mercaptopurine and Demyelinating-Diseases

The ENCORE registry aimed at comparing the long-term safety of Crohn's disease [CD] treatment with infliximab [Remicade®] and with conventional therapies in real-world clinical practice.. The 5-year, prospective, observational ENCORE registry followed patients with CD in nine European countries, who received treatment with infliximab, conventional therapies, or switched to infliximab from conventional therapy. Adverse events [AEs] in pre-specified categories and serious AEs were recorded at least every 6 months of the 5-year observation period. Frequency of events was evaluated, and multivariable analyses using follow-up time [Cox proportion hazards model] and exposure time [Poisson regression] were used to identify risk factors for time to AEs in pre-specified categories.. Patients who received infliximab [N = 1541], conventional therapies [N = 1121], or switched to infliximab [N = 298] were followed for medians of 60.4, 55.6, and 42.5 months, respectively. Infliximab median exposure was 18.7 and 19.3 months in the infliximab and switched-to-infliximab groups, respectively. In time-to-event Cox proportion hazards [PH] analyses adjusting for confounders, infliximab [vs conventional therapy] was associated with serious infections (hazard ratio [HR] = 1.64, 95% confidence interval [CI]: 1.17, 2.31] and haematological conditions [HR = 2.91, CI: 1.51, 5.59], and not associated with lymphoproliferative disorders/malignancy [HR = 1.44, CI: 0.86, 2.42] or death [HR = 1.22, CI: 0.63, 2.36]. Prednisone use was associated with higher mortality [HR = 3.58, CI: 1.49, 8.61]. In exposure-adjusted Poisson regression analyses, infliximab was associated with lower mortality (risk ratio [[RR] 0.39, CI: 0.17, 0.88]).. Data from 5-year safety follow-up of patients with CD in the ENCORE registry demonstrate that infliximab [Remicade®] exposure is associated with increased risk of serious infections and haematological conditions, whereas mortality may be decreased.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents; Azathioprine; Crohn Disease; Demyelinating Diseases; Drug Substitution; Drug Therapy, Combination; Female; Gastrointestinal Agents; Hematologic Diseases; Humans; Immunosuppressive Agents; Infections; Infliximab; Infusions, Intravenous; Lymphoproliferative Disorders; Male; Mercaptopurine; Mesalamine; Methotrexate; Middle Aged; Mortality; Narcotics; Prednisone; Prospective Studies; Registries; Risk Factors; Sulfasalazine; Time Factors; Young Adult

Topics: Amino Acids; Animals; Cyclopentanes; Demyelinating Diseases; Encephalomyelitis, Autoimmune, Experimental; Fluorescent Antibody Technique; Freund's Adjuvant; Immunosuppressive Agents; Lymph Nodes; Male; Mercaptopurine; Mycobacterium; Myelin Basic Protein; Rats; Rats, Inbred Lew; Spinal Cord

Topics: Demyelinating Diseases; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental; Immunosuppressive Agents; Mercaptopurine; Methotrexate; Methylprednisolone; Pharmacology