RESUMEN
BACKGROUND: Direct head-to-head studies comparing the long-term outcomes of infliximab (IFX) to adalimumab (ADA) in Crohn's disease (CD) are sparse. AIMS: We compared the short-term and long-term efficacy and safety of IFX and ADA in CD. METHODS: We performed a single-center retrospective study including biologic-naïve adult patients with CD who were started on IFX or ADA at the McGill University Health Center. The primary end points were clinical response and remission at 12 months. Secondary end points included corticosteroid-free remission at 12 months, durable remission, and treatment failure with need for steroids, hospitalization or surgery. Safety was also assessed. RESULTS: Two hundred and twenty patients were included (143 IFX, 77 ADA). Patients on IFX had a higher prevalence of fistulizing or perianal disease and corticosteroid treatment at baseline. Rates of clinical remission and corticosteroid-free remission at 12 months were similar between both groups: 63.8 versus 76.3% (p = 0.139) and 54.1 versus 44.7% (p = 0.354), respectively, for IFX and ADA. Combination therapy led to significantly higher remission rates at 12 months compared to monotherapy for patients on IFX (81.2 vs. 52.1%, p = 0.008), but not for those on ADA. Higher rates of adverse events were reported with IFX compared to ADA (p = 0.006). CONCLUSIONS: Our real-life experience in biologic-naïve CD patients demonstrated that patients started on IFX were more likely to have a harder-to-treat phenotype. Despite that, efficacy end points were similar between both groups. Clinical remission was higher in patients with combination therapy for IFX, but not for those on ADA. This warrants further investigation.
Asunto(s)
Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Infliximab/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Investigación sobre la Eficacia Comparativa , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Clinical efficacy and risk of complications are associated with intracellular levels of thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurines (6-MMP) in patients with Crohn's disease. Therapeutic monitoring of thiopurine metabolites is not widely available. Surrogate markers such as hematologic indices (MCV, leukopenia) have been proposed. AIMS: To evaluate accuracy of hematologic indices for prediction of therapeutic levels of thiopurine metabolites. METHODS: A retrospective cross-sectional study. We included patients treated with thiopurines for IBD between February 2008 and November 2013. Hematologic indices were correlated with thiopurine metabolites and compared to pre-treatment levels. RESULTS: A total of 168 patients with 608 measurements were included. Macrocytosis was observed in 4.5 % of the patients. On multivariate analysis, macrocytosis was associated with 6-TGN levels >235 pmol/8 × 10(8) erythrocytes and 6-mmp levels >5,700 pmol/8 × 10(8) erythrocytes. Therapeutic 6-TGN levels were associated with MCV, ΔMCV, macrocytosis and lymphocyte count. Sensitivity and Spearman's r correlation for prediction of therapeutic metabolite levels were poor for all hematologic indices. CONCLUSION: Although macrocytosis and an elevated MCV are associated with therapeutic 6-TGN levels, the correlation is weak. None of the evaluated hematologic indices is a reliable surrogate marker for thiopurine metabolite levels.