Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: Results from the VERNE study.

BACKGROUND: Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. AIMS: To assess the treatment patterns with the first anti-TNFα in IBD. METHODS: Retrospective, observational study. RESULTS: 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. CONCLUSIONS: Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control.

Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study.

BACKGROUND AND AIMS: The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS: This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS: A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS: The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.

Does the Antitumor Necrosis Factor-α Therapy Decrease the Vertebral Fractures Occurrence in Inflammatory Bowel Disease?

BACKGROUND/OBJECTIVE: Osteoporosis and osteoporotic fracture risk are extraintestinal manifestations of the inflammatory bowel disease, whose etiopathogenic mechanisms have not been determined yet. Anti-tumor necrosis factor (TNF)-α are used in treatment of inflammatory bowel disease (IBD), but it is unknown if they play a role in osteoporotic fracture prevention. The objective of this study was to know if anti-TNF decreases fracture risk or modifies bone mineral density. To determine the possible risk factors associated with fractures, and assess the incidence of vertebral fractures in IBD patients. METHODS: Longitudinal prospective cohort study (7 yr of follow-up); which included 71 IBD patients, 23 received anti-TNF-α; the remaining 48 received conventional treatment, constituted the control group. Patients participated in a questionnaire which gathered risk factors associated with the development of osteoporosis and fractures. Radiographs of the dorsolumbar-spine were performed and also a bone density measurement. Their biochemical and bone remodeling parameters were determined. RESULTS: Although patients who did not receive anti-TNF-α, suffered more fractures but biologic therapy did not reduce the risk of new vertebral fractures. The increase of bone mass was significantly higher the group treated with anti-TNF-α. The increase in the lumbar spine was of 8% and in the femoral neck was of 6.7%. The only determinant factor for the incidence of vertebral fractures was a history of previous fractures (odds ratio of 12.8; confidence interval 95% 2.37-69.9; p = 0.003). The incidence of vertebral fractures in IBD patients was considerably high: 26.7/700 patient-yr. CONCLUSIONS: Anti-TNF-α, although increased bone mass in these patients, did not reduce the risk of new vertebral fractures. In this study, patients with IBD have a considerably high incidence of fractures. Only the existence of previous vertebral fractures was a predictive factor for consistent fractures.

Effectiveness and Safety of CT-P13 (Biosimilar Infliximab) in Patients with Inflammatory Bowel Disease in Real Life at 6 Months.

BACKGROUND: CT-P13 is a biosimilar of Remicade®, an agent approved in some countries for use in inflammatory bowel disease (IBD). Controlled clinical trials have demonstrated the efficacy and safety of CT-P13 in rheumatic diseases, but not in IBD. AIMS: To assess the effectiveness and safety of CT-P13 in IBD patients in real clinical practice. METHODS: This is a prospective observational study in patients with moderate to severe Crohn's disease or ulcerative colitis treated with CT-P13. The study was performed in one single center. Patients included were naive or switched to anti-TNF treatment from the reference infliximab (Remicade®) to CT-P13. Efficacy and safety were assessed in naive and switched patients who were in remission at the time of the switch at months 3 and 6 of therapy. RESULTS: 87.5 and 83.9% of switched CD patients who were in remission at the time of the switch continued in remission, and 66.7 and 50% of naive CD patients reached remission, at months 3 and 6. In UC switched cases, 92 and 91.3% of patients in remission at the time of the switch continued in remission, at 3 and 6 months. In naive UC patients, the remission rates were 44.4 and 66.7%, at months 3 and 6. Adverse events occurred in 7.5% of patients during 6 months of study. CONCLUSIONS: CT-P13 was efficacious and well tolerated in patients with CD or UC.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Characteristics and treatment of pyoderma gangrenosum in inflammatory bowel disease.

BACKGROUND: Pyoderma gangrenosum is a serious cutaneous complication seen in approximately 1 % of patients with inflammatory bowel disease (IBD). Oral corticosteroids are the mainstay treatment, although the evidence supporting their use is weak. AIMS: The purpose of this study was to investigate the characteristics of pyoderma gangrenosum associated with Crohn's disease or ulcerative colitis and which treatments are prescribed in Spanish clinical practice. METHODS: In this retrospective, observational study, the medical records from all patients with IBD and a diagnosis of pyoderma gangrenosum attended by the gastroenterology departments of 12 Spanish hospitals were reviewed. Data on patient demographics and characteristics, underlying IBD and treatment, and pyoderma gangrenosum characteristics, treatment, and outcome were collected and analyzed. RESULTS: The data from 67 patients were analyzed (41 [61.2 %] women, 41 [61.2 %] with Crohn's disease, 25 [37.3 %] with ulcerative colitis, and 1 [1.5 %] with indeterminate disease). The underlying disease was in remission in approximately one-third of patients at the time of presentation of pyoderma gangrenosum. Healing was achieved in all patients (in 3 without any systemic therapy). Oral corticosteroids were taken by 51 patients (76.1 %), almost always as first-line treatment, although definitive healing was attained in 19 (28.4 %). Biologic agents such as infliximab and adalimumab were taken by 31 patients (46.3 %) at some point (first-line in 6 patients [9.0 %]), with definitive healing in 29 patients (93.5 %). CONCLUSIONS: Oral corticosteroid therapy remains the most common treatment for pyoderma gangrenosum associated with inflammatory bowel disease. Biologic therapies such as infliximab and adalimumab should also be considered.

