Medical management of Crohn's disease

The medical approach to Crohn's 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 Crohn's disease in the different settings of the disease.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: Crohn's disease, clinical trial, therapy, 5-aminosalicylic acid, ste…

Letter: psoriasiform eruption during vedolizumab therapy

IL-23R determines susceptibility in Crohnʼs disease in a mediterranean area

Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants.

Abstract Background Few studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics. Aims To evaluate clinical benefit and tolerability profile of mycophenolate mofetil in patients with inflammatory bowel disease and limited treatment options. Methods All consecutive patients with previous multiple intolerances and/or nonresponses to immunosuppressants and biologics who started an off-label treatment with mycophenolate mofetil from January 2014 to February 2016 were entered in a prospectively maintained datab…

P215 Blood-based prognostic biomarkers in Crohn’s patients treated with biologics: a new promising tool to predict endoscopic outcomes

Abstract Background There is a growing need for biomarkers of inflammation to monitor and predict therapeutic outcome in Crohn’s disease (CD) patients. We aimed to evaluate whether the level of circulating blood cells, expressed as ratios (NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; ELR, eosinophil-to-lymphocyte ratio and ENLR, eosinophil*neutrophil-to-lymphocyte ratio), could be used as early prognostic biomarker of endoscopic response (ER) in patients starting biological therapy with infliximab, adalimumab, vedolizumab and ustekinumab. Association with steroid-free clinical remission at week 54 and endoscopic disease activity at baseline, as well as other varia…

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in post-operative Crohn's disease

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease. Renna S, Cammà C, Modesto I, Cabibbo G, Scimeca D, Civitavecchia G, Mocciaro F, Orlando A, Enea M, Cottone M. Dipartimento di Medicina, Pneumologia e Fisiologia della Nutrizione Umana, Università di Palermo, Palermo, Italy. BACKGROUNDS & AIMS: The benefit of therapy for prevention of postoperative recurrence of Crohn's 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 recurr…

Letter: switching from one to another anti-tumour necrosis factor alpha agent, and the risks of an overlap of exposure

Comparing medical treatments for Crohn’s disease

The drugs available for inflammatory bowel disease are aminosalicylates, antibiotics, steroids, immunosuppressors and biologics. The effectiveness of these drugs has been evaluated in many randomized clinical trials, mainly versus placebo. Few studies have been conducted comparing the different drugs among themselves, owing to the methodological problems raised by comparative trials, such as sample size and blindness. This review focuses mainly on the randomized clinical trials that have compared different treatments. Of course comparisons are mainly between drugs used in a particular setting (mild, moderate and severe disease). However, on many occasions there is no homogeneity in these cl…

Multifocal Pyoderma Gangrenosum Resistant to Infliximab in Active Ulcerative Colitis: Donʼt Forget the Role of Cyclosporin

The Italian clinical experience with adalimumab in Crohn's disease: Eleven clinical cases

Is 5-ASA Still the Treatment of Choice for Ulcerative Colitis?

5-Amino-salacylic acid (5-ASA) is up to now the treatment of choice in the induction and maintenance of remission of mild-to-moderate ulcerative colitis (UC). Sulfasalazine, despite similar efficacy, is hampered by more side effects, but in presence of peripheral arthopaties it remains the treatment of choice. The new delayed release MMX formulation seems to be promising in reducing compliance problems, but further studies are warranted to show the superiority of new MMX formulation compared with the older formulations of 5-ASA. Some trials evaluated also the efficacy and safety of once-daily dosing of older 5-ASA formulations in maintenance of remission, finding a greater adherence to ther…

Combined treatment with adalimumab and surgery in a patient with steroid-dependent Crohn's disease complicated by perianal disease

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 Crohn's 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 hypothe…

Oral lichen planus after certolizumab pegol treatment in a patient with Crohn's disease

Dear Sir , Lichen planus (LP) is a relatively uncommon inflammatory dermatosis of the mucocutaneous surfaces that can present with a variety of clinical manifestations and, most commonly, affecting middle-aged adults. The disease course may be short or chronic, although most cases may resolve after 1 month to 7 years. The real prevalence of LP is unknown, but is estimated to be 1% in the USA.1 The pathogenesis of LP is not entirely understood. In general, activated T lymphocytes are recruited to the dermal–epidermal junction and induce apoptosis in basal keratinocytes. Both CD4+ and CD8+ T lymphocytes are found in the lichenoid infiltrate of LP, with a predominance of the latter cell type b…

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 Crohn’s disease bu…

W1113 Efficacy and Safety of Endoscopic Balloon Dilation of Symptomatic Intestinal Crohn's Disease Strictures

Aim: To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn’s disease strictures. Methods: Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn’s disease patients with 39 intestinal symptomatic strictures (4 naive and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtaine…

Physicians’ Knowledge and Application of Immunization Strategies in Patients with Inflammatory Bowel Disease: A Survey of the Italian Group for the Study of Inflammatory Bowel Disease

<b><i>Background:</i></b> No data on European countries about knowledge and application of immunization strategies in patients with inflammatory bowel disease (IBD) are available. <b><i>Objectives:</i></b> We designed a questionnaire aimed at exploring these issues among Italian gastroenterologists dealing with adult and paediatric IBD. <b><i>Methods:</i></b> An anonymous, 24-item, questionnaire was sent via e-mail to all members of the Italian Group for the study of Inflammatory Bowel Disease. Three sets of questions were formulated: (1) Characteristics of respondents; (2) General opinions on the role of vaccines in IB…

The METEOR Trial: The Burial of Methotrexate in Ulcerative Colitis?

