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M J Casanova,
M Chaparro,
E Domènech, M Barreiro-de Acosta,
F Bermejo,
E Iglesias,
F Gomollón,
L Rodrigo,
X Calvet,
M Esteve, [......],
B Beltrán,
M Piqueras,
C Saro,
B Botella,
C Dueñas,
A Ponferrada,
M Mañosa,
V García-Sánchez,
J Maté,
J P Gisbert
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ABSTRACT: OBJECTIVES:The safety of thiopurines and anti-tumor necrosis factor-α (TNF-α) 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-α 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-α 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-α drugs was not associated with an unfavorable GPO.CONCLUSION:The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.Am J Gastroenterol advance online publication, 15 January 2013; doi:10.1038/ajg.2012.430.
The American Journal of Gastroenterology 01/2013; · 7.28 Impact Factor
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ABSTRACT: Introduction: the low prevalence of enterocutaneous fistulas (ECF) in patients with Crohn´s disease (CD) justifies the scarcity of studies that analyze the effect of medical treatment and the need for surgery in these patients. The objective of this study was to evaluate the clinical characteristics of patients with CD who have ECF and the response to different treatments.Materials and methods: patients with CD who presented ECF fistula between 1970 and 2009 in three tertiary centers in Spain were analyzed retrospectively for their clinical characteristics, response to treatment as well as the correlation between the response to biological therapies for ECF and perianal disease. The inflammatory activity of the disease was measured using the Harvey-Bradshaw index. The definitions of partial or complete response were based on the treating physician´s judgment.Results: twenty six patients were included (18 women); in more than half of cases (67%), anti-TNF treatment improved fistula drainage. Postoperative fistulas responded better to anti-TNF treatment than did spontaneous fistulas (80 versus 57%). One hundred percent and 60% of spontaneous and postoperative fistulas closed after surgery, respectively.Conclusions: although the majority of patients required surgery as the ultimate treatment, anti-TNF drugs improved fistula output in an acceptable percentage of patients who were treated. Therefore, this may be a treatment strategy prior to surgery in a select group of patients.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 01/2013; 105(1):3-6. · 1.55 Impact Factor
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ABSTRACT: Biological drugs or biopharmaceutical products, manufactured with or from living organisms using biotechnology, have represented a therapeutic revolution for the control of inflammatory bowel disease (IBD). At present, in this indication and in our country, only two biological are approved, infliximab (IFX) and adalimumab (ADA), both of them monoclonal antibodies against tumor necrosis factor alpha. Effectiveness data are strong for both therapies, with maximum levels of scientific evidence.The upcoming expiry date for these biologicals´ patents has allowed the potential marketing of so-called biosimilar agents for the IBD indication. While biosimilars are conceptually for biological what generics are for chemical drugs, the structural complexity of biosimilars and their biological and manufacturing variability lead to consider validation processes for these two types in humans as highly differential. Thus, in our setting, under the coverage of "Agencia Española del Medicamento y Productos Sanitarios (AEMPS)" (Spanish Agency of Medicines and Medical Devices), guidelines issued by the European Medicines Agency (EMA) are to be applied, which states that a number of stages or steps must be overcome in order to obtain approval for a biosimilar agent.However, despite the presence of these recommendations by EMA, which must be met by a biosimilar in order to be licensed in our marketplace, relevant uncertainties persist that only future decisions by EMA and AEMPS may clarify. The present stance by our task force is that biosimilar development should be undertaken according to established regulations, thus certifying their efficacy and safety. Similarly, this task force considers that results obtained from studies in rheumatoid arthritis (RA) should not be extrapolated to IBD since the biological variability of these complex structures will not ensure a lack of noticeable changes in efficacy and safety.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 01/2013; 105(1):37-43. · 1.55 Impact Factor
