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Remo Panaccione

Publications and source records attributed to Remo Panaccione.

14 recordsLinked to original sources
PubMed2006

Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial.

BACKGROUND & AIMS: Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn's disease (CD). Adalimumab is a human immunoglobulin G1 (IgG(1)) monoclonal antibody targeting tumor necrosis factor (TNF). A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD. METHODS: A total of 299 patients with moderate to severe CD naive to anti-TNF therapy were randomized to receive subcutaneous injections at weeks 0 and 2 with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg or placebo. The primary endpoint was demonstration of a significant difference in the rates of remission at week 4 (defined as a Crohn's Disease Activity Index score <150 points) among the 80 mg/40 mg, 160 mg/80 mg, and placebo groups. RESULTS: The rates of remission at week 4 in the adalimumab 40 mg/20 mg, 80 mg/40 mg, and 160 mg/80 mg groups were 18% (P = .36), 24% (P = .06), and 36% (P = .001), respectively, and 12% in the placebo group. Adverse events occurred at similar frequencies in all 4 treatment groups except injection site reactions, which were more common in adalimumab-treated patients. CONCLUSIONS: Adalimumab was superior to placebo for induction of remission in patients with moderate to severe Crohn's disease naive to anti-TNF therapy. The optimal induction dosing regimen for adalimumab in this study was 160 mg at week 0 followed by 80 mg at week 2. Adalimumab was well tolerated.

Adalimumab↗
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

Advances in medical therapy of inflammatory bowel disease.

The past few years have seen increased knowledge and optimism on the use of biological therapy in Crohn's disease. Important lessons have been learned from the expanding clinical experience with infliximab, fuelling belief that current treatment will continue to evolve as therapy is aimed at specific targets within the immune cascade. Several other studies of agents that target tumour necrosis factor-alpha revealed mixed and sometimes disappointing results. However, this was balanced by encouraging results with agents that inhibit lymphocyte trafficking, as well as with other biological agents. Previous disappointing results of biological therapy in ulcerative colitis have been overcome with recent positive clinical trials with infliximab and the anti-CD3 antibody visilizumab. There now appears to be an expanding array of treatment options available to clinicians; however, as the number of potential molecular targets expands, unanswered questions remain regarding optimal treatment strategies, the long-term safety of biologicals and the ability of these novel and often expensive therapies to alter the natural history of the disease.

Adalimumab↗
PubMed2005

Inappropriate use of intravenous pantoprazole: extent of the problem and successful solutions.

BACKGROUND & AIMS: Indications for intravenous proton pump inhibitors (IV PPI) include upper gastrointestinal bleeding (UGIB) from peptic ulcer disease with high-risk stigmata and patients receiving nothing by mouth (NPO). The objectives were to assess the extent of errors in indications for IV PPI use and to determine whether multidisciplinary interventions could improve IV PPI use and costs. METHODS: Part 1: Patients prescribed IV PPI during a period of 4 months were divided into 2 settings, UGIB or non-UGIB. The setting-specific appropriateness of the IV PPI indication and dosing regimen was determined. Part 2: Patients prescribed IV PPI before and after multidisciplinary interventions (educating physicians, a computerized dose template, pharmacists altering IV PPI orders in non-UGIB patients who were not NPO, and recommending a GI consult when a continuous infusion was ordered) were studied. Incidence of prescribing errors, IV PPI costs, and potential confounders were compared. RESULTS: Part 1: Only 50% of UGIB (n = 145) patients received IV PPI for an appropriate indication. Both indication and dosing regimen were appropriate in 21%. In the non-UGIB group (n = 95), 33% were truly NPO; 51% had a correct dosing frequency. Part 2: The postintervention (n = 105) group (vs the preintervention group, n = 113) showed a significant absolute reduction in the degree of inappropriate indication in the UGIB (26%; 95% confidence interval [CI], 10%-42%; P < .0001) and in the non-UGIB (41%; 95% CI, 24%-58%; P < .0001) subgroups. However, a greater improvement in underspending than overspending meant that overall costs were unchanged. CONCLUSIONS: IV PPI was frequently prescribed inappropriately and incorrectly; simple maneuvers resulted in reductions in errors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Medical therapy of Crohn disease.

