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.

OBJECTIVES: The safety of thiopurines and anti-tumor necrosis factor-alpha (TNF-alpha) drugs during pregnancy remains controversial, as the experience with these drugs in this situation is limited. Our aim is to assess the safety of thiopurines and anti-TNF-alpha drugs for the treatment of inflammatory bowel disease (IBD) during pregnancy.METHODS: Retrospective, multicenter study in IBD patients. Pregnancies were classified according to the therapeutic regimens during pregnancy or during the 3 months before the conception: non-exposed group, pregnancies exposed to thiopurines alone (group A), and pregnancies exposed to anti-TNF-alpha drugs (group B). An unfavorable Global Pregnancy Outcome (GPO) was considered if pregnancy developed with obstetric complications in the mother and in the newborn.RESULTS: A total of 187 pregnancies in the group A, 66 pregnancies in the group B, and 318 pregnancies in the non-exposed group were included. The rate of unfavorable GPO was different among the three groups (31.8% in non-exposed group, 21.9% in group A, and 34.8% in group B), being lower in pregnancies under thiopurines than among non-exposed (P=0.01). The rate of pregnancy complications was similar among the three groups (27.7% in non-exposed, 20.9% in group A, and 30.3% in group B). The rate of neonatal complications was different among the three groups (23.3% in non-exposed group, 13.9% in group A, and 21.2% in group B), being lower in pregnancies under thiopurines than among non-exposed (P=0.01). In the multivariate analysis, the treatment with thiopurines (odds ratio=0.6; 95% confidence interval=0.4-0.9, P=0.02) was the only predictor of favorable GPO, whereas maternal age >35 years at conception was the only predictor of unfavorable GPO. The treatment with anti-TNF-alpha drugs was not associated with an unfavorable GPO.CONCLUSION: The treatment with thiopurines and anti-TNF-alpha drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn. Am J Gastroenterol 2013;108:433-440; doi:10.1038/ajg.2012.430; published online 15 January 2013

Clinical: Therapy and observation S225 our preliminary experience suggested that oral B12 could also be effective in CD.Objective: To analyze the efficacy of oral route to treat B12 deficiency in CD within a large group of patients, to confirm its convenience.Methods: We performed a retrospective analysis of B12 deficiency in CD patients treated by oral cobalamin, in 4 centers following quite similar protocol.CD diagnosis was established by Lennard-Jones criteria and Montreal Classification was used.Data on previous surgery, concomitant drugs and hematological values were reviewed.B12 deficiency was defined according to local laboratory criteria, measured by RIA (levels <200 250 pg/ml).We evaluate the efficacy both in the correction of the deficit and the ability to maintain normal levels long-term.Results: 95 CD patients were included in the analysis (49 men and 44 women, average age 44.4 years, range 72 21).The classification of the patients was (in %): Age at diagnosis (A): A1: 4, A2: 66, A3: 25; Location (L): L1: 44, L2: 3, L3: 43 and Behavior (B): B1: 42, B2: 26, B3: 32.Thirty-seven patients (38.9%, 37/95) had been operated on: 23 had any resection of distal ileum.Seventy-seven patients with B12 deficiency (average value prior to start oral therapy 152 pg/ml) were included.Oral supplements were effective in 90.1% of these cases (70/77), normalizing cobalamin levels (average value post therapy 456 pg/ml).Oral cobalamin was also used to maintain normal levels in 82 cases (those previous patients who get normal levels and were followed after, long term (n = 64) and 18 more patients in which parenteral therapy was changed to oral route).Efficacy to maintain normal levels was 80.4% (average level of 363.70 pg/ml, with a medium followup of 36.3 months).Poor adherence is one of the non-response causes, at least of 31.2% of cases.Conclusions: Our quite large data show that oral cobalamin seems to be an effective and convenient alternative to parenteral route.We suggest that oral route should be considered even as standard treatment also in CD related B12 deficiency.