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ABSTRACT: Background and aims: Crohn´s disease (CD) is commonly associated with inflammatory processes located in organs and systems others than the gut, which are known as extraintestinal manifestations (EIM) of the disease. The aim of this study was to assess the effectiveness of adalimumab (ADA) for the treatment of EIM in patients with CD.Methods: forty two consecutive CD patients with at least one EIM were prospectively included in a open-label study. Patients received ADA (160 mg at week zero, 80 mg at week two and 40 mg every other week) over six months and the effectiveness and safety of ADA for EIMs were assessed. The influence of gender, age, smoking habits, family history of inflammatory bowel disease, phenotype and previous anti-TNF treatment on EIM resolution was also investigated.Results: at month six, 76.2% of the patients showed remission or response in CD (33.3% remission and 42.9% any response). EIM showed a parallel course with CD in most cases, and showed remission or response in 66.7% of patients (38.1% remission and 28.5% any response). Patients with any response of their EIM condition were younger than those with no response (p = 0.04). No relationship was found between sex, tobacco, family history of IBD, phenotype and previous treatment with anti-TNF, and EIM resolution.Conclusions: adalimumab is effective in reducing EIM of CD. Age but not tobacco, CD phenotype and anti-TNF-naïve status appears to influence the response.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 10/2012; 104(9):468-472. · 1.55 Impact Factor
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Alimentary Pharmacology & Therapeutics 08/2012; 36(3):297-8; author reply 298-9. · 3.77 Impact Factor
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M Chaparro,
P Burgueño,
E Iglesias,
J Panés,
F Muñoz,
G Bastida,
L Castro,
C Jiménez,
J L Mendoza, M Barreiro-de Acosta,
S Gómez Senent,
F Gomollón,
X Calvet,
E García-Planella,
M Gómez,
V Hernández,
J Hinojosa,
M Mañosa,
O Pérez Nyssen,
J P Gisbert
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ABSTRACT: Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown.
To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC.
Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan-Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered.
The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia.
Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin-infliximab) should be taken on an individual basis.
Alimentary Pharmacology & Therapeutics 12/2011; 35(2):275-83. · 3.77 Impact Factor
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ABSTRACT: A higher incidence of inflammatory bowel disease (IBD) in industrialized areas has been previously reported, but the effect of emigrating to western industrialized countries for a period of time and returning to the country of origin is unknown. Aim of the study was to evaluate the effect of emigrating to another country and returning to the place of origin on the risk of IBD.
A prospective case-control study was performed. Inclusion criteria were all patients >18 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) in the last 10 years. Healthy, unrelated controls, matched by sex, age and smoking habits, with no family history of IBD were included. All patients and controls were interviewed and emigration was defined as living for at least one year in another country.
242 consecutive patients with IBD (105 CD and 137 UC) and 242 controls were included. Patients who had previously emigrated developed more frequently IBD than controls (OR 1.93, 95%CI 1.19-3.15, p<0.01). Patients who emigrated to European countries developed more frequently IBD than controls (OR 1.91, 95%CI 1.07-3.47, p=0.02), but not those who had emigrated to Latin America (OR 1.48, 95%CI 0.67-3.27, p=0.32). Emigration plays a significant role in the development of UC (OR 2.24, 95%CI:1.29-3.88, p<0.01), but not in CD (OR 1.56, 95%IC:0.83-2.92, p=0.15).
People who emigrate to westernised countries have a higher risk for developing IBD, especially UC. Environmental factors related with industrialization seem to play an important role in the pathogenesis of these diseases.
Journal of Crohn s and Colitis 12/2011; 5(6):566-9. · 2.57 Impact Factor
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M Barreiro-de Acosta,
O García-Bosch,
R Souto,
M Mañosa,
J Miranda,
V García-Sanchez,
J Gordillo,
S Chacon,
C Loras,
D Carpio,
N Maroto,
L Menchén,
M Rojas-Feria,
M Sierra,
A Villoria,
I Marin-Jimenez
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ABSTRACT: 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.
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.
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.
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.
