Drug Therapies and the Risk of Malignancy in Crohn's Disease: Results From the TREAT™ Registry.
ABSTRACT OBJECTIVES:We assessed potential associations between malignancy and antitumor necrosis factor therapy in patients with Crohn's disease (CD), as this relationship is currently poorly defined.METHODS:Utilizing data from the Crohn's Therapy, Resource, Evaluation, and Assessment Tool (TREAT™) Registry, a prospective cohort study examining long-term outcomes of CD treatments in community and academic settings, infl uences of baseline patient/disease characteristics and medications were assessed by survival analysis and multivariate models. Standardized incidence ratios and exact 95 % confi dence intervals were determined as the ratio of events observed (TREAT) vs. expected (general population of USA).RESULTS:As of 23 February 2010, 6,273 CD patients (infliximab during registry=3,420 (during or within 1 year before registry=3,764); other-treatments-only: 2,509), were enrolled and, on average, had been followed for 5.2/7.6 years, respectively, for all/currently active patients. Crude cancer incidences were similar between infliximab- and other-treatments-only-exposed patients. Multivariate Cox regression analysis demonstrated that baseline age (hazard ratio (HR)=1.59/10 years; P<0.001), disease duration (HR=1.64/10 years; P=0.012), and smoking (HR=1.38; P=0.045) but neither immunosuppressive therapy alone (HR=1.43; P=0.11), infliximab therapy alone (HR=0.59; P=0.16), nor their combination (HR=1.22, P=0.34) were independently associated with the risk of malignancy. When compared with the general population, no significant increase in incidence was observed in any malignancy category. In an exposure-based analysis, use of immunosuppressants alone (odds ratio=4.19) or in combination with infliximab (3.33) seemed to be associated with a numerically, but not significantly, greater risk of malignancy than did treatment with infliximab alone (1.96) relative to treatment with neither.CONCLUSIONS:In the TREAT Registry, age, disease duration, and smoking were independently associated with increased risk of malignancy. Although results for immunosuppressant use were equivocal, no significant association between malignancy and infliximab was observed.Am J Gastroenterol advance online publication, 7 January 2014; doi:10.1038/ajg.2013.441.
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ABSTRACT: Background The efficacy and safety of certolizumab pegol (CZP) in moderate-to-severe Crohn's disease were demonstrated in two 26-week double-blind studies (PRECiSE 1 & 2). AimTo report the safety and efficacy outcomes of long-term, CZP therapy from PRECiSE 3, in which patients received treatment up to 7years treatment. Methods Patients completing PRECiSE 1 or 2 were eligible to enter PRECiSE 3 in which they received CZP 400mg, open-label, every 4weeks (without additional induction therapy) for up to 7years, for up to 91 doses from study start. Safety (adverse events, including infections and malignancies) and efficacy (Harvey-Bradshaw Index, faecal calprotectin, C-reactive protein) were prospectively monitored. Remission was analysed using observed cases, last observation carried forward imputation and nonresponder imputation. ResultsA total of 595 patients entered the study; 117 (20%) completed 7years. Discontinuation rates were 29.2%, 13.6%, 16.1%, 7.9%, 5.0%, 4.5% and 3.9% (years 1-7 respectively). During 1920 patient-years of exposure to CZP, no new safety signals were observed. Incidence rates (new cases/100 patient-years) for serious infections and malignant neoplasms were 4.37 and 1.06 respectively. No lymphoproliferative malignancies were reported. Clinical remission rates were 68% at each year (observed cases); rates by last observation carried forward and nonresponder imputation were 58% and 45% at year 1, 56% and 26% at year 3 and 55% and 13% at year 7 respectively. Conclusion Certolizumab pegol was well tolerated in the long-term treatment of Crohn's disease, with sustained remission in some patients continuing in the study for up to 7years. ClinicalTrials.gov identifier NCT00552058.Alimentary Pharmacology & Therapeutics 08/2014; 40(8). DOI:10.1111/apt.12930 · 4.55 Impact Factor
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ABSTRACT: Biological therapy revolutionized the treatment of inflammatory bowel disease (IBD) during the last decade. These monoclonal antibodies, which target tumor necrosis factor (TNF), integrins or IL12/23, have been approved-or are in development for-both Crohn's disease (CD) and ulcerative colitis (UC). Early use of these agents taught clinicians that induction and maintenance therapy, coupled with immunomodulator agents, reduced the immunogenicity of these agents, and led to sustained remission in many patients. More recent data has demonstrated that, through dose adjustments, optimizing serum drug levels may also provide more durable maintenance of remission, and improved mucosal healing. This review examines clinical practices that may enhance clinical outcomes from biological therapy in IBD. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.01/2015; 3(1). DOI:10.1093/gastro/gou087
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ABSTRACT: The treatment of Crohn’s disease in children has undergone a revolution in the past decade following studies that have demonstrated the efficacy of anti-TNFα agents in producing durable clinical response/remission as well as reversal of growth delay in many patients. The positioning of biologic therapy continues to be debated. Should it be reserved for children failing conventional therapy including immunomodulators or should it be used as primary therapy shortly after diagnosis in children with more severe disease likely to suffer a more complicated disease course? Risk stratification will be crucial to any therapeutic decisions and emerging data hold promise that identification of those most likely to benefit will be available in the near future.Expert Review of Clinical Immunology 10/2014; 10(11). DOI:10.1586/1744666X.2014.955017 · 3.34 Impact Factor