Mariam Aguas

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohns disease in high-risk patients. METHODS A multicenter, prospective, observational study was conducted from June 2009 until June 2010. We consecutively included high-risk Crohns disease patients who had undergone an ileal/ileocolonic resection. High-risk patients were defined as two or more criteria: smokers, penetrating pattern, one or more previous surgical resections or prior extensive resection. Subcutaneous adalimumab was administered 2 wk (± 5 d) after surgery at a dose of 40 mg eow, with an initial induction dose of 160/80 mg at weeks 0 and 2. Demographic data, previous and concomitant treatments (antibiotics, 5-aminosalicylates, corticosteroids, immunomodulators or biologic therapies), smoking status at the time of diagnosis and after the index operation and number of previous resections (type and reason for surgery) were all recorded. Biological status was assessed with C-reactive protein, erythrocyte sedimentation rate and fecal calprotectin. One year (± 3 mo) after surgery, an ileocolonoscopy and/or magnetic resonance enterography was performed. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. Morphological recurrence was based on magnetic resonance (MR) score ≥ MR1. RESULTS Twenty-nine patients (55.2% males, 48.3% smokers at diagnosis and 13.8% after the index operation), mean age 42.3 years and mean duration of the disease 13.8 years were included in the study. A mean of 1.76 (range: 1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection. 51.7% had previously received infliximab. Immunomodulators were given concomitantly to 17.2% of patients. Four of the 29 (13.7%) developed clinical recurrence, 6/29 (20.7%) endoscopic recurrence and 7/19 (36.8%) morphological recurrence after 1-year. All patients with clinical recurrence showed endoscopic and morphological recurrence. A high degree of concordance was found between clinical-endoscopic recurrence (κ = 0.76, P < 0.001) and clinical-morphological recurrence (κ = 0.63, P = 0.003). Correlation between endoscopic and radiological findings was good (comparing the 5-point Rutgeerts score with the 4-point MR score, a score of i4 was classified as MR3, i3 as MR2, and i2-i1 as MR1) (P < 0.001, r(s) = 0.825). During follow-up, five (17.2%) patients needed adalimumab dose intensification (40 mg/wk); Mean time to intensification after the introduction of adalimumab treatment was 8 mo (range: 5 to 11 mo). In three cases (10.3%), a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk. One patient suffered an adverse event. CONCLUSION Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

Role of oxidative stress and antioxidant enzymes in Crohn's disease.

There is increasing interest in oxidative stress being a potential aetiological factor and/or a triggering factor in Crohns disease, rather than a concomitant occurrence during the pathogenesis of the disease. Recent research has shown that the immune mononuclear cells of Crohns disease patients are induced to produce hydrogen peroxide (H2O2). Similarly, the regulation of antioxidant enzymes during disease in these cells has been unravelled, showing that SOD (superoxide dismutase) activity and GPx (glutathione peroxidase) activity is increased during active disease and returns to normal in remission phases. However, catalase remains constantly inhibited which supports the idea that catalase is not a redox-sensitive enzyme, but a regulator of cellular processes. ROS (reactive oxygen species) can be produced under the stimulus of different cytokines such as TNFα (tumour necrosis factor α). It has been shown in different experimental models that they are also able to regulate apoptosis and other cellular processes. The status of oxidative stress elements in Crohns disease and their possible implications in regulating cellular processes are reviewed in the present paper.

Infliximab and adalimumab-induced psoriasis in Crohn's disease: a paradoxical side effect.

