Elena Garrido

Safety of Thiopurines and Anti-TNF-α Drugs During Pregnancy in Patients With Inflammatory Bowel Disease

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.

Optimized Protocol for Diagnosis of Acute Ileitis

BACKGROUND & AIMS Suspected acute ileitis (AI) is a poorly defined clinical condition with multiple causes; its diagnostic protocol has not been standardized properly. We performed a prospective evaluation of the incidence and causes of AI to create a standard protocol for diagnosis. METHODS The definition of AI included abdominal pain, diarrhea, fever, and at least 1 confirmatory imaging method (abdominal computed tomography scan or ultrasound) showing pathologic changes in the terminal ileum that indicated ileal inflammation. We studied all patients with a presumptive diagnosis of AI seen in the Emergency Room at the Ramón y Cajal Hospital in Madrid, from March 2005 to May 2007, according to a pre-established protocol. Sixty-six patients with primary AI were followed up for at least 6 months. RESULTS An infectious cause was found in 33.3% of cases; the most frequently detected microorganism was Yersinia spp. A gynecologic condition was identified in 9.1% of cases initially diagnosed as AI, representing 13.95% of the cases among female patients. Crohns disease was identified in 12.1% of patients. The diagnostic protocol led to negative results in 33.4% of the patients; 6.1% of patients did not complete the study. The initial diagnosis did not change among any of the patients during the follow-up period. CONCLUSIONS This protocol led to a definitive diagnosis of AI in more than 60% of potential cases. The most common cause was acute infection. About 10% of cases were of gynecologic origin and about 12% of patients presented with Crohns disease.

Rescate con sulfasalazina antes de inmunosupresores o agentes biológicos en la colitis ulcerosa mal controlada con mesalazina

INTRODUCTION In ulcerative colitis, aminosalicylates are the mainstay of maintenance therapy. Sulfasalazine was the first aminosalicylic used in the maintenance therapy of this disease. Later, mesalazine was preferred due to its supposedly better tolerability. However, recent studies indicate certain benefits of the use of sulfasalazine because of its possible superior effectiveness. The aim of this study was to determine whether patients with ulcerative colitis poorly controlled by mesalazine as maintenance therapy respond to sulfasalazine, thus avoiding the use of immunosuppressive or biological therapies. METHODS The Inflammatory Bowel Disease Clinic of the Ramón y Cajal Hospital maintains a database in which all drug exposures are registered. We selected patients poorly controlled with mesalazine who had received sulfasalazine as rescue maintenance therapy. We determined the percentage of patients poorly controlled with mesalazine who responded to sulfasalazine. RESULTS Of 415 patients with ulcerative colitis, 49 had been treated with sulfasalazine at some time. Of these, sulfasalazine was selected as an alternative therapy due to poor disease control with mesalazine. The median duration of mesalazine therapy until the switch was 20.8 months, with a median dose of 3.35 g/day. In 21 of the 31 patients (67.7%), sulfasalazine was able to control symptoms and maintain remission. CONCLUSION Despite the limitations of this study, we found that 67.7% of patients with ulcerative colitis poorly controlled with mesalazine responded to a switch to sulfasalazine. These patients would normally have progressed to immunosuppressive, biological or surgical treatments. This option merits further studies. Meanwhile sulfasalazine should not be forgotten in the management of ulcerative colitis.

Mercaptopurine and inflammatory bowel disease: the other thiopurine.

BACKGROUND Data about use and effectiveness of mercaptopurine in inflammatory bowel disease are relatively limited. AIMS To assess the possible therapeutic indications, efficacy and safety of mercaptopurine as an alternative to azathioprine in inflammatory bowel disease. METHODS Retrospective observational study in patients treated with mercaptopurine in a total cohort of 1,574 patients with inflammatory bowel disease. RESULTS One hundred and fifty-two patients received mercaptopurine, 15.7% of these patients as an initial thiopurine, 5.3% after azathioprine failure, and 79% after azathioprine intolerance. In 52.6% of patients (n = 80), adverse effects of mercaptopurine occurred, resulting in withdrawal in 49 of them. Mercaptopurine was effective in 39% of cases (95% CI 31-48%). In the remaining patients, failure was due mainly to withdrawal due to side effects (55.1%) and therapeutic step-up (33.7%). The average total time of mercaptopurine exposure was 36 months (IQR: 2-60). Myelotoxicity with mercaptopurine was more common in patients with intermediate TPMT activity than in those with normal activity (p = 0.046). CONCLUSIONS In our setting, mercaptopurine is primarily used as a rescue therapy in patients with azathioprine adverse effects. This could explain its modest efficacy and the high rate of adverse effects. However, this drug is still an alternative in this group of patients, before a therapeutic step-up to biologics is considered.

Efficacy of Different Therapeutic Options for Spontaneous Intraabdominal Abscesses in Crohn's Disease

of IBD and pneumologist experts. Clinical data included age, sex, smoking status, disease duration, IBD phenotype according to Montreal classification, concomitant medication and disease activity at the time of diagnosis of bronchopulmonary manifestations. Clinical and morphological description (HRCT), bronchoscopy, bronchoalveolar lavage, histology, and outcome were reviewed. Results: Eighty patients (F 53%, median age 33.5 yrs, UC 47.5%, active smoking 9%) were included. Pulmonary disease was revealed by cough or dyspnoea (90%), frequently after the onset of IBD (85%; median delay after diagnosis was 6 years). At the time of diagnosis of lung disorder, bowel disease was inactive in 41 cases (51%) and lightly to moderately active in 28 cases (35%). Airway disease was present in 53% cases (bronchiectasis: n=25, chronic bronchitis: n=8 and tracheal involvement: n=5) and parenchymal disease in 45% cases (diffuse interstitial lung disease (ILD): n=20,granulomatous lung disease: n=16). Airway disease occurred mainly in UC (n=23/33; 70%) and followed colectomy in 15 cases with a median delay of 4 years (5 months-23 years). Fifty five patients (69%) had steroids with different modalities (inhaled, oral or intravenous). In 89% of cases, improvement or stabilisation were observed (median follow-up of 4 years). Efficacy of immunosuppressants (n=10) was inconsistent and difficult to assess. In granulomatous lung diseases, outcome was constantly favourable, mainly under steroids (n=10). Airway diseases were complicated by infectious diseases in approximately 50% of cases. The prognosis of ILD depended on the parenchymal disease type. Four deaths were reported, 3 of which were secondary to respiratory failure (tracheal involvement: n=1, ILD: n=2). Conclusions: Bronchopulmonary manifestations associated with IBD can be classified in three different types: airway disease, interstitial lung disease and granulomatous disease. Prognosis appears severe in cases of tracheal involvement or interstitial lung disease.

Percutaneous liver biopsy.

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