Background. Methotrexate is an effective treatment for inflammatory bowel disease (IBD). However, long-term treatments have been associated with the development of liver fibrosis. FibroScan (R) is a noninvasive, safe, and effective technique to evaluate liver fibrosis. Aim. To evaluate the presence of significant liver fibrosis by transient elastography (FibroScan (R)) in IBD patients treated with methotrexate. Methods. Cross-sectional study including IBD patients treated with methotrexate from different hospitals. Clinical and analytical data, duration of treatment, and cumulative dose of methotrexate were obtained. Liver stiffness was assessed by FibroScan (R). The cutoff value for significant liver fibrosis (according to METAVIR) was F >= 2: 7.1 kPa. Results. In the study, 46 patients were included, 30 women (65%), with a mean age of 43 +/- 10 years. 31 patients had Crohn's disease (67.4%), 13 ulcerative colitis (28.3%), and 2 indeterminate colitis (4.3%). The mean cumulative dose of methotrexate was 1242 +/- 1349 mg, with a mean treatment duration of 21 +/- 24 months. The mean value of liver stiffness was 4.7 +/- 6.9 kPa. There were 35 patients (76.1%) with F01, 8 patients (17.4%) with F = 2, and 3 patients with F 3 (6.5%). There were no differences in liver stiffness depending on sex, age, type of IBD, or cumulative dose of methotrexate. Conclusions. (1) Development of advanced liver fibrosis in IBD patients treated with methotrexate is exceptional. (2) There were no differences in liver stiffness depending on the type of IBD or the cumulative dose of methotrexate. (3) FibroScan (R) may be potentially useful for evaluation and follow-up of liver fibrosis in methotrexate-treated patients.

BackgroundLow thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice.AimTo identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy.MethodsProspective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred.ResultsA total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels.ConclusionsOur results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

colectomy.Among the initial responders, the probability of maintaining sustained response was 74%, 51%, and 27% at 1, 2, and 3 years, respectively.In the whole cohort of patients, the probability of maintaining the colectomy-free survival was 92%, 82%, and 79% at 1, 2, and 3 years, respectively.Duration of UC was inversely associated with the long-term efficacy.Two years after infliximab start the cumulative probability of sustained clinical benefit in patients with disease duration of ≤2 and > 2 years was 28% and 55% respectively (log rank test, p=0.014).Neither concomitant immunosuppressive therapy, nor the shortterm endoscopic response affected the long-term efficacy of infliximab.Conclusion: Infliximab is highly effective in achieving clinical remission in patients with UC.However, the ability to keep sustained response seems to be lower as compared with Crohn's disease patients.Despite this fact, infliximab is very effective colon saving therapy.

M.J. Casanova1, M. Chaparro1 *, E. Domenech2, M. Barreiro-de Acosta3, F. Bermejo4, E. Iglesias5, F. Gomollon6, L. Rodrigo7, X. Calvet8, M. Esteve9, E. Garcia-Planella10, S. Garcia11, C. Taxonera12, M. Calvo13, M. Lopez14, D. Ginard15, M. Gomez16, E. Garrido17, J. Perez-Calle18, B. Beltran19, M. Piqueras20, C. Saro21, B. Botella22, C. Duenas23, A. Ponferrada24, M. Manosa2, M. Iglesias3, A. Algaba4, V. Garcia-Sanchez5, J. Mate1, J.P. Gisbert1. 1Hospital Universitario de La Princesa, IP, Gastroenterology and CIBEREHD, Madrid, Spain, 2Hospital Germans Trias i Pujol, Badalona, Spain, 3Hospital Clinico Santiago, Santiago de Compostela, Spain, 4Hospital de Fuenlabrada, Madrid, Spain, 5Hospital Reina Sofia, Cordoba, Spain, 6Hospital Clinico Lozano Blesa, Zaragoza, Spain, 7Hospital Central de Asturias, Asturias, Spain, 8Hospital Parc Tauli, Barcelona, Spain, 9Hospital Mutua de Terrassa, Terrassa, Spain, 10Hospital Santa Creu i Sant Pau, Barcelona, Spain, 11Hospital Miguel Servet, Zaragoza, Spain, 12Hospital Clinico San Carlos, Madrid, Spain, 13Hospital Puerta de Hierro, Madrid, Spain, 14Hospital de Galdakao, Galdakao, Spain, 15Hospital Son Espases, Mallorca, Spain, 16Hospital Virgen de Las Nieves, Granada, Spain, 17Hospital Ramon y Cajal, Madrid, Spain, 18Hospital Fundacion Alcorcon, Madrid, Spain, 19Hospital La Fe, Valencia, Spain, 20Consorcio Sanitario Terrassa, Terrassa, Spain, 21Hospital de Cabuenes, Gijon, Spain, 22Hospital Infanta Cristina, Madrid, Spain, 23Hospital San Pedro Alcantara, Caceres, Spain, 24Hospital Infanta Leonor, Madrid, Spain

