BACKGROUND: Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown.
AIM: To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC.
METHODS: Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan-Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered.
RESULTS: The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia.
CONCLUSIONS: Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin-infliximab) should be taken on an individual basis.
BACKGROUND: Corticosteroids are the treatment of choice for moderate-to-severe active ulcerative colitis (UC) but up to 30%-40% of patients fail to respond. It has been reported that early clinical-biological parameters may identify those patients at high risk of colectomy. The aim was to identify predictors of rapid response to systemic steroids in moderate-to-severe attacks of UC.
METHODS: Consecutive patients treated with prednisone 1 mg/kg/day for moderate-to-severe attacks of UC were prospectively included. Clinical and biological parameters at 3 and 7 days after starting steroids were recorded. Response was defined as mild or inactive UC activity at day 7 (as assessed by the Montreal Classification of severity) together with no need for rescue therapies (cyclosporin, infliximab, or colectomy). A logistic regression analysis was performed to identify those independent predictors of response. In addition, a decision-tree analysis was also performed.
RESULTS: Sixty-eight percent of patients (64 out of 94) responded to steroids. In the univariate analysis the number of bowel movements, rectal bleeding, platelet count, and C-reactive protein (CRP) levels at day 3 were associated with response at day 7, but only rectal bleeding was found to be an independent predictor in the logistic regression analysis. Conversely, the classification and regression tree (CART) model included these four variables. The decision-tree model showed a higher sensitivity in predicting a rapid response to steroids than the logistic regression one.
CONCLUSIONS: Rapid response to steroids in active UC attacks can be predicted after 3 days of treatment by simple clinical and biological parameters. A decision-tree model for early introduction of rescue therapies is provided.
OBJETIVOS: La terapia de rescate, ya sea con ciclosporina (CYS) o infliximab (IFX) es una opción efectiva en pacientes con ataques refractarios a esteroides intravenosos de la colitis ulcerosa (CU). En pacientes que no, colectomía generalmente se recomienda, pero un tratamiento de rescate de segunda línea con IFX o CYS es una alternativa. Los objetivos de este estudio fueron investigar la eficacia y tolerancia de IFX y CYS como terapia de rescate de segunda línea en la CU refractaria a esteroides o colitis indeterminada (CI) sin éxito tratados con CYS o IFX.
MÉTODOS: Se realizó un estudio retrospectivo de los pacientes atendidos durante el período 2000-2008 en los centros GETAID. Los criterios de inclusión incluyeron un retraso de <1 mes entre la retirada CYS (cuando se utiliza en primer lugar) y IFX, o un retraso de <2 meses entre IFX (cuando se utiliza en primer lugar) y CYS, y un seguimiento de al menos 3 meses después de la inclusión. Se analizó el tiempo de lanzamiento a la colectomía, la respuesta clínica, y la ocurrencia de eventos adversos graves.
RESULTADOS: Un total de 86 pacientes (edad media 34 años; 49 varones; 71 UC y 15 CI) se trata sucesivamente con CYS y IFX. La mediana (± se) el tiempo de seguimiento fue de 22,6 (7,0) meses. Durante el período de estudio, 49 pacientes no respondieron a la terapia de rescate de segunda línea y se les realizó una colectomía. La probabilidad de supervivencia libre de colectomía (± SE) fue 61,3 ± 5,3% a los 3 meses y 41,3 ± 5,6% a los 12 meses. Un caso de embolia pulmonar fatal ocurrió en 1 día después de la cirugía en un hombre de 45 años de edad. Además, se observaron nueve complicaciones infecciosas durante el tratamiento de rescate de segunda línea.
Conclusiones: En los pacientes con CU refractaria a esteroides por vía intravenosa y que no responden a CYS o IFX, una terapia de rescate de segunda línea puede ser eficaz en pacientes cuidadosamente seleccionados, evitando la colectomía plazo de 2 meses en dos tercios de ellos. La relación riesgo / beneficio aún debe ser considerado individualmente.
ANTECEDENTES Y OBJETIVOS: En los pacientes con colitis ulcerosa grave refractaria corticosteroides, ciclosporina o infliximab se pueden añadir en un esfuerzo para inducir la remisión. Si el paciente luego falla cualquiera de estos fármacos, se desconoce si el éxito se puede lograr mediante el uso de otro agente. El objetivo de este estudio fue evaluar los resultados de la utilización de ciclosporina tras el fracaso de infliximab, y viceversa.
MÉTODOS: Se revisaron retrospectivamente las historias clínicas de 19 pacientes con colitis ulcerosa corticosteroides refractario que recibieron infliximab ciclosporina o ciclosporina infliximab tras fracaso tras fracaso. Terapia de rescate aguda se define como haber recibido el medicamento alternativo dentro de las 4 semanas de descontinuar el primer agente.
RESULTADOS: Diez pacientes recibieron infliximab tras no ciclosporina; 9 pacientes recibieron ciclosporina después de no infliximab. Cuatro pacientes (40%) en el grupo de infliximab-rescate alcanzaron la remisión, al igual que 3 (33%) en el grupo ciclosporina salvamento. La remisión duró una media de 10,4 meses (rango, 4,4 a 17,03 mo) y 28,5 meses (rango, 5,0-41,5 meses), respectivamente. Los eventos adversos graves incluido un paciente que desarrolló sepsis y murió después de recibir rescate con infliximab. Un paciente que recibió ciclosporina salvamento desarrolló esofagitis herpética, y otro paciente que recibió ciclosporina salvamento desarrollado pancreatitis y bacteriemia.
Conclusiones: En los pacientes con colitis ulcerosa grave corticosteroides refractaria que no tratamiento con ciclosporina o infliximab, las tasas de remisión que utilizan la terapia de rescate aguda por cruzar a la otra droga ocurren en aproximadamente un tercio de los pacientes y han duración limitada. Los eventos adversos graves se produjeron en el 16%, incluyendo 1 muerte, lo que sugiere que los riesgos de la terapia de rescate aguda pueden ser mayores que los beneficios.
Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown.
AIM:
To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC.
METHODS:
Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan-Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered.
RESULTS:
The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia.
CONCLUSIONS:
Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin-infliximab) should be taken on an individual basis.
