P618 Adalimumab dose escalation is effective for managing loss of response in Ulcerative Colitis
C. Taxonera*1, 2, E. Iglesias3, F. Muñoz4, M. Calvo5, M. Barreiro-de Acosta6, D. Busquets7, X. Calvet8, A. Rodríguez9, R. Pajares10, J.P. Gisbert11, 12, J.L. Pérez-Calle13, P. López-Serrano13, A. Ponferrada14, C. de la Coba15, F. Bermejo16, M. Chaparro11, 12, J.L. Mendoza1, 2, D. Olivares1, 2, I. Fernández-Blanco17
1Hospital Clínico San Carlos, IBD Unit, Madrid, Spain, 2Hospital Clínico San Carlos, IdISSC, Madrid, Spain, 3Hospital Reina Sofía, Gastroenterology, Córdoba, Spain, 4Hospital de León, Gastroenterology, León, Spain, 5Hospital Puerta de Hierro, Gastroenterology Unit, Madrid, Spain, 6Hospital Clínico de Santiago, Gastroenterology, Santiago de Compostela, Spain, 7Hospital Josep Trueta, Gastroenterology, Girona, Spain, 8Corporació Sanitària Parc Taulí, Servei d'Aparell Digestiu, Sabadell, Spain, 9Hospital Universitario de Salamanca, Gastroenterology, Salamanca, Spain, 10Hospital Infanta Sofía, Gastroenterology, San Sebastián de los Reyes. Madrid, Spain, 11Hospital La Princesa, Gastroenterology Unit, Madrid, Spain, 12Hospital La Princesa , IP and CIBERehd, Gastroenterology, Madrid, Spain, 13Hospital de Alcorcón, Gastroenterology Unit, Madrid, Spain, 14Hospital Infanta Leonor, Gastroenterology, Madrid, Spain, 15Hospital de Cabueñes, Digestive Department, Gijon, Spain, 16Hospital de Fuenlabrada, Gastroenterology Unit, Madrid, Spain, 17Hospital Moncloa, Gastrointestinal Surgery, Madrid, Spain
The outcomes of adalimumab dose escalation in ulcerative colitis (UC) are not well known. The aim of this study was to assess the short- and long-term outcomes of adalimumab dose escalation in a cohort of UC patients who had lost response to the drug.
This was a retrospective multicentre cohort study. All consecutive UC out-patients who required adalimumab dose escalation for loss of response were included. Post-escalation short-term clinical response and remission were evaluated. Clinical response was defined as a 3-point decrease in the Partial Mayo Score (PMS) or a decrease of at least 50% in the PMS and a final PMS of 2 or less. Clinical remission was defined as a PMS of 0 or 1. In the long-term, the cumulative probabilities of adalimumab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression and Cox proportional hazard regression analysis.
Of the 200 UC patients who received adalimumab therapy, 76 (38%) required escalation to weekly adalimumab dosing and composed the study population. Of these escalated patients, 41 (54%) were male, with a mean age of 46 (SD 14) years and a median disease duration of 11 (interquartile range [IQR] 2-20) years. Sixty-two patients (81%) had previous anti-TNF use. Thirty-six (47%) achieved short-term clinical response, of these 15 (20%) entered into clinical remission. The mean PMS was 6 (range 4-9; standard deviation [SD] 1.5) at baseline and 3.6 (range 0-8; SD 2.3) at week 8-12 (p<0.001). There were no factors associated with short-term response. After a median follow-up of 9 months (IQR 8-26), 43 patients (56%) had adalimumab failure. Patients with short-term response had a significantly lower adjusted rate of adalimumab failure (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.12-0.80; p<0.01). During a median follow-up of 17 months (IQR 13-34), 16 patients (21%) needed colectomy. Median time to colectomy was 5.9 months (IQR 4-14). Short-term response was identified as a predictor of colectomy avoidance (HR 0.53; 95% CI 0.03-0.69; p<0.007).
Adalimumab dose escalation was required in 38% of UC patients. Nearly 50% of patients regained response with weekly adalimumab dosing. In the long term, 44% of patients maintained sustained clinical benefit, and 8 of 10 avoided colectomy. Short-term response was associated with a 50% reduction in the relative risk of colectomy.