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Brian G Feagan

Publications and source records attributed to Brian G Feagan.

At least 19 recordsLinked to original sources
PubMed2006

Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry.

BACKGROUND & AIMS: Long-term safety data for infliximab and other therapies in Crohn's disease (CD) are needed. METHODS: We prospectively evaluated patients for prespecified safety-related outcomes. RESULTS: As of August 2004, 6290 patients were enrolled; 3179 received infliximab (5519 patient-years), 87% of whom received at least 2 infusions, and 3111 received other therapies (6123 patient-years). The mean length of follow-up evaluation was 1.9 years. More infliximab-treated patients had moderate-to-severe (30.8% vs 10.3%) or severe-fulminant (2.5% vs .6%) CD, and had surgical (17.5% vs 13.8%) or medical (14.4% vs 9.1%) hospitalizations in the previous year. More patients were taking prednisone (27.4% vs 16.1%), immunomodulators (49.4% vs 32.2%), or narcotic analgesics (9.8% vs 5.4%) when compared with those receiving other therapies (P<.001, all comparisons). The mortality rates were similar for infliximab- and non-infliximab-treated patients (.53 per 100 patient-years vs .43; relative risk, 1.24; 95% confidence interval [CI], .73-2.10). In multivariate logistic regression analysis, only prednisone was associated with an increased mortality risk (odds ratio [OR], 2.10; 95% CI, 1.15-3.83; P=.016). Although the unadjusted analysis showed an increased risk for infection with infliximab use, multivariate logistic regression analysis suggested that infliximab was not an independent predictor of serious infections (OR, .99; 95% CI, .64-1.54). Factors independently associated with serious infections included prednisone use (OR, 2.21; 95% CI, 1.46-3.34; P<.001), narcotic analgesic use (OR, 2.38; 95% CI, 1.56-3.63; P<.001), and moderate-to-severe disease activity (OR, 2.11; 95% CI, 1.10-4.05; P=.024). CONCLUSIONS: Mortality rates were similar between infliximab- and non-infliximab-treated patients. The increased risk for serious infection observed with infliximab likely was owing to disease severity and prednisone use.

Adult↗
PubMed2006

Factors associated with the development of intestinal strictures or obstructions in patients with Crohn's disease.

OBJECTIVE: Theoretical concern exists that rapid luminal healing in Crohn's disease (CD) with therapies like infliximab increases the risk of intestinal stenosis, stricture, or obstruction (SSOs). METHODS: Data were analyzed from the ongoing observational TREAT (the Crohn's Therapy, Resource, Evaluation, and Assessment Tool) Registry and ACCENT I (A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen) study. Investigators reported SSOs as adverse events or serious adverse events. RESULTS: In TREAT, SSOs occurred at a significantly higher rate in patients treated with infliximab compared with patients who received other treatments only (1.95 events/100 patient-years vs 0.99 events/100 patient-years; p < 0.001). Using multivariable analyses, however, infliximab therapy was not associated with SSO development. CD severity at the time of event onset (hazard ratio (HR) = 2.35, 95% confidence internal (CI) 1.35-4.09); CD duration (HR = 1.02, 95% CI 1.00-1.04); ileal disease (HR = 1.56, 95% CI 1.04-2.36); and new corticosteroid use (HR = 2.85, 95% CI 1.23-6.57) were associated with SSOs. In ACCENT I, no increase in SSOs was reported in patients who received infliximab maintenance therapy compared with those who received episodic therapy, despite higher median cumulative infliximab exposure. Additionally, there was no increase in SSO development with rapid mucosal healing (healing at week 10). CONCLUSIONS: Although unadjusted analyses suggested that patients who received infliximab were twice as likely to develop SSOs, multivariable analysis adjusting for other factors demonstrated that only disease duration, disease severity, ileal disease, and new corticosteroid use were significantly associated with SSO development.

Adolescent↗
PubMed2005

Infliximab for induction and maintenance therapy for ulcerative colitis.

BACKGROUND: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis. METHODS: Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. RESULTS: In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0.001 for both comparisons with placebo). A response was defined as a decrease in the Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute rectal-bleeding subscore of 0 or 1. In ACT 2, 64 percent of patients who received 5 mg of infliximab and 69 percent of those who received 10 mg had a clinical response at week 8, as compared with 29 percent of those who received placebo (P<0.001 for both comparisons with placebo). In both studies, patients who received infliximab were more likely to have a clinical response at week 30 (P< or =0.002 for all comparisons). In ACT 1, more patients who received 5 mg or 10 mg of infliximab had a clinical response at week 54 (45 percent and 44 percent, respectively) than did those who received placebo (20 percent, P<0.001 for both comparisons). CONCLUSIONS: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo. (ClinicalTrials.gov numbers, NCT00036439 and NCT00096655.)

Adult↗
PubMed2005

Natalizumab induction and maintenance therapy for Crohn's disease.

