RESUMO
Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission.
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BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/administração & dosagem , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Sistema de Registros , Indução de Remissão , Espanha , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Adulto JovemRESUMO
INTRODUCTION: Autologous haematopoietic stem cell transplantation (AHSCT) is an accepted treatment in refractory Crohn's disease (CD). MATERIAL AND METHODS: Data on patients with refractory CD subjected to AHSCT are collected at the Hospital Universitario Ramón y Cajal in Madrid and the results obtained are described retrospectively. RESULTS: Seven patients in total have received AHSCT due to refractory CD in our centre. Three patients (43%) presented with clinical and endoscopic remission; one patient (14%) clinical improvement without remission and three patients (43%) remained active with the need to restart treatment in the assessment of the initial response to the AHSCT (after six months). Symptoms recurred in five of the seven patients (71%) and all of them had to restart medical treatment after an average of 13.8 months (range: 3-30 months). Only one patient needed surgery after the AHSCT. At the end of the follow-up, after a mean of 48 months (range: 17-78 months), 5/7 (71%) of the patients were in clinical remission with or without treatment. CONCLUSION: AHSCT may be a promising therapeutic option for patients with refractory CD. Its usefulness lies in the fact that it can produce clinical remission without treatment in some patients, but also that it can make the disease treatable, obtaining a response to certain treatments in patients who had previously lost it.
Assuntos
Doença de Crohn/cirurgia , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Feminino , Hospitais Universitários , Humanos , Masculino , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto JovemAssuntos
Hérnia Ventral/cirurgia , Herniorrafia , Laparoscopia , Complicações Pós-Operatórias/etiologia , Enteropatias Perdedoras de Proteínas/etiologia , Feminino , Humanos , Hipoalbuminemia/etiologia , Linfangiectasia Intestinal/etiologia , Pessoa de Meia-Idade , Pancreatectomia , Pancreatite/complicações , Pancreatite/cirurgia , Pancreatite/terapia , Nutrição Parenteral , Indução de Remissão , Esplenectomia , Veia Esplênica , Trombose Venosa/etiologiaRESUMO
La microbiota intestinal se define como el conjunto de microorganismos que habitan de forma natural en el tubo digestivo. Bacterias, hongos y virus se incluyen dentro de este ente fisiológico que va mucho más allá de ser un mero espectador pasivo de la mucosa intestinal. La microbiota interviene de forma activa en la homeostasis y su desregulación se ha relacionado con múltiples enfermedades de naturaleza infecciosa, metabólica y autoinmunitaria. El trasplante de microbiota fecal (TMF) consiste en la introducción de una solución de materia fecal debidamente procesada procedente de un donante sano en el tracto gastrointestinal de otro individuo con el fin de manipular las características de la microbiota del receptor. Aunque pueda parecer algo novedoso, los primeros casos se remontan a la época de la China Imperial; no obstante, no ha sido hasta los últimos 20 años cuando el interés y la actividad investigadora en este campo se han multiplicado de forma exponencial. Fruto de este trabajo el TMF constituye hoy en día una herramienta eficaz y validada en casos refractarios de diarrea por C. Difficile. Aunque la evidencia científica es menor, ya existen ensayos clínicos que evalúan su beneficio en la enfermedad inflamatoria intestinal y en el síndrome metabólico. Lo atractivo de su mecanismo fisiopatológico, la sencillez del procedimiento y su bajo coste lo sitúan como un tratamiento prometedor en múltiples enfermedades extradigestivas. El objetivo de esta revisión es resumir de una forma concisa, rigurosa y actualizada las indicaciones, metodología y seguridad del TMF.