PillCamColon Capsule for the study of colonic pathology in clinical practice. Study of agreement with colonoscopy.

INTRODUCTION: several studies have pointed out the effectiveness of the PillCam colon capsule endoscopy (CCE) compared with the colonoscopy in the study of the colonic pathology. AIMS AND METHODS: the objective of our study was to assess the agreement in the diagnosis of CCE with conventional colonoscopy as well as its sensitivity and specificity, and to describe the findings of the CCE in our clinical practice. Consecutive patients with abdominal symptoms were included in the study. The CCE was performed as previously reported (with PEG and sodium phosphate as laxative agents). The nature and location of the findings, colonic transit time, complications, cleanliness degree and consistency with diagnostic colonoscopy, when performed, were analyzed. RESULTS: a total of 144 subjects (67 women and 77 men); (52.17 ± 16.71 years) with the following indications were included: screening of Colorectal cancer (88 patients), control after polipectomy (24), incomplete colonoscopy (7), rectal bleeding (10), anemia (8), diarrhea (7). The CCE exploration was complete in 134/144 cases (93%), with no case of retention. The preparation was good-very good in 88/134 (65,6%), fair in 26/134 (19,4%) and poor in 20/134 (15%) of the cases. The average colonic transit was of 140.76 min (9-603). Any adverse effect was notified.In 44 cases a colonoscopy was carried out after CCE (results were hidden from another endoscopist). Compared to colonoscopy, the rate of agreement was 75,6%, the sensitivity was 84% and the specificity 62,5%, PPV was 77,7% and NPV was 71,4%.The colonic findings in 134 CCE were: in 34 cases CCE it did not show lesions, diverticulosis in 63 explorations, polyps in 43, angiodysplasias in 15, Crohn's Disease in 9 and ulcerative colitis in other 8 cases. CONCLUSIONS: the CCE is an effective and reliable technique for the detection of lesions in colon, and because of its high agreement with the colonoscopy, it could be useful in clinical practice. Further studies with large seria and cost-effectiveness analysis are needed to confirm these data.

Macroscopic small bowel mucosal injury caused by chronic nonsteroidal anti-inflammatory drugs (NSAID) use as assessed by capsule endoscopy.

OBJECTIVE: To evaluate the type, frequency, and severity of macroscopic small bowel mucosal injury after chronic NSAID intake as assessed by capsule endoscopy (CE), as well as to correlate the severity of gastroduodenal and intestinal damage in these patients. MATERIAL AND METHODS: A prospective, endoscopist-blind, controlled trial. Sixteen patients (14F/2M; age: 57.06 +/- 10.16 yrs) with osteoarthritis (OA) on chronic therapy with NSAIDs underwent CE and upper gastrointestinal endoscopy (UGE). Seventeen patients with OA (9F/2M; age: 57.47 +/- 9.82 yrs) who did not take NSAIDs were included as a control group. A scale ranging from 0 to 2 (0 = no lesions, 1-minor = red spots or petechiae, denuded areas and/or 1-5 mucosal breaks; 2-major = > 5 mucosal breaks and/or strictures, or hemorrhage) was designed to assess the severity of small bowel mucosal injuries. RESULTS: CE found intestinal lesions in 75% (12/16) of patients in the study group and in 11.76% (2/17) of controls (p < 0.01). Seven out of 16 NSAID consumers (43.75%) and none in the control group (0%) had a major small bowel mucosal injury (p < 0.01). The percentages of patients with grade 1 and 2 gastroduodenopathy in the study group, as assessed by UGE, were 37.14 and 23.81%, respectively. There was no significant difference in the rate of major enteropathy between patients with none or minor gastroduodenal injury, and those with major gastroduodenopathy (43.75 vs. 40%; p = N.S.). CONCLUSIONS: Chronic NSAID intake is associated with a high rate of small bowel mucosal injuries. Our data have failed to demonstrate a relationship between the severity of gastroduodenal and intestinal injury.