BACKGROUND: Natalizumab, a humanized monoclonal antibody against alpha4 integrin, inhibits leukocyte adhesion and migration into inflamed tissue. METHODS: We conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn's disease. In the first trial, 905 patients were randomly assigned to receive 300 mg of natalizumab or placebo at weeks 0, 4, and 8. The primary outcome was response, defined by a decrease in the Crohn's Disease Activity Index (CDAI) score of at least 70 points, at week 10. In the second trial, 339 patients who had a response to natalizumab in the first trial were randomly reassigned to receive 300 mg of natalizumab or placebo every four weeks through week 56. The primary outcome was a sustained response through week 36. A secondary outcome in both trials was disease remission (a CDAI score of less than 150). RESULTS: In the first trial, the natalizumab and placebo groups had similar rates of response (56 percent and 49 percent, respectively; P=0.05) and remission (37 percent and 30 percent, respectively; P=0.12) at 10 weeks. Continuing natalizumab in the second trial resulted in higher rates of sustained response (61 percent vs. 28 percent, P<0.001) and remission (44 percent vs. 26 percent, P=0.003) through week 36 than did switching to placebo. Serious adverse events occurred in 7 percent of each group in the first trial and in 10 percent of the placebo group and 8 percent of the natalizumab group in the second trial. In an open-label extension study, a patient treated with natalizumab died from progressive multifocal leukoencephalopathy, associated with the JC virus, a human polyomavirus. CONCLUSIONS: Induction therapy with natalizumab for Crohn's disease resulted in small, nonsignificant improvements in response and remission rates. Patients who had a response had significantly increased rates of sustained response and remission if natalizumab was continued every four weeks. The benefit of natalizumab will need to be weighed against the risk of serious adverse events, including progressive multifocal leukoencephalopathy. (ClinicalTrials.gov numbers, NCT00032786 and NCT00032799.)

Adult↗
PubMed2005

Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin.

BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.

Adult↗
PubMed2005

A review of activity indices and end points for clinical trials in children with Crohn's disease.

The necessity to include children and adolescents in clinical trials is increasingly recognized. Two recent workshops provided the impetus for pediatric gastroenterologists to develop evidence-based recommendations concerning end points and outcome assessment in cases of pediatric Crohn's disease. The overall goal was to facilitate clinical trial design by standardizing the methodology. This article critically reviews the available assessment tools and provides consensus recommendations for the evaluation of linear growth, disease activity, and health-related quality of life in clinical trials in pediatric Crohn's disease.

Adolescent↗
PubMed2005

Budesonide for maintenance of remission in patients with Crohn's disease in medically induced remission: a predetermined pooled analysis of four randomized, double-blind, placebo-controlled trials.

OBJECTIVES: To evaluate the efficacy and safety of oral budesonide for maintenance of remission in patients with mild to moderately active Crohn's disease (CD) of the ileum and/or ascending colon. METHODS: Four double-blind, placebo-controlled trials with identical protocols were combined according to a predetermined analysis plan. Three hundred eighty patients with CD in medically induced remission (CD activity index [CDAI]< or =150) were randomized to receive oral budesonide 3 mg, 6 mg, or placebo daily for 12 months. The primary outcome measure was time to relapse (increase in CDAI of 60 points above baseline and >150). RESULTS: The median time to relapse was 268, 170, and 154 days for budesonide 6 mg, budesonide 3 mg, and placebo groups, respectively (p= 0.0072). The frequency of adverse events and glucocorticosteroid side effects were similar in all groups. CONCLUSION: Budesonide 6 mg/day is effective for prolonging time to relapse and for significantly reducing rates of relapse at 3 and 6 months but not 12 months in patients with CD in medically induced remission.

Adolescent↗
PubMed2004

Infliximab maintenance therapy for fistulizing Crohn's disease.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

Adult↗
PubMed2004

Methotrexate in inflammatory bowel disease.

Over the past decade methotrexate has emerged as a new treatment for chronically active Crohn's disease. Although controlled trials to compare the relative efficacy and safety of azathioprine and methotrexate in therapy-resistant patients are desirable, these studies will be difficult, if not impossible, to conduct because of the relatively small differences in potency and tolerability between these agents. A more productive area for future investigations is to explore the use of these drugs in combination with infliximab and other biologic treatments.

Antibodies, Monoclonal↗
PubMed2004

High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn's disease: a pilot study.

In Crohn's disease, antibiotics are used with variable efficacy, suggesting that some patients are more likely to respond. The aim of this study was to determine whether Crohn's patients with predominant serum antibody reactivity toward bacterial antigens OmpC and/or I2 were more likely to achieve remission with antibiotics. Patients with ileal or ileal with right-sided colonic Crohn's disease were studied in a double-blind trial of budesonide alone or budesonide plus metronidazole and ciprofloxacin. In the budesonide plus metronidazole and ciprofloxacin group, patients with OmpC/I2 predominant profiles had the highest remission rate, whereas the group with no antibody predominant profiles had the lowest rate. In the budesonide group, patients with the OmpC/I2 predominant profile had the lowest remission rate, and the no-antibody group rate was higher. Although not statistically significant, these results support further testing to determine whether predominant serum reactivity to certain bacterial antigens may be a marker for efficacious use of antibiotics.

Anti-Infective Agents↗
PubMed2004

Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease.

