RESUMEN
BACKGROUND: To predict primary failure of infliximab (IFX) therapy in Crohn's disease (CD) and to identify patients who maintain long-term effectiveness to IFX is currently not feasible. Some genetic variations are proposed as potential biomarkers. AIM: We assessed a set of single nucleotide polymorphisms (SNPs) in genes related to the IFX mechanism of action and the presence of HLA-DQA1 * 05 allele on the primary response and long-term durability in CD patients. METHODS: A multi-centre cross-sectional study of IFX-exposed adult patients with CD was undertaken. Treatment persistence and time to failure were co-primary endpoints. DNA from the 131 patients was genotyped. Association between SNPs and clinical variables with IFX persistence was assessed. RESULTS: Failure to IFX was documented in 65 (49.6%) out of 131 patients. IFX persistence was associated either with carrying the TT genotype in ADAM17 rs10929587 (ORa=0.2; 95%CI=0.1-0.8; p = 0.021), or the CC genotype in SLCO1C1 rs3794271 (ORa=0.2; 95%CI=0.1-0.7; p = 0.008), according to multivariate logistic regression. In contrast, previous bowel resection increased the risk of IFX failure (ORa=2.8; 95%CI=1.1-7.3; p = 0.025). Cox regression analysis confirmed these findings and also identified IL23R rs10489629-TT (HRa 0.41; 95%CI=0.22-0.75; p = 0.004) and concomitant immunosuppressants (HRa 0.46; 95%CI=0.27-0.77; p = 0.003) as protection from IFX failure. However, no association between HLA-DQA1 * 05 allele and persistence of IFX therapy was found, with similar failure rates among carriers and non-carriers (52.8% vs. 47.4%, respectively; p = 0.544). CONCLUSIONS: SNPs rs10929587-TT in ADAM17, rs10489629-TT in IL23R and rs3794271-CC in SLCO1C1, together with no previous bowel surgery and concomitant immunosuppression, were identified as protection from failure to IFX.
Asunto(s)
Enfermedad de Crohn , Humanos , Adulto , Infliximab/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/genética , Polimorfismo de Nucleótido Simple/genética , Fármacos Gastrointestinales/uso terapéutico , Estudios Transversales , Resultado del Tratamiento , Proteína ADAM17/genética , Receptores de Interleucina/genética , Receptores de Interleucina/uso terapéuticoRESUMEN
BACKGROUND: Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. AIMS: To assess the treatment patterns with the first anti-TNFα in IBD. METHODS: Retrospective, observational study. RESULTS: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. CONCLUSIONS: Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.
Asunto(s)
Adalimumab/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Infliximab/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adulto , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Privación de Tratamiento/estadística & datos numéricosRESUMEN
We present a series of general and specific recommendations based on pathophysiologic considerations for managing the most common adverse effects of apremilast that lead to treatment discontinuation: diarrhea, nausea, and headache. The recommendations are based on a review of the literature and the experience of a multidisciplinary team of 14 experts including dermatologists, rheumatologists, neurologists, gastroenterologists, pharmacists, and nurses. We propose a series of simple algorithms that include clinical actions and suggestions for pharmacologic treatment. The adverse effects of apremilast can be managed from a multidisciplinary approach. The purpose of optimizing management is to bring clinical benefits to patients.
Asunto(s)
Diarrea/inducido químicamente , Cefalea/inducido químicamente , Náusea/inducido químicamente , Inhibidores de Fosfodiesterasa 4/efectos adversos , Talidomida/análogos & derivados , Terapia Combinada , Diarrea/dietoterapia , Diarrea/tratamiento farmacológico , Diarrea/fisiopatología , Manejo de la Enfermedad , Cefalea/tratamiento farmacológico , Cefalea/fisiopatología , Cefalea/prevención & control , Humanos , Náusea/dietoterapia , Náusea/tratamiento farmacológico , Náusea/fisiopatología , Grupo de Atención al Paciente , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Guías de Práctica Clínica como Asunto , Psoriasis/tratamiento farmacológico , Talidomida/efectos adversos , Talidomida/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS: This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS: A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS: The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.
