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Stephen B Hanauer

Publications and source records attributed to Stephen B Hanauer.

83 records · Page 5Linked to original sources
PubMed2003

The state of the art in the management of inflammatory bowel disease.

Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as inflammatory bowel disease (IBD), afflict an estimated one million Americans and produce symptoms that impair quality of life and ability to function. Progress in IBD management strategies has led to optimized approaches for achieving the two primary clinical goals of therapy: induction and maintenance of remission. Although surgery is indicated to treat refractory disease or specific complications, pharmacotherapy is the cornerstone of IBD management. The efficacy of aminosalicylates for induction of remission in mild to moderate UC and CD is well established, as is their role for maintenance of remission in UC. The sulfa-free mesalamine formulation offers an adverse effect profile similar to that of placebo, enabling the administration of higher, more effective doses. Although corticosteroids provide potent anti-inflammatory effects, their benefits are countermanded by the risk of intolerable and serious adverse effects, and they are ineffective for maintenance therapy. Other agents effective in inducing or maintaining remission are azathioprine, 6-mercaptopurine, infliximab, cyclosporine, methotrexate, and antibiotics. Ongoing clinical trials of experimental therapies will generate new tools for IBD treatment. Currently, a broad range of options allows physicians to tailor treatment to each patient's needs and preferences. Such considerations are essential for maximizing adherence to therapy.

Administration, Oral↗
PubMed2002

Evidence for an inflammatory bowel disease locus on chromosome 3p26: linkage, transmission/disequilibrium and partitioning of linkage.

Crohn's disease and ulcerative colitis, the two major forms of idiopathic inflammatory bowel disease (IBD), are heritable, complex traits that appear to share some but not all susceptibility loci. We report that transmission/disequilibrium test analysis of a Crohn's disease genome scan dataset has detected an inflammatory bowel disease locus on chromosome 3p26 (nominal P=0.000052 and genome-wide corrected P=0.039 at D3S1297). An allele sharing method shows significant linkage (multipoint lod=3.69) in a larger, independent sample of inflammatory bowel disease-affected sibling pairs. A survey of 16 chromosome 3p26 short tandem repeat polymorphisms in a combined sample of 234 independent nuclear families with 324 IBD-affected sibling pairs shows significant linkage to chromosome 3p26 (multipoint lod=3.78) and significant transmission/disequilibrium test results at two adjacent markers (nominal P values in two different transmission/disequilibrium analysis methods=0.00011 and 0.0011 for the first marker, and 0.00071 and 0.00013 for the second marker). There is highly significant under-transmission of a common allele and modest over-transmission of other alleles at both markers. Families with no transmission to affected individuals of the under-transmitted alleles show significant linkage (multipoint lod=4.50) that is significantly greater in four simulation studies (P=0.0001, 0.0000625, 0.0000625 and 0.0000625, respectively) than the linkage evidence in families with transmission of the under-transmitted alleles (multipoint lod=0.12). Thus, the existence of an inflammatory bowel disease locus on chromosome 3p26 is supported by significant linkage, transmission/disequilibrium and partitioning of linkage evidence.

Chromosome Mapping↗
PubMed2002

Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial.

BACKGROUND: We did a randomised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn's disease who respond to a single infusion of infliximab. METHODS: 573 patients with a score of at least 220 on the Crohn's disease activity index (CDAI) received a 5 mg/kg intravenous infusion of infliximab at week 0. After assessment of response at week 2, patients were randomly assigned repeat infusions of placebo at weeks 2 and 6 and then every 8 weeks thereafter until week 46 (group I), repeat infusions of 5 mg/kg infliximab at the same timepoints (group II), or 5 mg/kg infliximab at weeks 2 and 6 followed by 10 mg/kg (group III). The prespecified co-primary endpoints were the proportion of patients who responded at week 2 and were in remission (CDAI <150) at week 30 and the time to loss of response up to week 54 in patients who responded. Analyses of the co-primary endpoints were by intention to treat. FINDINGS: 335 (58%) patients responded to a single infusion of infliximab within 2 weeks. At week 30, 23 of 110 (21%) group I patients were in remission, compared with 44 of 113 (39%) group II (p=0.003) and 50 of 112 (45%) group III (p=0.0002) patients. Thus, patients in groups II and III combined were more likely to sustain clinical remission than patients in group I (odds ratio 2.7, 95% CI 1.6-4.6). Throughout the 54-week trial, the median time to loss of response was 38 weeks (IQR 15 to >54) and more than 54 weeks (21 to >54) for groups II and III, respectively, compared with 19 weeks (10-45) for group I (p=0.002 and p=0.0002, respectively). Infliximab safety was consistent with that seen in other trials of infliximab in Crohn's disease and rheumatoid arthritis. In particular, the incidence of serious infections was similar across treatment groups. INTERPRETATION: Patients with Crohn's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54, to discontinue corticosteroids, and to maintain their response for a longer period of time, if infliximab treatment is maintained every 8 weeks.