BACKGROUND & AIMS: This analysis of Crohn's disease patients treated with infliximab in ACCENT I compared episodic and scheduled treatment strategies under conditions that simulate clinical practice. METHODS: After 5 mg/kg infliximab at week 0, 573 patients were randomized to infusions at weeks 2 and 6 and every 8 weeks until week 46 of placebo (episodic), infliximab 5 mg/kg at weeks 2 and 6 followed by 5 mg/kg (5 mg/kg scheduled) every 8 weeks, or infliximab 5 mg/kg at weeks 2 and 6 followed by 10 mg/kg (10 mg/kg scheduled) every 8 weeks. At or after week 14, treatment could be given with a dose of infliximab 5 mg/kg higher upon loss of response. RESULTS: The efficacy of scheduled infliximab therapy was better than episodic treatment. Crohn's Disease Activity Index (CDAI) scores were consistently significantly better in the 10 mg/kg scheduled maintenance group from weeks 10 to 54, and response and remission rates (combined scheduled) were significantly higher from weeks 10 to 30. A greater proportion of patients achieved complete mucosal healing at week 54 (P = 0.041). A lower proportion developed antibodies to infliximab in the scheduled groups than in the episodic group (9% [5 mg/kg], 6% [10 mg/kg], 28% [episodic], respectively). Scheduled strategy patients had fewer Crohn's disease-related hospitalizations (P = 0.014) and surgeries (P = 0.01) than episodic strategy patients. CONCLUSIONS: The scheduled infliximab groups, particularly the 10 mg/kg group, had better CDAI and Inflammatory Bowel Disease Questionnaire (IBDQ) responses than those in the episodic group. Both scheduled groups had fewer hospitalizations, higher rates of mucosal healing, and fewer developed antibodies than those in the episodic group, with no increase in side effects.

Adrenal Cortex Hormones↗
PubMed2003

Maintenance therapy for inflammatory bowel disease.

Crohn's disease and ulcerative colitis frequently recur after effective induction therapy. Accordingly, improved maintenance therapy remains the greatest unmet medical need in treating these disorders. Although 5-aminosalicylate compounds are widely used to maintain remission in Crohn's disease, the scientific evidence supporting this practice is poor. Antimetabolites (azathioprine, 6-mercaptopurine, and methotrexate) and infliximab are moderately effective in high-risk patients; however, these drugs might cause significant adverse effects. For patients with ulcerative colitis, maintenance therapy with 5-aminosalicylate compounds is a mainstay of treatment, being both effective and safe. However, this approach is not effective in a minority of patients. Although the purine metabolites can be used to treat these patients, strong scientific evidence that supports this practice is lacking. An initial experience with probiotic bacteria for maintenance of remission in ulcerative colitis seems promising. This article reviews the data from randomized, controlled trials of maintenance therapy in inflammatory bowel disease.

Colitis, Ulcerative↗
PubMed2003

Tacrolimus for the treatment of fistulas in patients with Crohn's disease: a randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas. METHODS: The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg. kg(-1). day(-1) or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of >/=50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks. RESULTS: Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients (P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients (P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction. CONCLUSIONS: Oral tacrolimus 0.2 mg. kg(-1). day(-1) is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated.

Adolescent↗
PubMed2003

The effects of infliximab maintenance therapy on health-related quality of life.

OBJECTIVES: The ACCENT I study evaluated the long term effects of infliximab as maintenance therapy for patients with Crohn's disease. Health-related quality of life (HRQL) was also assessed in the trial. METHODS: In ACCENT I, a total of 573 patients received a single infusion of 5 mg/kg infliximab at baseline. After assessment of response at wk 2, patients were randomly assigned repeat infusions of placebo at wk 2 and 6 and then every 8 wk thereafter until wk 46 (single dose), repeat infusions of 5 mg/kg of infliximab at the same time points (5 mg/kg maintenance), or 5 mg/kg of infliximab at wk 2 and 6 followed by 10 mg/kg (10 mg/kg maintenance). HRQL analyses presented include the 335 patients classified as wk-2 responders. The treatment regimens were compared with regard to their change from baseline in the IBDQ and Short Form-36 (SF-36) scores. RESULTS: Baseline scores indicated substantial impairment in HRQL. Throughout the study, all IBDQ and SF-36 scores were improved at all time points compared to baseline. After wk 10 and through wk 54, these improvements were greater in the two infliximab maintenance groups than in the single-dose group. The mean change from baseline to wk 54 in total IBDQ was greater in the 5-mg/kg maintenance group (22.1, p < 0.05) and 10-mg/kg maintenance group (30.2, p < 0.001) than in the single-dose group (8.9). Similarly, the mean change from baseline to wk 54 in the PCS of the SF-36 was greater in the 5-mg/kg maintenance group (6.1, p < 0.05) and 10-mg/kg maintenance group (7.2, p < 0.01) than in the single-dose group (2.5). CONCLUSIONS: Infliximab therapy provides substantially improved HRQL as measured by both the disease-specific IBDQ and the generic SF-36. A maintenance regimen of either 5 mg/kg or 10 mg/kg of infliximab is more effective than a single 5-mg/kg infliximab infusion in sustaining this benefit.

Adult↗