Infliximab improves quality of life in patients with Crohn's disease

OBJECTIVE: The aim of this study was to assess the effect of infliximab on quality of life in patients with active Crohn's disease (CD) inadequately responsive to concomitant therapies. METHODS: We examined responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) from patients enrolled in a previously reported, randomized, placebo-controlled study. Patients with active CD received a single intravenous infusion of either placebo or infliximab 5, 10, or 20 mg/kg. Most patients received stable doses of mesalamine, corticosteroids, azathioprine, or 6-mercaptopurine throughout the study. Changes from baseline in overall IBDQ score and individual dimensions at 4 weeks postinfusion were compared. RESULTS: Patients treated with infliximab had a significantly larger improvement in overall IBDQ score than those treated with placebo at 4 weeks (p < 0.001). Infliximab-treated patients also had larger improvements in all IBDQ dimensions: bowel (p = 0.007), social (p = 0.002), emotional (p < 0.001), and systemic (p < 0.001). A significantly larger proportion of infliximab-treated patients reported having normal or near-normal frequency of bowel movements in the past week (p < 0.001), full or a lot of energy (p = 0.019), and no or hardly any difficulty doing leisure or sports activities (p = 0.011), and being extremely or very satisfied with their personal life (p = 0.046). They also significantly differed in responses regarding fatigue, frustration, ability to work, general well-being, depression, anxiety, and anger resulting from bowel problems. CONCLUSIONS: These results indicate that infliximab significantly improved quality of life in patients with active CD, increasing their ability to work and participate in leisure activities, and decreasing feelings of fatigue, depression, and anger.     

Infliximab therapy improves the bone metabolism in fistulizing Crohn's disease

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the pathogenesis of inflammatory bowel diseases and bone resorption as well. Limited data exist about the effect of anti-TNF-alpha infliximab on bone metabolism in inflammatory-type Crohn's disease (CD). AIM: Our aim was to evaluate the effect of infliximab treatment on rapid changes of bone metabolism in fistulizing CD patients. METHODS: 27 patients with fistulizing CD were treated with three series of infliximab. Serum osteocalcin (OC) and beta-CrossLaps (bCL) were measured before administration of each infliximab infusion. 54 patients with inactive CD were controls. RESULTS: In treated patients, there were significant differences in bCL concentrations on days 0 and 14 (p < 0.01) and days 0 and 42 (p < 0.05). OC levels increased significantly between day 0 and 42 (p < 0.05). The values of bCL and OC of control groups differed from serum levels in active patients before the treatment, but not on day 42. Bone markers improved significantly in responder patients, but not in non-responders. CONCLUSION: The beneficial effect of infliximab to the bone metabolism is more expressive in patients whose fistulizing disease improves with this therapy. Our results suggest that TNF-alpha has an important role in the alteration of bone metabolism in fistulizing CD patients.     

Infliximab in fistulizing Crohn's disease

The treatment of fistulizing CD has evolved greatly in the last 15 years, largely caused by improvements in medical therapy. Tables 2 and 3 summarize all published controlled and uncontrolled trials of immunomodulator and biologic therapy for the treatment of Crohn's fistulae. The advent of immunomodulators and anti-TNF-alpha agents has transformed the treatment of Crohn's fistulae from almost exclusively surgical to placing a much larger emphasis on medical therapy, either as initial therapy alone, with surgery reserved for refractory cases, or in combination with surgery from the start. For this reason, surgeons and gastroenterologists must work in concert to provide the best care for each patient. Proper fistula management also relies heavily on accurate diagnosis, especially defining the anatomy of the fistula, ascertaining whether abscess formation is present, and determining the location and extent of intestinal inflammation.     

Predictors of response to infliximab in patients with fistulizing Crohn's disease.

OBJECTIVE: To evaluate the efficacy and toxicity of infliximab for the treatment of fistulizing Crohn's disease. METHODS: Consecutive patients with fistulizing Crohn's disease receiving infliximab were prospectively enrolled. Partial response was defined as a reduction of 50% or more from base-line in the number of draining fistulae. Complete response was defined as the closure of all fistulae. The influence of different variables on the efficacy of infliximab was evaluated. RESULTS: 108 patients were included. The disease was inflammatory plus fistulizing in 18% and only fistulizing in 82%. After the third infusion of infliximab the response was partial in 26% and complete in 57%. Response (%) rates (partial/complete) depending on fistula location were: enterocutaneous (25/68%), perianal (35/60%), rectovaginal (36/64%), and enterovesical (20/40%). None of the studied variables (including concomitant immunosuppressive therapy) correlated with efficacy of infliximab in the multivariate analysis. Incidence of adverse effects (21%) depending on the dose of infliximab was: first dose (5.6%), second (7.4%), and third (11.1%). CONCLUSIONS: Infliximab is an efficacious treatment for fistulizing Crohn's disease. Partial response was achieved in approximately one third of the patients, and complete response in more than half. No studied variable was predictive of response. Adverse effects were relatively infrequent and mild.     

