Yamile Zabana

Steroid-refractory ulcerative colitis: predictive factors of response to cyclosporine and validation in an independent cohort.

Background: One‐third of patients with steroid‐refractory ulcerative colitis (UC) do not respond to cyclosporine and require colectomy. Since alternative pharmacological treatments for this condition are available, it is pertinent to identify factors that predict response. The objective of this study was to determine predictive factors of response prior to cyclosporine administration, with validation in an independent cohort. Methods: The 2 cohorts of patients were identified from prospectively established databases. All patients had received 1 mg/kg/day prednisolone or equivalent for at least 5 days before cyclosporine. The efficacy measure was need of early surgery (within 3 months). Results: From 1998 to 2005, 34 patients were treated in 1 institution (derivation cohort) and 38 patients in the second institution (validation cohort). Eleven patients in the derivation cohort and 9 patients in the validation cohort underwent early colectomy. Univariate analysis in the derivation cohort demonstrated a significant association of colectomy with C‐reactive protein (P = 0.012) and the Ho index before initiation of cyclosporine (P = 0.013). Regression analysis showed that only the Ho index (P = 0.011) had an independent predictive value. The Ho index predicted need of colectomy, with an area under the characteristic receiver operating curve of 0.79 (95% confidence interval [CI], 0.59–0.99) in the derivation cohort and 0.74 (95% CI, 0.53–0.96) in the validation cohort. The cutoff point with the best sensitivity and specificity ratio was ≥5. Conclusions: The Ho‐based predictive score is a good predictor of response to cyclosporine and avoidance of colectomy, and may aid in the indication of this treatment for management of steroid‐resistant UC.

Fecundity, pregnancy outcomes, and breastfeeding in patients with inflammatory bowel disease: a large cohort survey

Abstract Aim. The aim was to assess the impact of inflammatory bowel disease (IBD) and its treatment on fertility, pregnancy outcomes, and breastfeeding. IBD is a chronic inflammatory condition that is usually diagnosed in young adulthood. Patients are often concerned about fertility and pregnancy outcomes. Methods. A structured questionnaire was posted to 850 adults with IBD followed-up on in a single center. Results. A total of 503 patients (59%) with a median age of 40 years and equally distributed for gender and type of IBD returned the questionnaire. Overall, 71% of the patients had a total of 659 children, 36% of whom were born after the diagnosis. A total of 132 miscarriages were registered, 46% after the diagnosis of IBD. Most childless patients stated that having no children was a personal decision, and only 6% of them were evaluated and diagnosed with infertility. Pregnancies after diagnosis of IBD had a higher probability of caesarean section and preterm delivery. IBD-related drug therapy was discontinued in 16% of the pregnancies, mainly as a result of medical advice. Babies born after the diagnosis of IBD were less often breastfed. Conclusions. The infertility rate among IBD patients seems to be similar to that seen in the general population. However, a large proportion of patients chose to remain childless. Vaginal delivery and breastfeeding are less likely to occur in babies born after the diagnosis. Suitable information for patients to avoid unwarranted concerns about adverse reproductive outcomes, as well as improved obstetrical and perinatal management, still seems to be necessary.

Long-term methotrexate for Crohn's disease: safety and efficacy in clinical practice.

Goals To assess the efficacy and safety profile of methotrexate (MTX) for the treatment of Crohns disease (CD) in clinical practice. Background MTX is widely used for some chronic immunologic diseases. Although some randomized controlled trials suggest its efficacy in CD, this drug remains a second-line, underused, immunomodulator. Study Medical records of all patients treated with MTX for CD in our center (n=44) were reviewed. Clinical and epidemiologic parameters, including risk factors for hepatotoxicity, were registered. Results MTX was prescribed mainly for steroid-dependency (n=22) and as concomitant treatment to infliximab (n=18). Mean duration of treatment was 22.9±19 months, with a mean cumulative dose of MTX of 1169±784 mg. Thirty-nine percent of patients developed drug-related side effects, hepatotoxicity being the most frequent [13 patients (30%)]. However, only 5 patients (11%) had to discontinue MTX. In steroid-dependent CD patients, disease remission and complete steroid withdrawal was achieved in 77% of cases. Seven patients lost their initial response to MTX during follow-up, leading to a cumulative probability of remission of 39% after 3 years of treatment. Conclusions MTX is well tolerated in most CD patients. Although a great proportion of steroid-dependent CD patients achieve disease remission and steroid withdrawal, there is a trend to a loss of efficacy with time. Larger, long-term studies are necessary to establish the role of MTX in the management of CD.

Infliximab reintroduction is not associated to a higher rate of immune-related adverse effects in patients with inflammatory bowel disease initially treated with a three-infusion induction regimen.