The intestinal microbiota is defined as the set of organisms that live in the digestive tract. Bacteria, fungi and viruses are included in a physiological entity that goes far beyond being a passive spectator of the intestinal mucosa. The microbiota is actively involved in homeostasis and its imbalance has been linked to multiple infectious, metabolic and autoimmune diseases. Fecal microbiota transplantation (FMT) consists in the introduction of a solution made with processed stool from a healthy donor into the gastrointestinal tract of another individual in order to manipulate the characteristics of the receiver microbiota. Although it may seem new, the first cases date back to the days of Imperial China; however, it was not until the past 20 years when the interest and research in this field have grown exponentially. Nowadays, TMF is an effective and validated treatment in refractory cases of C.difficile diarrhea. Although the scientific evidence is less, there are clinical trials evaluating its benefit in inflammatory bowel disease and metabolic syndrome. The appeal of its pathophysiological mechanism, the simplicity of the procedure and its low cost place FMT as a promising treatment for multiple extraintestinal diseases. The objective of this review is to summarize in a concise, thorough and updated form its indications, methodology and safety.
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Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Transplante de Microbiota Fecal/métodos , Transplante de Microbiota Fecal/normas , Microbioma Gastrointestinal/fisiologia , Seleção do Doador , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/história , Doenças Inflamatórias Intestinais/terapia , Técnicas Microbiológicas , EspanhaAssuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Osso e Ossos/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Beclometasona/administração & dosagem , Beclometasona/efeitos adversos , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Compostos de Cálcio/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , Atenção Primária à Saúde/normas , Espanha , Vitamina D/administração & dosagem , Vitaminas/administração & dosagemAssuntos
Anticoagulantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Enoxaparina/efeitos adversos , Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Substituição de Medicamentos , Enoxaparina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Trombose Venosa/tratamento farmacológicoRESUMO
Motor involvement in herpes zoster is very infrequent, occurring in 3%-5% of cases, and it is caused by extension of the inflammatory process to the anterior horn motor neurons, with the subsequent development of segmental motor paralysis. The authors report a 37-yr-old woman with history of paresis in both lower limbs secondary to spinal cord atrophy associated with Vogt-Koyanagi-Harada disease and immunosuppression caused by chronic corticosteroid and azathioprine treatment of ulcerative colitis, who developed worsening of her baseline residual muscle strength in the right lower limb shortly after herpes zoster eruption. Electromyography revealed acute denervation in territories corresponding to L3-L4 and moderate widespread axonal polyneuropathy affecting both lower limbs. The patient recovered her baseline muscle strength after this event. To the best of the authors' knowledge, this is the first reported case of herpes zoster motor neuropathy in a patient with a previous motor sequel.
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Herpes Zoster/complicações , Polineuropatias/virologia , Síndrome Uveomeningoencefálica/complicações , Adulto , Azatioprina/administração & dosagem , Colite Ulcerativa/complicações , Progressão da Doença , Eletromiografia , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Imageamento por Ressonância Magnética , Paresia/etiologia , Prednisona/administração & dosagemRESUMO
