OP29 Tofacitinib in ulcerative colitis: Real-world evidence from Eneida Registry
M. Chaparro1, A. Garre1, F. Mesonero2, C. Rodríguez3, M. Barreiro-de Acosta4, J. Martínez-Cadilla5, M.T. Arroyo6, N. Manceñido7, M. Sierra-Ausín8, I. Vera-Mendoza9, M.J. Casanova1, P. Nos10, C. González-Muñoza11, T. Martínez12, M. Boscá-Watts13, D. Busquets14, M. Calafat15, E. Girona16, J. Llaó17, M.D. Martín-Arranz18, M. Piqueras19, L. Ramos20, G. Suis21, F. Bermejo22, A.Y. Carbajo23, D. Casas-Deza24, A. Fernández-Clotet25, M.J. García26, D. Ginard27, A. Gutiérrez-Casbas28, L. Hernández-Villalba29, A.J. Lucendo30, L. Márquez31, O. Merino-Ochoa32, F.J. Rancel33, C. Taxonera34, A. López Sanromán2, S. Rubio3, E. Domènech15, J.P. Gisbert1
1Gastroenterology Unit, Hospital Universitario de La Princesa- IIS-IP- Universidad Autónoma de Madrid- and CIBEREHD, Madrid, Spain, 2Gastroenterology Unit, Hospital Universitario Ramón y Cajal, Madrid, Spain, 3Gastroenterology Unit, Complejo Hospitalario de Navarra, Pamplona, Spain, 4Gastroenterology Unit, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain, 5Gastroenterology Unit, Hospital Álvaro Cunqueiro- Complexo Hospitalario Universitario de Vigo, Vigo, Spain, 6Gastroenterology Unit, Hospital Clínico Universitario Lozano Blesa- IIS Aragón and CIBEREHD, Zaragoza, Spain, 7Gastroenterology Unit, San Sebastián de los Reyes, Hospital Universitario Infanta Sofía., Spain, 8Gastroenterology Unit, Complejo Asistencial Universitario de León, León, Spain, 9Gastroenterology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, 10Department of Gastroenterology Unit, Hospital Universitario y Politécnico La Fe and CIBEREHD, Valencia, Spain, 11Department of Gastroenterology Unit, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain, 12Gastroenterology Unit, Hospital Virgen de la Luz, Cuenca, Spain, 13Gastroenterology Unit, Hospital Clinico de Valencia and Universitat de Valencia, Valencia, Spain, 14Gastroenteroloy Unit, Hospital Universitario de Gerona Dr Josep Trueta, Gerona, Spain, 15Gastroenterology Unit, Hospital Germans Trials i Pujol and CIBERehd, Barcelona, Spain, 16Gastroenterology Unit, Hospital General Universitario de Elche, Elche, Spain, 17Gastroenterology Unit, Hospital Sant Joan de Déu- Althaia- Xarxa Assistencial Universitària de Manresa, Barcelona, Spain, 18Gastroenterology Unit, Hospital Universitario La Paz and IdiPaz, Madrid, Spain, 19Gastroenterology Unit, Consorci Sanitari de Terrasa, Barcelona, Spain, 20Gastroenterology Unit, Hospital Universitario de Canarias, Islas Canarias, Spain, 21Gastroenterology Unit, Hospital de Bellvitge and IDIBELL, Barcelona, Spain, 22Gastroenterology Unit, Hospital Universitario de Fuenlabrada. Instituto de Investigación de La Paz IdiPaz, Madrid, Spain, 23Gastroenterology Unit, Hospital Universitario Río Hortega, Valladolid, Spain, 24Gastroenterology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain, 25Gastroenterology Unit, Hospital Clìnic de Barcelona, Barcelona, Spain, 26Gastroenterology Unit, Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain, 27Gastroenterology Unit, Hospital Universitario Son Espases, Palma de Mallorca, Spain, 28Gastroenterology Unit, Hospital General Universitario de Alicante and CIBERehd, Alicante, Spain, 29Gastroenterology Unit, Hospital Santos Reyes de Aranda del Duero, Burgos, Spain, 30Gastroenterology Unit, Hospital General de Tomelloso and CIBEREHD, Ciudad Real, Spain, 31Gastroenterology Unit, Hospital del Mar and Institut Hospital del Mar d’Investigacions Mèdiques, Barcelona, Spain, 32Gastroenterology Unit, Hospital Universitario de Cruces, Vizcaya, Spain, 33Gastroenterology Unit, Complejo Hospitalario de Palencia, Palencia, Spain, 34Gastroenterology Unit, Hospital Clínico San Carlos and IdISSC, Madrid, Spain
Background
Our aim was to evaluate the effectiveness and safety of tofacitinib in ulcerative colitis (UC) in real life.
Methods
Patients from the prospectively maintained ENEIDA registry treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 4, 8 and 16. The last-observation-carried-forward method was used in patients that stopped tofacitinib before the time-points for clinical assessment. Variables associated with short-term remission at week 8 were identified by logistic regression analysis. The cumulative retention rate and the cumulative incidence of relapse over time were assessed by survival curves. Cox-regression analysis was performed to identify predictive factors of tofacitinib discontinuation or relapse over time. Data quality was assessed by remote monitoring.
Results
113 patients were included (Table 1 and Figure 1) and exposed to tofacitinib a median of 44 (interquartile range = 30–66) weeks. Response and remission at week 8 were 60% and 31%, respectively (Figure 2). In multivariate analysis, higher PMS at week 4 [odds ratio (OR)=0.2; 95% confidence interval (CI) = 0.1–0.4] was the only variable associated with the likeliness of achieving remission at week 8. Higher PMS at week 4 (OR = 0.5; 95% CI = 0.3–0.7) and higher PMS at week 8 (OR = 0.2; 95% CI = 0.1–0.5) were associated with lower probability of achieving remission at week 16. Twenty per cent of those without remission at week 4, and 12% of those without remission at week 8, achieved remission at week 16. A total of 45 patients (40%) discontinued tofacitinib over time (Figure 3); the discontinuation rate was 34% and 46% at 24 and 52 weeks, respectively. PMS at week 8 was the only factor associated with tofacitinib discontinuation [Hazard ratio (HR) = 1.5; 95% CI = 1.3–1.6)]. A total of 33 patients had remission at week 8; from them, 65% relapsed 52 weeks after achieving remission; 9 patients increased the dose to 10 mg /12 h and 5 reached remission again. No factors associated with relapse over time were identified. Eighteen patients had adverse events (4 hypercholesterolaemia, 2 herpes zoster, 3 infections, 2 dyspnoea, 1 neoplasia, 1 lymphopenia, 1 headache, 1 hypertriglyceridaemia and 4 others). No thromboembolic events were reported.
Conclusion
Tofacitinib is relatively effective in UC patients in real practice even in a highly refractory cohort. Only 10% of the patients without remission at week 8 reached remission at week 16. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure. Over 60% of patients that achieve remission, relapse over time. Safety was consistent with the known profile of tofacitinib