Inflammatory Bowel Diseases 08/2011; 18(5):812-7. · 4.86 Impact Factor
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ABSTRACT: In inflammatory bowel disease (IBD) iron deficiency anaemia (IDA) is a very common disorder. Until recently,oral iron has been the mainstay therapy, nevertheless it has been associated with intolerance and noncompliance. Therefore, the goal of our study was to evaluate the efficacy of intravenous iron in IDA in IBD patients and the secondary aim was to investigate whether other potencial factors could influence in the response to the treatment.
An open-label, prospective, consecutive, single centre study.
We performed our study in patients with ulcerative colitis (UC) or Crohn´s disease (CD) with severe anaemia or intolerance with oral iron. All of them received intravenous sacarose iron and did biochemistry profile with hemoglobin (Hb). Moreover, the correlation with other variables was studied: age,sex, smoking habit, IBD type, previous surgery and type of surgery and other treatments. Response was defined as Hb increase of ≥ 2 g/dL or normalization of the levels.
Fifty-four patients were included into the study, 34(63%) with UC y 20 (37%) with CD, 18 (33.3%) men and 36 wo-men (66.6%) and the average was 48 +/- 14 years. The total proportion of responders was 52% (SD +/- 05); 43% of the patients reached Hb ≥ 2 g/dl and y 9% of them normalized Hb. Only the utilization of 5-ASA was associated with low response to iron treatment (p < 0.05).
Our study suggests that response to intravenous iron is achievable in the majority of patients with IBD and severe IDA or intolerance treatment with oral iron. Moreover, the patients with consumption of 5-ASA could had less response to the treatment.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 05/2011; 103(5):245-9. · 1.55 Impact Factor
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C Taxonera,
J Estellés,
I Fernández-Blanco,
O Merino,
I Marín-Jiménez, M Barreiro-de Acosta,
C Saro,
V García-Sánchez,
E Gento,
G Bastida,
J P Gisbert,
I Vera,
P Martinez-Montiel,
S Garcia-Morán,
M C Sánchez,
J L Mendoza
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ABSTRACT: The long-term efficacy of adalimumab in patients with ulcerative colitis is not well known.
To evaluate the short- and long-term outcomes of adalimumab in ulcerative colitis patients previously treated with infliximab.
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.
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.
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.
Alimentary Pharmacology & Therapeutics 02/2011; 33(3):340-8. · 3.77 Impact Factor
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ABSTRACT: Crohn's disease (CD) affects Health Related Quality of Life (HRQoL) especially in patients with clinical activity but their impact over the disease during periods of remission has not been sufficiently studied.
To evaluate HRQoL in CD patients in remission and to identify socio-demographic and clinical factors related.
We included patients with CD in remission for at least 6 months, defined as a CDAI < 150 and a CRP < 5 mg/L. Socio-demographic and clinical parameters were recorded. HRQoL was evaluated with Short Form 36 Questionnaire (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ). Results were analyzed using multiple regressions with a confidence interval of 95%.
Nine two patients (X = 37 +- 11.4 years, 52.2% men) were consecutively included. Two patients failed to fill correctly the questionnaire and were excluded. Scores on the SF-36 were lower than in the general population of similar age and sex. The most affected dimension in the SF-36 was General Health (47.98 +- 19.58) and the IBDQ Systemic Symptoms (5.15 +- 1.27). Age, colonic location and previous surgery was related with worse HRQoL, while higher educational status, more time since diagnosis, steroid-resistance and inflammatory behavior, was associated with better HRQoL.
Despite being in remission, CD patients had affected their HRQoL, so we must continue working to achieve improvement in HRQL of these patients during these periods of the disease.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 11/2010; 102(11):624-30. · 1.55 Impact Factor
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ABSTRACT: Adalimumab is a recombinant fully-human monoclonal immunoglobulin (IgG1) antibody utilized in the treatment of Crohn's disease. Unfortunately no clinical or genetic markers exist to predict response to anti-tumor necrosis factor-alpha (TNF) therapy. The aim of this study was to evaluate the association between selected genes involved in cytokine regulation and response to adalimumab treatment in Crohn's disease.
twenty-four patients with Crohn's disease either naïve (n = 8) or had lost response or were unable to tolerate the chimeric anti-TNF antibody infliximab (n=16) were enrolled in the study. Patients were genotyped for main polymorphisms in NOD2, CD14 and TLR4 genes. Response to adalimumab treatment was defined as a decrease of Crohn's disease activity index of at least 100 points or a closure of at least 50% of fistulas in case of fistulizing Crohn's disease.
overall, 75% of patients did respond to treatment. However, no statistically significant association was found between any of the genotypes and the response to adalimumab.