Results of a survey about specific inflammatory bowel disease units in Andalusia.

BACKGROUND: Inflammatory bowel disease (IBD) has become one of the most prevalent pathologies in Gastroenterology Units, which added to its clinical outcome, treatment, the complexity of affected patients and the need to be continuously updated for the correct management of the disease, have made essential the presence of specific IBD units in each hospital. OBJECTIVES: The primary aims of this study were: a) to reveal the existence of these units in our area and how they work; and b) to draw conclusions regarding the necessary resources in these units and their aims. MATERIAL AND METHODS: In order to analyse the presence of these specialized units and the available resources in Andalusian hospitals, a 24-question survey was designed, being answered by 11 hospitals. The evaluated questions included the number of days patients are attended and the number of physicians attending the unit, the number of available healthcare assistants, if emergencies are attended or not, if there is an activated telephone number for patient consultation, if a day care unit is available and if new treatments are easily accessible. RESULTS: A specific IBD unit is present in all studied hospitals attending more than 11 patients each, although in the 63.4% of the cases patients are not attended more than 3 days per week. On the other hand, the 81.8% of the included hospitals attend emergencies although only the 54.5% of them had a specific telephone number for patient attendance. CONCLUSIONS: A specific IBD unit is present in many Andalusian hospitals, although some deficiencies can be observed. The general opinion of this Group is that these units are necessary in order to properly attend, monitorize and treat patients affected by IBD.

[A high-resolution gastroenterology clinic in Andalusia: what is it, and how should it work]. / Consulta de alta resolución de digestivo en Andalucía: qué es y cómo debe funcionar?

INTRODUCTION: The present concept in our healthcare system is that medical care should be given on an outpatient basis with hospitalization occurring only when essential. We therefore put forth the development of the "all in one" outpatient office or "high resolution" outpatient clinic. For such purpose we administered a questionnaire to various Andalusian hospitals to define and determine those aspects necessary in the development of the aforementioned outpatient office. MATERIALS AND METHODS: The questionnaire was filled out by 10 Andalusian hospitals. This is a prospective-descriptive study of responses from all 10 participating hospitals. The 27 questions inquired on the existence of such an outpatient office and the infrastructure needed to develop this service: How many patients are seen, where is it physically located, where do patients come from, criteria for assigning patients to this medical office, condition of incoming patients, whether ultrasound scans are performed, whether an integrated hospital computer system exists, nursing staff, how many visits are required before coming to a diagnosis, and finally whether this type of outpatient office is needed, and if so, why. RESULTS: Of all 10 hospitals, 5 of them had this type of clinic. All of them considered this type of outpatient service essential. The number of patients treated should be "10", in the hospital itself. There are differences as to whether patients should come from the emergency room or a primary care physician. It seems logical to assume that only patients who can be diagnosed via ultrasounds or endoscopy should be chosen. To allow an ultrasonogram the patient should visit the outpatient office in a state of "fasting" and with standard blood counts from the primary care physician. The outpatient clinic should have a computer system and its own nurse. According to participating hospitals this type of outpatient visits is very useful in our present healthcare system, as it allows higher levels of collaboration between Primary Care and the specialist; it also provides a rapid orientation regarding patient pathology, and acts as a "filter" for the rest of the healthcare system. CONCLUSIONS: The outpatient office should be tended to by an attending specialist in the field (FEA) with knowledge and experience in ultrasounds and gastrointestinal endoscopy, as well as user competency with the required computer programs. In our present-day system this can be considered a modality of high-resolution outpatient services and a model of efficiency.

[Is capsule endoscopy useful in children with chronic abdominal pain?]. / Es útil la cápsula endoscópica en niños con dolor abdominal crónico?

Chronic abdominal pain is highly prevalent in school-aged children and is one of the most frequent disorders in our environment. The aim of the present study was to evaluate the usefulness of capsule endoscopy (CE) in patients with chronic abdominal pain. Sixteen patients (nine boys and seven girls), aged between 5 and 16 years old, with chronic abdominal pain for at least 12 months were studied. In all patients the results of hemograms, biochemical investigations, urine sediment test, Helicobacter pylori breath test and celiac serology were normal. In all children, gastroscopy, small bowel follow-through, abdominal ultrasound and colonoscopy were normal. All patients received CE by mouth. In 43.75 % of the patients studied (7/16), the capsule showed evidence of nodular lymphoid hyperplasia, mainly located in the ileum. In one girl, oxyuriasis was observed in the cecum and in another girl aphthous lesions were observed in the ileum. These lesions suggested small bowel Crohn's disease. CE mainly showed images compatible with nodular lymphoid hyperplasia, with unknown clinical significance. Consequently, we conclude that CE does not provide useful information in patients with abdominal pain without other symptoms.

