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Colleen Marano

Bio: Colleen Marano is an academic researcher from Janssen Pharmaceutica. The author has contributed to research in topics: Ulcerative colitis & Ustekinumab. The author has an hindex of 21, co-authored 91 publications receiving 4123 citations. Previous affiliations of Colleen Marano include Johnson & Johnson Pharmaceutical Research and Development.


Papers
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Journal ArticleDOI
TL;DR: The degree of mucosal healing after 8 weeks of infliximab was correlated with improved clinical outcomes including colectomy, and similar trends were observed for all outcomes except coLECTomy among the subgroup with clinical response at week 8.

754 citations

Journal ArticleDOI
TL;DR: Golimumab (50 mg or 100 mg) maintained clinical response through week 54 in patients who responded to induction therapy with golimumab and had moderate-to-severe active ulcerative colitis; patients who received 100 mg Golimumab had clinical remission and mucosal healing at weeks 30 and 54.

595 citations

Journal ArticleDOI
TL;DR: Infliximab treatment resulted in a rapid and significant improvement in the signs and symptoms of psoriasis.
Abstract: Background Tumor necrosis factor–α is a key mediator in the pathogenesis of psoriasis. Infliximab is a monoclonal antibody that specifically binds to tumor necrosis factor-α, blocking its biologic activity. Objective The purpose of this study was to access the efficacy and safety of infliximab induction therapy for patients with severe plaque psoriasis. Methods In this multicenter, double-blind, placebo-controlled trial, 249 patients with severe plaque psoriasis were randomly assigned to receive intravenous infusions of either 3 or 5 mg/kg of infliximab or placebo given at weeks 0, 2, and 6. The primary end point was the proportion of patients who achieved at least 75% improvement in Psoriasis Area and Severity Index score from baseline at week 10. At week 26, patients whose Physician Global Assessment indicated moderate or severe disease were eligible for a single intravenous infusion of their assigned treatment to assess the safety of retreatment after a 20-week, treatment-free interval. Results At week 10, 72% of patients treated with infliximab (3 mg/kg) and 88% of patients treated with infliximab (5 mg/kg) achieved a 75% or greater improvement from baseline in Psoriasis Area and Severity Index score compared with 6% of patients treated with placebo ( P Conclusions Infliximab treatment resulted in a rapid and significant improvement in the signs and symptoms of psoriasis. Infliximab was generally well tolerated.

546 citations

Journal ArticleDOI
01 Dec 2009-Gut
TL;DR: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-response) response to infliximab, and further study of the pathways involved should allow a better understanding of the mechanisms of resistance to inflIXimab therapy in ulceratives colitis.
Abstract: Background and aims: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor α (anti-TNFα) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. Methods: Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. Results: For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. Conclusion: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis. ClinicalTrials.gov number, NCT00639821.

336 citations


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Journal ArticleDOI
TL;DR: Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or inflIXimab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azATHioprine monotherapy.
Abstract: In this randomized, double-blind trial, we evaluated the efficacy of infliximab monotherapy, azathioprine monotherapy, and the two drugs combined in 508 adults with moderate-to-severe Crohn’s disease who had not undergone previous immunosuppressive or biologic therapy. Patients were randomly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0, 2, and 6 and then every 8 weeks plus daily oral placebo capsules; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the standard schedule; or combination therapy with the two drugs. Patients received study medication through week 30 and could continue in a blinded study extension through week 50. Results Of the 169 patients receiving combination therapy, 96 (56.8%) were in corticosteroid-free clinical remission at week 26 (the primary end point), as compared with 75 of 169 patients (44.4%) receiving infliximab alone (P = 0.02) and 51 of 170 patients (30.0%) receiving azathioprine alone (P<0.001 for the comparison with combination therapy and P = 0.006 for the comparison with infliximab). Similar numerical trends were found at week 50. At week 26, mucosal healing had occurred in 47 of 107 patients (43.9%) receiving combination therapy, as compared with 28 of 93 patients (30.1%) receiving infliximab (P = 0.06) and 18 of 109 patients (16.5%) receiving azathioprine (P<0.001 for the comparison with combination therapy and P = 0.02 for the comparison with infliximab). Serious infections developed in 3.9% of patients in the combination-therapy group, 4.9% of those in the infliximab group, and 5.6% of those in the azathioprine group. Conclusions Patients with moderate-to-severe Crohn’s disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy. (ClinicalTrials.gov number, NCT00094458.)

2,715 citations

Journal ArticleDOI
TL;DR: The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of T NF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis.
Abstract: TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases

1,645 citations

Journal ArticleDOI
TL;DR: The biology of T NF and related family members are discussed in the context of the potential mechanisms of action of TNF antagonists in a variety of immune-mediated inflammatory diseases.

1,517 citations

Journal ArticleDOI
TL;DR: This paper is the second in a series of three publications relating to the European evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the management of active disease, maintenance of medically induced remission and surgery.
Abstract: This paper is the second in a series of three publications relating to the European evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the management of active disease, maintenance of medically induced remission and surgery. The aims and methods of the ECCO Consensus, as well as sections on diagnosis and classification are covered in the first paper [van Assche et al. JCC 2009a]. The final paper covers post-operative recurrence, fistulating disease, the management of paediatric and adolescent IBD, pregnancy, psychosomatics, extraintestinal manifestations and complementary or alternative therapy for Crohn's disease [Van Assche et al JCC 2009b]. #### Principal changes with respect to the 2006 ECCO guidelines The early use of azathioprine/mercaptopurine or methotrexate in combination with steroids is an appropriate option in moderately active localised ileocaecal CD. Anti-TNF therapy should be considered as an alternative for patients with objective evidence of active disease who have previously been steroid-refractory, steroid-dependent, or steroid-intolerant (based on Statement 5B). For those patients with severely active localised ileocaecal Crohn's disease and objective evidence of active disease who have relapsed, anti-TNF therapy with or without an immunomodulator is an appropriate option [EL1a, RG B for infliximab]. For some patients who have infrequently relapsing disease, restarting steroids with an immunomodulator may be appropriate (based on Statement 5C). All currently available anti-TNF therapies appear to have generally similar efficacy and adverse-event profiles for inflammatory (‘luminal’) Crohn's disease, so the choice depends on availability, route of delivery, patient preference, cost and national guidelines \[EL5, RG D\] (Statement 5I). Patients receiving azathioprine or mercaptopurine who relapse should be evaluated for adherence to therapy and have their dose optimised. Changing their maintenance therapy to methotrexate [EL1b RG B] or anti-TNF therapy [EL1a RGB] should be considered. Surgery should always be considered as an option in localised disease [EL4, …

1,477 citations

Journal ArticleDOI
TL;DR: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available and future studies are needed to determine how these targets will change disease course and patients’ quality of life.

1,329 citations