P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies

Abstract

Background Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab. Methods In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8. Results Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up. Conclusion After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis

“…Of the 202 citations identified with the search strategy, 17 studies including 1162 patients with UC were eligible to be included in this review. [5][6][7][11][12][13][14][15][16][17][18][19][20][21][22][23][24] (Supplementary Table 1). Six studies were reported as full-text articles, and 11 were conference proceedings.…”

“…Dose escalation rates were reported in 4 studies. 6,12,13,20 During follow-up, dose escalation to 10 mg twice daily was required in 46.3% of patients (95% CI, 35.8-56.9; range, 27%-79%). Three studies 6,12,13 reported dose escalation outcomes with 22 of 38 of the patients (57.9%; 95% CI, 40.9%-74.9%; range, 47%-80%) recovering clinical response.…”

Effectiveness and Safety of Tofacitinib for Ulcerative Colitis

“…After excluding 32 studies for reasons documented in Figure 1, 24 articles representing 26 independent studies were included in our analysis. 7,[10][11][12][13][14][15][16][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] An RCT study design was used in 4 studies, 7,34 and the rest were observational designs. Twenty studies reported efficacy outcomes 7,[10][11][12][13][14][15][16]31,[33][34][35][36][37][38][39][40]42,44,45 and 25 studies reported safety outcomes.…”

Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis

“…To safeguard our findings against the emergence of future publications, we repeated our analyses with the inclusion of conference abstracts that have not to date been published in full. 29 , 31 , 37 – 40 This search had yielded an additional six studies including a total of 332 patients on top of those reported here. The results from this analysis did not deviate substantially from the findings we have reported (data not shown).…”