Background: The usefulness of thiopurines has been poorly explored in pouchitis and other pouch disorders. Objective: To evaluate the effectiveness and safety of azathioprine as maintenance therapy in inflammatory pouch disorders. Design: This was a retrospective and multicentre study. Methods: We included patients diagnosed with inflammatory pouch disorders treated with azathioprine in monotherapy. Effectiveness was evaluated at 1 year and in the long term based on normalization of stool frequency, absence of pain, faecal urgency or fistula discharge (clinical remission), or any improvement in these symptoms (clinical response). Endoscopic response was evaluated using the Pouchitis Disease Activity Index (PDAI). Results: In all, 63 patients were included [54% males; median age, 49 (28-77) years]. The therapy was used to treat pouchitis (n = 37) or Crohn's disease of the pouch (n = 26). The rate of clinical response, remission and non-response at 12 months were 52%, 30% and 18%, respectively. After a median follow-up of 23 months (interquartile range 11-55), 19 patients (30%) were in clinical remission, and 45 (66%) stopped therapy. Endoscopic changes were evaluated in 19 cases. PDAI score decreased from 3 (range 2-4) to 1 (range 0-3). In all, 21 patients (33%) presented adverse events and 16 (25%) needed to stop therapy. Conclusion: Azathioprine may be effective in the long term for the treatment of inflammatory pouch disorders and could be included as a therapeutic option.
BACKGROUND: Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking. AIMS: To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. METHODS: This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. RESULTS: Fifty-two patients were included. Median golimumab trough concentrations (µg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 µg/g) (2.21 vs. 1.47, p = 0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p = 0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p = 0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p = 0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p = 0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] µg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively. CONCLUSIONS: Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.
Colitis, Ulcerative , Antibodies, Monoclonal , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Colonoscopy , Cross-Sectional Studies , Humans , Leukocyte L1 Antigen Complex/analysis , Remission Induction
BACKGROUND: A recently registered device containing 80 mg of adalimumab (ADA) allows an alternative dose escalation regimen with ADA 80 mg every other week (EOW) given as a single subcutaneous injection instead of 40 mg every week. The ADASCAL study evaluated the preferences and satisfaction of inflammatory bowel disease (IBD) patients after switching their ADA regimen from 40 mg weekly to 80 mg EOW given with a single-dose pen. METHODS: In this multicentre cross-sectional study, patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW completed the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), a four-item questionnaire [a Likert-type 5-point scale for preferences, two closed questions for convenience and a 100-point visual analogue scale (VAS) to assess which escalated ADA regimen patients would prefer to continue] and two Health-Related Quality of Life (HRQoL) questionnaires: the generic European Quality of Life-5 Dimensions (EQ-5D) and disease-specific Spanish version of the Inflammatory Bowel Disease Questionnaire (SIBDQ-9). RESULTS: In total, 77 patients (64 Crohn's disease and 13 ulcerative colitis) were included. The TSQM score showed a notably high global satisfaction [83.4, standard deviation (SD) = 14.1] of patients with ADA 80 mg EOW given with a single-dose pen, with high TSQM scores for individual components: effectiveness (77.6, SD = 16.9), convenience (83.7, SD = 14.5) and side effects (86.1, SD = 23.4). Most of the patients (74%) preferred the ADA EOW regimen (59.7% had strong preference, 14.3% slight preference). ADA EOW interferes less with daily activity (59.7%) and with travel plans (81.8%). Most patients (77%) would prefer to continue with ADA EOW (mean VAS score of 84.7, SD = 24.1, where 100 indicates a preference for ADA EOW). Patients reported high HRQoL scores on both the EQ-5D (72.3, SD = 20.1) and SIBDQ-9 (75.1, SD = 14.7). CONCLUSION: IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen and therefore most decided to continue with a single self-injection EOW.
In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD.