Asunto(s)
Fatiga , Glucocorticoides , Enfermedades Inflamatorias del Intestino , Calidad de Vida , Adulto , Ansiedad/diagnóstico , Ansiedad/epidemiología , Ansiedad/fisiopatología , Depresión/diagnóstico , Depresión/epidemiología , Depresión/fisiopatología , Fatiga/diagnóstico , Fatiga/epidemiología , Fatiga/etiología , Fatiga/psicología , Femenino , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/psicología , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/fisiopatología , España/epidemiología , Encuestas y CuestionariosRESUMEN
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.
Asunto(s)
Antirreumáticos/uso terapéutico , Infecciones/epidemiología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Nacimiento Prematuro/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Adulto , Estudios de Casos y Controles , Certolizumab Pegol/uso terapéutico , Preescolar , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Infliximab/uso terapéutico , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Embarazo , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.
Asunto(s)
Adalimumab/uso terapéutico , Antirreumáticos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Deprescripciones , Factores Inmunológicos/uso terapéutico , Infliximab/uso terapéutico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Colitis Ulcerosa/fisiopatología , Colon , Constricción Patológica , Enfermedad de Crohn/fisiopatología , Progresión de la Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Íleon , Incidencia , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Masculino , Mesalamina/uso terapéutico , Metotrexato/uso terapéutico , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores Protectores , Recurrencia , Inducción de Remisión , Retratamiento , Estudios Retrospectivos , Factores de Riesgo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto JovenRESUMEN
BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug.
Asunto(s)
Anticuerpos/sangre , Enfermedad de Crohn/tratamiento farmacológico , Ensayo de Cambio de Movilidad Electroforética/métodos , Infliximab/uso terapéutico , Enfermedad de Crohn/sangre , Humanos , Estudios ProspectivosRESUMEN
The current controversy in the setting of dermatology surrounding the treatment of inflammatory diseases, and specifically hidradenitis suppurativa, bears strong similarities with the debate concerning inflammatory bowel disease (IBD) that took place several years ago. That debate led to new perspectives on this disease and, in particular, its treatment after the development of biological agents.
Asunto(s)
Enfermedad de Crohn/terapia , Hidradenitis Supurativa/terapia , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Factores Biológicos/uso terapéutico , Terapia Combinada , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/patología , Fístula Cutánea/tratamiento farmacológico , Fístula Cutánea/etiología , Fístula Cutánea/cirugía , Fístula del Sistema Digestivo/tratamiento farmacológico , Fístula del Sistema Digestivo/etiología , Fístula del Sistema Digestivo/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Manejo de la Enfermedad , Progresión de la Enfermedad , Drenaje , Hidradenitis Supurativa/patología , Humanos , Proctitis/tratamiento farmacológico , Proctitis/etiología , Proctitis/cirugía , Inducción de Remisión , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a high prevalence in the population. Treatment options are both medical and surgical. Medical treatment is based on the use of antibiotics, retinoids, and anti-inflammatory drugs, in which anti-TNFα agents (infliximab y adalimumab) play a central role in the treatment of moderate-to-severe HS and enjoy the highest level of scientific support. Currently, adalimumab is the only drug approved in the summary of product characteristics for the treatment of this disease. Due to the scarcity of clinical trials in HS, there is still no therapeutic guideline backed by solid evidence and the evidence for most drugs is low. However, early treatment in patients with HS would probably reduce the complications of this disease. This review analyses the distinct treatments used in this dermatological disease and provides a therapeutic algorithm with different treatment options.
