Long-term efficacy of infliximab maintenance therapy for perianal Crohn’s disease

AIM:To assess the long-term efficacy of seton drainage with infliximab maintenance therapy in treatment of stricture for perianal Crohn’s disease(CD). METHODS:Sixty-two patients with perianal CD who required surgical treatment with or without infliximab between September 2000 and April 2010 were identified from our clinic’s database.The activities of the perianal lesions were evaluated using the modified perianal CD activity index(mPDAI)score.The primary endpoint was a clinical response at 12-15 wk after su...     

Advances in medical therapy for Crohn’s disease

Therapeutic research in Crohn’s disease has been intensified in recent years. This has led to many novel approaches and insights into the mechanism of action of ‘classic’ drugs. Antibiotics remain valuable but do not offer benefit when used in addition to corticosteroids. Immunomodulators remain the cornerstone for maintenance therapy, although certain corticosteroid-dependent patients can be switched to maintenance therapy with topical steroids. Azathioprine and 6-mercaptopurine remain efficient beyond 4 years in patients with relapses and elevated C-reactive protein in spite of this therapy. Infliximab has shown efficiency in maintenance of active and fistulizing Crohn’s disease. In addition, ‘automatic reinfusion’ was found to be superior to ‘on-demand’ treatment. Infusion reactions and loss of response, most often caused by antibodies against infliximab, can be prevented with immunomodulators and corticosteroid infusions before dosing. Such alternative anti-tumor necrosis factor agents as adalimumab or CDP-870 may be less immunogenic. Other biologic agents, such as the anti-integrin monoclonal antibody natalizumab, were shown to be effective in maintaining remission and somewhat less so in induction of remission. Finally, much attention is being paid to alteration of the luminal flora with probiotics and helminth ova. Extracorporeal apheresis and even stem cell transplantation were found to be effective in isolated patients, but these therapies warrant further prospective and controlled investigation.     

Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn’s disease

AIM:To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn’s disease(CD).METHODS:The work was performed as a prospective study.All patients received infliximab combined withsurgery to treat perianal fistulizing CD,which was followed by an immunosuppressive agent as maintenance therapy.RESULTS:A total of 28 patients with perianal fistulizing CD were included.At week 30,89.3%(25/28)of the patients were clinically cured with an average healing time of 31.4 d.The CD activity index decreased to70.07±77.54 from 205.47±111.13(P0.01)after infliximab treatment.The perianal CD activity index was decreased to 0.93±2.08 from 8.54±4.89(P0.01).C-reactive protein,erythrocyte sedimentation rate,platelets,and neutrophils all decreased significantly compared with the pretreatment levels(P0.01).Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up.After a median follow-up of 26.4 mo(range:14-41 mo),96.4%(27/28)of the patients had a clinical cure.CONCLUSION:Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD,and this treatment was associated with better longterm outcomes.     

Approach to medical therapy in perianal Crohn’s disease

Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn’s disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.     

Time of infliximab therapy initiation and dose escalation in Crohn’s disease

AIM:To determine if early initiation of anti-tumor necrosis factor therapy affects the need for dose escalation.METHODS:This was a retrospective review of patients receiving infliximab therapy for Crohn’s disease(CD)at two outpatient gastroenterology clinics during July2009 to October 2010.All patients included in the study were biologic agent na?ve and had moderate to severe CD(Harvey Bradshaw index>8).Patients were divided into groups based on length of time between diagnosis to therapy initiation and concurrent immunosuppressant therapy.Kaplan-Meier survival analysis was used to compare the time to dose escalation for the four groups.RESULTS:There were 68 patients,51% female and 49% male,with an average age at diagnosis of 24.7±11.9 years.The average age at infliximab initiation was 34.8±14.8 years.Of the 68 patients,19%initiated inflixiamb within 2 years of diagnosis,and 51%had concurrent immunosuppressant therapy at the time of therapy initiation.Fifty percent of patients required dose escalation and the median time from therapy initiation to dose escalation was 10 mo(interquartile range:5.3-14.8).There was a statistically significant higher probability of requiring dose esclataion in patients who initiated biologic therapy within 2 years of diagnosis,without concurrent immunosuppressant therapy(P<0.01).CONCLUSION:Those who receive infliximab within 2years of CD diagnosis require more intense immunosuppressant therapy than those who received infliximab later.     

