P512 Efficacy of tofacitinib for the treatment of moderate-to-severe ulcerative colitis: real-world data

Abstract

Background A significant proportion of patients do not respond to therapy for moderate to severe ulcerative colitis (UC), including thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-a and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, data on its real-life efficacy remains sparse. Methods We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included the rate of biomarker normalisation, corticosteroids-free clinical remission and severe infections. We conducted a multi-centre retrospective observational study of adult patients with active UC started on tofacitinib from January 1, 2015 to October 1, 2019 at the McGill University Health Center and Hotel-Dieu de Lévis. A positive clinical response was defined as a decrease of ≥3 in the partial Mayo score. Clinical remission was defined as partial Mayo score of ≤2. Biomarker normalisation was defined as faecal calprotectin ≤250 μg/g. Severe infection was defined as an infection requiring hospitalisation. Results During the study period, 40 patients with UC were started on tofacitinib at 10 mg/kg twice a day. Amongst the patients, 85% (n = 34) had failed ≥1 biologic and 50% (n = 20) had failed ≥3 biologics. At the time of this preliminary analysis, 38 patients had undergone 3 months of treatment; 30 patients had undergone 6 months of treatment. At 3 months, a clinical response was seen in 89.5% of patients (n = 34) and clinical remission occurred in 63.2%(n = 24). At 6 months, clinical response occurred in 73.3% of patients (n = 22) and clinical remission was sustained in 53.33% (n = 16). Biochemical normalisation occurred in 29.0% (n = 11) and 30.0% (n = 9) at 3 and 6 months respectively. Additionally, 63.2% (n = 24) of patients and 43.3% (n = 13) of patients achieved steroid-free clinical remission at 3 and 6 months respectively. In the interim, one patient developed a serious infection requiring discontinuation of the drug. Conclusion Our preliminary analysis demonstrates that in a real-life setting, tofacitinib is an effective treatment for inducing clinical remission in refractory UC patients. Further data will be complied to better assess the efficacy over a longer follow-up.

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).…”

“…Therefore, extracting data for predictors of response or testing for differences in outcomes between real-world patients and the OCTAVE trials was not achievable. Second, real-world studies comprising patients treated before 30 May 2018 12 , 16 , 39 used off-label medication or accessed it through compassionate programmes which restricted the selection criteria to severe, refractory cases. Other studies 42 exclusively included patients refractory to other biologics (anti-TNF and vedolizumab).…”

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

“…There is limited evidence on the use of tofacitinib for moderately-to-severe UC outside RCTs. 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 31,17,21,32,33,34 . This search had yielded an additional 6 studies including a total of 332 patients on top of those reported here.…”

“…Therefore, extracting data for predictors of response or testing for differences in outcomes between real-world patients and the OCTAVE trials was not achievable. Secondly, real-world studies comprising patients treated before the 30 th of May 2018 22, 36, 33 used off-label medication or accessed it through compassionate programs which restricted the selection criteria to severe, refractory cases. Other studies 37 exclusively included patients refractory to other biologics (anti-TNF and vedolizumab).…”