AIM To evaluate the use of anorectal manometry to select patients for controlled anal dilatation. METHODOLOGY A prospective study was performed using anorectal manometry on all patients with chronic anal fissure who did not have a good response to conservative treatment. Those with increased anal resting pressure were treated with controlled anal dilatation using a two valved anuscope. A second anorectal manometry was indicated after controlled anal dilatation. RESULTS 19 patients without anorectal pathology (Healthy Control Group) and 57 patients with chronic anal fissure were included in this study. Controlled anal dilatation was performed on 27 patients, maximum resting pressure 122 ± 19 mmHg. In the controlled anal dilatation group the healing rate was 92.5%, mean maximum resting pressure post-controlled anal dilatation was 91 ± 30 mmHg. We found one case of transitory anal incontinence (3.7%). None of the patients had anal incontinence at 18 months of the follow-up. In the remaining 30 patients non selected for controlled anal dilatation (chronic anal fissure control group), a proportion of 53.3% recurrences were registered after conservative treatment. CONCLUSIONS Anal healing of chronic anal fissure and a significant decrease in maximum resting pressure recorded by manometry confirms the success of this procedure. The manometric evaluation of the maximum resting pressure is useful in the selection of chronic anal fissure patients for controlled anal dilatation. The efficacy of dilatation to treat chronic anal fissure in patients with raised anal sphincter pressure was high and complications were rare.

Los brotes de actividad de la EII son habitualmente impredecibles. Si dispusiéramos de un marcador que permitiera estimar con fiabilidad el riesgo de sufrir una recidiva, podríamos administrar precozmente fármacos con intención preventiva o terapéutica. Puesto que la inflamación es un proceso continuo, la estimación del nivel de ésta mediante un marcador biológico podría proporcionarnos una medida cuantitativa presintomática del riesgo de sufrir una recidiva clínica inminente. Determinar la utilidad de la calprotectina y lactoferrina fecales para predecir la recidiva de la EII. Estudio multicéntrico en el que se incluyeron prospectivamente pacientes con enfermedad de Crohn (EC) o colitis ulcerosa (CU) en remisión clínica (según CDAI y Truelove) al menos durante los 6 meses previos. Se determinaron basalmente las concentraciones fecales de calprotectina y lactoferrina, momento en que se recogieron datos relativos a la enfermedad y al tratamiento. Los pacientes fueron seguidos hasta que presentaran un brote de actividad o hasta completar un año de seguimiento sin recidiva. Se incluyeron 163 pacientes, 89 con EC y 74 con CU. Veintiséis pacientes (16%) recidivaron durante el seguimiento. Los valores medios de calprotectina fueron de 153±161 μg/g (rango, 6–1.217). Las concentraciones de calprotectina en los pacientes con EII que recidivaron fueron superiores a las de aquellos que permanecieron en remisión (239±150 vs. 136±158 μg/g; p< 0,001). El riesgo de sufrir una recidiva fue mayor en los pacientes con concentraciones fecales elevadas de calprotectina (>150 μg/g) (30% vs. 7,8%; p<0,001) o de lactoferrina (25% vs. 10%; p<0,05). La sensibilidad y la especificidad de la calprotectina fecal (>150 μg/g) para predecir la recidiva de la EII fue del 62% y del 62%. Las cifras correspondientes para la lactoferrina fueron del 62% y 65%. El área bajo la curva ROC para la predicción de la recidiva mediante la determinación de calprotectina fue de 0,73 (0,69 para la UC y 0,77 para la EC). Los resultados fueron mejores cuando se incluyeron exclusivamente pacientes con EC o cuando únicamente se consideró la predicción de la recidiva ocurrida durante los primeros 3 meses (sensibilidad del 100%). En el análisis de supervivencia (curvas de Kaplan-Meier) unas concentraciones elevadas de calprotectina o lactoferrina fecal se asociaron con la recidiva clínica, y ambos marcadores fecales se asociaron con ésta en el estudio multivariante. La determinación de las concentraciones de calprotectina y lactoferrina fecal puede ser útil para predecir la recidiva clínica inminente –fundamentalmente en los siguientes 3 meses– tanto en la EC como en la CU.

