Sara Renna

Meta-Analysis of the Placebo Rates of Clinical Relapse and Severe Endoscopic Recurrence in Postoperative Crohn's Disease

BACKGROUNDS & AIMSnThe benefit of therapy for prevention of postoperative recurrence of Crohns disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurrence in postoperative CD and to identify factors influencing these rates.nnnMETHODSnWe performed a meta-analysis of placebo-controlled, randomized clinical trials, evaluating therapies for postoperative maintenance of CD identified on MEDLINE from 1990 to 2006. Primary outcomes were clinical relapse and severe endoscopic recurrence.nnnRESULTSnThe pooled estimate of the placebo relapse rate was 23.7% (95% confidence interval [CI], 13-35; range 0-78). There was a statistically significant heterogeneity among studies (P < .0001). Heterogeneity in clinical relapse was present even if the trials were stratified according to the time of outcome. The pooled estimate of the severe endoscopic recurrence rate was 50.2% (95% CI, 28-73; range, 30-79). There was significant heterogeneity among the studies (P = .00038). This heterogeneity was less apparent in studies carried out within 12 months. The logistic analysis identified only duration of follow-up as a variable associated with different placebo relapse rates. No variable was identified as a predictor of a placebo endoscopic recurrence rate.nnnCONCLUSIONSnThere is significant heterogeneity among placebo rates in postoperative CD. No single design variable was identified that explained the heterogeneity in placebo outcomes for clinical or endoscopic recurrence.

Cyclosporine or infliximab as rescue therapy in severe refractory ulcerative colitis: early and long-term data from a retrospective observational study.

INTRODUCTIONnAbout 30-40% of patients with acute severe ulcerative colitis (UC) fail to respond to intensive intravenous (iv) corticosteroid treatment. Iv cyclosporine and infliximab are an effective rescue therapy in steroid-refractory UC patients but up to now it is still unclear which is the best therapeutic choice.nnnMETHODSnWe reviewed our series of severe steroid-refractory colitis admitted consecutively since 1994 comparing two historical cohort treated with iv cyclosporine (2 mg/kg) or iv infliximab (5 mg/kg). The main outcome was the colectomy rate at 3 months, 12 months and at the end of the follow-up.nnnRESULTSnA total of 65 patients were included: 35 in the cyclosporine group and 30 in the infliximab one. At 3 months the colectomy rate was 28.5% in the cyclosporine group and 17% in the infliximab group (p=0.25), while 48% versus 17% at 12 months (p=0.007, OR 4.7; 95% CI: 1.47-15.16). The 1-2-3 year cumulative colectomy rates were 48%, 54%, 57% in the cyclosporine group, and 17%, 23%, 27% in the infliximab group. At the end of the follow-up the colectomy rate was 60% versus 30% (p=0.04, HR 2.2; 95% CI: 1.11-4.86). High level of C reactive protein (p=0.04), extensive disease (p=0.01) and no azathioprine treatment (p<0.001) were related to the risk of colectomy.nnnCONCLUSIONnThis study, despite being retrospective, indicates that both cyclosporine and infliximab are effective in avoiding a colectomy in steroid-refractory UC patients. During the follow-up the risk of a colectomy is higher in patients treated with cyclosporine than with infliximab.

Adalimumab in active ulcerative colitis: A “real-life” observational study

BACKGROUND AND AIMSnThe effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres.nnnMETHODSnAll patients with active disease treated with adalimumab were retrospectively reviewed. Co-primary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy.nnnRESULTSnEighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twenty-two patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36-19.44; OR 2.63, 95% CI 2.32-14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, 95% CI 0.08-0.66) and with a higher rate of colectomy (HR 9.7, 95% CI 1.46-9.07).nnnCONCLUSIONnIn this large real-life experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.