Treatment with antitumor necrosis factor-alpha (anti-TNF-α) offers a significant improvement in several immune-based diseases, including Crohns disease (CD) and psoriasis. Different cutaneous side effects have been described for anti-TNF-α therapy such as psoriasis. Previous reports showed that inhibition of TNF-α can induce over expression of cutaneous IFN-α, which in turn caused a predisposition to psoriasis. We report a 31-year-old woman with extensive CD and perianal lesions, without response to conventional treatment. She paradoxically developed a cutaneous eruption with psoriasiform morphology and distribution during treatment with both anti-TNF-α approved in Europe for CD, infliximab and adalimumab. These lesions cleared after topical application of corticosteroids and cessation of the anti-TNF-α treatment. Due to uneffectiveness of pharmacological treatment on disease, the patient had to undergo surgery. TNF-induced psoriasis in patients with CD is rare and has been previously documented with infliximab or adalimumab. The reason for this apparently paradoxical effect of the therapy is still unclear. This is the first case of psoriasis induced first by infliximab and later by adalimumab in the same CD patient. We would like to review and to draw attention about psoriasis as a cutaneous side effect with anti-TNF-α treatments.

Septic thrombophlebitis of the superior mesenteric vein and multiple liver abscesses in a patient with Crohn's disease at onset

BackgroundPortal-mesenteric vein thrombosis, pylephlebitis and liver abscesses are rare complications of inflammatory bowel disease (IBD). The purpose of this case report is to relate an unusual presentation of CD in order to show how conservative treatment could be an appropriate option as a bridge to the surgery, in patients with septic thrombophlebitis and multiple liver abscesses with CD.Case presentationWe report a case of a 25-year-old man with Crohns disease (CD) who developed a superior mesenteric venous thrombosis, multiple liver abscesses and pylephlebitis, diagnosed through abdominal ultrasound and an abdominal computed tomography (CT) scan. The patient was successfully treated with conservative treatment consisting of intravenous antibiotics, subcutaneous anticoagulation and percutaneous catheter drainage of liver abscesses.ConclusionWe reported an unnusual case of pylephlebitis in CD. Until now this association has not been reported in adult patients at onset. We hypothesise that the infection developed as a result of mucosal disease and predisposed by corticoid therapy. Adequated management was discussed.

The effects of thiopurine therapy on health-related quality of life in Inflammatory Bowel Disease patients

BackgroundThe effect of thiopurine immunomodulators on health-related quality of life (HRQoL) in patients with inflammatory bowel disease (IBD) has been controversial. The aims were to evaluate the HRQoL in patients with IBD treated with thiopurines and assess the short- and long-term impacts of the treatment on HRQoL.MethodsNinety-two consecutive patients who started treatment with thiopurines were prospectively included. Evaluation of HRQoL was performed at months 0, 6, and 12 using two questionnaires, the Short-Form Health Survey (SF-36) and the Inflammatory Bowel Disease Questionnaire (IBDQ).ResultsBaseline score of IBDQ was 4,6, range (2,31-6,84), with an impairment of the five dimensions of HRQoL compared with inactive patients. Results obtained in 8 dimensions of SF-36 showed worse HRQoL than Spanish general population. At 6 months patients had a significant improvement in overall IBDQ score -5,8 (1,58 -6,97)- and also in all IBDQ dimensions. All the 8 dimensions of SF-36 obtained a significant improvement. At twelve months score of IBDQ was 6,1, range (2,7-6,98), with improvement in all dimensions compared with baseline and 6 months. SF-36 showed a similar significant improvement in all subscales.ConclusionsThiopurine immunomodulators alone or with other treatments have a positive and long lasting impact on HRQoL of IBD patients.

Prevalence of irritable bowel syndrome (IBS) in first-degree relatives of patients with inflammatory bowel disease (IBD)