PURPOSE OF REVIEW: This review will outline the current management of Crohn disease and highlight the knowledge gained from published studies and abstracts in the year 2003. RECENT FINDINGS: The year 2003 was highlighted by further knowledge on the use of biologic therapy in Crohn disease. Important lessons were learned from the expanding clinical experience with infliximab. Several other studies of agents targeting tumor necrosis factor-alpha revealed mixed and sometimes disappointing results. However, this was balanced by encouraging results of several studies of biologic agents that inhibit lymphocyte trafficking. Other studies evaluated a variety of small molecules, including tacrolimus, leflutamide, and mycophenolate. Finally, controversy was raised with published studies looking at the efficacy and safety of 6-thiogunaine. SUMMARY: There appears to be an expanding array of treatment options that will become available to clinicians for the treatment of Crohn disease. New treatment paradigms have emerged for managing mild to moderate disease. Small molecules may provide alternatives for immunomodulation other than the purine antimetabolites and methotrexate. Increased understanding of the pathophysiologic mechanisms of Crohn disease has allowed the development of novel therapeutics directed at specific molecular targets. However, as the treatment options expand, questions regarding optimal combination treatment strategies will need to be answered.

Journal Article↗
PubMed2004

Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study.

BACKGROUND: Genetic factors may play a role in determining the development of extraintestinal manifestations (EIMs) and autoimmune diseases (AD) in patients with inflammatory bowel disease (IBD). We sought to determine the association between EIMs and AD in patients with first-degree familial IBD and sporadic IBD. METHODS: All patients evaluated in the IBD Clinic at the Mayo Clinic between January and September 1999 were offered enrollment. One clinic patient who was matched on age, gender, and geographic area of residence to each case served as controls. Information regarding EIMs and AD was obtained from a questionnaire completed by all IBD patients and controls. The adjusted odds ratios (95% CIs) for EIM as a function of first-degree familial IBD compared with sporadic IBD and AD as a function of first-degree familial IBD compared with sporadic IBD were estimated with a matched one-to-one conditional logistic regression model. RESULTS: Two hundred forty-three patients with IBD (47 first-degree familial IBD, 196 sporadic IBD) were enrolled. Forty percent of IBD patients had one or more EIMs compared with 14% matched controls [p < 0.001; OR = 3.1 (95% CI: 1.8 to 5.2)]. A total of 259 of the 1122 IBD patients and their first-degree family members indicated one or more EIM diagnoses (23%). The association between "familial versus sporadic" status and any EIM diagnosis was not significant [p = 0.59, the odds for an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.2 (95% CI: 0.8 to 1.7)]. Ten percent of IBD patients had one or more AD diagnoses compared with 19% matched controls [p = 0.04; OR = 0.4 (95% CI: 0.1 to 0.96)]. A total of 153 of the 1122 IBD patients and their first-degree family members indicated one or more AD diagnoses (14%). The association between disease status ("familial or sporadic") versus any AD diagnosis was not significant [p = 0.68, the odds for any AD in an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.4 (95% CI: 0.9 to 2.3)]. CONCLUSIONS: There was a positive association between IBD status (patient vs control) versus EIM, but not AD. A significant positive association between disease type (familial or sporadic) versus either EIM or AD was not detected.

Adolescent↗
PubMed2004

Isolated visceral small artery fibromuscular hyperplasia-induced ischemic colitis mimicking inflammatory bowel disease.

