Impact of Smoking Cessation on the Clinical Course of Crohn's Disease Under Current Therapeutic Algorithms: A Multicenter Prospective Study.

OBJECTIVES: Given the importance of tobacco smoking (TS) as the only environmental factor repeatedly linked to the development of the Crohn's disease (CD), it is surprising that very few prospective studies have assessed whether TS is associated with an increased frequency of clinical relapse. Our aim was to evaluate the current impact of TS on disease relapse and the clinical benefit of quitting smoking in the present era of widespread use of anti-TNF drugs and immunosuppressants. METHODS: This was a multicenter prospective cohort study, which included 573 CD patients in clinical remission with various smoking habits. All smokers were advised to quit. Patients not exposed to tobacco before inclusion (non- and former smokers), continuing smokers, and quitters were compared regarding differences in disease outcomes during a follow-up of 4 years. RESULTS: A total of 148 continuing smokers, 190 nonsmokers, 160 former smokers, and 75 quitters were included. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval (CI): 1.10-2.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers. Smoking was an independent predictor for disease relapse in the multivariate analysis (hazard ratio: 1.58 (95% CI 1.20-2.09). In the time-dependent analysis, continuing smokers had earlier relapse, regardless of anti-TNF or immunosuppressant use. CONCLUSIONS: Continuing smokers have more disease relapses, and patients who quit smoking have a similar relapse incidence compared with nonsmokers.

Pancreatitis-associated protein does not predict disease relapse in inflammatory bowel disease patients.

BACKGROUND: The pancreatitis-associated protein (PAP) is increased in the serum of active inflammatory bowel disease (IBD) patients and its levels seem to be correlated with disease activity. Our aim was to evaluate the usefulness of serum and fecal PAP measurements to predict relapse in patients with inactive IBD. MATERIALS AND METHODS: We undertook a 12-month prospective study that included 66 Crohn's disease (CD) and 74 ulcerative colitis (UC) patients. At inclusion, patients were in clinical remission, defined by a Harvey-Bradshaw (HB) Index≤4 (CD) or a partial Mayo Score (MS)<3 (UC), along with a normal serum C reactive protein (CRP) and fecal calprotectin. Patients were followed every 3 months. Blood and stool samples were collected and a clinical evaluation was performed at each visit. Serum PAP and CRP levels as well as fecal concentrations of PAP and calprotectin were assessed. RESULTS: Active CD patients had an increased mean serum PAP at the diagnosis of the flare (104.1 ng/ml) and 3 months prior to activity (22.68 ng/ml) compared with patients in remission (13.26 ng/ml), p<0.05. No significant change in serum PAP levels in UC and fecal PAP levels in CD and UC were detected during disease activity. In CD, serum PAP was a poor diagnostic predictor of disease activity, with an AUC of 0.69. In patients in remission, fecal PAP was barely detectable in UC compared with CD patients. CONCLUSION: Serum PAP is increased only in active CD patients, but this marker does not predict disease activity. Inactive UC patients have marked low levels of PAP in fecal samples compared with CD patients.

High smoking cessation rate in Crohn's disease patients after physician advice--the TABACROHN Study.

INTRODUCTION: Tobacco smoking has a significant impact on the development of Crohn's disease (CD) and its clinical course, making smoking cessation one of the main goals in CD therapeutic strategy. AIMS: To evaluate the effectiveness of an advice-based smoking cessation strategy among CD patients. METHODS: We have performed a prospective multicenter study which enrolled 408 CD smokers. At inclusion all patients were instructed about the risks of smoking and subsequently followed every 3 months. Each center used additional smoking cessation strategies based on available resources. Urinary cotinine and exhaled carbon monoxide levels were evaluated in a subgroup of patients. RESULTS: Median study follow up was 18 months. 31% of the patients achieved complete smoking cessation and 23% were smoking-free at the end of their follow up with 8% of smoking relapse. Most patients not achieving smoking cessation did not change their smoking habit with only 5% presenting a decrease in tobacco load. 63% of patients willing to quit smoking received help from another specialist, most frequently the pulmonologist (47%). Surprisingly, most patients (88%) tried to quit smoking with no pharmacological therapy and bupropion, varenicline and nicotine replacement treatment were used in few patients. Urinary cotinine and exhaled CO levels tested in a subgroup of patients proved to have a good correlation with the self-reported smoking habit. No predictors of successful smoking cessation were identified. CONCLUSION: Our results underline that an anti-tobacco strategy mostly based on CD patients's education and counseling is feasible and effective in helping patients reach complete abstinence.

Does smoking influence Crohn's disease in the biologic era? The TABACROHN study.

BACKGROUND: While most studies have found a negative effect of smoking on Crohn's disease (CD) phenotype, more recent data have failed to reproduce this association, which might be due to a current wider use of thiopurines and biologic therapy. The TABACROHN study aimed at defining the impact of smoking on CD in the largest published series. METHODS: This multicenter cross-sectional study included 1170 CD patients. Patients were classified as nonsmokers, current smokers, or former smokers according to their present smoking status. Clinical data regarding disease characteristics, treatment, and complications were collected. RESULTS: Smokers were more frequently under maintenance treatment when compared to nonsmokers. In addition, current smokers presented higher use of biologic drugs compared to nonsmokers. Tobacco exposure and a higher tobacco load were independent predictors of need for maintenance treatment and stenosing phenotype, respectively. CONCLUSIONS: In the era of early and widespread use of immunosuppressants and biologics, tobacco exposure is an independent predictor of need for maintenance treatment, specifically biologic therapy. The wider use of biologics and immunosuppressants could account for the existence of no major differences in disease behavior and complications between nonsmokers and current smokers.