Asunto(s)
Hidradenitis Supurativa/tratamiento farmacológico , Adalimumab/uso terapéutico , Algoritmos , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Factores Biológicos/uso terapéutico , Manejo de la Enfermedad , Quimioterapia Combinada , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/cirugía , Hormonas/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Retinoides/uso terapéutico , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
The recent approval of adalimumab as the first treatment to be approved for the management of hidradenitis suppurativa has represented a before and after in the control of this chronic inflammatory disease. Given the inflammatory burden of this cutaneous disease, in the last few years hidradenitis suppurativa has been compared with inflammatory bowel disease, particularly with Crohn disease, to the point of considering hidradenitis suppurativa as "Crohn disease of the skin". These two chronic inflammatory diseases show sufficient similarities to consider whether treatment response based on the inflammatory load could also be similar. The present article aims to analyse the efficacy of adalimumab in hidradenitis suppurativa in comparison with a truly comparable disease, Crohn disease, with a view to evaluating therapeutic response rates and to drawing conclusions on the therapeutic success obtained in this disabling cutaneous disease.
Asunto(s)
Adalimumab/uso terapéutico , Factores Biológicos/uso terapéutico , Hidradenitis Supurativa/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Absceso/tratamiento farmacológico , Absceso/etiología , Adalimumab/efectos adversos , Factores Biológicos/efectos adversos , Ensayos Clínicos como Asunto , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/tratamiento farmacológico , Fístula Cutánea/tratamiento farmacológico , Fístula Cutánea/etiología , Manejo de la Enfermedad , Hidradenitis Supurativa/complicaciones , Humanos , Fístula Intestinal/tratamiento farmacológico , Fístula Intestinal/etiología , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Resultado del TratamientoRESUMEN
Hidradenitis suppurativa and inflammatory bowel disease are chronic inflammatory diseases mainly affecting young people. Their aetiology is complex and multifactorial and numerous case series have shown that the two diseases can manifest concurrently, although the strength of this association varies widely among distinct reports. An additional problem is the difficulty of distinguishing between cutaneous Crohn disease and hidradenitis. In the last few years, epidemiological cohort studies have revealed that 1.2%-23% of inflammatory bowel disease patients also have hidradenitis suppurativa. This wide variability is influenced by geographical variables and the biases inherent in the distinct data collection methods, among other factors. There is a clear predominance of Crohn disease over ulcerative colitis. When hidradenitis suppurativa and inflammatory bowel disease manifest concurrently, the bowel disease is more severe and shows a predominance of colon involvement.
Asunto(s)
Hidradenitis Supurativa/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Distribución por Edad , Causalidad , Estudios de Cohortes , Comorbilidad , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/patología , Diagnóstico Diferencial , Susceptibilidad a Enfermedades , Hidradenitis Supurativa/diagnóstico , Humanos , Obesidad/epidemiología , Especificidad de Órganos , Distribución por SexoRESUMEN
BACKGROUND: Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. AIM: To develop an evidence-based clinical practice guide on MC current concepts. METHODS: Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. RESULTS: Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. CONCLUSIONS: This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence.
Asunto(s)
Colitis Microscópica/epidemiología , Colitis Microscópica/fisiopatología , Adalimumab/uso terapéutico , Corticoesteroides/uso terapéutico , Factores de Edad , Antiinflamatorios/uso terapéutico , Biopsia , Budesonida/uso terapéutico , Colitis Microscópica/tratamiento farmacológico , Colonoscopía , Humanos , Infliximab/uso terapéutico , Factores Sexuales , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
INTRODUCTION AND OBJECTIVES: Patients with psoriasis often have comorbidities, including other immune-mediated inflammatory diseases (IMIDs), and cardiovascular risk factors. In this article we describe the baseline prevalence of comorbidities-including other IMIDs-in a cohort of patients with psoriasis. PATIENTS AND METHODS: AQUILES was a prospective observational multicenter study of 3 patient cohorts (patients with psoriasis, spondyloarthritis, or inflammatory bowel disease) undertaken to investigate the prevalence of comorbidities, including other IMIDs, in these settings. The psoriasis cohort comprised patients aged at least 18 years who were seen in hospital dermatology clinics. A predefined protocol was used to collect demographic and clinical data. RESULTS: The study enrolled 528 patients with psoriasis (60.2% men and 39.8% women). Mean age was 46.7 years; 89.8% of the participants had plaque psoriasis, and the median Psoriasis Area Severity Index score (PASI) was 3.2 (1.5-7.4). Comorbid IMIDs were present in 82 (15.5%) of the patients (CI 95%, 12.7%-18.9%). Spondyloarthritis was observed in 14% of patients (95% CI, 11.3%-17.2%), mostly in the form of psoriatic arthritis, for which the overall prevalence was 13.1% (95% CI, 10.5%-16.2%). Inflammatory bowel disease was present in 1.3% (95% CI, 0.6%-2.7%) and uveitis in .2% (95% CI, 0.1%-1.4%). Psoriatic arthritis was associated with male sex (odds ratio, 1.75 [.98-2.98]) and a disease duration of over 8 years (OR, 4.17 [1.84-9.44] vs a duration of < 4 years). In 73.1%, at least 1 cardiovascular risk factor was identified: smoking (40.5%), obesity (26.0%), dyslipidemia (24.8%), hypertension (24.3%), and diabetes mellitus (12.3%). CONCLUSION: In patients with psoriasis the prevalence of other IMIDs was 15.5%, a level slightly higher than that found in the general population. Nearly three-quarters of these patients had at least 1 cardiovascular risk factor.