Results of a survey in Andalusian endoscopy units.

INTRODUCTION: In Spain, there is no indication of the resources that an endoscopy unit should have. As a consequence only the experience of professionals who have been working for years in this field can be used as a guide. However, there are some recent surveys on sedation in Spain that indicate how sedation is use in other units. OBJECTIVES: The objectives of the present study were: a) to find out the human and material resources available in endoscopy units in Andalusia; b) to analyze the number of endoscopies performed in our country; and c) to identify factors that can be improved. MATERIAL AND METHODS: In order to make an assessment of the conditions and resources of said units in Andalusia, a survey was designed for the staff of gasteroenterology department. Hospitals involved are those specified in this paper. The survey, which included 90 questions, covers all aspects concerning each unit. There are questions on the real conditions of the unit, and on what would be considered as ideal or at least as minimal requirement for each hospital or Health Area. CONCLUSIONS: Even though some shortcomings were found in some hospitals, a high percentage of them have acceptable equipment. However, due to fast advances in the field of endoscopy, an improvement in the conditions should be provided, especially in aspects concerning anesthesia.

The value of capsule endoscopy in pediatric patients with a suspicion of Crohn's disease.

BACKGROUND AND STUDY AIMS: The aim of this study was to assess the safety and usefulness of capsule endoscopy (CE) in pediatric patients with a suspicion of Crohn's disease. PATIENTS AND METHODS: CE was used in 12 patients (four girls, eight boys; age 12-16; weight range 43-87 kg). The indication was a clinical suspicion of Crohn's disease not confirmed with traditional methods. Gastroscopy, colonoscopy, and small-bowel follow-through examinations were carried out in all of the patients, without any diagnostic findings. Ileoscopy was possible in 50 % of the patients, and the ileal mucosa and biopsies were normal in all cases. RESULTS: The capsule was easily swallowed by all of the patients. They all excreted the capsule normally, and no complications were observed in any case. CE identified lesions suggestive of Crohn's disease in seven of the 12 (58.3 %), and the majority of the lesions were in the ileum. CONCLUSIONS: CE is safe in pediatric patients over 12 years of age. The procedure appears to be a very useful diagnostic tool in children with Crohn's disease.

[Utility of capsule endoscopy in pediatric gastroenterology]. / Utilidad de la cápsula endoscópica en gastroenterología pediátrica.

Wireless endoscopy is a new noninvasive diagnostic method that is able to visualize small bowel lesions. The instrument is small and carries a battery and microcamera that takes two photographs per second. It is indicated in cases of bleeding of unknown origin and for the diagnosis of inflammatory bowel disease, among other disorders. To date, it has mainly been used in adults. We believe that this instrument could play an important role in the pediatric age group since it is noninvasive and can be used to diagnose small bowel lesions, thus avoiding unnecessary diagnostic tests. We report the case of a girl with suspicion of Crohn's disease that was unconfirmed by conventional endoscopic techniques. The capsule showed small bowel lesions compatible with Crohn's disease. Corticosteroid treatment was initiated and the patient is now in clinical remission.

Posterior laryngitis: effects of treatment with omeprazole alone.

OBJECTIVE: To evaluate the effect of omeprazole treatment on the symptoms and lesions of patients with posterior laryngitis (PL). PATIENTS AND METHOD: Twenty-one patients with a clinical and laryngoscopic diagnosis of PL were studied. Results for each laryngeal symptom (dysphonia, hoarseness, cough, foreign body sensation, and burning) and laryngoscopic finding (mucus stasis, erythema, oedema, hypertrophy, ulceration, and granulation) at baseline, 12 weeks after treatment with omeprazole, 20 mg twice daily, and 12 weeks after treatment discontinuation were compared. No changes in their hygienic-dietary or postural habits were recommended. RESULTS: A reduction in symptom severity and frequency was observed (p < 0.05), as well as in the severity of laryngoscopic findings (p < 0.05)--except for granulation--immediately after treatment discontinuation. A relapse of laryngoscopic findings was seen at 12 weeks after treatment discontinuation (p < 0.01). The trend towards symptom recurrence was not significant. CONCLUSION: Treatment with omeprazole alone modifies clinical manifestations and endoscopic findings in patients with PL. Controlled clinical trials with a high number of patients and longer-term follow-up are needed to define the best therapeutic regimen for these patients.