Adult↗
PubMed2002

Medical treatment of Crohn's disease.

Crohn's disease is not medically (and is rarely surgically) curable. Patients do, however, live a normal life span. The goal of therapy is to optimize the quality of life, minimize disease activity and disease-related complications, and avoid therapeutic toxicity.

Crohn Disease↗
PubMed2002

Budesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States.

OBJECTIVES: Budesonide controlled ileal release (CIR) capsules deliver budesonide, a glucocorticosteroid with high topical and low systemic activity, to the distal ileum and the proximal colon. In four previous controlled trials in Crohn's disease, remission rates ranged from 51% to 69%. We sought to evaluate the efficacy and safety of this drug in a population of patients in the United States with Crohn's disease. METHODS: In this multicenter, double blind, randomized trial, 200 patients in the United States with mild to moderate Crohn's disease (Crohn's Disease Activity Index [CDAI] between 200 and 450) involving the distal ileum and/or ascending colon received 9 mg of budesonide CIR once daily, 4.5 mg b.i.d., or placebos for 8 wk. The primary outcome was remission defined by a CDAI of 150 or less. RESULTS: Remission was achieved in 48%, 53%, and 33% with 9 mg once daily, 4.5 mg b.i.d., and placebos, respectively, after 8 wk of treatment. Differences between the groups were not significant. The differences in mean change from baseline CDAI between the combined budesonide and placebo groups was significant (p < 0.05). There was no difference in observed adverse events between treatment groups, although a modest decrease in plasma cortisol levels was observed relative to the placebo (p < 0.01). CONCLUSIONS: Treatment of symptomatic Crohn's disease with budesonide CIR capsules (9 mg daily) was safe, and remission rates were similar to those achieved in previous trials. Although the remission rate did not significantly differ from the placebo response in this study, there was a significant change in the mean CDAI from baseline in the combined treatment groups relative to the placebo.

Adult↗
PubMed2002

Infliximab in the treatment of Crohn's disease: a user's guide for clinicians.

Induction therapy with infliximab is indicated for treatment of signs and symptoms, and induction and maintenance of remission in patients with moderate to severely active inflammatory Crohn's disease with an inadequate response to conventional therapy, and for reduction in the number of draining fistulas in patients with fistulizing Crohn's disease. Emerging indications for infliximab therapy in patients with Crohn's disease include maintenance of fistula improvement (reduction in the number of draining perianal or enterocutaneous fistulas) and complete fistula response (no draining fistulas) in patients with fistulizing Crohn's disease, steroid sparing in steroid-treated patients, early use in hospitalized patients who have not failed conventional medical therapy where there is either a severe clinical presentation or a rapid onset of action is desired, and in a variety of unusual and extra-intestinal manifestations of Crohn's disease. An infliximab dose of 5 mg/kg is recommended initally, but some patients who require maintenance dosing may benefit from increasing the infliximab dose over a range of 5-10 mg/kg. An induction regimen of 3 doses at 0, 2, and 6 weeks is the preferred dosing strategy for inducing remission. The optimal dosing interval for patients who require retreatment appears to be every 8 weeks for most patients. Concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate may result in improved outcomes due to a reduction in the frequency of human anti-chimeric antibody formation, acute infusion reactions, and a reduced risk of delayed hypersensitivity-like reactions and formation of antinuclear antibodies. Pretreatment with diphenhydramine (and in selected cases of acetaminophen and, rarely, corticosteroids) is recommended in patients with a history of infusion reactions and patients at risk for delayed hypersensitivity-like reactions. Patients with evidence of active infection should not receive infliximab until the infection is adequately treated, and all patients should be screened for tuberculosis prior to initiating infliximab therapy.

Antibodies, Monoclonal↗