of the 4th Congress of ECCO the European Crohn's and Colitis Organisation S73Conclusions: This study reveals discrepancy in psychosocial symptoms, and competence between reports of parents and adolescents with IBD.Chronically ill adolescents may deny their problems as part of coping strategy.Further, it is possible that the parents of chronically ill IBD patients observe their children more than the parents of healthy children, and thus report more concerns.Complementary methods should be used while assessing psychosocial well-being of adolescents with IBD.

Background and Aims: Availability of HCV RNA assays with increased sensitivity necessitates re-assessment of pegylated interferon and ribavirin (PEG-IFN/RBV) treatment stopping rules based on detectable HCV RNA.The aims of this study were to compare the use of the COBAS AMPLICOR™ HCV Test, v2.0 (AMPLICOR™) (limit of detection [LOD]=50 IU/mL), and the COBAS AmpliPrep/TaqMan™ (TaqMan) assay (LOD=15 IU/mL) for the detection of low-level HCV viraemia, and examine the impact of week-24 low-level viraemia on treatment response.Methods: A total of 871 treatment-naive genotype 1 patients were treated with Peg-IFNa-2a/RBV within CHARIOT.Eighty-seven patient samples having TaqMan-based HCV RNA levels of 15-155 IU/mL (50±3 SD from TaqMan precision data) were tested in parallel with AMPLICOR, and concordance examined based on a level above and below 50 IU/mL.The impact of week-24 low-level HCV viraemia on HCV treatment response was evaluated by comparing sustained virological response (SVR) among three subgroups: TaqMan undetectable (UD); detectable <15 IU/mL and detectable 15-50 IU/mL.Results: Among 87 subject samples with low-level HCV viraemia tested by TaqMan and AMPLICOR, HCV RNA level concordance was 62%.In the overall CHARIOT population, week-24 response levels were 64.6% (563/871), 71.4% (622/871) and 72.2% (629/871) for TaqMan UD, <15 IU/mL and <50 IU/mL, respectively.Among low-HCV viraemia subgroups, SVR rates were 72.3% (407/563), 68.2% (424/622) and 67.6% (425/629) TaqMan UD, <15 IU/mL and <50 IU/mL, respectively, and 72.3% (407/563), 28.8% (17/59) and 14.3% (1/7) for TaqMan UD, detectable <15 IU/mL and 15-50 IU/mL, respectively.Conclusions: There is significant discordance between TaqMan and AMPLICOR assays in the evaluation of low-level HCV viraemia.The enhanced sensitivity of the TaqMan assay produces considerable heterogeneity in treatment response rates based on different low-HCV viraemia cut-offs.The significant proportion of subjects with detectable but lowlevel viraemia (<15 IU/mL) who developed an SVR suggests that when the TaqMan assay is used a week-24 stopping rule should be based on detectable levels above 15 IU/mL, while the small numbers of patients in the detectable 15-50 IU/mL category could either cease therapy at week 24, or consider therapy prolongation beyond 48 weeks.