Incidence of HSV and HPV with azathioprine

IBd Incidence of HSV and HPV with azathioprine Mario Cottone and Sara Renna severe infections are an established risk of immunosuppressive therapy; however, the risk of opportunistic infections in patients with IBd who receive immunosuppressive therapy has so far only been studied retrospectively. the increased incidence of herpes flares and development or worsening of viral warts in patients with IBd who receive azathioprine has now been demonstrated for the first time in a prospective study. the rate of opportunistic infections in patients with iBD is dependent on the patient’s nutritional status, degree of innate immune system activity, whether the patient has undergone surgery and their…

P717 Ustekinumab in Crohn’s disease: Real-world outcomes from the Sicilian Network for inflammatory bowel diseases (SN-IBD):–Preliminary results

Abstract Background Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients. Methods Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 …

Investigational agents for Crohn's disease.

IMPORTANCE OF THE FIELD: Increased understanding of the biological mechanisms of Crohn's disease has opened the door to a large number of new molecules; some of these are approved for clinical use, while others remain under evaluation. In this review, we examine the clinical efficacy of all the new drugs that have been evaluated in controlled trials in the last 12 years. AREAS COVERED IN THIS REVIEW: Anti-TNF therapy has been reviewed briefly, given the many comprehensive reviews on this topic; attention is focused mainly on the other biological therapies. In assessing the clinical efficacy of these molecules, we consider only the remission rate, as this is considered the most meaningful en…

Diagnostic and vaccine strategies to prevent infections in patients with inflammatory bowel disease.

Summary Objectives The treatment of inflammatory bowel disease (IBD) has been revolutionized by the use of immunomodulatory agents. Although these potent drugs are effective in controlling disease activity, they also cause an increased risk of new infections or reactivation of latent infections. On these premises, we aimed to provide guidance on the definitions of immunocompromised patients, opportunistic infections and the risk factors associated with their occurrence in an IBD context, and to suggest the proper screening tests for infectious diseases and the vaccination schedules to perform before and/or during therapy with immunomodulators. Methods All the most recent evidences – filtere…

A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by propensity score analysis

Abstract Background Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis. Aims We reported the comparative effectiveness of adalimumab and golimumab in ulcerative colitis. Methods 118 patients treated with adalimumab and 79 treated with golimumab were included and evaluated at 8 weeks and at the end of follow up. Results Overall clinical benefit was 72.6% at 8 weeks and 58.9% at the end of follow up. Patients with longer disease duration and those treated with adalimumab had a better outcome. Clinical benefit was 78.8% in adalimumab patients and 63.3% in golimumab patients (p = 0.026) after 8 weeks; it was 66.9% in adalimumab patients and 46.8% in…

Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together …

P255 Efficacy and safety of a restrictive ferric carboxymaltose infusion strategy for iron deficiency anemia in inflammatory bowel disease patients

Abstract Background Iron deficiency anemia (IDA) is a common condition in patients with inflammatory bowel disease (IBD) and ferric carboxymaltose (FCM) has shown fast correction of hemoglobin (Hb) levels and good tolerability. We evaluated the response to FCM in IBD patients with IDA. The primary outcome was the assessment of the rate of response to single or multiple FCM infusions after 12 months from the first infusion. Secondary outcomes were the response to a single FCM infusion after 3 months and the assessment of FCM safety. Methods We retrospectively included 185 consecutive patients from IBD Unit of “Villa Sofia-V. Cervello” Hospital who received at least a dose of 500 mg FCM infus…

P288 Vedolizumab May Be An Effective Option For The Management Of Postoperative Recurrence Of Crohn’s Disease

Abstract Background The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn’s disease (CD) following ileocolonic resection is currently unknown. We aimed to assess the effectiveness of VDZ in this setting. Methods All consecutive CD patients with an available baseline colonoscopy at 6-12 months from the ileocolonic resection and treated with VDZ for the postoperative recurrence after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ. In patients with Rutgeerts score i0 or i1 at …

Six year adalimumab efficacy in steroid-dependent Crohn's disease patients: A prospective single-center real life study.