Background Episodic infliximab (IFX) treatment is associated with a higher risk for acute infusion reactions (AIR) and secondary loss of response (SLR), but this has not been evaluated in patients initially treated with an induction regimen with 3 IFX infusions. Aims To evaluate whether IFX reintroduction after ≥4 months in patients treated with a 3-infusion induction regimen is associated with a higher incidence of AIR or SLR. Methods Incidence of immunogenic adverse effects was assessed in patients with inflammatory bowel disease who received ≥4 consecutive IFX infusions (3 infusions at weeks 0, 2, and 6, plus ≥1 maintenance infusion) (Continuous, n=47) and patients who were treated with a successful initial 3-infusion induction scheme and in whom IFX was then discontinued because of a complete response but reintroduced ≥4 months later (Reintro, n=29). Results AIR rate was 17% in both groups, and SLR rate was 26% in the Continuous group and 15% in the Reintro group (not significant). The lack of concomitant immunomodulators and/or pretreatment with hydrocortisone were associated with AIR development (P=0.002). Conclusions In patients who completed a 3-infusion induction regimen, IFX can be safely reintroduced even after a long time from discontinuation.

Long-term outcome of ulcerative colitis in patients who achieve clinical remission with a first course of corticosteroids.

BACKGROUND Although the early outcomes of ulcerative colitis after a first course of corticosteroids are well known, data on long-term disease evolution in patients responding to a first corticosteroid course are scarce. AIMS To evaluate the long-term clinical evolution in ulcerative colitis patients responding to a first course of corticosteroids and to identify those factors associated with a poorer outcome. METHODS Retrospective review of 114 patients diagnosed with ulcerative colitis who responded to the first corticosteroid course, and did not start thereafter maintenance therapy with thiopurines were included. RESULTS Corticosteroids were prescribed because of a moderate (78%) or a severe flare (22%). All but two patients followed maintenance treatment with mesalazine after corticosteroid discontinuation. After a median follow-up of 83 months (7-156), 72% of patients suffered new relapses leading to corticosteroid reintroduction in 65% of patients. The earlier corticosteroids were introduced in the course of ulcerative colitis, the higher the risk of relapse and corticosteroid reintroduction. Thiopurines were started in 51%, and infliximab in 19%. Eleven percent of patients underwent colectomy. No predictors of thiopurine use or colectomy were found. CONCLUSIONS Half of the ulcerative colitis patients responding to a first course of corticosteroids will require immunosuppressors mainly because of steroid-dependence.

Decision tree for early introduction of rescue therapy in active ulcerative colitis treated with steroids

Background: Corticosteroids are the treatment of choice for moderate‐to‐severe active ulcerative colitis (UC) but up to 30%–40% of patients fail to respond. It has been reported that early clinical‐biological parameters may identify those patients at high risk of colectomy. The aim was to identify predictors of rapid response to systemic steroids in moderate‐to‐severe attacks of UC. Methods: Consecutive patients treated with prednisone 1 mg/kg/day for moderate‐to‐severe attacks of UC were prospectively included. Clinical and biological parameters at 3 and 7 days after starting steroids were recorded. Response was defined as mild or inactive UC activity at day 7 (as assessed by the Montreal Classification of severity) together with no need for rescue therapies (cyclosporin, infliximab, or colectomy). A logistic regression analysis was performed to identify those independent predictors of response. In addition, a decision‐tree analysis was also performed. Results: Sixty‐eight percent of patients (64 out of 94) responded to steroids. In the univariate analysis the number of bowel movements, rectal bleeding, platelet count, and C‐reactive protein (CRP) levels at day 3 were associated with response at day 7, but only rectal bleeding was found to be an independent predictor in the logistic regression analysis. Conversely, the classification and regression tree (CART) model included these four variables. The decision‐tree model showed a higher sensitivity in predicting a rapid response to steroids than the logistic regression one. Conclusions: Rapid response to steroids in active UC attacks can be predicted after 3 days of treatment by simple clinical and biological parameters. A decision‐tree model for early introduction of rescue therapies is provided.

Systemic amyloidosis in inflammatory bowel disease: Retrospective study on its prevalence, clinical presentation, and outcome

BACKGROUND Systemic amyloidosis is a rare but life-threatening complication of inflammatory bowel disease (IBD), most cases being reported among Crohns disease (CD) patients. The only two available retrospective studies showed a prevalence ranging from 0.9% to 3% among CD patients. AIMS To evaluate the prevalence of secondary systemic amyloidosis in a large IBD cohort of a referral centre, and to describe its clinical characteristics and outcome. METHODS Patients diagnosed with amyloidosis were identified among 1006 IBD patients included in the IBD database of our centre, and their medical records were carefully reviewed. RESULTS Among a total of 1006 IBD patients, 5 cases of amyloidosis were identified, all of them with CD, resulting in a prevalence of 0.5% for IBD and 1% for CD. Two patients died after developing renal failure. Two patients were treated with anti-TNF agents, showing a clinical improvement of their amyloidosis. CONCLUSIONS Secondary amyloidosis occurs mainly in long-lasting, complicated, Crohns disease and seems to be as prevalent among IBD patients as previously reported.