S26Poster Presentations have pseudopolyposis in 20/146 pts (13%) (c 2 test=1.02;p value NS).In the group of UC pts there are 31with left-sided disease and 61 with pancolitis.In the left sided group indidence of pseudopolyposis is 29% (9/29), and in pancolitis 11% (10/61) (c 2 test 0.75, p value NS).Conclusion: There is no difference in prevalence of pseudopolyposis in patients with ulcerative colitis and Crohn colitis in our cohort, also no difference in incidence regarding the initial extension of the disease in UC.We can conclude that phenotype (UC:CC) isn't relevant for the development of colonic pseudopolyposis.

s of the 4th Congress of ECCO the European Crohn’s and Colitis Organisation S67 therapy (IFX+AZA+steroids). Patients were followed prospectively from Jan 2000 until Nov 2008 with monthly visits to the outpatient clinic or the infusion area. Adherence to IFX was determined as the ratio of active to expected visits for infusion. Turning on for an infusion that was not performed for other reasons was considered as adherence. At each visit a review of the medical history between infusions, physical examination, adverse events check, and concomitant medication were assessed, and routine haematological, biochemical and immunologic tests were performed. The study was prematurely stopped for loss of response or severe adverse events to IFX, moving area, or for personal choice or other medical reasons. Results: Sixty patients with luminal (43) or luminal/perianal (17) CD [39 males; median age 27 (17 55) y; 21 of rural origin; 15 active/15 ex-smokers; 24 with extraintestinal manifestations (EIM)] received scheduled IFX monotherapy (23), or IFX+AZA (8), or initially IFX+AZA that was switched to IFX monotherapy (29) for a mean (range) of 36 (12 85) months. Eighteen of 60 patients received top-down therapy. Fourteen patients with extensive (10) or left-sided (4) UC of median duration 2.1 (range 0.4 3.2)y [8 males; median age 42 (range 21 59) y; 4 of rural origin; 2 active/4 ex-smokers; 5 with EIM] received scheduled IFX monotherapy (11) or comboRx (3) for a mean 27 (24 34) months. All patients had received a mean (range) of 21 (11 42) infusions in a period of 5 y (0.2 8) (median, range). Treatment was switched to ADA or AZA in 16 patients for loss of response (7), infusion reactions (5), and adverse events (4) to IFX. Three patients stopped treatment temporarily (pregnancy and personal choice) and 11 (15%) are currently receiving 10 mg/kg IFX. Only one appointment was classified as ’non show’. Adherence to IFX was 99%. Adherence to AZA was 67%. Conclusion: Even in quiescent IBD, adherence to IFX approximates 100%. This may be due to selection bias (severity of disease, severe EIM), effectiveness of treatment, acceptable dose regimen and/or excellent quality of life achieved by treatment.

