Abstract and Introduction
Abstract
Background: Data comparing tofacitinib and vedolizumab in ulcerative colitis (UC) are lacking.
Aims: To compare the effectiveness of tofacitinib and vedolizumab in patients with UC who had prior exposure to anti-TNF therapy
Methods: In this multicentre study, we included consecutive patients with UC ≥18 years old with partial Mayo score >2 and prior anti-TNF exposure, who started tofacitinib or vedolizumab between January 2019 and June 2021. Comparisons were performed using propensity score analyses (inverse probability of treatment weighting).
Results: Overall, 126 and 178 patients received tofacitinib and vedolizumab, respectively. Intensified induction (vedolizumab infusion at week 10 or tofacitinib 10 mg b.d until week 16) was performed in 28.5% and 41.5% of patients, respectively.
After propensity-score analysis, corticosteroid-free clinical remission (partial Mayo score ≤2) was achieved at week 16 in 45.1% and 40.2% of patients receiving tofacitinib and vedolizumab, respectively (aOR = 0.82 [0.35–1.91], p = 0.64). Endoscopic improvement (corticosteroid-free clinical remission and endoscopic Mayo score ≤1) (aOR = 0.23[0.08–0.65], p = 0.0032) and histological healing (endoscopic improvement + Nancy histological index ≤1) (13.4% vs 3.2%, aOR = 0.21[0.05–0.91], p = 0.023) were higher at week 16 in patients treated with tofacitinib. No factor was predictive of tofacitinib effectiveness. At least one primary failure to a biologic (OR = 0.46[0.22–0.99], p = 0.049), partial Mayo score >6 (OR = 0.39[0.17–0.90], p = 0.029) and CRP level > 30 mg/L at baseline (OR = 0.08[0.01–0.85], p = 0.036) were associated with vedolizumab failure.
Conclusion: Tofacitinib and vedolizumab are effective in UC after failure of anti-TNF agents. However, tofacitinib seems more effective, especially in severe disease and primary failure to biologics.
Introduction
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that dramatically affects patients' quality of life.[1,2] In addition, its chronic course can lead to colonic motility disorders, decreased rectal compliance, colectomy or colorectal cancer.[2] After failure of conventional therapies (salicylates, corticosteroids or immunosuppressants), anti-TNF agents are the most frequently used medications as first line of biologics in patients with UC. However, only 20%–30% of them achieve clinical and endoscopic remission on anti-TNF drugs.[3] Thus, the use of a second line-biological therapy is a common situation in patients with UC. Apart from the other anti-TNF agents and interleukin 12/23 antagonists (ustekinumab), two other therapeutic classes are currently available: JAK inhibitors (tofacitinib) and anti-integrins (vedolizumab). These treatments have been shown to be effective in randomised controlled trials against placebo.[4–6] Vedolizumab has recently shown its superiority over adalimumab (anti-TNF) in biologics-naïve patients with UC.[6] Even if the efficacy of vedolizumab seems to be less important as second line of biologics, the results of the VARSITY study have prompted clinicians to use this treatment more frequently, especially because it induces very few side effects. However, it currently requires intravenous infusions at the IBD clinic, at least for induction period (subcutaneous vedolizumab has been recently approved), which can affect patients' quality of life of patients.[7] More recently, tofacitinib, which has the advantage of being administered orally, has shown promising efficacy in some network meta-analyses after biologics failure.[8,9] Three options are possible to compare tofacitinib and vedolizumab. While there is currently no head-to-head randomised controlled trial and the comparisons from network meta-analysis seem inconclusive, real-world evidence is still lacking to compare these two drugs. Only one small sample size Dutch cohort recently suggest a superiority of tofacitinib over vedolizumab without identification of any predictor and absence of endoscopic and histological data.[10]
In our study, we aimed to compare the effectiveness of tofacitinib and vedolizumab in a large and multicenter cohort of UC patients with prior exposure to at least one anti-TNF agent.
Aliment Pharmacol Ther. 2023;57(6):676-688. © 2023 Blackwell Publishing