INTRODUCTION: In ulcerative colitis, aminosalicylates are the mainstay of maintenance therapy. Sulfasalazine was the first aminosalicylic used in the maintenance therapy of this disease. Later, mesalazine was preferred due to its supposedly better tolerability. However, recent studies indicate certain benefits of the use of sulfasalazine because of its possible superior effectiveness. The aim of this study was to determine whether patients with ulcerative colitis poorly controlled by mesalazine as maintenance therapy respond to sulfasalazine, thus avoiding the use of immunosuppressive or biological therapies. METHODS: The Inflammatory Bowel Disease Clinic of the Ramón y Cajal Hospital maintains a database in which all drug exposures are registered. We selected patients poorly controlled with mesalazine who had received sulfasalazine as rescue maintenance therapy. We determined the percentage of patients poorly controlled with mesalazine who responded to sulfasalazine. RESULTS: Of 415 patients with ulcerative colitis, 49 had been treated with sulfasalazine at some time. Of these, sulfasalazine was selected as an alternative therapy due to poor disease control with mesalazine. The median duration of mesalazine therapy until the switch was 20.8 months, with a median dose of 3.35 g/day. In 21 of the 31 patients (67.7%), sulfasalazine was able to control symptoms and maintain remission. CONCLUSION: Despite the limitations of this study, we found that 67.7% of patients with ulcerative colitis poorly controlled with mesalazine responded to a switch to sulfasalazine. These patients would normally have progressed to immunosuppressive, biological or surgical treatments. This option merits further studies. Meanwhile sulfasalazine should not be forgotten in the management of ulcerative colitis.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Sulfassalazina/uso terapêutico , Fatores Biológicos/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Mesalamina/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: Active smoking has been associated with a higher risk of developing Crohn's disease (CD). However, its impact on clinical outcomes has been controversial among studies. AIMS: To evaluate the influence of active smoking on initial manifestations of CD, the development of disease-related complications, and therapeutic requirements. METHODS: Patients diagnosed with CD within a ten-year period (1994-2003) were identified. Clinical and therapeutic features until October 2008 or loss of follow-up were recorded. Smoking status was assessed at each major disease-related event (e.g. penetrating and stricturing complications, perianal disease, intestinal resection, introduction of immunomodulators or biological agents). RESULTS: A total of 259 patients were included in the study with a median follow-up period of 91 months. At diagnosis, 50.5% were active smokers and only 12% of them quit smoking during follow-up, mostly after a major disease-related event occurred. Smoking at diagnosis was not associated with a particular CD presentation. Active smoking did not influence the development of strictures, intraabdominal and perianal penetrating complications, or increased resectional surgery, biological therapy or immunomodulators requirements. CONCLUSIONS: Patients who develop CD while smoking seem to have a similar disease course to those who never smoked.
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Doença de Crohn/patologia , Progressão da Doença , Fumar/efeitos adversos , Adulto , Doença de Crohn/complicações , Doença de Crohn/terapia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Abandono do Hábito de Fumar/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Although the early outcomes of ulcerative colitis after a first course of corticosteroids are well known, data on long-term disease evolution in patients responding to a first corticosteroid course are scarce. AIMS: To evaluate the long-term clinical evolution in ulcerative colitis patients responding to a first course of corticosteroids and to identify those factors associated with a poorer outcome. METHODS: Retrospective review of 114 patients diagnosed with ulcerative colitis who responded to the first corticosteroid course, and did not start thereafter maintenance therapy with thiopurines were included. RESULTS: Corticosteroids were prescribed because of a moderate (78%) or a severe flare (22%). All but two patients followed maintenance treatment with mesalazine after corticosteroid discontinuation. After a median follow-up of 83 months (7-156), 72% of patients suffered new relapses leading to corticosteroid reintroduction in 65% of patients. The earlier corticosteroids were introduced in the course of ulcerative colitis, the higher the risk of relapse and corticosteroid reintroduction. Thiopurines were started in 51%, and infliximab in 19%. Eleven percent of patients underwent colectomy. No predictors of thiopurine use or colectomy were found. CONCLUSIONS: Half of the ulcerative colitis patients responding to a first course of corticosteroids will require immunosuppressors mainly because of steroid-dependence.
