Rate of Malignancies and Infections in a Large Single Center Cohort of IBD Patients Treated With Thiopurines and Anti-TNF-Antibodies.

in American Journal of Gastroenterology (2011, May)

Risk Of Malignancies In A Single Center Cohort Of IBD-Patients Treated with Immunosuppressives and Anti-TNF-antibodies

in Journal of Crohn’s and Colitis (2011)

Kinetics of C-Reactive Protein (CRP) following maintenance infliximab treatment in Crohn's disease identifies profiles of patients with better outcome

in Gastroenterology (2010), 138(5 (Suppl I)), -686

Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis

in Gut (2009), 58(12), 1612-9

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 ... [more ▼]

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 alpha (anti-TNFalpha) 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. [less ▲]

Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort

in Gut (2009), 58(4), 492-500

BACKGROUND AND AIMS: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow ... [more ▼]

BACKGROUND AND AIMS: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow-up of 55 months (interquartile range (IQR) 27-83). METHODS: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of follow-up. The long-term effects of IFX on the course of CD as reflected by the rate of surgery and hospitalisations and need for corticosteroids were also analysed. RESULTS: 10.9% of patients were primary non-responders to IFX. Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long-term treatment. In 68.3% of these, treatment with IFX was ongoing and in 31.7% IFX was stopped, with the patient being in remission. Seventy patients (12.8%) had to stop IFX due to side effects and 118 (21.6%) due to loss of response. Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and scheduled treatment (7.1%) were similar, the need for hospitalisations and surgery decreased less in the episodic than in the scheduled group. Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group. CONCLUSIONS: In this large real-life cohort of patients with CD, long-term treatment with IFX was very efficacious to maintain improvement during a median follow-up of almost 5 years and changed disease outcome by decreasing the rate of hospitalisations and surgery. [less ▲]

Mucosal Healing Predicts Long-term Outcome of Maintenance Therapy with Infliximab in Crohn's Disease

in Inflammatory Bowel Diseases (2009), 15(9), 1295-1301

Background: Infliximab (IFX) treatment induces mucosal healing (MH) in patients with Crohn's disease (CD) but the impact of MH oil the long-term outcome of IFX treatment in CID is still debated. Methods ... [more ▼]

Background: Infliximab (IFX) treatment induces mucosal healing (MH) in patients with Crohn's disease (CD) but the impact of MH oil the long-term outcome of IFX treatment in CID is still debated. Methods: We studied MH during long-term treatment with IFX in 214 CID patients. A total of 193 patients (85.5%) responded to induction therapy and 31 patients (14.5%) were primary nonresponders. They underwent lower gastrointestinal (GI) endoscopy within a median of 0.7 months (interquartile range [IQR] 0.1-6.9) prior to first IFX and after a median of 6.7 months (IQR 1.4-24.6) after start of IFX and were further analyzed. The relationship between the outcome of IFX treatment long-term and MH was studied. Results: MH was observed in 67.8% of the 183 initial responders (n = 124), with 83 patients having complete healing (45.4%) and 41 having partial healing (22.4%). Scheduled IFX treatment from the start resulted in MH more frequently (76.9% MH rate) than episodic treatment (61.0% MH rate; P = 0.0222, odds ratio [OR] 2.14, 95% confidence interval [CI] 1.11-4.12). Concomitant treatment with corticosteroids (CS) had a negative impact on MH (37.9% in patients with CS versus 63.2% in patients without CS; P = 0.021, OR 0.36, 95% CI 0.16-0.80). MH was associated with a significantly lower need for major abdominal surgery (MAS) during long-term follow-up (14.1% of patients with MH needed MAS versus 38.4% of patients Without MH: P < 0.0001). Conclusions: MH induced by long-term maintenance IFX treatment is associated with an improved long-term outcome of the I disease especially with a lower need for major abdominal surgeries. [less ▲]

Long-term outcome after infliximab for refractory ulcerative colitis

in Journal of Crohn’s and Colitis [=JCC] (2008), 2(3), 219-225

Background and aims: Infliximab (IFX) has been shown efficacious for moderate-to-severe ulcerative colitis (UC), but data on long-term efficacy are tacking. We investigated long-term outcome including ... [more ▼]

Background and aims: Infliximab (IFX) has been shown efficacious for moderate-to-severe ulcerative colitis (UC), but data on long-term efficacy are tacking. We investigated long-term outcome including colectomy rates in outpatients treated with IFX for refractory UC in a single referral centre, and evaluated if predictors could be identified. Methods: The first 121 outpatients (median age 38.0 years) with refractory UC treated with IFX were included. The primary outcome was colectomy-free survival. Secondary measures were sustained clinical response and serious adverse events. Results: From the 81 patients (67%) with an initial clinical response to IFX, 68% had a sustained clinical response. No independent predictors of sustained clinical response could be identified. Over a median (IQR) follow-up period of 33.0 (17.0-49.8) months, 21 patients (17%) came to colectomy. Independent predictors of colectomy were absence of short-term clinical response [Hazard ratio 10.8 (95% Cl 3.5-32.8), p < 0.001], a baseline CRP level >= 5 mg/L [Hazard ratio 14.5 (95% Cl 2.0-108.6), p=0.006] and previous IV treatment with corticosteroids and/or cyctosporine [Hazard ratio 2.4 (95% Cl 1.1-5.9), p=0.033]. Six patients developed a serious infection, three a malignancy, two a post-operative complication and one patient died (suicide). Conclusions: With a median follow-upof 33.0 months after start of IFX, 17% of patients with refractory UC needed colectomy, while sustained clinical response was present in 68% of initial responders. (c) 2008 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. [less ▲]