Asunto(s)
Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/inmunología , Psoriasis/complicaciones , Psoriasis/inmunología , Espondiloartropatías/complicaciones , Espondiloartropatías/inmunología , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Espondiloartropatías/epidemiologíaRESUMEN
BACKGROUND: Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. AIM: To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. METHODS: 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. RESULTS: In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. CONCLUSION: When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course.
Asunto(s)
Colitis Ulcerosa/genética , Colitis Ulcerosa/patología , Enfermedad de Crohn/genética , Enfermedad de Crohn/patología , Adulto , Edad de Inicio , Enfermedades del Ano/etiología , Colitis Ulcerosa/inmunología , Colon , Enfermedad de Crohn/inmunología , Femenino , Humanos , Íleon , Masculino , Fenotipo , Sistema de Registros , Índice de Severidad de la Enfermedad , España , Adulto JovenRESUMEN
AIM: To evaluate the use of health care resources and the associated costs of complex perianal Crohn's disease (CD) from the National Health System perspective. METHODS: We conducted a multicenter, retrospective, observational study in which gastroenterologists from 11 hospitals in the Community of Madrid took part. Data was collected on the direct healthcare resources (pharmacological treatments, surgical procedures, laboratory/diagnostic tests, visits to specialists and emergency departments, and hospitalizations) consumed by 97 adult patients with complex perianal CD which was active at some point between January 1, 2005, and case history review. RESULTS: We recorded 527 treatments: 73.1% pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and 26.9% surgical. Mean annual global cost was 8,289/patient, 75.3% (6,242) of which was accounted for by pharmacological treatments (13.44 antibiotics; 1,136 immunomodulators; 5,093 biological agents), 12.4% (1,027) by hospitalizations and surgery, 7.7% (640) by medical visits, 4.2% (350) by laboratory/diagnostic tests, and 0.4% (30) by emergency department visits. CONCLUSIONS: Pharmacological therapies, and in particular biological agents, are the main cost driver in complex perianal CD; costs due to surgery and hospitalizations are much lower.