BACKGROUND Epidemiological studies have shown a greater prevalence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) among first-degree relatives of patients diagnosed of these diseases. However, it is not known whether relatives of patients with IBD have a greater prevalence of IBS than the general population. AIMS To analyse the prevalence of IBS among first-degree relatives by consanguinity (parents, siblings and offspring) and affinity (spouses) of patients with IBD. MATERIALS AND METHODS A prevalence study was conducted identifying 490 relatives of 91 patients with IBD. Of these, 404 met inclusion criteria; and 360 (response rate: 89.1%) answered the questionnaires. Subjects were invited to participate in the study through index cases (patients with IBD). The following variables were collected: age, sex, history of digestive diseases, kinship and cohabitation with the index case. The relatives completed a questionnaire to identify those who met Rome I and Rome II criteria for IBS. RESULTS The overall prevalence of IBS among the first-degree relatives of patients with IBD was 49.4% and 10% according to Rome I and Rome II criteria respectively. IBS prevalence was higher in first-degree blood relatives than in spouses of patients (Rome I: 53.1% vs 29.1%, p=0.001; Rome II: 10.8% vs 5.4%, NS). No differences were found in IBS prevalence depending on whether relatives were living with the index case or not. CONCLUSION IBS prevalence in first-degree relatives of patients with IBD is elevated. It is significantly greater in blood relatives, which suggests involvement of genetic and psychological factors rather than environmental factors.

Sa1903 Effectiveness and Safety of Ustekinumab as Rescue Therapy in Multi-Drug Resistant Crohn's Disease

Shortand Long-Term Outcomes of Infliximab Dose Intensification in Patients With Ulcerative Colitis Carlos Taxonera, Manuel Barreiro-de Acosta, Marta Calvo, Cristina Saro, Guillermo Bastida, Maria Dolores Martin Arranz, Javier P. Gisbert, Valle Garcia-Sanchez, Ignacio Marin-Jimenez, Fernando Bermejo, Maria Chaparro, Angel Ponferrada Diaz, Ignacio Fernandez-Blanco, Pilar Martinez-Montiel, R. Pajares, Celia de Gracia, David Olivares, Fermin Estremera Arevalo, Juan L. Mendoza

Small intestinal bacterial overgrowth in inactive Crohn's disease: influence of thiopurine and biological treatment.

AIM To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohns disease (CD). METHODS This was a prospective study in patients with CD in remission and without corticosteroid treatment, included consecutively from 2004 to 2010. SIBO was investigated using the hydrogen glucose breath test. RESULTS One hundred and seven patients with CD in remission were included. Almost 58% of patients used maintenance immunosuppressant therapy and 19.6% used biological therapy. The prevalence of SIBO was 16.8%. No association was observed between SIBO and the use of thiopurine Immunosuppressant (12/62 patients), administration of biological drugs (2/21 patients), or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine (1/13 patients). Half of the patients had symptoms that were suggestive of SIBO, though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis (P < 0.05). Multivariate analysis revealed that the presence of meteorism and a fistulizing pattern were associated with the presence of SIBO (P < 0.05). CONCLUSION Immunosuppressants and/or biological drugs do not induce SIBO in inactive CD. Fistulizing disease pattern and meteorism are associated with SIBO.

Su1132 Toxicity and Mortality Related to the Use of Ciclosporin in Steroid Refractory Ulcerative Colitis: A Multicentric Nationwide Study (ENEIDA)

years. Among the included patients, 4,734 used thiopurines with median duration of one year. Numbers of lymphoma cases identified were 119 and 18 among non-users and while using thiopurines respectively. The incidence rate of lymphoma among those who never used thiopurines was 0.6 compared to 0.9, 1.6, 1.6, 5, 8.9 per 1000 person-year for the 1st, 2nd, 3th, 4th and .4 years of thiopurine use respectively (Figure). The incidence rates of the fourth and more than four years were significantly different from the incidence rate of non-users, yielding HR of lymphoma of 8 and 14 for the fourth year and more than four year of thiopurines use respectively (p,0.001). Conclusion: In this nationwide cohort of UC patients, the incidence rate of lymphoma significantly increased after the third year of cumulative exposure to thiopurines.

Telemedicine in Inflammatory Bowel Disease: Opportunity Ahead.