Nutritional therapy for active Crohn’s disease

Nutritional therapy for active Crohn’s disease （CD） is an underutilised form of treatment in adult patients, though its use is common in the paediatric population. There is evidence that nutritional therapy can effectively induce remission of CD in adult patients. Enteral nutrition therapy is safe and generally well tolerated. Meta-analysis data suggest that corticosteroids are superior to nutritional treatment for induction of remission in active CD. However, the potential side effects of such pharmacotherapy must be taken into consideration. This review examines the evidence for the efficacy of elemental and polymeric diets, and the use of total parenteral nutrition in active CD.     

Outcome of continued infliximab therapy in Crohn’s disease patients with response but without remission after one year of infliximab – a retrospective cohort study

Background: Optimal management of Crohn’s disease patients having responded to infliximab but without achieving remission is not well defined. The present study examined if these patients benefit from continued long-term infliximab maintenance therapy.

Method: Retrospective cohort study including all patients treated with infliximab for 1 year until the end of 2017 who have had a response but not reached remission on infliximab. Clinical outcomes were defined by the physicians’ global evaluation, supported by clinical indices and objective markers of disease activity.

Results: In total, 376 Crohn’s disease patients received infliximab. Among these, 76 (20%) were classified as having response but non-remission (RNR) after 1 year of therapy. A great majority (n?=?54; 71%) experienced no additional therapeutic benefit after a further year of infliximab maintenance therapy, thus still having RNR. Nineteen patients (25%) obtained remission during continued infliximab, whereas only 4% (n?=?3) experienced treatment failure. Although infliximab therapy beyond 2 years (follow-up median 35 months, IQR: 23–55) was accompanied by a higher proportion attaining remission (40%), nearly half (46%) still failed to improve. Among patients who had discontinued infliximab while having RNR (n?=?21), half (n?=?11) experienced disease flare within five months (median 22 weeks, IQR: 12–31).

Conclusion: Most patients (71%) had no additional therapeutic benefit after an additional year of infliximab therapy, and after a median maintenance infliximab treatment period of 3 years, half still failed to improve further. Considering the importance of achieving complete remission, these patients appear to have an unmet medical need.     

The role of ABO blood groups in Crohn’s disease and in monitoring response to infliximab treatment

BackgroundThe variation in ABO blood groups is reported to be associated with multiple diseases. Infliximab (IFX) has been widely used in the treatment of Crohn’s disease (CD). We aim to investigate the distribution of ABO blood groups in Chinese patients with CD and to explore its impact on response to IFX.ResultsIn 293 patients with CD, most patients (40.6%) had blood type O (119/293). The odds ratio (OR) of CD in blood type O patients was 1.06 (95%CI: 0.6–1.86; p=0.84) compared to all other blood types. Among those CD patients, 107 patients received IFX treatment. One year after the first course of IFX, a significant association was found between the overall ABO system and outcomes of IFX treatment (p<0.001). CD patients with blood type AB (OR=4.42, 95% CI: 1.04–18.76; p=0.044) were more likely to achieve mucosal healing, while CD patients with blood type A had a high risk of losing response (OR=0.38, 95% CI: 0.15–0.96; p=0.040).DiscussionABO blood groups are not associated with prevalence of CD. Patients with blood type AB had a better response to IFX while those with blood type A appeared to have a risk of losing response to IFX.     

Optimizing biological therapy in Crohn’s disease

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn’s disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn’s disease and identify strategies to optimize biological treatment.     