Anti-Inflammatory Agents/therapeutic use , Drug Discovery/trends , Gastrointestinal Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Molecular Targeted Therapy/trends , Animals , Anti-Inflammatory Agents/pharmacokinetics , Forecasting , Gastrointestinal Agents/pharmacokinetics , Humans , Incidence , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/epidemiology , Pharmacogenetics/trends
BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] are at increased risk for developing some types of neoplasia. Our aims were to determin the risk for cancer in patients with IBD and to describe the relationship with immunosuppressive therapies and clinical management after tumor diagnosis. METHODS: Retrospective, multicenter, observational, 5-year follow-up, cohort study. Relative risk [RR] of cancer in the IBD cohort and the background population, therapeutic strategies, and cancer evolution were analyzed. RESULTS: A total of 145 cancers were diagnosed in 133 of 9100 patients with IBD (global cumulative incidence 1.6% vs 2.4% in local population; RR = 0.67; 95% confidence interval [CI]: 0.57-0.78). Patients with IBD had a significantly increased RR of non-melanoma skin cancer [RR = 3.85; 2.53-5.80] and small bowel cancer [RR = 3.70; 1.23-11.13]. After cancer diagnosis, IBD treatment was maintained in 13 of 27 [48.1%] patients on thiopurines, in 2 of 3 on methotrexate [66.6%], none on anti-TNF-α monotherapy [n = 6] and 4 of 12 [33.3%] patients on combined therapy. Rate of death and cancer remission during follow-up did not differ [p > 0.05] between patients who maintained the treatment compared with patients who withdrew [5% vs 8% and 95% vs 74%, respectively]. An association between thiopurines [p = 0.20] or anti-TNF-α drugs [p = 0.77] and cancer was not found. CONCLUSIONS: Patients with IBD have an increased risk for non-melanoma skin cancer and small bowel cancer. Immunosuppresive therapy is not related to a higher overall risk for cancer or worse tumor evolution in patients who maintain these drugs after cancer diagnosis.
Anti-Inflammatory Agents/therapeutic use , Disease Management , Immunosuppressive Agents/therapeutic use , Inflammatory Bowel Diseases/complications , Neoplasms/epidemiology , Risk Assessment/methods , Female , Follow-Up Studies , Humans , Incidence , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/epidemiology , Male , Middle Aged , Neoplasms/etiology , Neoplasms/prevention & control , Retrospective Studies , Risk Factors , Spain/epidemiology , Time Factors
BACKGROUND AND AIMS: While it is commonly accepted that Inflammatory bowel disease (IBD) Comprehensive Care Units (ICCUs) facilitate the delivery of quality care to Crohn's disease and ulcerative colitis patients, it remains unclear how an ICCU should be defined or evaluated. The aim of the present study was to develop a comprehensive set of Quality Indicators (QIs) of structure, process, and outcomes for defining and evaluating an ICCU. METHODS: A Delphi consensus-based approach with a standardized three-step process was used to identify a core set of QIs. The process included an exhaustive search using complementary approaches to identify potential QIs, and two Delphi voting rounds to select the QIs defining the core requirements for an ICCU. RESULTS: The consensus selected a core set of 56 QIs (12 structure, 20 process and 24 outcome). Structure and process QIs highlighted the need for multidisciplinary management and continuity of care. The minimal IBD team should include an IBD nurse, gastroenterologists, radiologists, surgeons, endoscopists and stoma management specialists. ICCUs should be able to provide both outpatient and inpatient care and admission should not break the continuity of care. Outcome QIs focused on the adequate prophylaxis of disease complication and drug adverse events, the need to monitor appropriateness of treatment and the need to reinforce patient autonomy by providing adequate information and facilitating the patients' participation in their own care. CONCLUSIONS: The present Delphi consensus identified a set of core QIs that may be useful for evaluating and certifying ICCUs.
