P373 Real world evidence of tofacinitib in ulcerative colitis: short and long-term effectiveness, impact of extraintestinal manifestations and immunomediated diseases and safety
Authors: Chaparro M , Acosta D , Rodríguez C , Vicuña M , Mesonero F , Barreiro-de Acosta M , Fernández-Clotet A , Hernández Martínez Á , Arroyo M T , Vera Mendoza I , Sicilia B , Muñoz Villafranca C , Castro-Poceiro J , Martínez Cadilla J , Vázquez Morón J M , Montil E , Sierra-Ausín M , Calafat M , Leo Carnerero E , Manceñido Marcos N , Torrealba M L , Alonso-Galán H , Benítez J M , Ber Nieto Y , Cabello Tapia M J , Diz-Lois Palomares M T , García M J , Armesto González E M , Calvet Calvo X , Piqueras M , Dueñas Sadornil C , Pérez Calle J L , Botella B , Martínez-Pérez T D J , Ramos L , Rodríguez-Grau M C , Fernández Forcelledo J L , Gutiérrez A , Sesé Abizanda E , Gisbert J P 
Published: January 2022

Abstract

Background
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.

Methods
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)&gt;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.

Results
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.

Conclusion
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