RESUMEN
INTRODUCTION: 5-aminosalicylic acid (5-ASA) is the first-line drug for the treatment of mild-to-moderate ulcerative colitis (UC). Three oral sustained-release formulations are often used. However, no unified view of their actual use in routine medical practice has been presented to date. METHODS: Using a health insurance claims database, we extracted patients with an initial diagnosis of mild-to-moderate UC during the period from December 1, 2017, to March 31, 2022. For the three types of oral 5-ASA formulation, we calculated and compared descriptive statistics of medication persistence rates (MPR), proportions of days covered (PDC), and adherence proportion (PDC ≥80%) in the extracted population. RESULTS: An oral 5-ASA formulation was used in combination with a topical preparation (cohort 1) in 899 patients, and oral 5-ASA was used alone (cohort 2) in 1,829 patients. In cohort 1, MPR at days 151-180 with concomitant use of topical formulation was significantly higher for the Multi Matrix System™ (MMX) formulation (65.2%) compared with that for pH-dependent formulation (51.7%, p < 0.025), while MPR tended to be higher for MMX than for the time-dependent formulation (56.4%, not significant). During days 151-180 after starting the oral formulation, MPR for MMX (66.7% and 65.8%) was higher than for pH-dependent (55.9% and 55.3%) and time-dependent (57.6% and 55.9%) formulations in cohorts 1 + 2 and 2, respectively. In cohort 1, there was a significant difference between MMX (68.3%) and pH-dependent (57.1%) formulations, but no significant difference was seen with time-dependent formulations (61.8%). In terms of the proportion of adherence until day 180, MMX was significantly better than the other formulations. CONCLUSION: The analyses of the three oral 5-ASA formulations suggested that both MPR and medication adherence were better for the MMX formulation than for time-dependent or pH-dependent formulations.
Asunto(s)
Antiinflamatorios no Esteroideos , Colitis Ulcerosa , Bases de Datos Factuales , Cumplimiento de la Medicación , Mesalamina , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Mesalamina/administración & dosificación , Mesalamina/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Masculino , Femenino , Administración Oral , Persona de Mediana Edad , Adulto , Japón , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Anciano , Preparaciones de Acción Retardada , Estudios Retrospectivos , Adulto Joven , Administración Tópica , Pueblos del Este de AsiaRESUMEN
Nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive activity and may be suitable for treatment of colorectal cancer. A popular and potent NSAID, indomethacin, is known to cause serious side-effects, for this reason its therapeutic usefulness is limited. However, these side-effects are likely to be attributed to the additional effects of indomethacin besides its cyclooxygenase inhibition. In this study, we examined the effect of indomethacin on arachidonic acid uptake using LS174T human colon cancer cells. We here show that treatment of LS174T cells with indomethacin reduced arachidonic acid uptake as well as reduced expressions of fatty acid translocase/CD36 and peroxisome proliferators-activated receptor gamma. Since arachidonic acid is a major substrate of inflammatory mediators such as prostaglandins and leukotrienes, we believe this novel effect of indomethacin may apply to new treatment strategies that aim to suppress these mediators by decreasing the uptake of their substrates, which would eventually inhibit colorectal cancer malignancy.
Asunto(s)
Ácido Araquidónico/metabolismo , Neoplasias del Colon/metabolismo , Inhibidores de la Ciclooxigenasa 2/farmacología , Indometacina/farmacología , Western Blotting , Antígenos CD36/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Proteínas de Transporte de Ácidos Grasos/metabolismo , Humanos , PPAR gamma/metabolismoRESUMEN
Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of colorectal cancer. However, evidence is accumulating that NSAIDs have anti-cancer effects in addition to inhibiting cyclooxygenase (COX)-mediated prostanoid biosynthesis. We now show that indomethacin, a popular NSAID, significantly reduced the [3H]-arachidonic acid uptake in HCA-7 human colon cancer cells. Interestingly, no decrease in the uptake of [3H]-arachidonic acid occurred when the cells were treated with aspirin, diclofenac, and sulindac even though the concentrations of these NSAIDs were high enough to inhibit COX-2 activity. These findings suggest that indomethacin has a novel anti-cancer effect that may be independent of COX-2 inhibition.