To the Editor: Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease, is a chronic and relapsing gastrointestinal disorder requiring continuous and personalized follow-up to achieve long remission and minimize short-term and long-term damage. Beyond a medical problem, IBD also generates a significant social and financial impact. To provide a response to these difficulties, information and communication technologies have recently been used to proportion health care services remotely, also known as telemedicine. These technological systems have successfully been used in patients with IBD, allowing for a closer follow-up with better communication between physicians and patients, promoting patients’ empowerment with treatment optimization and better medication adherence. Our research group reviewed the evidence about telemedicine applications in the management of patients with IBD, to give an overview of the acceptance and impact of these interventions on health outcomes. A ground-breaking evaluation of telemonitoring in patients with IBD was developed by Cross et al using a home-automated telemanagement system (HAT system). This telemanagement system was well accepted with high satisfaction, increased knowledge about the disease, and facilitated greater control of their IBD symptoms in most patients. However, in a randomized controlled trial with 47 patients in remission or with mild activity UC, no significant differences were noted in disease activity and quality of life between patients followed with the HAT system and the usual care with medical visits after 12 months, because in part of a higher discontinuation rate in the HAT group and low variation in the disease course in these patients with remission or mild disease. Nevertheless, the HAT system required home installation and eventual repairs, which could impair patient recruitment and participation. To avoid this problem, there is actually an ongoing multicenter, randomized, clinical trial to determine whether patients’ control with a web-based system using text messages to participants’ mobile phones could improve adherence and consequently disease activity and quality of life. Web-based systems to control patients with IBD were previously implemented by Elkjaer et al This group compared a web versus standard care in 333 patients, from Denmark and Ireland, with mild-to-moderate UC treated with 5-aminosalicylic acid for 12 months. The remote care method was shown to be safe and feasible, and most patients wanted to continue using it. There was a trend toward higher medication adherence in web patients and, the duration of relapses was shorter than in the control group, associated with the ability of the web program to empower patients to self-initiate 5-aminosalicylic acid in case of flare-ups. Therefore, these patients performed less outpatient visits and more phone calls and e-mails than control group with cost saving per patient-year. However, improvement in quality of life and disease knowledge questionnaires was inconsistent between both countries, reflecting variations in reproducibility according to the population and health care system in which it was applied. The same web program was used to optimize the dose of multi matrix system (MMX) mesalazine in a single-arm trial with 95 patients with mild-to-moderate active UC, and it was associated with significant improvement of disease activity and quality of life after 12 weeks, with better medication adherence than reported previously. Beyond providing good physician– patient communication, telemedicine has also been used with the aim of giving a multidisciplinary advice. Krier et al developed a “collaborative system,” which was based on remote patient consultation by different specialists contacted in a hospital where access to subspecialties was not possible. They compared this approach with conventional in-person encounter, and there was a high level of patient satisfaction, similar to that achieved with a direct clinical encounter. As a result of the development of telemedicine in recent years, different distance management projects have been designed to improve collaboration and delivery of health services in the community, especially in remote areas. Casellas-Jordá et al implemented a continuous care program in their Crohn-Colitis Care Unit. This model made possible an integrated patient control and empowered patients through education programs, as demonstrated by an increase in distance demands and a reduction of inperson visits. Nevertheless, there are some practical and medico-legal limitations to application of telemedicine in clinical practice, especially web-based systems. Confidentiality requires safe servers, but not all institutions have the infrastructure and economic resources needed. In addition, transcription errors in writing e-mails could induce incorrect decisions. It is important to select trained patients and those technologically unqualified to distance control may use other follow-up methods. In summary, telemedicine systems provide safe and feasible management of IBD, with excellent patient acceptance. The use of information and communication technologies allows continuous and personalized care, also in areas with decreased access to health services. These technologies can be implemented to improve treatment adherence and education, empowering patients to control their disease and optimize medication during flare-ups. Moreover, telemedicine applications are a promising option that could modify the structure of health systems if they demonstrate to be cost-effective. However, randomized controlled trials are still necessary to evaluate the effectiveness of telemedicine programs in comparison with conventional clinical The authors have no conflict of interest to disclose. Supported by grants from the Instituto de Salud Carlos III-Fondo de Investigaciones Sanitarias (FIS PI12/00277). Copyright