Existe evidencia de la utilidad del metotrexato (MTX) en la enfermedad inflamatoria intestinal (EII), pero su papel en la actualidad es secundario, principalmente por una falta de experiencia en su uso y un supuesto perfil desfavorable de efectos adversos. Presentar una serie retrospectiva de pacientes con EII tratados con MTX en diferentes hospitales de la Comunidad de Madrid. Se incluyeron 77 pacientes: 80% enfermedad de Crohn (EC), 37% varones, 41 años de edad media (rango 20–60). Las características de los pacientes según la clasificación de Montreal fueron, para la EC: 5%A1, 75%A2, 19%A3; 39%L1, 12%L2, 42%L3, 7%L4; 54%B1, 19%B2, 26%B3; y 21%p; y para la colitis ulcerosa (CU): 43%E2, 57%E3. El 94% de los pacientes recibieron MTX por corticodependencia y el resto por corticoresistencia. El MTX se inició a una dosis media de 21 (rango 13–28) mg/semana; el 82% de los pacientes respondió (remisión clínica 28%). El 88% de los pacientes siguieron tratamiento de mantenimiento, a una dosis media de 15 mg/semana (rango 8–25) durante una media de 17 meses (rango 1–108), ya fuera por vía oral (33%), intramuscular (22%) o subcutánea (44%). En este periodo, el 39% de los pacientes perdió respuesta, una media de 57 semanas después de iniciar el tratamiento, y sólo un 2% mejoraron el resultado obtenido durante la fase de inducción. Esto obligó a cambiar de tratamiento en la mayoría de los casos, salvo en 5 pacientes, en los que se aumentó la dosis (consiguiéndose la respuesta en 3). No se encontraron diferencias estadísticamente significativas en la obtención de respuesta clínica en función del tipo de enfermedad, la vía de administración o la clasificación de Montreal. La dosis media acumulada de MTX a lo largo del seguimiento fue de 1.108 mg (rango 25–6.480). Se detectó hepatotoxicidad en 10 pacientes (15%) y sólo en 1 caso (2,4%) se encontraron datos ecográficos de hepatopatía crónica. Hubo 4 casos de mielotoxicidad (5%), 1 (1,5%) de enterocolitis, alopecia, estomatitis o rash cutáneo, y 10 (13%) de síntomas gastrointestinales. No se detectó ningún caso de neumonitis. Fue necesario suspender el tratamiento en 4 (5%) pacientes. El riesgo de sufrir hepatotoxicidad no se relacionó con la dosis acumulada de MTX. Se realizó elastografía hepática (FibroScan) a 47 pacientes. En los pacientes con hepatotoxicidad la elasticidad media fue de 6.2 KPa (rango 3,5–15,3); la prueba fue normal o con fibrosis leve (F0 o F1) en el 86%, y avanzada en 1 caso, sin encontrarse diferencias en la elasticidad ni en el grado de fibrosis frente a los pacientes sin hepatotoxicidad por MTX. El MTX es un tratamiento eficaz en la inducción de la remisión de la EII, aunque su eficacia disminuye frecuentemente a lo largo del seguimiento. Es seguro a largo plazo, con una frecuencia baja de efectos secundarios. La hepatotoxicidad por MTX es poco frecuente y rara vez supone un problema clínicamente relevante.

La respuesta al tratamiento con IFX es inicialmente elevada, aunque con el paso del tiempo se ha observado, con cierta frecuencia, una pérdida de eficacia. En estos pacientes con pérdida de respuesta se ha recomendado “intensificar” el tratamiento con IFX. No obstante, se desconoce si el efecto beneficioso de esta estrategia se mantiene en el tiempo o es sólo transitorio. 1) Estudiar la respuesta (tanto a corto como a largo plazo) de los pacientes que precisan intensificar el tratamiento con IFX (aumentando la dosis o disminuyendo el intervalo). 2) Evaluar los efectos adversos asociados a la intensificación del tratamiento. Estudio multicéntrico retrospectivo. Se incluyeron pacientes con enfermedad de Crohn que hubieran recibido al menos las 3 dosis de inducción del tratamiento estándar con IFX (5 mg/kg) y que después precisaran intensificación del tratamiento (10 mg/kg cada 8 semanas o 5 mg/kg cada 4 semanas) por pérdida de respuesta. Se analizó la eficacia del tratamiento intensificado en el momento inicial (tras la 1a infusión de la dosis intensificada) y final (en la última revisión). Se utilizó el índice de Harvey-Bradshaw en el caso de enfermedad de Crohn no fistulizante. En la enfermedad fistulizante, la respuesta completa se definió como el cese del drenaje de todas las fístulas y la respuesta parcial como la reducción en al menos un 50% del número o del débito fistuloso. Se valoró la seguridad del tratamiento con la dosis intensificada. Se incluyeron 34 pacientes (edad media, 43 años; 50% varones; 31% fumadores; 64% con afectación ileocólica; 47% con patrón fistulizante; 60% con enfermedad perianal). La mayoría (72%) recibía tratamiento concomitante con inmunomoduladores. El tiempo medio de seguimiento con el tratamiento intensificado fue de 56 semanas (rango: 4–169 semanas). El tiempo medio de tratamiento con IFX antes de la intensificación de la dosis fue de 15 meses (rango: 3–43 meses). Con la primera dosis de tratamiento intensificado respondió el 78% de los pacientes (32% respuesta completa y 46% parcial). Mientras que con la última dosis de tratamiento intensificado sólo un 61% de los pacientes presentaban respuesta (22% respuesta completa y 39% respuesta parcial). Un paciente sufrió una reacción infusional tras 36 dosis de tratamiento intensificado, que se solucionó con el enlentecimiento de la infusión. Otro paciente presentó infección por virus del herpes zoster, no precisando suspensión del tratamiento. En ocasiones se requiere la intensificación del tratamiento con IFX, una media de 15 meses después del inicio del tratamiento con este fármaco. Un alto porcentaje de pacientes responden inicialmente al tratamiento intensificado, aunque éste pierde de nuevo su eficacia en más de un 10% de los casos. La intensificación del tratamiento presenta un buen perfil de seguridad, sin observarse reacciones adversas graves.

