos , Austrália , Azatioprina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Quimioterapia Combinada , Fadiga , Feminino , Humanos , Imunossupressores/efeitos adversos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
19.
Medicine (Baltimore) ; 97(8): e0004, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29465536

RESUMO

RATIONALE: Primary cutaneous amyloidosis (PCA) is a localized skin disorder characterized by the abnormal deposition of amyloid in the extracellular matrix of the dermis. The association between PCA and other diseases, although rare, has been documented for various autoimmune diseases. PCA associated with autoimmune hepatitis-primary biliary cirrhosis (AIH-PBC) overlap syndrome and Sjögren syndrome (SS) has not been previously reported in the literature. PATIENT CONCERNS: A 50-year-old woman presented with progressive abnormal liver enzyme levels and was referred to our department. DIAGNOSES: Due to the patient's symptoms, laboratory test results, radiographic findings, and pathologic results, she was diagnosed with PCA associated with AIH-PBC overlap syndrome and SS. INTERVENTIONS: She was subsequently treated with a combination of ursodeoxycholic acid (UDCA), prednisone, and azathioprine. OUTCOMES: While this treatment can achieve therapeutic success, it cannot prevent complications from cirrhosis. This patient remains alive but experienced an emergent gastrointestinal hemorrhage. LESSONS: While we acknowledge that this is a single case, these findings extend our knowledge of immunological diseases associated with PCA and suggest a common, immune-mediated pathogenic pathway between PCA, AIH-PBC overlap syndrome, and SS. After 12 years of follow up, clinical manifestations have developed, and these autoimmune diseases have progressed. The combination of UDCA, prednisone, and azathioprine can achieve therapeutic success but cannot prevent disease progression. Routine follow up for this patient is necessary to document disease progression.


Assuntos
Amiloidose Familiar/imunologia , Hepatite Autoimune/complicações , Cirrose Hepática Biliar/complicações , Síndrome de Sjogren/complicações , Dermatopatias Genéticas/imunologia , Doenças do Tecido Conjuntivo Indiferenciado/complicações , Amiloidose Familiar/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Azatioprina/administração & dosagem , Colagogos e Coleréticos/administração & dosagem , Quimioterapia Combinada , Feminino , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Humanos , Imunossupressores/administração & dosagem , Cirrose Hepática Biliar/tratamento farmacológico , Cirrose Hepática Biliar/imunologia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/imunologia , Dermatopatias Genéticas/tratamento farmacológico , Resultado do Tratamento , Doenças do Tecido Conjuntivo Indiferenciado/tratamento farmacológico , Doenças do Tecido Conjuntivo Indiferenciado/imunologia , Ácido Ursodesoxicólico/administração & dosagem
20.
Rheumatol Int ; 38(4): 557-568, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29450636

RESUMO

Cyclophosphamide (CYC) has been the backbone immunosuppressive drug to achieve sustained remission in lupus nephritis (LN). The aim was to evaluate the efficacy and compare adverse effects of low and high dose intravenous CYC therapy in Indian patients with proliferative lupus nephritis. An open-label, parallel group, randomized controlled trial involving 75 patients with class III/IV LN was conducted after obtaining informed consent. The low dose group (n = 38) received 6 × 500 mg CYC fortnightly and high dose group (n = 37) received 6 × 750 mg/m2 CYC four-weekly followed by azathioprine. The primary outcome was complete/partial/no response at 52 weeks. The secondary outcomes were renal and non-renal flares and adverse events. Intention-to-treat analyses were performed. At 52 weeks, 27 (73%) in high dose group achieved complete/partial response (CR/PR) vs 19 (50%) in low dose (p = 0.04). CR was higher in the high dose vs low dose [24 (65%) vs 17 (44%)], although not statistically significant. Non-responders (NR) in the high dose group were also significantly lower 10 (27%) vs low dose 19 (50%) (p = 0.04). The change in the SLEDAI (Median, IQR) was also higher in the high dose 16 (7-20) in contrast to the low dose 10 (5.5-14) (p = 0.04). There was significant alopecia and CYC-induced leucopenia in high dose group. Renal relapses were significantly higher in the low dose group vs high dose [9 (24%) vs 1(3%), (p = 0.01)]. At 52 weeks, high dose CYC was more effective in inducing remission with decreased renal relapses in our population. TRIAL REGISTRATION: The study was registered at http://www.clintrials.gov . NCT02645565.


Assuntos
Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Administração Intravenosa , Azatioprina/administração & dosagem , Ciclofosfamida/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Humanos , Imunossupressores/efeitos adversos , Índia , Quimioterapia de Indução , Análise de Intenção de Tratamento , Nefrite Lúpica/diagnóstico , Recidiva , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento
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