Abstract Background Adalimumab is effective in the treatment of Crohn's disease. We have already reported data on the efficacy of adalimumab in 110 steroid-dependent patients. At the end of the study 90 patients (64.5%) maintained clinical remission. Aims To assess efficacy and safety of adalimumab after 6 years in patients of the original cohort who responded to treatment. Methods The present study is an extension of the published paper on 90/110 patients. We report results on clinical remission and safety of 6 year maintenance therapy with adalimumab. Results Of the original cohort 90 patients completed the study, 17 were lost to follow-up and 3 died. At the end of follow-up (74.16 ± 10.3…

Adalimumab in steroid-dependent Crohn's disease patients: prognostic factors for clinical benefit.

Background: Corticosteroids are effective in the treatment of Crohn's disease but some patients relapse during tapering or after discontinuation. We report data on efficacy and prognostic factors of response of adalimumab in steroid-dependent patients. Methods: In all, 110 steroid-dependent patients were treated with adalimumab (80/40 or 160/80 mg every other week followed by 40 mg every other week). Clinical remission was defined as steroid discontinuation without symptomatic recurrence and clinical response as the reduction or maintenance of the initial Crohn's Disease Activity Index (CDAI) value reducing steroid dosage but without its discontinuation at week 6 and at the end of follow-up…

A Propensity Score-matched Comparison of Infliximab and Adalimumab in Tumour Necrosis Factor-α Inhibitor-naïve and Non-naïve Patients with Crohn's Disease: Real-Life Data from the Sicilian Network for Inflammatory Bowel Disease

Background and aims There is an unmet need to better understand the effectiveness of different biologics in inflammatory bowel diseases. We aimed at performing a multicentre, real-life comparison of the effectiveness of infliximab [IFX] and adalimumab [ADA] in Crohn's disease [CD]. Methods Data of consecutive patients with CD treated with IFX and ADA from January 2013 to May 2017 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. We used propensity score-matching accounting for the main baseline characteristics in TNF-α inhibitor-naive and non-naive patients. Results A total of 632 patients [735 total treatments] were included. Among naive patients, a cli…

Placebo Therapy in Crohn's disease

The knowledge of the outcome among patients receiving placebo is important for evaluating the response to therapy, for evaluating the natural history of a disease and for calculating the sample size for future clinical trials. In Crohn's disease placebo has been used in therapeutic trials in every relevant setting: active disease, prevention of relapse after induced medical remission and after surgery and fistulising disease. The analysis of the placebo response shows that in every setting there is a high heterogeneity demonstrating mainly that the selection of patients is not often homogeneous and that the outcome criteria used in the trials is not highly reliable. Better selection of pati…

Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes

There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD).The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics.Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calcul…

The Addition of an Immunosuppressant After Loss of Response to Anti-TNFα Monotherapy in Inflammatory Bowel Disease: A 2-Year Study

Background The addition of an immunosuppressant (IM) after loss of response to anti-TNFα monotherapy is an emerging strategy of therapeutic optimization in patients with inflammatory bowel disease (IBD). However, few clinical data have been reported to date. We aimed to evaluate the efficacy and safety of this selective combination therapy in patients with IBD. Methods All consecutive patients with loss of response to anti-TNFα monotherapy despite an intensive dose optimization who added an IM from October 2014 to October 2016 were entered into a prospective database. Results Among 630 patients treated with anti-TNFα agents during the study period, 46 (7.3%) added an IM. A total of 31 patie…

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

Introduction: About 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. Methods: We 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. Results: A total of 65 patients were included: 35 in the cyclosporine group and…

P611 Outcome in ulcerative colitis after switch from subcutaneous anti-TNF to intravenous anti-TNF: A multicentre study

Early postoperative recurrence of severe crohnʼs disease, with colonic involvement and associated human cytomegalovirus infection, treated with oral valganciclovir and adalimumab

The PROSIT Cohort of Infliximab Biosimilar in IBD: A Prolonged Follow-up on the Effectiveness and Safety Across Italy.

BACKGROUND We report a prospective, nationwide cohort evaluating the safety and effectiveness of CT-P13. METHODS A structured database was used to record serious adverse events (SAEs), clinical remission/response, inflammatory biomarkers (CRP and calprotectin), and endoscopic findings. RESULTS Eight hundred ten patients with inflammatory bowel disease (IBD) (452 Crohn's disease [CD]) were enrolled. Four hundred fifty-nine patients were naive to anti-TNFα (group A), 196 had a previous exposure (group B), and the remaining 155 were switched to CT-P13 (group C). All patients were included in the safety evaluation with a mean follow-up of 345 ± 215 days and a total number of 6501 infusions. One…

Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience

The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting.All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurren…

P801 Physicians’ knowledge and application of immunisation strategies in patients with inflammatory bowel disease: a survey by the Italian Group for the study of inflammatory bowel disease (IG-IBD)

Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes

There is a growing need for biomarkers to predict therapeutic outcome in Crohn’s disease (CD). The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics. Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn’s disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calc…