1) Revisar sistemáticamente la eficacia de la azatioprina (AZA) y la mercaptopurina (MP) en la colitis ulcerosa (CU); y 2) realizar un metaanálisis de los ensayos clínicos aleatorizados que evalúan la eficacia de la AZA o la MP en la inducción o el mantenimiento de la remisión clínica de la CU. Selección de estudios: que evaluaran el tratamiento con AZA o MP oral para la inducción o el mantenimiento de la remisión clínica de la CU. En el metaanálisis se incluyeron los ensayos clínicos aleatorizados que compararan AZA/MP frente a placebo o 5-aminosalicilatos. Estrategia de búsqueda: electrónica y manual. Evaluación de la calidad de los estudios: independientemente por dos revisores. Síntesis de los datos: por “intención de tratar”. Se incluyeron 30 estudios no controlados (con un total de 1.632 pacientes) en la revisión sistemática. La eficacia media de la AZA/MP fue del 65% (IC 95%=62–67%): 65% en la inducción y 76% en el mantenimiento de la remisión. Se incluyeron 7 estudios controlados en el metaanálisis (uno evaluó la AZA/MP únicamente en la inducción, 3 en el mantenimiento de la remisión, y 3 tanto en inducción como en mantenimiento). Tres estudios incluyeron un grupo control con placebo, y en 4 la mesalazina/sulfasalazina se empleó como control. 1) Inducción de la remisión: Cuatro estudios (incluyendo 89 pacientes tratados con AZA/MP) demostraron una eficacia media del 73%, frente al 64% en el grupo control (OR=1,59; IC 95%=0,59–4,29). 2) Mantenimiento de la remisión: Seis estudios (incluyendo 124 pacientes tratados con AZA/MP) demostraron una eficacia media del 60%, frente al 37% en el grupo control (OR=2,56; IC 95%=1,51–4,34). Cuando únicamente se consideraron los 3 estudios que comparaban AZA/MP frente a placebo, la OR fue de 2,59 (IC 95%=1,26–5,3), la reducción absoluta del riesgo fue del 23%, y el “número necesario a tratar” (NNT) para prevenir una recidiva fue de 5. Los resultados de los 3 estudios que comparaban AZA/MP frente a 5-aminosalicilatos fueron heterogéneos, por lo que no pudieron ser combinados. Los fármacos tiopurínicos son eficaces tanto para la inducción como, sobre todo, para el mantenimiento de la remisión clínica de la CU. El presente metaanálisis confirma que la AZA/MP es más efectiva que el placebo para prevenir la recidiva de la CU, con un NNT de 5 y una reducción absoluta del riesgo del 23%.