Colitis, Ulcerative/therapy , Crohn Disease/therapy , Delphi Technique , Hospital Units/standards , Outcome and Process Assessment, Health Care/methods , Patient Care Team/standards , Quality Indicators, Health Care , Ambulatory Care , Colitis, Ulcerative/diagnosis , Continuity of Patient Care/standards , Crohn Disease/diagnosis , Hospital Units/organization & administration , Hospitalization , Humans , Patient Care Team/organization & administration
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antibodies, Monoclonal/adverse effects , Chemical and Drug Induced Liver Injury/etiology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antibodies, Monoclonal/therapeutic use , Chemical and Drug Induced Liver Injury/pathology , Colitis, Ulcerative/drug therapy , Female , Humans , Infliximab , Middle Aged
Objetivo Evaluar la eficacia y seguridad de adalimumab en pacientes con enfermedad de Crohn (EC) de la comunidad de Madrid e identificar los factores predictivos de respuesta.MétodosEstudio multicéntrico retrospectivo de todos los pacientes con EC tratados con adalimumab en 9 hospitales de la Comunidad de Madrid (España). Se llevó a cabo análisis univariado y multivariado de predictores de respuesta.Resultados174 pacientes incluidos (50% varones) con una mediana de seguimiento de 40 semanas. El 30% tenía enfermedad fistulosa perianal activa al inicio de la terapia con adalimumab. El 59% habían sido tratados previamente con infliximab, siendo la pérdida de respuesta (42,2%) la causa más frecuente de la retirada del fármaco. Un 33% de los pacientes necesitaron aumentar la dosis de todos los demás cada semana. La mediana del tiempo para este aumento de la dosis fue de 33 semanas (rango 2-120). Los porcentajes de respuesta completa a las 4 semanas, 6 meses y al final del seguimiento fueron de 63, 70 y 63% en la enfermedad luminal y 49, 50 y 41% en la enfermedad perianal, respectivamente. La prevalencia de eventos adversos fue de 18% (más frecuente: 5 abscesos) provocando la retirada del fármaco en el 21% de ellos.ConclusionesEl adalimumab es eficaz y seguro en el tratamiento de la EC, incluso en los casos refractarios a infliximab(AU)
Objective To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response.MethodsMulticenter 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.Results174 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 everyweek. 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.ConclusionsAdalimumab is effective and safe for the management of CD, even in refractory cases to infliximab(AU)
Humans , Crohn Disease/drug therapy , Antibodies, Monoclonal/therapeutic use , Retrospective Studies , Drug Tolerance , Treatment Outcome
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.
Antibodies, Monoclonal, Humanized/therapeutic use , Crohn Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Abscess/chemically induced , Adalimumab , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Azathioprine/administration & dosage , Azathioprine/therapeutic use , Combined Modality Therapy , Crohn Disease/complications , Crohn Disease/pathology , Crohn Disease/surgery , Cutaneous Fistula/drug therapy , Dose-Response Relationship, Drug , Drug Evaluation , Drug Therapy, Combination , Female , Follow-Up Studies , Hospitals, Urban , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Rectal Fistula/drug therapy , Retrospective Studies , Smoking/adverse effects , Smoking/epidemiology
BACKGROUND/AIMS: Results of randomized controlled trials showing efficacy of infliximab in ulcerative colitis (UC) should be confirmed in clinical practice. We aimed to evaluate the efficacy and safety of infliximab in UC patients of the Madrid area, looking for clinical predictors of response. METHODOLOGY: Multicenter retrospective survey of all UC patients treated with infliximab in the region of Madrid (Spain). RESULTS: 47 UC patients were included (45% males, mean age 44 +/- 15 yrs), mean follow up of 4.7 months (range 0.5-21), and a total number of 211 infliximab infusions. Clinical response and steroid-free remission rates were, respectively, 97/42% in the 2nd week, 93/69% in the 6th week, and 80/65% at the long-term follow up (mean 8.2 months, range 3.5-21). Colectomy rate was 10.6% (five patients). Age, gender, disease duration, indication (steroid-resistance/dependence), disease severity, C-reactive protein, concomitant thiopurinic therapy or smoking habit did not influence on efficacy. Extent of the disease was the only predictive factor (p=0.02). Only 4 cases of mild adverse events were reported. CONCLUSIONS: Infliximab is effective and safe for UC. Real life clinical practice may have better outcome than showed in randomized controlled trials. Extent of the disease was the only predictive factor for clinical response in our experience.
Antibodies, Monoclonal/therapeutic use , Colitis, Ulcerative/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Female , Humans , Infliximab , Male , Middle Aged , Randomized Controlled Trials as Topic , Retrospective Studies
BACKGROUND: Efficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response. METHODS: Multicenter retrospective survey of all CD patients treated with infliximab in 8 University hospitals of the Madrid area (Spain) with a minimum follow up of 14 wks. RESULTS: 169 patients included (48%males, mean age 39 +/- 12 yrs). 64% of them had perianal disease. 82% were under immunosuppressants. 1,355 infliximab infusions administered (mean 8, range 1-30). 90% response rate and 48% remission rate were obtained with induction therapy. 73% followed maintenance treatment, and 78% of them maintained or improved the response after a mean follow up of 28 months (range 3.5-86). 24 patients lost response during the follow up, after a mean of 41 wks (range 6-248). Only the prescription of maintenance therapy was predictive factor for favourable response (p < 0.01). 17 infusion reactions were reported (10% of the patients, 1.2% of the infusions; only one case was severe) and were the cause of treatment withdrawal in 7 patients. Co-treatment with immunosuppressive drugs and maintenance infliximab therapy were protective factors for infusion reactions (p < 0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients. CONCLUSIONS: Infliximab is effective and safe for CD management but concomitant immunosuppressive drugs and maintenance treatment should be prescribed to obtain the best outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials.