Infliximab for Crohn's disease in clinical practice at the Mayo Clinic: the first 100 patients

OBJECTIVE: The aim of this study was to report the clinical outcome and adverse events in the first 100 patients with refractory inflammatory and/or fistulizing Crohn's disease treated with infliximab at the Mayo Clinic. METHODS: Patient data was abstracted from medical records. Clinical response was classified as complete response, partial response, and nonresponse. RESULTS: Indications for infliximab therapy were: inflammatory disease (61 patients), fistulizing disease (26 patients), or both (13 patients). Patients received one to seven infusions of infliximab (5 mg/kg) for a total of 242 infusions. In all, 50 patients had complete response, 22 had partial response, and 28 had nonresponse. Median time to response was 7 days (range 1-21 days). Median duration of response was 10.3 weeks (range 3-25 wk). A total of 95 patients received concomitant treatment with immune modifiers. Steroid withdrawal was possible in 29/40 patients (73%). Median time of follow-up was 34 wk (range 14-48 wk). Clinically significant adverse events after infliximab included: abscess formation in two patients (perianal, peristomal), pneumonia in two patients, varicella zoster in three patients, candida esophagitis in one patient, and infusion-related reactions in 19 patients. A total of 23 patients were continued on infliximab as maintenance treatment. CONCLUSIONS: This study provides additional evidence that infliximab is safe and beneficial in clinical practice for refractory Crohn's disease.     

Perception of improved state of health and subjective quality of life in Crohn's disease patients treated with Infliximab

Background and aims and methodAlthough Infliximab is a very potent therapy of refractory Crohn's disease, its administration requires iterative infusions in hospital and there are concerns regarding its long-term safety. The aim of this study was to assess in a sample of 51 patients suffering from CD the impact of type of treatment (intravenous Infliximab versus conventional therapy without Infliximab) on the evaluation of the state of health (CGI) and the quality of life (MOS-SF36). Secondary variables were also assessed: the impact of depression (MADRS), the impact of activity of the disease (Harvey–Bradshaw Index).ResultsOverall, the assessments made using the CGI and the SF-36 revealed that the two types of treatment did not differ on the assessment of state of health and quality of life. A downward influence of depression and activity of the disease was observed.ConclusionPatients considered more efficacy of Infliximab than its potential side effects. It seems important to assess and to consider depression in order to improve medical care setting of Crohn's disease.     

Factors associated with surgery in patients with intra-abdominal fistulizing Crohn's disease

AIM To characterize radiological and clinical factors associated with subsequent surgical intervention in Crohn's disease(CD) patients with intra-abdominal fistulae.METHODS From a cohort of 1244 CD patients seen over an eight year period(2006 to 2014), 126 patients were identified as having intra-abdominal fistulae, and included in the study. Baseline patient information was collected from the medical records. Imaging studies were assessed for: anatomic type and number of fistulae; diameter of the inflammatory conglomerate; length of diseased bowel; presence of a stricture with pre-stenotic dilatation; presence of an abscess; lymphadenopathy; and the degree of bowel enhancement. Multivariate analysis for the prediction of abdominal surgery was calculated via Generalized Linear Models.RESULTS In total, there were 193 fistulae in 132 patients, the majority(52%) being entero-enteric. Fifty-nine(47%) patients underwent surgery within one year of the imaging study, of which 36(29%) underwent surgery within one month. Radiologic features that were associated with subsequent surgery included: multiple fistulae(P = 0.009), presence of stricture(P = 0.02), and an entero-vesical fistula(P = 0.01). Evidence of an abscess, lymphadenopathy, or intense bowel enhancement as well as C-reactive protein levels was not associated with an increased rate of surgery. Patients who were treated after the imaging study with combination immunomodulatory and anti-TNF therapy had significantly lower rates of surgery(P = 0.01). In the multivariate analysis, presence of a stricture [RR 4.5(1.23-16.3), P = 0.02] was the only factor that increased surgery rate.CONCLUSION A bowel stricture is the only factor predicting an increased rate of surgery. Radiological parameters may guide in selecting treatment options in patients with fistulizing CD.     

Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease

BACKGROUND & AIMS: Infliximab is effective in closing fistulas in patients with Crohn's disease. We examined the effect of infliximab maintenance treatment on hospitalizations, surgeries, and procedures in patients with fistulizing Crohn's disease enrolled in the ACCENT II study. METHODS: After 5 mg/kg infliximab at weeks 0, 2, and 6, a total of 282 patients were separately randomized at week 14 as responders (at least a 50% reduction from baseline in the number of draining fistulas at both weeks 10 and 14) or nonresponders to receive placebo or 5 mg/kg infliximab maintenance every 8 weeks. At week 22 and later, patients who lost response could be treated with a maintenance dose 5 mg/kg higher. Data on Crohn's disease-related hospitalizations, surgeries, and procedures were compared between the treatment groups for responders and all randomized patients. RESULTS: A total of 282 patients were randomized at week 14, of whom 195 were randomized as responders. Among patients randomized as responders, those who received infliximab maintenance had significantly fewer mean hospitalization days (0.5 vs. 2.5 days; P < .05), mean numbers (per 100 patients) of hospitalizations (11 vs. 31; P < .05), all surgeries and procedures (65 vs. 126; P < .05), inpatient surgeries and procedures (7 vs. 41; P < .01), and major surgeries (2 vs. 11; P < .05), compared with those who received placebo maintenance. CONCLUSIONS: In patients with fistulizing Crohn's disease, infliximab 5 mg/kg every 8 weeks significantly reduced hospitalizations, surgeries, and procedures compared with placebo.     

Life prospects and quality of life in patients with Crohn's disease.

A regional prevalence group of 106 patients with Crohn's disease were interviewed about their familial, social, and professional conditions. The results were compared with results from similar interviews of an age and sex matched control group of 75 previously healthy patients admitted to the hospital for acute diseases of less than 28 days' duration. An equal percentage of the patients and the controls were married (67% vs 71%) and had become parents (68% vs 79%). The number of children was slightly lower among Crohn's disease patients. The occurrence of familial problems and sexual problems did not differ among patients and controls. The intake of sedatives was low in both groups and no difference was found in alcohol and tobacco intake between patients and controls. A combined score for social activities comprising cultural, sporting, educational and private social arrangements showed that about one-third of patients and controls had high social activity and about half of both groups had moderately high social activity. A similar physical activity score showed no difference between the two groups. The socioeconomic level of the Crohn's disease patients was slightly, but significantly higher than that of the controls. Sixty five per cent of Crohn's disease patients were employed, 64% of controls; 6% and 7% respectively unemployed. Three per cent of Crohn's disease patients had disablement pension. Of Crohn's disease patients employed, a higher percentage (77%) had remained in the same job for more than five years (64% of controls). The number of sick leave days during previous year was less than 11 in 72/69% of patients and controls. In spite of these objectively good results 54% of patients with Crohn's disease felt exacerbations of their disease strained their professional and personal life. During the previous year 23% reported decreased working capacity and 21% reported decreased leisure activities, compared with their own expectations.     

Infliximab improves inflammation and anthropometric measures in pediatric Crohn's disease

Background and Aim: Infliximab (IFX) is a monoclonal antibody licensed to treat medically refractory Crohn's disease (CD). Our aim was to elucidate the effects of IFX therapy on clinical, growth and serum parameters in children with CD in a single pediatric center in Sydney, Australia. Methods: A retrospective case series review of children treated with IFX for CD at Sydney Children's Hospital, Australia was undertaken, with a review of outcomes after starting IFX. Main outcome measures were response and remission (as measured according to improvements in Pediatric Crohn's Disease Activity Index scores and Physician Global Assessment), laboratory markers (C‐reactive protein, erythrocyte sedimentation rate, hemoglobin, white cell count, lymphocytes, neutrophils, platelets, albumin) and growth (Z scores). Results: The 16 patients included had a mean age at first infusion of 13.0 years (1.25–17.5 years). Six of 12 patients (with adequate data available) were in remission at 2 weeks following the first infusion. At 1 year, 10 of 12 patients (83%) were in remission. Mean C‐reactive protein and erythrocyte sedimentation rate had fallen significantly (P < 0.05) at 2 weeks (from 29 to 7 mg/L and 40 to 19 mm/h, respectively). Positive trends were observed for all other parameters, excluding lymphocytes and white cell count. At 1 year, mean Z score for body mass index improved significantly from ?0.9 to ?0.1 (P < 0.01). Conclusions: Disease activity subsides in most children treated with IFX for CD. IFX therapy also improves some growth parameters. The pattern of improvement requires further elucidation, as the results in the present study suggest differing dosing frequency of infusion may achieve better efficacy.     

Treatment of fistulizing Crohn's disease

The primary goals of the clinician in the treatment of fistulizing Crohn's disease (CD) include (1) defining the anatomy of the fistula, (2) draining any associated infectious material, (3) eradicating the fistulous tract through medical or surgical therapies, and (4) preventing recurrence of fistulas. Evaluation and therapeutic decisions require close collaboration between the gastroenterologist and surgeon. Appropriate evaluation should include identification of septic complications, delineation of the fistulous tract including the origin and terminus of the fistula, and determination of the extent of bowel involvement with active CD. Drainage of abscesses and control of septic complications through the placement of drains or setons is essential. Conservative therapy with avoidance of sphincter muscle-cutting procedures is the standard approach. The appropriate approach to asymptomatic patients is uncertain because there are little data to indicate if treatment alters the natural course of disease.     