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Corticosteroides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Distribuição de Qui-Quadrado , Colectomia , Colite Ulcerativa/cirurgia , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Infliximab , Estimativa de Kaplan-Meier , Masculino , Mesalamina/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response. METHODS: Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed. RESULTS: 174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to every week. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them. CONCLUSIONS: Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Imunossupressores/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Abscesso/induzido quimicamente , Adalimumab , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Azatioprina/administração & dosagem , Azatioprina/uso terapêutico , Terapia Combinada , Doença de Crohn/complicações , Doença de Crohn/patologia , Doença de Crohn/cirurgia , Fístula Cutânea/tratamento farmacológico , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Hospitais Urbanos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Fístula Retal/tratamento farmacológico , Estudos Retrospectivos , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
OBJECTIVES: Inflammatory bowel disease is associated with a high risk of deficient adherence to therapy. Our study was designed to analyze the adherence to treatment in a specialized inflammatory bowel disease clinic, and to study which factors could influence it. METHODS: 107 consecutive patients (64% Crohn's disease, 36% ulcerative colitis) filled up an anonymous survey with data on demography, disease, therapy and a self-applied adherence declaration. RESULTS: A 69% (95%CI: 60-77%) showed some type of non-adherence. A 66% (95 CI%: 57-75%) acknowledged some involuntary non-adherence: either forgetting to take their dose (63%) or being careless about having taken it (27%). A 16% (95 CI%: 9-22%) showed some voluntary non-adherence: interrupting the therapy when feeling better (13%) or when feeling worse (6%). A 25% forgot at least a dose a week in the last 12 months. Multivariate analysis identified as risk factors for a lower adherence the dosing in three or more takes a day (OR 3; 95%CI: 1.1-8.4; p=0.03) and feeling little informed about their disease (OR 4.9; 95%CI: 1.1-23.8; p=0.04). Immunomodulator therapy predicted better adherence (OR 0.29; 95%CI: 0.11-0.74; p=0.01). CONCLUSIONS: Adherence to therapy in inflammatory bowel disease patients is not satisfactory, and worse in patients treated with mesalazine. Optimizing the information on the disease and giving the medication in one or two daily doses could enhance therapeutic adherence.
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Doenças Inflamatórias Intestinais/tratamento farmacológico , Adesão à Medicação , Adulto , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/psicologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/psicologia , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/psicologia , Masculino , Adesão à Medicação/psicologia , Análise Multivariada , Razão de Chances , Educação de Pacientes como AssuntoRESUMO
OBJECTIVES: Immunomodulators are used as maintenance treatment of inflammatory bowel disease (IBD). Data regarding their possible effects in the course of pregnancy when the father is exposed at the time of conception are limited. METHODS: To evaluate the outcomes of pregnancies of which the fathers were exposed to thiopurines at the time of conception. A series of male patients followed in seven IBD clinics in Madrid, Spain, was studied. Any exposure to thiopurines during the 3 months preceding conception was considered significant. Controls were pregnancies fathered by patients who either had never been treated with thiopurines or had interrupted them >3 months before conception. Statistical comparisons and multivariate analysis were carried out with the generalized estimating equations model. RESULTS: There were 46 conceptions in the exposed group (mercaptopurine 9, azathioprine 37) and 84 in the control group. In the exposed group, there were more Crohn's patients (82.6% vs. 53.6%), the duration of the disease was longer (median: 8 vs. 5 years), fathers were slightly older (mean: 34.2 vs. 32.7 years), and there were fewer patients on mesalamine (15.2% vs. 47.6%). Otherwise, baseline characteristics were similar in both groups. There were no significant differences regarding unsuccessful pregnancies-namely, spontaneous abortions, ectopic pregnancies, anembryonic pregnancies, or fetal deaths (10.9% exposed group vs. 13.1% control group; odds ratio (OR): 0.79, confidence interval (CI): 0.22-2.85), preterm births (4.3% vs. 2.4%; OR: 1.3, CI: 0.22-7.61), low birth weight (6.5% vs. 6%; OR: 1.06, CI: 0.25-4.54), or congenital malformations (2.2% vs. 2.4%; OR: 0.82, CI: 0.08-9). No infant neoplasms were detected. The proportion of conceptions that needed >1 year to be achieved was higher in the exposed group, but this was not statistically significant (15.2% vs. 8.3%; OR: 1.92, CI: 0.54-6.88). Multivariate analysis was carried out for unsuccessful pregnancies and fertility impairment, and it showed that, although mesalamine exposure confounded the effect of the exposure to thiopurines on these outcomes, this effect was still nonsignificant (respectively, OR: 0.49, CI: 0.17-1.44; OR: 2.82, CI: 0.7-11.38). CONCLUSIONS: Our data do not support the practice of routinely recommending to male patients that they interrupt thiopurines when wanting to conceive.