Internet use among inflammatory bowel disease patients : an Italian multicenter survey

Background The internet has been increasingly used as a resource for accessing health-related information. A recent US survey found that approximately half of inflammatory bowel disease (IBD) patients in an IBD clinic use the internet to gather IBD-specific information. Aim The aim of this study was to evaluate the use of the internet among Italian IBD patients. Methods The study was performed in seven Italian IBD referral centers by using a 28-item anonymous questionnaire. Results In all, 495 questionnaires were returned for analysis, in which 305 of 495 patients (61.6%) indicated that they are able to access the internet. A large proportion used the internet to gather health-related information (180 of 305, 59.1%) and IBD-related information (226 of 305, 74.2%). The use of the internet increased significantly with level of education (P<0.0001) and household income (P<0.0001). In addition, the use of the internet to gather IBD-related information increased significantly with the increase of disease activity and severity. Conclusion Approximately half of the patients in Italian IBD referral centers used the internet to gather IBD-related information. This use positively correlated with disease activity and severity. The great majority of patients indicated that it was very important for IBD referral centers to have their own IBD-dedicated website.

Optimization of the treatment with immunosuppressants and biologics in inflammatory bowel disease.

Many placebo controlled trials and meta-analyses evaluated the efficacy of different drugs for the treatment of inflammatory bowel disease (IBD), including immunosuppressants and biologics. Their use is indicated in moderate to severe disease in non responders to corticosteroids and in steroid-dependent patients, as induction and maintainance treatment. Infliximab, as well as cyclosporine, is considered a second line therapy in the case of severe ulcerative colitis, or non-responders to intravenous corticosteroids. An adequate dosage and duration of therapy with thiopurines should be reached before evaluating their efficacy. Methotrexate is a valid option in patients with Crohns disease but its use is confined to patients who are intolerant or non-responders to thiopurines. Evidence for the use of methotrexate in ulcerative colitis is insufficient. The use of thalidomide and mycophenolate mofetil is not recommended in patients with inflammatory bowel disease, these treatments could be considered in case of failure of all other therapeutic options. In patients with moderately active ulcerative colitis, refractory to thiopurines, the use of tacrolimus is considered an alternative to biologics. An increase of the dose or a decrease in the interval of administration of biological treatment could be useful in the presence of an incomplete clinical response. In the case of primary failure of an anti-tumor necrosis factor alpha a switch to another one should be considered. Data on the efficacy of combination therapy are up to now insufficient to consider this strategy in all IBD patients. The final outcome of the treatment should be considered the clinical remission, with mucosa healing, and not the clinical response. The evaluation of serum concentration of thiopurine methyl transferase activity, thiopurine metabolites, biologic serum levels and antibiologic antibodies could be useful for the management of the treatment but it has not been routinely applied in clinical practice. The evidence of high risk development of lymphoma and cutaneous malignancies should be considered in patients treated with immunosuppressants and biologics for a long period.

Early post-operative endoscopic recurrence in Crohn's disease patients: Data from an Italian Group for the study of inflammatory bowel disease (IG-IBD) study on a large prospective multicenter cohort

INTRODUCTIONnThe incidence of endoscopic recurrence (ER) in Crohns disease following curative resection is up to 75% at 1 year. Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1 year seems to predict a clinical relapse.nnnMETHODSnThe aim of this prospective study was to evaluate the incidence of early ER 6 months after curative resection. Secondary outcome was to evaluate the role of 5-aminosalicylic acid (5-ASA) in the prevention of ER at 6 months. A total of 170 patients were included in the study. They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER. All the patients started 5-ASA treatment 2 weeks after surgery.nnnRESULTSnSix months after surgery ER was observed in 105 patients (62%). The endoscopic score was reported as severe in 78.1% of them (82 out of 105). At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER (p=0.04; OR 0.52, 95% CI 0.277-0.974).nnnCONCLUSIONnIn this prospective Italian multicenter IG-IBD study a great proportion of ER occur within 6 months from ileo-colonic resection, with a significant rate of severe ER. Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER. This suggests that post-surgical endoscopic evaluation should be performed at 6 months instead of 1 year to allow an adequate early treatment.

Severe cutaneous psoriasis after certolizumab pegol treatment: report of a case.