Diet counselling improves the clinical course of patients with Crohn's disease

A prospective study was undertaken to establish the role of individualized diet counselling in the management of 137 outpatients with Crohn's disease. Individualized dietary counselling for 6 months was associated with a significant decrease in the Crohn's disease activity index, an increased incidence of disease remission, a decreased need for prednisone and Salazopyrin therapy, a reduction in the number of days spent in hospital, and a reduction in the amount of time lost from work due to Crohn's disease, when compared with control patients who did not receive dietary counselling but who were seen regularly in follow-up under similar circumstances. Improvement with diet counselling was more likely to occur in patients who had not previously been subjected to small bowel resection, and occurred in patients with active or inactive disease. The effect of counselling 58 patients was assessed over a further 6 months (for a total 12-month period); there was a persistently reduced Crohn's disease activity index and a continued decreased number of lost days of work. The mechanism for these beneficial effects of diet counselling was not established. It is suggested that individualized diet counselling, aimed at optimizing the patient's nutritional status, may play a role in the management of patients with Crohn's disease.     

Treatment of fistulizing Crohn's disease

The appropriate treatment of patients with fistulas in the setting of Crohn's disease requires a knowledge of the specific medical and surgical literature of fistulizing Crohn's. The patient with symptomatic fistulizing Crohn's disease may respond differently to specific medical therapy than a patient with symptomatic obstructing Crohn's disease. Certain medications that are useful for the treatment of patients with obstructive Crohn's disease may not be helpful in the treatment of fistulas in patients with fistulizing Crohn's disease (e.g., corticosteroids and mesalamine); in fact, some medications are believed to be detrimental (e.g., corticosteroids). Few studies have been performed to assess the efficacy of specific medications on fistulas directly. To date, there has been only one published prospective randomized controlled trial that was designed to assess the efficacy and safety of a specific medication on fistulas in patients with Crohn's disease; it showed clinical efficacy over placebo in a statistically significant manner. The judicious use of surgery remains an integral part of the management of certain presentations of fistulizing Crohn's disease, and the appropriate integration of surgical and medical therapy is of paramount importance in the management of these patients. This review provides an overview of pertinent medical and surgical literature as it pertains to management of patients with fistulizing Crohn's disease.     

A girl with severe fistulizing Crohn's disease

We report the case of a girl with a severe perianal fistulizing Crohn's disease who during intravenous infusion of cyclosporine developed headache, general seizures and cortical blindness. Head magnetic resonance imaging showed spread, cortical-subcortical nonenhancing signal changes. Full neurological recovery was achieved in 24 hours. Cyclosporine was stopped and a single dose of infliximab was infused with rapid improvement of the fistula that at 7 months' follow-up is still closed.     

Infliximab improves health related quality of life and physical function in patients with psoriatic arthritis

OBJECTIVES: To evaluate the effect of infliximab on health related quality of life (HRQoL) and physical function in patients with active psoriatic arthritis (PsA) in the IMPACT 2 trial. METHODS: 200 patients with PsA unresponsive to conventional treatment were randomised to intravenous infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, 6, 14, and 22; patients with inadequate response entered early escape at week 16. HRQoL was assessed using the Short Form-36 (SF-36) at weeks 0, 14, and 24. Functional disability was assessed using the Health Assessment Questionnaire (HAQ) at every visit through week 24. Associations between changes in quality of life (SF-36) and articular (American College of Rheumatology (ACR)) and dermatological (Psoriasis Area and Severity Index (PASI)) responses were examined. RESULTS: Mean percentage improvement from baseline in HAQ was 48.6% in the infliximab group compared with worsening of 18.4% in the placebo group at week 14 (p < 0.001). Furthermore, 58.6% and 19.4% of infliximab and placebo treated patients, respectively, achieved a clinically meaningful improvement in HAQ (that is, > or = 0.3 unit decrease) at week 14 (p < 0.001). Increases in physical and mental component summary (PCS and MCS) scores and all eight scales of the SF-36 in the infliximab group were greater than those in the placebo group at week 14 (p < or = 0.001). These benefits were sustained through week 24. Patients achieving ACR20 and PASI75 responses had the greatest improvements in PCS and MCS scores. CONCLUSIONS: In patients with PsA, infliximab 5 mg/kg significantly improved HRQoL and physical function compared with placebo through 24 weeks.