Predictive value of mucosal TNF-alpha transcripts in steroid-refractory Crohn's disease patients receiving intensive immunosuppressive therapy

• Verfasst von: Schmidt, Carsten [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Verfasst von: Hermann, Eva [VerfasserIn]
• Verfasst von: Zeuzem, Stefan [VerfasserIn]
• Verfasst von: Meuer, Stefan [VerfasserIn]
• Verfasst von: Stallmach, Andreas [VerfasserIn]
• Titel: Predictive value of mucosal TNF-alpha transcripts in steroid-refractory Crohn's disease patients receiving intensive immunosuppressive therapy
• Verf.angabe: Carsten Schmidt, Thomas Giese, Eva Hermann, Stefan Zeuzem, Stefan C. Meuer, and Andreas Stallmach
• Jahr: 2007
• Umfang: 6 S.
• Teil: volume:13
• Teil: year:2007
• Teil: number:1
• Teil: pages:65-70
• Teil: extent:6
• Fussnoten: Gesehen am 16.06.2021
• Titel Quelle: Enthalten in: Inflammatory bowel diseases
• Ort Quelle: Oxford : Oxford University Press, 1995
• Jahr Quelle: 2007
• Band/Heft Quelle: 13(2007), 1, Seite 65-70
• ISSN Quelle: 1536-4844
• DOI: doi:10.1002/ibd.20012
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adolescent
• Sach-SW: Adult
• Sach-SW: Antibodies, Monoclonal
• Sach-SW: Chemokines
• Sach-SW: Crohn Disease
• Sach-SW: Cyclophosphamide
• Sach-SW: Cytokines
• Sach-SW: Drug Resistance
• Sach-SW: Female
• Sach-SW: Gastrointestinal Agents
• Sach-SW: Glucocorticoids
• Sach-SW: Humans
• Sach-SW: Immunosuppressive Agents
• Sach-SW: Infliximab
• Sach-SW: Intestinal Mucosa
• Sach-SW: Male
• Sach-SW: Middle Aged
• Sach-SW: Prednisolone
• Sach-SW: Remission Induction
• Sach-SW: Tumor Necrosis Factor-alpha
• K10plus-PPN: 1760544183

Abstract

BACKGROUND: Concentrations of proinflammatory cytokines are increased in the intestinal mucosa of patients with active Crohn's disease (CD). In a prospective study we investigated whether cytokines can predict long-term remission (>6 months) in patients with steroid-refractory CD receiving treatment with infliximab or cyclophosphamide, followed by azathioprine or methotrexate. METHODS: Cytokine transcripts were quantified using real-time polymerase chain reaction (PCR) in mucosal biopsies from 19 patients with active, steroid-refractory CD before and 8 weeks after initiation of therapy. Patients were treated with cyclophosphamide (monthly treatment of 750 mg cyclophosphamide intravenously) or infliximab (5 mg/kg body weight) and were followed until relapse of the disease. Statistical analysis was performed to identify predictive factors to discriminate between patients with or without long-term remission. RESULTS: Seventeen out of 19 patients achieved remission of the disease, two patients were nonresponders, while six out of 17 patients exhibited an early recurrence. Pretreatment TNF-alpha, IL-18, MRP-14, and IL-8 transcripts were significantly correlated with long-term remission. While several cytokines, most importantly MMP-1, determined after 8 weeks were able to predict patients achieving long-term remission, only a decrease of TNF-alpha levels after 8 weeks was predictive. Overall, statistical analysis identified lower pretreatment TNF-alpha levels as the strongest predictor of long-term remission among baseline variables. CONCLUSIONS: Quantification of mucosal TNF-alpha transcripts prior to therapy allows identification of patients achieving long-term remission upon immunosuppression with infliximab or cyclophosphamide. Real-time PCR might have considerable potential in the analysis of disease activity and subsequent clinical management of patients with immunosuppressive therapies.