Asunto(s)
Costo de Enfermedad , Enfermedad de Crohn/economía , Costos de la Atención en Salud/estadística & datos numéricos , Fístula Rectal/economía , Adulto , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/terapia , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fístula Rectal/etiología , Fístula Rectal/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Despite medical therapy, 30% of patients with ulcerative colitis (UC) need to undergo surgery. Around 50% of patients with proctocolectomy with ileal pouch-anal anastomosis (IPAA) develop complications of the pouch. Clinical evidence for the use of infliximab (IFX) in refractory pouchitis is limited. The aim of this study was to report efficacy of IFX in these patients. METHODS: A retrospective, multicenter study was designed. Patients older than 18 years with chronic refractory pouchitis treated with IFX (5 mg/kg) were included. Short-term IFX efficacy was evaluated at week 8 and mid-term efficacy at weeks 26 and 52. Complete response was defined as cessation of diarrhea and urgency and partial response as marked clinical improvement but persisting symptoms. The modified Pouchitis Disease Activity Index (mPDAI) without endoscopy was calculated when available. RESULTS: Thirty-three consecutive UC patients with chronic refractory pouchitis were included (18 male, mean age 45 years, range 21-67). At week 8, 21% patients achieved complete response and 63% showed partial clinical response. At weeks 26 and 52, 33% and 27% achieved complete response and 33% and 18% showed partial clinical response, respectively. Thirteen patients (39%) withdrew treatment (four for lack of efficacy, four for loss of response and five for adverse events). None of the potential factors analyzed had an influence on response to IFX. CONCLUSIONS: IFX was effective in the short- and mid-term in patients with chronic refractory pouchitis. However, medication had to be discontinued in a high number of patients.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/complicaciones , Fármacos Gastrointestinales/uso terapéutico , Complicaciones Posoperatorias , Reservoritis/tratamiento farmacológico , Adulto , Anciano , Enfermedad Crónica , Colitis Ulcerosa/cirugía , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Reservoritis/diagnóstico , Reservoritis/etiología , Proctocolectomía Restauradora , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The long-term efficacy of adalimumab in patients with ulcerative colitis is not well known. AIM: To evaluate the short- and long-term outcomes of adalimumab in ulcerative colitis patients previously treated with infliximab. METHODS: Patients with active ulcerative colitis were treated with adalimumab after failure of other therapies including infliximab. Short-term clinical response and remission were assessed at weeks 4 and 12. The proportion of patients who continued on adalimumab and the proportion of patients who remained colectomy free were assessed over the long term. RESULTS: Clinical response at weeks 4 and 12 was achieved in 16 (53%) and 18 (60%) patients, respectively, and clinical remission was obtained in 3 (10%) and 8 (27%) patients, respectively. After a mean 48 weeks' follow-up, 15 patients (50%) continued on adalimumab. Six patients (20%) required colectomy. All patients who achieved clinical response at week 12 were colectomy free at long term. CONCLUSIONS: Adalimumab was well tolerated and induced durable clinical response in many patients with otherwise medically refractory ulcerative colitis. Patients achieving clinical response at week 12 avoided colectomy over the long term.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Adalimumab , Adulto , Anticuerpos Monoclonales Humanizados , Colectomía , Colitis Ulcerosa/cirugía , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Análisis de Regresión , Retratamiento , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Pólipos del Colon/cirugía , Colonoscopía/efectos adversos , Pancreatitis/etiología , Anciano , Humanos , MasculinoRESUMEN
BACKGROUND: Patients with Crohn's disease have an increased risk for systemic thromboembolism. Their platelets are hyperactive and possess an elevated endogenous content of CD40 ligand (CD40L), a tumour necrosis factor alpha family protein member. Under basal conditions and after stimulation, these platelets express more CD40L on their surface and release higher amounts of soluble (s)CD40L than control platelets, through a mechanism that might be mediated by matrix metalloproteinases (MMPs). OBJECTIVE: The aim of this work is to study whether enhanced sCD40L release secondary to changes in the platelet content of MMPs contributes to the higher state of activation of platelets from patients with Crohn's disease. METHODS: State of activation, CD40L and metalloproteinases content of platelets isolated from patients with Crohn's disease and age- and sex-matched control individuals were analysed, respectively, by flow cytometry, western blot and gelatin zymography. RESULTS: The hyperactive state of platelets from patients with Crohn's disease might rely on their enhanced release of sCD40L, since its inhibition by a broad-range inhibitor of MMPs (GM6001) reduced fibrinogen binding induced by platelet stimulation. Analysis of the content of MMPs in platelets from patients with Crohn's disease showed an exclusive increase in MMP-9 activity. Moreover, MMP-9 inhibition diminished sCD40L release and fibrinogen binding to activated platelets. CONCLUSIONS: The results suggest that platelets from patients with Crohn's disease release more sCD40L than controls as a consequence of their higher endogenous content of CD40L and of MMP-9, which is involved in CD40L shedding. The increased levels of released sCD40L might be responsible, at least in part, for the high state of activation of platelets from patients with Crohn's disease.