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Crohn Disease/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal/adverse effects , Female , Humans , Infliximab , Male , Middle Aged , Retrospective Studies , Time Factors , Young Adult
OBJETIVO: La eficacia de infliximab en la enfermedad deCrohn (EC), demostrada por los diferentes ensayos clínicos,ha de ser confirmada en la práctica clínica. Nuestro objetivofue evaluar la eficacia y la seguridad del infliximab en pacientescon EC del área de Madrid, buscando predictores derespuesta.MÉTODOS: Estudio retrospectivo y multicéntrico que incluyelos pacientes con EC tratados con infliximab en 8 hospitalesde la Comunidad de Madrid, con un seguimiento mínimo de14 semanas.RESULTADOS: Se incluyó a un total de 169 pacientes (un 48%varones, con una edad de 39 ± 12 años), un 64% con enfermedadperianal y un 82% bajo tratamiento inmunosupresor.Se administraron un total de 1.355 perfusiones de infliximab(media, 8; rango, 1-30): un 90% de los pacientesrespondió, un 48% alcanzó la remisión clínica, un 73% siguiótratamiento de mantenimiento, y un 78% mantuvo omejoró su respuesta tras un seguimiento medio de 28 meses(rango, 3,5-86). Se perdió la respuesta durante el seguimientode 24 pacientes, tras una media de 41 semanas (rango, 6-248). Sólo la prescripción de tratamiento de mantenimientofue un predictor favorable de respuesta (p < 0,01); se contabilizaron 17 reacciones infusionales (en el 10% de los pacientes,el 1,2% de las perfusiones; sólo se constató un casograve) y fueron causa de la suspensión del tratamiento en 7pacientes. El cotratamiento con los inmunosupresores y eltratamiento de mantenimiento con infliximab fueron los factoresprotectores para sufrir reacciones infusionales (p <0,05). Otros efectos adversos se produjeron en el 26% de lospacientes, y fueron causa de suspensión del tratamiento en 7pacientes.CONCLUSIONES: Infliximab es eficaz y seguro en el tratamientode la EC, pero deberían prescribirse el tratamientode mantenimiento y el concomitante con inmunosupresorespara obtener los mejores resultados. Esto confirma en un escenariode práctica clínica real los resultados obtenidos enensayos clínicos
BACKGROUND: Efficacy of infliximab in Crohns disease(CD) showed by randomized controlled trials must beconfirmed in clinical practice. We aimed to evaluate efficacyand safety of infliximab in CD patients of the Madrid area,looking for clinical predictors of response.METHODS: Multicenter retrospective survey of all CD patientstreated with infliximab in 8 University hospitals of theMadrid area (Spain) with a minimum follow up of 14wks.RESULTS: 169 patients included (48%males, mean age 39 ±12 yrs). 64% of them had perianal disease. 82% were underimmunosuppressants. 1355 infliximab infusions administered(mean 8, range 1-30). 90% response rate and 48%remission rate were obtained with induction therapy. 73%followed maintenance treatment, and 78% of them maintainedor improved the response after a mean follow up of 28months (range 3.5-86). 24 patients lost response during thefollow up, after a mean of 41wks (range 6-248). Only theprescription of maintenance therapy was predictive factorfor favourable response (p < 0.01). 17 infusion reactionswere reported (10% of the patients, 1.2% of the infusions;only one case was severe) and were the cause of treatmentwithdrawal in 7 patients. Co-treatment with immunosuppressivedrugs and maintenance infliximab therapy wereprotective factors for infusion reactions (p < 0.05). Other adverseevents occurred in 26% of the patients, and were causeof treatment withdrawal in 7 patients.CONCLUSIONS: Infliximab is effective and safe for CD managementbut concomitant immunosuppressive drugs andmaintenance treatment should be prescribed to obtain thebest outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials (AU)
Humans , Crohn Disease/drug therapy , Antibodies, Monoclonal/pharmacokinetics , Retrospective Studies , Efficacy , Immunosuppressive Agents/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors
