P373 Real world evidence of tofacinitib in ulcerative colitis: short and long-term effectiveness, impact of extraintestinal manifestations and immunomediated diseases and safety

Chaparro, M.(1);Acosta, D.(1);Rodríguez, C.(2);Vicuña, M.(2);Mesonero, F.(3);Barreiro-de Acosta, M.(4);Fernández-Clotet, A.(5);Hernández Martínez, Á.(6); Arroyo, M.T.(7);Vera Mendoza, I.(8);Sicilia, B.(9);Muñoz Villafranca, C.(10);Castro-Poceiro, J.(11);Martínez Cadilla, J.(12);Vázquez Morón, J.M.(13);Montil, E.(14);Sierra-Ausín , M.(15);Calafat, M.(16); Leo Carnerero, E.(17);Manceñido Marcos, N.(18);Torrealba M, L.(19); Alonso-Galán, H.(20); Benítez, J.M.(21);Ber Nieto, Y.(22);Cabello Tapia, M.J.(23);Diz-Lois Palomares, M.T.(24);García, M.J.(25);Armesto González, E.M.(26);Calvet Calvo, X.(27);Piqueras, M.(28);Dueñas Sadornil, C.(29); Pérez Calle, J.L.(30);Botella, B.(31); Martínez-Pérez, T.D.J.(32);Ramos, L.(33);Rodríguez-Grau, M.C.(34);Fernández Forcelledo, J.L.(35); Gutiérrez, A.(36);Sesé Abizanda, E.(37);Gisbert, J.P.(1);

(1)Hospital Universitario de La Princesa- Instituto de Investigación Sanitaria Princesa IIS-IP and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBEREHD, Gastroenterology Unit, Madrid, Spain;(2)Hospital Universitario de Navarra HUN and Instituto de Investigación Sanitaria de Navarra IdiSNA, Gastroenterology Unit, Pamplona, Spain;(3)Hospital Universitario Ramón y Cajal, Gastroenterology Unit, Madrid, Spain;(4)Hospital Clínico Universitario de Santiago de Compostela, Gastroenterology Unit, Santiago de Compostela, Spain;(5)Hospital Clinic of Barcelona- Institut d'Investigacions Biomèdiques August Pi i Sunyer IDIBAPS and CIBERehd, Gastroenterology Unit, Barcelona, Spain;(6)Hospital Universitario Torrecárdenas, Gastroenterology Unit, Almería, Spain;(7)Hospital Clínico Universitario Lozano Blesa and Fundación del Instituto de Investigación Sanitaria de Aragón IIS Aragón and CIBEREHD, Gastroenterology Unit, Zaragoza, Spain;(8)Hospital Universitario Puerta de Hierro Majadahonda, Gastroenterology Unit, Madrid, Spain;(9)Hospital Universitario de Burgos, Gastroenterology Unit, Burgos, Spain;(10)Hospital de Basurto, Gastroenterology Unit, Basurto, Spain;(11)Hospital Sant Joan Despí-Moisès Broggi, Gastroenterology Unit, Barcelona, Spain;(12)Hospital Álvaro Cunqueiro. Xerencia Xestión Integrada de Vigo- SERGAS. Grupo de Investigación en Patología Digestiva. Instituto de Investigación Sanitaria Galicia Sur IIS Galicia Sur. SERGAS-UVIGO, Gastroenterology Unit, Vigo, Spain;(13)Hospital Universitario Juan Ramón Jiménez, Gastroenterology Unit, Huelva, Spain;(14)Hospital Universitario Miguel Servet, Gastroenterology Unit, Zaragoza, Spain;(15)Complejo Asistencial Universitario de León, Gastroenterology Unit, León, Spain;(16)Hospital Universitari Germans Trias i Pujol and CIBEREHD, Gastroenterology Unit, Badalona, Spain;(17)Hospital Universitario Virgen del Rocío, Gastroenterology Unit, Sevilla, Spain;(18)Hospital Universitario Infanta Sofía, Gastroenterology Unit, Madrid, Spain;(19)Hospital Universitario Dr. Josep Trueta, Gastroenterology Unit, Girona, Spain;(20)Hospital Universitario Donostia- Instituto Biodonostia, Gastroenterology Unit, San Sebastián, Spain;(21)Hospital Universitario Reina Sofía and IMIBIC, Gastroenterology Unit, Córdoba, Spain;(22)Hospital San Jorge, Gastroenterology Unit, Huesca, Spain;(23)Hospital Universitario Virgen de las Nieves, Gastroenterology Unit, Granada, Spain;(24)Complejo Hospitalario Universitario A Coruña, Gastroenterology Unit, A Coruña, Spain;(25)Hospital Universitario de Valdecilla and Instituto de Investigación Sanitaria Valdecilla IDIVAL, Gastroenterology Unit, Santander, Spain;(26)Hospital San Agustín, Gastroenterology Unit, Avilés, Spain;(27)Hospital Universitari Parc Taulí- Universitat Autònoma de Barcelona and CIBERehd, Gastroenterology Unit, Sabadell, Spain;(28)Consorci Sanitari de Terrassa, Gastroenterology Unit, Barcelona, Spain;(29)Hospital Universitario de Cáceres, Gastroenterology Unit, Cáceres, Spain;(30)Hospital Universitario Fundación Alcorcón, Gastroenterology Unit, Alcorcón, Spain;(31)Hospital Universitario Infanta Cristina, Gastroenterology Unit, Madrid, Spain;(32)Hospital Virgen de la Luz, Gastroenterology Unit, Cuenca, Spain;(33)Hospital Universitario de Canarias, Gastroenterology Unit, Santa Cruz de Tenerife, Spain;(34)Hospital Universitario del Henares, Gastroenterology Unit, Madrid, Spain;(35)Hospital Sierrallana, Gastroenterology Unit, Torrelavega, Spain;(36)Hospital General Universitario de Alicante- CIBERehd and Instituto de Investigación Sanitaria y Biomédica de Alicante ISABIAL, Gastroenterology Unit, Alicante, Spain;(37)Hospital Universitario Arnau de Vilanova, Gastroenterology Unit, Lleida, Spain; on behalf of To-ReWard study group


Main aim: To assess the retention rate of tofacitinib treatment in patients with ulcerative colitis (UC). Secondary aims: To assess the short-term effectiveness and the durability of response; to evaluate the evolution of extraintestinal manifestations (EIMs) and immunomediated inflammatory diseases (IMIDs); to assess the tolerability of tofacitinib in clinical practice.


Retrospective, multicenter study. UC patients who had received the first tofacitinib dose at least 8 weeks before the start date of recruitment. Patients were followed-up from the first tofacitinib dose to treatment discontinuation or last visit, whichever came first. Only patients with active disease [Partial Mayo Score (PMS)>2] were considered in the short-term effectiveness analysis. Clinical response was based on the PMS. Variables associated with short-term remission were identified by logistic regression analysis. Kaplan-Meier curves and Cox-regression analysis were used to evaluate the long-term effectiveness and durability of tofacitinib treatment.


335 patients have been included so far (recruitment still ongoing) (Table 1).

A total of 70 patients (21%) would have met the criteria for entering A3921133 trial. A total of 155 patients interrupted tofacitinib during follow-up (Figure 1a),
mainly due to primary non-response (46%) and loss of response (25%); predictive factors of tofacitinib discontinuation are shown in figure 1b.

Short-term effectiveness and predictive factors of remission are shown on figure 2; 16% of non-responders and 35% with partial response at week 4 reached remission at week 8, and 19% of non-responders and 37% of partial responders at week 8 reached remission at week 16. Of 151 patients in remission at week 8, 68 (45%) lost response (Figure 3);

tofacitinib dose was increased in 27%, and 71% of them reached remission again. Obvious blood with stool most of the time or blood alone passed at baseline was the only variable associated with losing response over time. There were 86 adverse events related to tofacitinib treatment (Table 2).

Fifty-seven patients (17%) had EIMs or IMIDs non-active at tofacitinib start; only 2 out of 12 patients with peripheral arthropathy worsened. 53 patients (16%) had active EIMs or IMIDs at the start of tofacitinib and some of them improved. A total of 17 EIMs or IMIDs occurred after starting tofacitinib but only 1 (vasculitis) caused tofacitinib withdrawal.


Tofacitinib is effective in inducing remission even in highly refractory UC patients. A relevant proportion of patients discontinue the treatment, mainly during the first months due to primary failure. The safety profile is similar to that previously reported for tofacitinib