Diagnostic accuracy of magnetic resonance colonography for the evaluation of disease activity and severity in ulcerative colitis: a prospective study.

OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of magnetic resonance colonography (MRC) for the evaluation of disease activity and severity in patients with ulcerative colitis (UC) using endoscopy as the reference standard. METHODS: Fifty patients with UC underwent colonoscopy and MRC for the evaluation of disease activity. All patients were prospectively and consecutively included. Endoscopic activity was evaluated globally and on a segment basis using the modified Baron score (MBS), and also classified as absent, mild to moderate (inflammation without ulcers) or severe (presence of ulceration). MRC parameters evaluated in each segment were: wall thickness, pre- and post-contrast wall signal intensity, relative contrast enhancement (RCE), mural oedema, ulcers, enlarged lymph nodes and the comb sign. RESULTS: Independent predictors for endoscopic activity on a segment basis were RCE (p=0.006), presence of oedema (p=0.003), enlarged lymph nodes (p<0.001) and the comb sign (p<0.001). A segmental simplified MRC index (MRC-S) ≥ 1 detected endoscopic inflammation with high diagnostic accuracy (sensitivity 87%, specificity 88%, area under the curve (AUC) 0.95; p<0.001). MRC-S index ≥ 2 detected severe lesions with high sensitivity (83%) and specificity (82%) with an AUC of 0.91 (p<0.001). The MRC-S index strongly correlated with the MBS (r=0.81, p<0.001) and with the subjective assessment of the radiologists for the evaluation of disease severity (r=0.77, p<0.001). CONCLUSIONS: MRC has a high accuracy for the diagnosis of disease activity and severity in UC.

Optimizing the use of tumour necrosis factor inhibitors in Crohn's disease: a practical approach.

Crohn's disease is a chronic, disabling, inflammatory condition of the gastrointestinal tract that has a segmental distribution and can affect the entire gastrointestinal tract. Treatment of patients with Crohn's disease represents a difficult challenge to physicians. Conventional therapy includes corticosteroids and immunosuppressants. Corticosteroids are highly effective for inducing response and remission, but the results in the long-term are disappointing and are associated with serious adverse events. Immunosuppressants are effective, but have a slow onset of action and are associated with intolerance and adverse events. In the last decade, as a result of a better understanding of the immunopathology of inflammatory bowel disease, novel therapeutic agents have been developed to target crucial components of the inflammatory cascade. Tumour necrosis factor (TNF) inhibitors (infliximab, adalimumab and certolizumab pegol) offer an effective alternative therapy, and are widely used in clinical practice for the management of Crohn's disease and ulcerative colitis. This article focuses on the latest evidence-based data on clinical effectiveness, mucosal healing, immunogenicity, dose optimization for induction and maintenance of response and remission, and step-up versus top-down approaches of the available TNF inhibitors for the treatment of Crohn's disease.

Risk factors and characteristics of extent progression in ulcerative colitis.

BACKGROUND: The main objective was to identify risk factors for extent progression in distal ulcerative colitis. The secondary objective was to determine clinical characteristics of disease at the time of progression. METHODS: Data were obtained from a prospective database. Distal colitis was defined as disease limited to rectum and sigmoid colon (n = 178), extensive colitis as involvement of at least the descending colon (n = 179), and colitis with progression when there was a change of category from distal to extensive (n = 63). To study clinical characteristics at the time of progression, a nested case-control study was performed. RESULTS: Compared to distal colitis, colitis with progression was associated to significantly higher prevalence of extraintestinal manifestations (42.9% versus 15.5%) steroid-refractory course (28.0% versus 2.2%), requirement of thiopurines (44.3% versus 17.3%), cyclosporine (25.4% versus 1.9%), infliximab (9.5% versus 1.2%), surgery (20.6% versus 0.6%), and incidence of neoplasia (6.3% versus 0%). However, these differences appeared after disease progression. Regression analysis demonstrated that preexisting independent predictive factors for progression were younger age at diagnosis (hazard ratio [HR] 0.979 95% confidence interval [CI] 0.959-0.999) and presence of sclerosing cholangitis (HR 12.83, 95% CI 1.36-121.10). The nested case-control study showed that at the time of progression the flare was more severe in cases than in matched controls, with significant differences in markers of disease severity, therapeutic requirements, hospitalizations, and surgery. CONCLUSIONS: Patients with distal ulcerative colitis diagnosed at a younger age or with associated sclerosing cholangitis are at higher risk for progression. Disease flare associated with progression follows a severe course with high therapeutic requirements.

Are we giving azathioprine too late? The case for early immunomodulation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) includes two entities, Crohn's disease and ulcerative colitis. Both are chronic conditions with frequent complications and surgical procedures and a great impact on patient's quality of life. The thiopurine antimetabolites azathioprine and 6-mercaptopurine are widely used in IBD patients. Current indications include maintenance therapy, steroid-dependent disease, fistula closure, prevention of infliximab immunogenicity and prevention of Crohn's disease recurrence. Surprisingly, the wide use of immunosuppressants in the last decades has not decreased the need of surgery, probably because these treatments are introduced at too late stages in disease course. An earlier use of immunosuppressants is now advocated by some authors. The rational includes: (1) failure to modify IBD natural history of present therapeutic approach, (2) demonstration that azathioprine can induce mucosal healing, a relevant prognostic factor for Crohn's disease and ulcerative colitis, and (3) demonstration that early immunosuppression has a very positive impact on pediatric, recently diagnosed Crohn's disease patients. We are now awaiting the results of new studies, to clarify the contribution of azathioprine, as compared to infliximab (SONIC Study), and to demonstrate the usefulness of azathioprine in recently diagnosed adult Crohn's disease patients (AZTEC study).