In our small study group no association between the studied polymorphisms and response to adalimumab was apparent. Systematic studies to search for genetic markers of response to anti-TNF therapy are necessary.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 10/2010; 102(10):591-5. · 1.55 Impact Factor
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ABSTRACT: Crohn's disease (CD) is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide), though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, at present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 05/2010; 102(5):321-6. · 1.55 Impact Factor
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ABSTRACT: the role of anxiety and depression in CD patients in remission has been poorly investigated.Objective: the aim of the study was to evaluate the frequency of anxiety and depression symptoms in CD patients in remission, and potential factors influencing the development of these symptoms.
CD patients older than 18 years in remission for at least 6 months before study entry were included. CD remission was defined as a Crohn s Disease Activity Index (CDAI) < 150 points together with C-reactive protein < 5 mg/L. A demographic questionnaire was filled in, and all patients were clinically classified. The therapy maintaining remission was also recorded. A Hospital Anxiety and Depression scale (HAD) was administered to all patients. Results are shown as OR and 95% CI, and analyzed by logistic regression.
92 consecutive patients were included (48 male, mean age 37 years, range from 18 to 71 years). One patient failed to correctly fill in the questionnaire. Anxiety and depression symptoms were present in 36 (39%) and 22 (24%) patients, respectively. Infliximab therapy was the only factor associated with anxiety (OR = 3.11; 95% CI: 1.03-9.43; p < 0.05). In contrast, the presence of depressive symptoms is less frequent in patients under infliximab therapy (OR = 0.16; 95% CI: 0.02-0.97; p < 0.05).
despite clinical remission, an important number of CD patients present with anxiety or depressive symptoms. Infliximab therapy in CD patients is associated to more anxiety but fewer depressive symptoms. CD patients in remission would probably benefit from psychological support.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 04/2009; 101(4):249-57. · 1.55 Impact Factor
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ABSTRACT: Amyloidosis is a clinical entity that results from the deposition of an extracellular protein material that causes disruption in the normal architecture of multiple organs and tissues, and impairs their function. Secondary amyloidosis is a rare but serious complication that may worsen the prognosis of patients with cancer, infection or chronic inflammatory disease, including inflammatory bowel disease, particularly Crohn's disease. We report two cases of Crohn's disease associated with secondary amyloidosis.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 01/2009; 100(12):792-7. · 1.55 Impact Factor
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ABSTRACT: We aimed at evaluating the frequency of acute severe bleeding in CD and its potential association to some risk factors, including clinical features of CD, environmental factors, and genetic alterations.
174 consecutive patients with CD (103 female (59%) and 71 men (41%), with a mean age of 37 years) were included. We analyzed all major acute lower gastrointestinal (GI) hemorrhage related to CD. Potential risk factors like smoking, site of disease, and presence of gene mutations in CARD15, TLR-4, and CD14 were also analyzed.
Three patients (1.7%) suffered from severe acute lower GI bleeding. All patients required surgery to resolve their hemorrhage, and this indication represented 3.4% of all surgical procedures related to CD. All three patients were young ( < 25 years) and suffered ileal CD with inflammatory pattern (L1-B1 in the Vienna Classification). No relationship was found between acute bleeding and any of the potential risk factors evaluated.
Acute severe GI bleeding is a rare, but severe complication in CD patients, and presents mainly in patients with inflammatory ileal disease. An association of endoscopy and arteriography is necessary for diagnosis. Urgent surgery is usually required in these patients.
Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva 07/2007; 99(7):388-91. · 1.55 Impact Factor
