RESUMEN
INTRODUCTION: The effective, but expensive, drug infliximab is used in patients with inflammatory bowel disease (IBD). Monitoring infliximab trough levels and anti-infliximab antibody (ATI) formation can lead to a more cost-effective use of infliximab therapy. The aim of our study was to investigate the effect of implementation of a treatment algorithm for infliximab in a single-centre IBD cohort, focussing on remission rates and drug costs. METHODS: IBD patients aged 18 years or older treated with infliximab were asked to participate in this study. Remission rates were assessed using faecal calprotectin levels and a validated questionnaire. Infliximab trough levels and ATIs were determined at baseline and at the third infliximab infusion. According to the advice given by the treatment algorithm, infliximab dosage adjustments were performed at the second infliximab infusion. RESULTS: Between January and December 2015 a total of 62 IBD patients in our centre were treated with infliximab, of whom 33 (53%) patients agreed to participate in this study. The number of patients in remission was 28 (85%) at baseline and there were 13 dose adaptations suggested by the treatment algorithm for the successive second infusion. Four patients possessed undetectable infliximab levels and positive ATI status at baseline. After the second infusion, there were 29 (88%) patients in remission at the third infusion. All of this resulted in an annual drug cost reduction of &OV0556;47 026 (7.4%). CONCLUSION: Our developed treatment algorithm of infliximab led to optimization of infliximab therapy in IBD patients by increasing remission rates and reducing drug costs.
Asunto(s)
Algoritmos , Fármacos Gastrointestinales/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/uso terapéutico , Adulto , Anticuerpos/sangre , Estudios de Cohortes , Costos de los Medicamentos , Femenino , Fármacos Gastrointestinales/sangre , Fármacos Gastrointestinales/economía , Fármacos Gastrointestinales/inmunología , Humanos , Infliximab/sangre , Infliximab/economía , Infliximab/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Resultado del TratamientoRESUMEN
BACKGROUND: Asthma is associated with airway hyperresponsiveness and enhanced T-cell number/activity on one hand and increased levels of exhaled nitric oxide (NO) with expression of inducible NO synthase (iNOS) on the other hand. These findings are in paradox, as NO also relaxes airway smooth muscle and has immunosuppressive properties. The exact role of the endothelial NOS (eNOS) isoform in asthma is still unknown. We hypothezised that a delicate regulation in the production of NO and its bioactive forms by eNOS might be the key to the pathogenesis of asthma. METHODS: The contribution of eNOS on the development of asthmatic features was examined. We used transgenic mice that overexpress eNOS and measured characteristic features of allergic asthma after sensitisation and challenge of these mice with the allergen ovalbumin. RESULTS: eNOS overexpression resulted in both increased eNOS activity and NO production in the lungs. Isolated thoracic lymph nodes cells from eNOS overexpressing mice that have been sensitized and challenged with ovalbumin produced significantly less of the cytokines IFN-gamma, IL-5 and IL-10. No difference in serum IgE levels could be found. Further, there was a 50% reduction in the number of lymphocytes and eosinophils in the lung lavage fluid of these animals. Finally, airway hyperresponsiveness to methacholine was abolished in eNOS overexpressing mice. CONCLUSION: These findings demonstrate that eNOS overexpression attenuates both airway inflammation and airway hyperresponsiveness in a model of allergic asthma. We suggest that a delicate balance in the production of bioactive forms of NO derived from eNOS might be essential in the pathophysiology of asthma.
Asunto(s)
Regulación Enzimológica de la Expresión Génica , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Óxido Nítrico Sintasa de Tipo III/genética , Hipersensibilidad Respiratoria/enzimología , Hipersensibilidad Respiratoria/prevención & control , Animales , Asma/enzimología , Asma/prevención & control , Hiperreactividad Bronquial/enzimología , Hiperreactividad Bronquial/prevención & control , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
We previously described two novel peptides, Ca2+-like peptide (CALP) 1 and CALP2, which interact with Ca2+-binding EF hand motifs, and therefore have the characteristics to define the role of the Ca2+-sensing regulatory protein calmodulin in asthma. In the present study, the effects of the calcium-like peptides were investigated in an animal model for allergic asthma. For that purpose, sensitized guinea pigs were intratracheally pretreated with CALP1 or CALP2. Thirty minutes later, the animals were challenged with aerosolized ovalbumin. Acute bronchoconstriction was measured as well as characteristic features of asthma 6 and 24 hours (h) after challenge. Neither CALP1 nor CALP2 prevented the anaphylactic response elicited by ovalbumin challenge. However, CALP1 pretreatment attenuated the influx of inflammatory cells in the lungs 6 h after challenge. Furthermore, radical production by these cells was diminished both 6 and 24 h after challenge. Moreover, CALP1 completely inhibited airway hyperresponsiveness in vitro 24 h after challenge. We conclude that CALP1, as a selective calmodulin agonist, inhibits the development of asthmatic features probably via the attenuation of mast cell degranulation and radical production. Specific modulation of calmodulin activity might therefore be a potential new target for the treatment of allergic asthma.