Perianal disease in patients with ulcerative colitis: A case-control study

BACKGROUND Patients with ulcerative colitis (UC) and concomitant perianal disease (PAD) are occasionally seen, but the impact of PAD on UC outcome has been scarcely assessed. AIMS To evaluate the prevalence, clinical features and outcomes of PAD among UC patients. METHODS Patients with an initial diagnosis of UC who ever developed PAD were identified from three IBD hospital databases. Each case was matched by age, disease extent at diagnosis, and year of diagnosis, with two UC patients who never developed PAD. RESULTS Thirty-seven UC patients (5% of the whole series) developed PAD (complex in about a half of them), being more frequent among men (62%), with distal (50%) or extense (34%) disease. Proximal spread of UC occurred in 19% of cases. No differences in demographic features, rate of proximal spread or colectomy during follow-up were found as compared to controls, but greater requirements of steroids (P=0.019) were detected in UC-PAD patients. A change in disease diagnosis occurred in 6 patients mainly because of transmural involvement in colectomy specimen, small intestinal involvement, and/or endoscopic appearance. CONCLUSIONS PAD may occur in up to 5% of UC patients. When complex it leads to a change in disease diagnosis in one third of cases. UC-related therapeutic requirements are not increased in these patients, except for steroids.

Does active smoking really influence the course of Crohn's disease? A retrospective observational study

BACKGROUND Active smoking has been associated with a higher risk of developing Crohns disease (CD). However, its impact on clinical outcomes has been controversial among studies. AIMS To evaluate the influence of active smoking on initial manifestations of CD, the development of disease-related complications, and therapeutic requirements. METHODS Patients diagnosed with CD within a ten-year period (1994-2003) were identified. Clinical and therapeutic features until October 2008 or loss of follow-up were recorded. Smoking status was assessed at each major disease-related event (e.g. penetrating and stricturing complications, perianal disease, intestinal resection, introduction of immunomodulators or biological agents). RESULTS A total of 259 patients were included in the study with a median follow-up period of 91 months. At diagnosis, 50.5% were active smokers and only 12% of them quit smoking during follow-up, mostly after a major disease-related event occurred. Smoking at diagnosis was not associated with a particular CD presentation. Active smoking did not influence the development of strictures, intraabdominal and perianal penetrating complications, or increased resectional surgery, biological therapy or immunomodulators requirements. CONCLUSIONS Patients who develop CD while smoking seem to have a similar disease course to those who never smoked.

Fecal Calprotectin Levels Are Closely Correlated with the Absence of Relevant Mucosal Lesions in Postoperative Crohnʼs Disease

Background:Fecal calprotectin (FC) is the best noninvasive biomarker of disease activity in inflammatory bowel disease. Its correlation with endoscopic mucosal lesions could save inconvenient, expensive, and repeated endoscopic examinations in particular clinical settings. Patients and Methods:To assess the correlation between FC and the existence and severity of endoscopic postoperative recurrence (POR), a group of clinically stable outpatients with Crohns disease for whom an ileocolonoscopy was routinely planned to assess POR were invited to collect a stool sample before starting bowel cleansing to measure FC. POR was graded by means of Rutgeerts endoscopic score. Results:One hundred nineteen ileocolonoscopies were included, 42% with endoscopic POR. FC was significantly lower in the absence of endoscopic POR and in the absence of any endoscopic lesion. The area under the receiver operating characteristic curve was 0.76 (95% confidence interval, 0.68–0.85) for the diagnosis of the absence of lesions and 0.75 (95% confidence interval, 0.66–0.84) for endoscopic POR. Better sensitivity and negative predictive value were observed when combining FC and serum C-reactive protein (CRP), leading to a sensitivity of 82%, a specificity of 53%, and negative and positive predictive values of 81% and 54%, respectively, for the prediction of endoscopic POR with a combination of FC 100 &mgr;g/g and CRP 5 mg/L cutoff values. Conclusions:FC correlates closely with endoscopic POR in clinically stable postoperative patients with Crohns disease and, when used in combination with CRP, might save endoscopic examinations and allow for a high-grade suspicion of endoscopic POR in the long-term monitoring of these patients.