Acute coronary syndrome after infliximab therapy in a patient with Crohn’s disease

INTRODUCTION Serious adverse events (infections, malignancies, serum sickness, lupus syndrome) that need hospitalization have been reported with a divergent frequency of 6%-18.9% for patients with inflammatory bowel disease (IBD) treated with infliximab[1…     

Need for infliximab dose intensification in Crohn’s disease and ulcerative colitis

AIM: To compare the need for infliximab dose intensification in two cohorts of patients with Crohn’s disease (CD) or ulcerative colitis (UC).METHODS: Single centre, uncontrolled, observational study. Consecutive patients with CD and UC who responded to infliximab induction doses were included. Data collected in a prospectively maintained database were retrospectively analysed. Differences in the rates of dose intensification per patient-month and the intensification-free survival time were compared. We also evaluated the interval between the first infliximab induction dose and the first infliximab escalated dose. The weight-adjusted infliximab administration costs were also calculated.RESULTS: Fifty nine patients with CD and 38 patients with UC were enrolled. The rate of intensification per patient-month was 3.9% for UC and 1.4% for CD (P = 0.005). The median time from baseline to intensification was significantly shorter in UC compared to CD [6.6 mo (IQR: 4.2-9.5 mo) vs 10.7 mo (IQR: 8.9-11.7 mo), P = 0.005]. In the survival analysis, the cumulative probability of avoiding infliximab dose intensification was significantly higher in CD (P = 0.002). In the multivariate analysis, disease (UC vs CD) was the only factor significantly associated with dose intensification. The infiximab administration costs during the first year were significantly higher for UC compared to CD (mean ± SD 234.9 ± 53.3 Euros/kg vs 212.3 ± 15.1 Euros/kg, P = 0.03).CONCLUSION: The rate of infliximab dose intensification per patient-month is significantly higher in UC patients. The infliximab administration costs are also significantly higher in patients with UC.     

Advances in biologic therapy for ulcerative colitis and Crohn’s disease

The medical management of inflammatory bowel disease (IBD) has changed considerably since the advent of biologic treatments. In this review we offer a critical evaluation of controlled studies with biologic agents for the management of both Crohn’s disease (CD) and ulcerative colitis (UC). Biologics under evaluation or approved for UC that are discussed include monoclonal antibodies to tumor necrosis factor ([TNF]) infrliximab), inhibitors of adhesion molecules (MLN02 and alicaforsen), anti-CD3 antibodies (visilizumab), and anti-interleukin (IL)-2 receptor antibodies (daclizumab). Biologics under evaluation or approved for CD that are reviewed include three monoclonal antibodies to TNF (infliximab, adalimumab, and certolizumab pegol), monoclonal antibodies against IL-12, interferon-γ, and IL-6 receptors, inhibitors of adhesion molecules (natalizumab, alicaforsen), and growth factors. Only the chimeric monoclonal anti-TNF antibody infliximab is currently available worldwide. The potency of this agent in moderate-to-severe UC and CD has been one of the most important advances in the care of IBD in the past decade.     

Medical therapy of Crohn’s disease

Opinion statement There is no medical or surgical treatment that provides a permanent cure for Crohn’s disease (CD). However, an evolving understanding of the pathogenesis of CD has provided clinicians with a diversity of medical treatment options for the disease. The goal of therapy is to induce and maintain clinical remission. The efficacy of immune-modifying agents such as azathioprine/6-mercaptopurine and infliximab have supported a paradigm shift in CD treatment in which maintenance agents are introduced earlier in the disease course. At the same time, it is imperative to balance the efficacy, safety, and tolerability of medical therapy. Given the variable and relapsing clinical course of CD, the physician and patient should ideally develop an ongoing relationship that allows for individualization of treatment regimens, monitoring of response and side effects, and modification of the therapeutic strategy in the absence of improvement.     