A unique case of fibromuscular hyperplasia (FMH) of the visceral vasculature is presented. A 31-yr-old patient presented with a chronic colitis initially diagnosed as ulcerative colitis 1 yr earlier. On presentation, the endoscopic appearance showed deep linear ulcerations and cobblestoning and was more consistent with Crohn's disease. Biopsies of the area, however, suggested an ischemic etiology. The patient failed to respond to local 5ASA and prednisone therapy and progression of the disease led to a left hemicolectomy. A diagnosis of a small vessel fibromuscular arteriopathy was made on the resected specimen. This is the first case presentation of FMH mimicking inflammatory bowel disease. The lack of any systemic involvement of FMH with isolated small vessel disease has never been reported and serves as an index case of which clinicians should be aware. The literature is reviewed and the possible implications are discussed.

Adult↗
PubMed2003

Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn's disease: a single center experience.

PURPOSE: Infliximab (anti-TNF alpha) has been used for the treatment of fistulizing Crohn's disease with variable efficacy. The aim of this study was to evaluate the efficacy of infliximab combined with selective seton drainage in the healing of fistulizing anorectal Crohn's disease. METHODS: This was a retrospective chart review of all patients with fistulizing Crohn's disease treated with infliximab between March 2000 and February 2002. RESULTS: Twenty-nine patients (12 male; mean age, 31 years) received a mean of 3 (range, 1-5) doses of infliximab 5 mg/kg. Twenty-one patients had perianal fistulas; eight had rectovaginal fistulas, four with combined rectovaginal/perianal fistula. Fourteen of 21 patients (67 percent) with perianal fistula had a complete response (mean follow-up, 9 months), 4 of the 14 relapsed (mean, 6 months), but all had a complete response to retreatment (mean, 9 months). A partial response occurred in four patients (19 percent), defined by decreased drainage (2 patients) or infliximab dependence (2 patients) requiring repeated dosing every six to eight weeks. Three patients (14 percent) had no response. Seton drainage was used before infusion in 13 perianal patients for perianal infection and 17 were treated with maintenance azathioprine or methotrexate. Of eight patients with rectovaginal fistula, complete response occurred in one, partial response in five, and no response in two. Two partial responders became infliximab dependent. A complete response was observed in one patient with isolated rectovaginal fistula, a partial response in five. No patient with a combined rectovaginal/perianal fistula had a complete response. Five rectovaginal fistula patients were taking maintenance immunosuppressive agents and two had seton drainage before infusion. CONCLUSIONS: Selective seton placement combined with infliximab infusion and maintenance immunosuppressives resulted in complete healing in 67 percent of Crohn's patients with perianal fistula and partial healing in 19 percent. Relapse was successfully treated with repeat infusion. Concomitant rectovaginal fistula was a poor prognostic indicator for successful infliximab therapy.

Adolescent↗
PubMed2002

The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota.

BACKGROUND & AIMS: Little is known about the cumulative incidence and natural history of fistulas in Crohn's disease in the community. METHODS: The medical records of all Olmsted County, Minnesota residents who were diagnosed with Crohn's disease from 1970 to 1993 and who developed a fistula were abstracted for clinical features and outcomes. Six patients denied research authorization. The cumulative incidence of fistula from time of diagnosis was estimated by using the Kaplan-Meier product-limit method. RESULTS: At least 1 fistula occurred in 59 patients (35%), including 33 patients (20%) who developed perianal fistulas. Twenty-six (46%) developed a fistula before or at the time of formal diagnosis. Assuming that the 9 patients with fistula before Crohn's disease diagnosis were instead simultaneous diagnoses, the cumulative risk of any fistula was 33% after 10 years and was 50% after 20 years (perianal, 21% after 10 years and 26% after 20 years). At least 1 recurrent fistula occurred in 20 patients (34%). Most fistulizing episodes (83%) required operations, most of which were minor. However, 11 perianal fistulizing episodes (23%) resulted in bowel resection. CONCLUSIONS: Fistulas in Crohn's disease were common in the community. In contrast to referral-based studies, only 34% of patients developed recurrent fistulas. Surgical treatment was frequently required.

Adolescent↗