To the Editor: Psoriasis is a papulosquamous skin disease recognized as one of the most common immune-mediated disorders (1); 90% of all cases are psoriasis vulgaris. In the past few years, anti–tumor necrosis factor alpha (TNF) agents had modified the management of severe psoriasis (2), as well as that of rheumatoid diseases and inflammatory bowel diseases. Nevertheless, several authors had reported the paradoxical development of psoriasis and psoriasiform lesions, mainly in patients with rheumatoid arthritis, using these kinds of drugs (3). An online survey showed that 63% of rheumatologists had observed psoriasis or other skin reactions during anti-TNF treatment (4). A recent review reported 18 cases of anti-TNF-induced psoriasis in patients with inflammatory bowel disease: 17 cases were infliximab induced and 1 was adalimumab induced (5). Harris et al. (6) also reported a case of adalimumab-induced psoriasis.

Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease

Vedolizumab (VDZ) is a new biological agent which was recently approved for the treatment of inflammatory bowel disease (IBD)1 following the good clinical responses reported by clinical trials for both Crohns disease2 and ulcerative colitis.3 However, the effects of VDZ on extraintestinal manifestations were not reported in these trials, and the ‘real life’ experience is still limited. On these premises, we read with interest the recent work by Varkas et al 4 reporting a series of five patients with IBD who were treated with VDZ and promptly developed new onset or exacerbation of spondyloarthritis (SpA), irrespective of the response to treatment on intestinal symptoms. Although the hypotheses proposed …

Medical management of Crohn's disease

Introduction: The medical approach to Crohns disease has been modified in recent years thanks to the introduction of new therapies, like biologics. Also, well-designed studies and systematic reviews have allowed better evaluation of the role of old drugs like steroids and immunosuppressors. This review aims to evaluate the recent evidence on the medical approach to Crohns disease in the different settings of the disease. Areas covered: Randomized controlled trials and meta-analyses were included in the review. The research on all the studies discussed was based on the Cochrane Library, Medline and Embase, using the following medical subject headings: Crohns disease, clinical trial, therapy, 5-aminosalicylicacid, steroid, budesonide, immunosuppressant, anti-meta-analysis TNF and biologics. Expert opinion: In a mild active inflammatory ileocecal disease, budesonide is considered the best approach. The efficacy of aminosalicylates is limited, but a trial that has recently compared aminosalicylates and budesonide has shown that the two drugs are comparable. In a mild colonic disease, sulfasalazine, antibiotics and steroids are effective but the evidence for antibiotics is less clear. The maintenance of remission in this setting is debatable, but sulfasalazine seems the better choice. In a moderate severe ileal and colonic disease, steroids are the best therapy to induce remission. Once remission is reached, immunosuppressors remain today the better choice to maintain the remission. Anti-TNF therapy is indicated in patients intolerant or not responding to steroids and immunosuppressors and in fistulizing Crohns disease. Early therapy with biologics may be considered in patients with severe disease.

Regional variations in the use of complementary and alternative medicines (CAM) for inflammatory bowel disease patients in Italy: an IG-IBD study.

BACKGROUND AND AIMnComplementary and alternative medicines (CAM) are being used increasingly by patients with Crohns disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and usage of CAM in different geographical areas of Italy and possible predictors of their use.nnnMETHODS AND MATERIALSnA structured questionnaire, administered to outpatients, attending 8 general hospitals and 9 tertiary referral centres, was completed by 2011 patients (909 CD, 1087 UC and 15 indeterminate colitis). 583 patients lived in the North, 659 in Central Italy and 769 in the South.nnnRESULTSnCAM users were 475 (23.6%) with no regional differences in their distribution. Usage correlated significantly with female gender (p=0.030), higher education (p=0.021), hospitalization rates (p=0.000), extra-intestinal complications (p=0.000), non-adherence to conventional treatments (p=0.054), adverse reactions to conventional treatments (p=0.000), and active disease (p=0.007); 5-ASA usage was associated with a more limited use of CAM (p=0.005). Dietary changes or supplements and prayer were significantly more frequently reported in South, while Northern Italian patients more frequently used homeopathy, herbal medicines and physical exercises. Patients in Central Italy adopted an intermediate behavior. CAM use ameliorated the patients general well-being according to two thirds of the users. Costs were higher for Northern patients than in Central or Southern Italy.nnnCONCLUSIONnOne in four IBD patients in Italy use CAM. More money is spent on CAM in Northern Italy. Regional differences emerged as regards the type of CAM but not in terms of disease features, frequency of and reasons for CAM use, or perceived effects.