Objective evaluation for treat to target in Crohn’s disease

Journal of Gastroenterology - Crohn’s disease (CD) is a chronic and destructive bowel disease; continued disease activity can lead to penetrating complications. With the recent advent of...     

C-reactive protein is an indicator of serum infliximab level in predicting loss of response in patients with Crohn’s disease

Background

The ability of serum infliximab level to predict clinical outcome in infliximab therapy in Crohn’s disease is unclear. Here, we aimed to clarify the correlation between the timing of loss of response (LOR) to treatment and a decrease in serum infliximab level, and, in addition, to identify an indicator of infliximab level.

Methods

The study used data from a previous clinical study of infliximab for Crohn’s disease, in which infliximab was initially given at 0, 2, 6 weeks at 5 mg/kg, and then at 8-week intervals to 62 week-10 responders. Of these 62, here we analysed data from 57 in whom Crohn’s disease activity index and serum infliximab level were evaluated at week 14.

Results

Twelve patients showed a clinical response despite an infliximab level <1 μg/mL at week 14; of these, 8 (67 %) experienced LOR by week 54. A decrease in infliximab level preceded LOR in 6 (75 %). In receiver operating characteristic curve analysis, C-reactive protein (CRP) showed better performance in detecting an infliximab level <1 μg/mL. Infliximab level was <1 μg/mL in 60–80 % of patients with CRP >0.5 mg/dL. Time to LOR (median: 22.0 weeks) was significantly longer than that to a decrease in infliximab level to <1 μg/mL (14.0 weeks, p < 0.05) or to an increase in CRP to >0.5 mg/dL (14.0 weeks, p < 0.01).

Conclusions

A decrease in serum infliximab level preceded LOR, and was easily detected by an increase in CRP. The CRP may be an indicator of serum infliximab level in predicting LOR.     

Conventional therapy for Crohn＇s disease

Crohn's disease (CD) is a multifactorial disorder of unknown cause. Outstanding progress regarding the patho-physiology of CD has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD over the last years. However, many drugs have not been approved by regulatory authorities due to lack of efficacy or severe side effects. Therefore, well-known drugs, including 5-ASA, systemic or topical corticosteroids, and immunosuppressants such as azathioprine, are still the mainstay of CD therapy. Importantly, biologicals such as infliximab have shown to be efficacious in problematic settings such as fistulizing or steroid-dependent CD. This review is intended to give practical guidelines to clinicians for the conventional treatment of CD. We concentrated on the results of randomized, placebo-controlled trials and meta-analyses, when available, that provide the highest degree of evidence. We provide evidence-based treatment algorithms whenever possible. However, many clinical situations have not been answered by controlled clinical trials and it is important to fill these gaps through expert opinions. We hope that this review offers a usefu] tool for clinicians in the challenging treatment of CD.     

Microbial manipulation as primary therapy for Crohn’s disease

While antimicrobials are clinically effective in preventing post-operative recurrence,the role for antibiotics in primary therapy for Crohn’s disease(CD) remains unclear.The recent multicenter phase 2 trial by Prantera et al received wide attention because it demonstrated an increase in the week 12 remission rate in patients with moderately active CD treated with rifaximin and renewed interest in microbial manipulation as primary therapy for CD.In this commentary,we discuss aspects of durability,immune cell polarization,and safety of microbial manipulation as primary therapy for CD.     

Hidradenitis suppurativa associated with Crohn’s disease and spondyloarthropathy: response to anti-TNF therapy

An association of hidradenitis suppurativa with Crohns disease is supported by previous repent. We here report a patient with hidradenitis suppurativa who subsequently developed peripheral arthritis, sacroiliitis, and Crohns disease. A significant attenuation of bowel, cutaneous, and joint symptoms was achieved after treatment with monoclonal antibody against tumor necrosis factor (TNF). The pathogenetic aspects according to the literature and response to the various therapeutic measures applied are also presented.